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Biomedical subjects

R M González

Publications and source records attributed to R M González.

At least 19 recordsLinked to original sources
PubMed2007

In Vitro effect of D-004, a lipid extract of the ground fruits of the Cuban royal palm (Roystonea regia), on rat microsomal lipid peroxidation.

D-004 is a lipid extract of the fruits of the Cuban royal palm (Roystonea regia) containing a mixture of saturated fatty acids. D-004 inhibits prostate hyperplasia (PH) induced with testosterone, in rodents. Since fatty acids inhibit lipid peroxidation (LP), this study investigated whether D-004 prevents in vitro LP. D-004 (0.9-1000 microg/mL) markedly and dose-dependently inhibited in vitro iron-induced LP in native brain and liver microsomes. D-004 showed hydroxyl radical scavenging activity, which could explain partially its antioxidant effect on microsomal iron-induced LP, but it was unable to scavenge superoxide and ABTS radicals, indicating a limited radical scavenging activity. Also, D-004 inhibited CCl4-mediated LP in active liver microsomes through a decreased generation of radical species rather than a radical trapping action on CCl(4)-derived radical species. D-004 also inhibited lipooxygenase (LOX) and cyclooxygenase (COX) activities, and the generation of protein-associated carbonyl groups after LP. Since increased oxidative stress has been linked to PH, the antioxidant effect of D-004 shown here could contribute to explaining its beneficial effects on T-induced PH in rodents. Nevertheless, this study shows only in vitro results. Further studies should investigate whether D-004 also exhibits antioxidant effects in vivo.

Animals↗
PubMed2006

Evaluation of the genotoxic potential of Mangifera indica L. extract (Vimang), a new natural product with antioxidant activity.

Mangifera indica L. extract (Vimang) consists of a defined mixture of components (polyphenols, terpenoids, steroids, fatty acids and microelements). It contains a variety of polyphenols, phenolic esters, flavan-3-ols and a xanthone (mangiferin), as main component. This extract has antioxidant action, antitumor and immunemodulatory effects proved in experimental models in both in vitro and in vivo assays. The present study was performed to investigate the genotoxicity potential activity of Vimang assessed through different tests: Ames, Comet and micronucleus assays. Positive and negative controls were included in each experimental series. Histidine requiring mutants of Salmonella typhimurium TA1535, TA1537, TA1538, TA98, TA100 and TA102 strains for point-mutation tests and in vitro micronucleus assay in primary human lymphocytes with and without metabolic activation were performed. In addition, genotoxic effects were evaluated on blood peripheral lymphocytes of NMRI mice of both sexes, which were treated during 2 days with intraperitoneal doses of M. indica L. extract (50-150 mg/kg). The observed results permitted to affirm that Vimang (200-5,000 microg/plate) did not increase the frequency of reverse mutations in the Ames test in presence or not of metabolic activation. Results of Comet assay showed that the extract did not induce single strand breaks or alkali-labile sites on blood peripheral lymphocytes of treated animals compared with controls. On the other hand, the results of the micronucleus studies (in vitro and in vivo) showed Vimang induces cytotoxic activity, determined as cell viability or PCE/NCE ratio, but neither increased the frequency of micronucleated binucleate cells in culture of human lymphocytes nor in mice bone marrow cells under our experimental conditions. The positive control chemicals included in each experiment induced the expected changes. The present results indicate that M. indica L. extract showed evidences of light cytotoxic activity but did not induce a mutagenic or genotoxic effects in the battery of assays used.

Animals↗
PubMed2004

Oral administration of D-003, a mixture of very long chain fatty acids prevents casein-induced endogenous hypercholesterolemia in rabbits.

D-003 is a mixture of very long chain saturated fatty acids (VLCSFA) purified from sugar cane wax with cholesterol-lowering effects proven in animal models and healthy volunteers. D-003 inhibits cholesterol biosynthesis through the regulation of HMG-CoA reductase activity. Rabbits fed diets enriched with casein develop endogenous hypercholesterolemia (EH), making them a very useful model for determining the mechanism of action of drugs affecting lipids. We examined whether D-003 prevented EH. Rabbits were fed a casein diet for 4 weeks, administered simultaneously with D-003 (5, 50, and 100 mg.kg-1.day-1). As expected, nontreated rabbits became hypercholesterolemic; however, as early as 15 days following administration, the treated group (50 and 100 mg.kg-1.day-1) had significantly decreased total cholesterol and low-density lipoprotein cholesterol (LDL-C). Triglycerides were not affected; however, at study completion, HDL-C levels significantly increased at all the doses assayed. D-003 inhibited de novo synthesis of cholesterol, since the incorporation of 3H2O into sterols in the liver and proximal small bowel was significantly depressed. Also, D-003 significantly raised the rate of removal of [125I]-LDL from serum and significantly elevated [125I]-LDL binding activity to liver homogenates. Taken together, these results show that the efficacy of D-003 in reducing casein-derived hypercholesterolemia could involve, at least partially, an inhibition of hepatic cholesterol biosynthesis, which may elicit a decreased cholesterol concentration in hepatocytes, preventing the loss of hepatic LDL receptors induced by casein administration. However, since casein-induced hypercholesterolemia is also a consequence of a stimulation of cholesterol absorption in the lumen and an increase of the output of cholesterol associated with LDL, the effect of D-003 on cholesterol absorption and LDL synthesis by the liver should be investigated.

