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Biomedical subjects

V Molina

Publications and source records attributed to V Molina.

At least 55 records · Page 3Linked to original sources

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↗

[Sub-trochanteric fractures. A comparative study between gamma nail and angular osteosynthesis with lateral cortical support].

PURPOSE OF THE STUDY: Treatment and outcome of sub-trochanteric fractures are at the origin of many problems. The aim of this study was to evaluate the superiority of the "Gamma Nail". MATERIAL AND METHODS: Two homogenous groups of patients were studied. Each group had 40 patients. The osteosynthesis performed in the first group (Group I) was an "angular" type with lateral cortical support (Nail plate, blade plate, dynamic screw). The second group (Group II) received the "Gamma Nail" implant. The 4 criteria employed to compare the 2 groups were: operatory (duration, blood loss, support-free walking); clinical (walking, pain, anatomy); radiological (reduction and healing); and finally complications and failures. RESULTS: The average operative duration in group I was 3 hrs vs 1 hr in group II. 90 per cent of group I received transfusions with 3 bloods units vs 40 per cent of group II, received 1 blood unit. Support-free walking was authorized 3 months later in group I, and immediately in group II. The results were identical for clinical criteria. The average time for radiological bone healing was 3.5 months in group 1 and 2 months in Group II. 12 complications occurred in group I and 3 in group II: 7 cases of dismantling, 4 non unions and 1 serious deep infection in Group I. In group II: 2 cases of dismantling and a diaphysis fracture beneath the nail. These complications were found in the beginning of our experience with the Gamma Nail. DISCUSSION: 30 per cent of patients in Group I were affected by complications vs 7.5 per cent in group II (with p = 0.01). The duration of surgery, blood loss, and support-free walking delay demonstrated the superiority of the Gamma nail technique. CONCLUSION: This study confirms the superiority of the Gamma nail for the treatment of sub-trochanteric fractures.

Adolescent↗

An endogenous opiate mechanism seems to be involved in stress-induced anhedonia.

This study assessed the effect of an uncontrollable stressor on the preference for a palatable solution (sucrose 1%), and on the preference for a context associated with a single administration of D-amphetamine (3 mg/kg i.p.) by means of the conditioning place preference test. We also evaluated the effect of prior naloxone (2 mg/kg, i.p.) administration on the influence of this stressful stimulus in both tests. Animals previously submitted to a 120-min--but not 60-min--restraint period showed a selective reduction in the preference for sucrose intake as compared to unstressed animals. Similarly, an identical restraint exposure elicited a diminished preference for the place previously paired with amphetamine. Both stress-induced effects were blocked by prior naloxone administration. These data demonstrate that a highly aversive experience decreased the reinforcing efficacy of sucrose and amphetamine, suggesting that uncontrollable stress may lead to an impaired capacity to experience pleasure, which could resemble the anhedonia observed in clinical depression. Furthermore, an endogenous opiate mechanism activated by stress seems to be involved in stress-induced anhedonia since naloxone normalized the reduction of the rewarding induced by both reinforcers.

Animals↗

Possible cytoprotective mechanism in rats of D-002, an anti-ulcerogenic product isolated from beeswax.

D-002 is an anti-ulcerogenic product, isolated from beeswax, which consists of a well-defined mixture of higher primary aliphatic alcohols. It is highly effective against ethanol-induced ulcers. This study was designed to determine if D-002 shows cytoprotective properties on gastric mucosa in ethanol-induced ulcers. The involvement of endogenous prostaglandins in the protective effect of D-002 was also investigated. When a subulcerogenic dose of indomethacin (10 mg kg-1) was injected simultaneously with oral administration of ethanol, oral pre-treatment with D-002 (5-100 mg kg-1) partially inhibited the gastric protection. D-002 (5 and 25 mg kg-1) administered to normal rats significantly increased the soluble mucus content and also prevented its reduction in rats with ethanol-induced ulcers. In addition, D-002 administered at 5 and 25 mg kg-1 prevented the increase of vascular permeability induced by ethanol (60%) and reduced the concentration of thromboxane B2 (TXB2) in gastric mucosa of rats with ethanol-induced ulcers. These results support the hypothesis that the anti-ulcerogenic properties of D-002 could be related to a cytoprotective mechanism.

Animals↗

Effect of policosanol on platelet aggregation in healthy volunteers.