Administration, Oral↗
PubMed2002

Inhibition of rat lipoprotein lipid peroxidation by the oral administration of D003, a mixture of very long-chain saturated fatty acids.

Previous results have demonstrated that policosanol, a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, whose main component is octacosanol, inhibited lipid peroxidation in experimental models and human beings. D003 is a defined mixture of very long-chain saturated fatty acids, also isolated and purified from sugar cane wax, whose main component is octacosanoic acid followed by traicontanoic, dotriacontanoic, and tetracontanoic acids. Since very long-chain fatty acids are structurally related to their corresponding alcohols, we investigated the effect of oral treatment with D003 (0.5, 5, 50, and 100 mg/kg) over 4 weeks in reducing the susceptibility of rat lipoprotein to oxidative modification. The combined rat lipoprotein fraction VLDL + LDL was subjected to several oxidation systems, including those containing metal ions (CuSO4), those having the capacity to generate free radicals 2,2-azobis-2-amidinopropane hydrochloride (AAPH), and a more physiological system (resident macrophages). D003 (5, 50, and 100 mg/kg) significantly inhibited copper-mediated conjugated-diene generation in a concentration-dependent manner. D003 increased lag phase by 53.1, 115.3, and 119.3%, respectively, and decreased the rate of conjugate-diene generation by 16.6, 21.5, and 19.6%, respectively. D003 also inhibited azo-compound initiated and macrophage-mediated lipid peroxidation as judged by the significant decrease in thiobarbituric acid reactive substance (TBARS) generation. In all the systems the maximum effect was attained at 50 mg/kg. There was also a parallel attenuation in the reduction of lysine amino groups and a significant reduction of carbonyl content after oxidation of lipoprotein samples. Taken together, the present results indicate that oral administration of D003 protects lipoprotein fractions against lipid peroxidation in the lipid as well in the protein moiety.

Animals↗
PubMed2001

Developmental impairment of auditory evoked N1/P2 component in rats undernourished in utero: its relation to brain serotonin activity.

In utero undernourishment produces an elevation of L-tryptophan and serotonin in the brain, including the auditory cortex (A1), such changes seem to be related to an increase in the free fraction (FFT) of plasma L-tryptophan that is transported into the brain through the blood-brain barrier, where it is taken up by serotonergic neurons for serotonin synthesis. Our observations support that FFT has a positive correlation with L-tryptophan (L-Trp) and serotonin levels in the auditory cortex (r=0.95 and 0.82, respectively). Interestingly, a decreased intensity dependence of the auditory evoked N1/P2 component was found in gestationally undernourished animals during their postnatal development. The N1/P2 component had a negative correlation (r=0.81) with A1 serotonin, such that it reflects changes in the neurotransmitter concentration. The present observations suggest a relevant role of serotonin in modulating the activity of the auditory cortex. Since the N1/P2 component is mainly associated with the activity of A1 neurons, it may well be that perception of auditory information is impaired during this developmental period, in the early undernourished animals, possibly affecting cognitive processes. This may be relevant to humans since low birth weight babies that also suffered gestational undernourishment (fetal-placental insufficiency) present an increase in plasma FFT from birth up to 3 months of age. These findings support that the plasma FFT and the intensity dependence of the auditory evoked N1/P2 component relate one another and may be markers of changes of the brain serotonergic activity.

Animals↗
PubMed2000

Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro.

AIMS: The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers. METHODS: The effect of policosanol (5 and 10 mg day(-1) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conducted in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks were subjected to in vitro tests of LDL-C oxidation. We tested the susceptibility of LDL-C to lipid peroxidation in a cell-free system by the addition of copper ions as well as in a more physiological system, macrophage-mediated oxidation. RESULTS: At baseline all groups were well matched regarding all variables. After 8 weeks of therapy policosanol administered at 5 and 10 mg, significantly and in a dose-dependent manner increased the lag phase of conjugated diene generation (mean +/- s.d.) from 83.79+/-29.16 min to 94.90+/-25.50 min (5 mg day(-1)) and from 82.74+/-17.16 min to 129.89+/-35.71 min (10 mg day(-1)), while in the placebo group LDL-C oxidation did not change significantly. Policosanol (10 mg day(-1)), but not placebo, significantly decreased the rate of conjugated diene generation. Comparison with placebo after therapy also showed significant differences. Macrophage mediated-oxidation was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day(-1)) significantly lowered malondialdehyde (MDA) generation from 8.50+/-0.91 to 5.76+/- 1.01 nmol mg(-1) protein. Comparison with placebo after 5 and 10 mg day(-1) showed significant differences. Policosanol significantly lowered total cholesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day(-1)) increased HDL-C by 15.2%. Five subjects withdrew from the study, none because of adverse experiences. No clinical or blood biochemical drug-related disturbances were found. CONCLUSIONS: The present study demonstrated that policosanol administered within its therapeutic dosage for lowering cholesterol (5 and 10 mg day(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.

Adult↗
PubMed2000

Inhibition of rat microsomal lipid peroxidation by the oral administration of D002.

The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS). When D002 (5-100 mg/kg body weight) was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46%) occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg) also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40%) and brain (28-44%) microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg) for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans.

Administration, Oral↗
PubMed1999

Oral administration of policosanol inhibits in vitro copper ion-induced rat lipoprotein peroxidation.

Policosanol, a new cholesterol-lowering agent, is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) wax, which prevents the onset of espontaneously and experimentally induced atherosclerotic lesions in experimental models. Because the oxidation of low-density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis, we investigate the effect of policosanol on copper oxidative susceptibility of rat lipoprotein fractions (VLDL + LDL). Rats fed normal diet were treated with policosanol (250-500 mg/kg/day) for up to 4 weeks. EDTA-free lipoprotein particles were oxidized in a cell-free system by the addition of copper ions, and conjugated dienes generation was monitored by changes of optical density at 234 nm. Thiobarbituric acid-reactive substances (TBARS) content and lysine-amino group reactivity were investigated. After administration, there was no change in cholesterol, triglycerides, and phospholipid content of lipoprotein fractions; however, policosanol significantly prolongs the lag time and reduces the propagation rate of diene generation. Also, policosanol reduces TBARS content and increases lysine reactivity in lipoprotein fractions treated with Cu2+. In conclusion, policosanol, in addition to its cholesterol-lowering effect, has other properties that enables it to reduce the potential of lipoprotein to undergo lipid peroxidation. Such effect can be considered of promissory value in the management of atherosclerosis.

Animals↗
PubMed1999

Self-assessment of all the health centres of a public health service through the European Model of total quality management.

The Basque Country Public Health Service has moved in the last years from considering quality as an attribute of patient care to thinking that all management can be subject to improvement. Consequently, its general management team has promoted and supported a self-assessment experience of all their centres by means of the European Quality Model. This strategy has been facilitated by the Basque Country Government, which has strongly encouraged total quality management in companies, and has created the Basque Foundation for Quality Promotion, a key institution in this whole process. A total of 26 centres of the Public Health Service concluded a self-assessment process. As the main result of this, different improvement areas were detected, and various necessary actions were implemented in the centres assessed. Advantages, troubles and future work lines to extend and improve the use of the EFQM model in the health sector are discussed.

Health Status Indicators↗
PubMed1997

Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet.

The effect of policosanol, a mixture of high-molecular-weight aliphatic alcohols isolated from sugarcane wax, on casein-induced hypercholesterolaemia in rabbits was studied. When policosanol was administered by the oral route once daily for 30 d (50 mg/kg) the increases in plasma total cholesterol and LDL-cholesterol (LDC-C) were significantly reduced when compared with the control group. The incorporation of 3H2O into sterols in the liver was significantly depressed, suggesting inhibition of hepatic cholesterol biosynthesis. The oral administration of policosanol raised the rate of removal of 125I-labelled LDL from serum. Kinetic parameters calculated following injection of [125I]LDL showed than in casein-fed rabbits, the terminal half-life (t1/2) was significantly decreased after policosanol treatment. The hepatic LDL-binding activity was increased after policosanol administration which suggested that the enhanced clearance was due, at least in part, to increased receptor-mediated uptake of LDL by the liver. Considered together, these results suggest that policosanol can significantly reduce the increase of plasma LDL-C in rabbits fed on a wheat starch-casein diet by reducing cholesterol biosynthesis in the liver. Such an effect could account for the enhancement of LDL catabolism through the receptor-mediated pathway.

Animals↗
PubMed1997

Effect of policosanol on in vitro and in vivo rat liver microsomal lipid peroxidation.

Policosanol, a defined mixture of high molecular weight aliphatic alcohol isolated and purified from sugar cane (Saccharum officinarum, L) wax is a new cholesterol-lowering agent effective in experimental models, healthy volunteers, and patients with type II hypercholesterolemia. Also, policosanol prevents the onset of spontaneously- and experimentally-induced atherosclerotic lesions and cerebral ischemia in Mongolian gerbils. Free radicals are linked to many diseases including atherosclerosis and ischemia/ reoxidation cellular injury. Therefore, in this study the authors evaluate the antioxidant activity of policosanol on rat liver microsomes. The extent of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS). When policosanol was administered orally (100 and 250 mg/kg) for up to 4 weeks, a partial prevention of rat in vitro microsomal lipid peroxidation was noted. The formation of TBARS in microsomes isolated from treated rats was significantly decreased by about 50%, when peroxidation was initiated by Fe3+/ADP/ NADPH, Fe2+/ascorbate and CCl4/NADPH-generating system. Also, oral administration of policosanol in rats provides a partial inhibition of lipid peroxidation, but the mechanism supporting such effect remains to be elucidated. This beneficial effect of policosanol on membrane lipid peroxidation may be useful in protecting to some extent against free radical-associated diseases.

Animals↗
PubMed1994

Effects of policosanol chronically administered in male monkeys (Macaca arctoides).

Policosanol, administered orally, has shown a cholesterol-lowering effect in different experimental models. Because lipid-lowering therapy is administered chronically, it is necessary to know the effects of these drugs after long-term administration. 18 adult male Macaca arctoides monkeys were used to study the cholesterol-lowering effects and possible toxicity produced by oral administration of policosanol (0.25, 2.5 and 25 mg/kg) for 54 wk. After 8 wk, a significant reduction of serum total cholesterol and low-density lipoprotein cholesterol was observed in policosanol-treated animals when compared with the controls; this effect persisted throughout the study. The animals' behavioural repertoire, physical condition, haematology and blood biochemistry, as well as spermiogram analysis and electrocardiography, were monitored during the study; ophthalmological and pathological anatomy examinations were performed at the end of the administration period. No drug-related toxicity was detected by any examination. The results gave further evidence of the marked and persistent cholesterol-lowering effects of policosanol that had been observed in different experimental models. There was a significant reduction of spontaneous aortic atherosclerotic lesions in treated animals compared with controls. Policosanol (0.25-25 mg/kg) administered orally for 54 wk brought about a persistent reduction in blood cholesterol levels and was very safe and well tolerated during long-term administration.

Administration, Oral↗
PubMed1989

[Karyotype-phenotype correlation in a child with an idic (Yp)].

An 8-year-old boy with hypospadias and a 45,X/46,X,idic(Yp) karyotype is described. This chromosome abnormality possibly originated in an early zygote. It is concluded that: a) phenotypic variability in patients with an idic(Yp) probably results from an unequal tissular distribution of the different clones, and (b) deletion of Yq in the present case was distal to the stature determinants.

Child↗
PubMed1987

Inv(4)(p16q21). A five-generation pedigree with 24 carriers and no recombinants.

A familial inv(4)(p16q21) ascertained through a woman who had a thanatophoric dwarf daughter and two abortions is presented. She and 23 other relatives were carriers, but no recombinants were found. The proportion of abortions and neonatal deaths in carriers' offspring was similar to that in non-carriers. A random segregation of the inverted chromosome was observed. The analysis of the present and previous familial chromosome 4 pericentric inversions indicates that: the breakpoint in q, with a limit between q21 and q25 determines the occurrence of inherited unbalances, and most recombinant chromosomes have duplication of the larger distal segment.

Adult↗
PubMed1987

Cross-reactivity among five major pollen allergens.

We have studied the cross-reactivity between L. perenne, S. cereale, P. pratense, C. dactylon, and Ph. communis. The results obtained demonstrate that L. perenne, S. cereale, and P. pratense have strong cross-reactivity. C. dactylon has a number of allergens that cross-react with the rest of the grasses studied but they are minor allergens. Ph. communis possesses a moderate cross-reactivity with the species of the group but it has, as well, individual allergens.

Allergens↗
PubMed1985

46,XX,-12,+der(12),rcp(3;12)(p25.1;p13.31)pat karyotype in a girl. Probable subregional assignment of glyceraldehyde-3-phosphate dehydrogenase locus to 12p13.1----p13.31 by exclusion mapping.

A female infant with partial trisomy 3p and a terminal deletion 12p, due to a paternal (3;12)(p25.1;p13.31) translocation is described. Normal glyceraldehyde-3-phosphate (GAPD) activity in the proposita tentatively excludes GAPD locus from the deleted segment. Therefore, the region for this locus is reduced to 12p13.1----p13.31.

Abnormalities, Multiple↗