Policosanol is a new drug whose cholesterol-lowering effects have been demonstrated in experimental models, healthy volunteers, and patients with type II hypercholesterolaemia. The effect of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted on healthy volunteers. This included a trial of the effects of single doses (5 to 50 mg) and a study of the effects of repeated doses administered for 7 days. In the single-dose study, the percentage of platelet aggregation in response to the threshold concentration of ADP and epinephrine measured from 8:00 to 10:00 increased significantly in the placebo group, while policosanol (5, 10, 25 and 50 mg), administered orally, inhibited the increase of platelet aggregation induced by ADP and epinephrine determined at the same time. Policosanol administered at 20 mg/day for 7 days significantly inhibited platelet aggregation induced by ADP and epinephrine, although the inhibition reached by the 10 mg/day dose tended to be less significant (p = 0.06). A modest effect (p = 0.068) on collagen-induced platelet aggregation was only observed at the highest dose (50 mg/day). The low dose (5 mg/day) was ineffective. Policosanol did not affect the coagulation time when administered at single or repeated doses. No side-effects were reported in treated or placebo groups.

Adult↗

Gas chromatography of 4,4'-diphenylmethane diisocyanate in the workplace atmosphere.

A sensitive gas chromatographic procedure for the determination of 4,4'-diphenylmethane diisocyanate concentration in air is described. Traps containing 20-40-mesh silica gel coated with phosphoric acid are used. After the aspiration of the air, the silica gel is eluted with sodium hydroxide in methanol. The amine formed is then separated with a gas chromatograph and measured with a nitrogen-phosphorus detector. This can be performed in 7 min. Virtually no breakthrough occurs if an air concentration of up to 128 nmol in 20 l is sampled. The detection limit based on a 20-1 air sample is 0.7 microgram/m3. Complete analysis requires about 30 min. The method was used to determine the concentration of 4,4'-diphenylmethane diisocyanate in working environments during spraying operations.

Air Pollutants, Occupational↗

Anti-ulcer activity of higher primary alcohols of beeswax.

The anti-ulcer effects of a natural mixture of higher aliphatic primary alcohols, designated D-002, isolated from beeswax, were compared with those of cimetidine on indomethacin-, ethanol-, water-immersion-induced ulcers and on gastric secretion in rats. D-002 (25-50 mg kg-1 p.o.) was similar to cimetidine in dose-dependently reducing the duration of indomethacin-induced ulcers while also being effective in preventing ethanol-induced ulcers, which are not affected by cimetidine. On the other hand, D-002 (100 mg kg-1) moderately decreased the volume of gastric basal secretion in pylorus-ligated rats, but not the acidity. Nevertheless, it inhibited gastric ulcer induced by pylorus-ligation at doses (50 mg kg-1) that were ineffective in decreasing the volume. In addition, 100 mg kg-1 of D-002 prevented the formation of acute gastric ulcers induced in rats by water-immersion stress. The results demonstrate the anti-ulcer activity of the preparation in different experimental models suggesting its potential value for ulcer therapy.

Administration, Oral↗

Cerebral perfusion, electrical activity and effects of serotonergic treatment in obsessive-compulsive disorder. A preliminary study.

An abnormally increased glucose metabolism has been described with positron emission tomography (PET) in frontal and caudate regions of obsessive-compulsive patients. Perfusion and electroencephalographic studies have been less conclusive. However, these techniques are, currently, more available than PET and, therefore, deserve further study because of their possible clinical applications. In this article, 13 obsessive-compulsive patients were studied with quantitative EEG and auditory and visual evoked potentials. Six of them were studied also with perfusion single photon emission tomography. A group of 4 patients was studied with both techniques before and after a serotonergic treatment. Increased global, beta, and theta electrical power together with an increased perfusion in frontal regions was observed. The patients also showed a delta power increase over right temporal and frontal regions, together with increased perfusion in the right basal ganglia region as well as a decreased amplitude of the P50 and N100 waves of the auditory evoked potentials over temporal electrodes; these alterations were reduced with treatment. These results are discussed in the context of current data about serotonergic neurotransmission.

Adult↗

Drug therapy and cerebral perfusion in obsessive-compulsive disorder.

Cerebral perfusion in a previously untreated patient with obsessive-compulsive disorder was studied qualitatively and semi-quantitatively with SPECT before, and during and 6 wk after treatment with clomipramine. The patient's symptoms disappeared while on medication and relapsed after drug withdrawal. At baseline, there was an increased perfusion ratio in the bilateral orbitofrontal, anterior cingular, frontotemporal and right caudate regions. These alterations disappeared during drug therapy. After treatment discontinuation and symptomatic relapse, the same pattern of hyperactivity was found. Semiquantitative measurements after treatment withdrawal showed a return to perfusion values similar to those observed before treatment in subcortical structures. In cortical areas, this level was not completely achieved. Subtraction SPECT images showed perfusion changes at the orbitofrontal, caudate and thalamic levels.

Adult↗

Effect of policosanol on experimental thrombosis models.

Policosanol is a natural product, obtained from sugar cane wax (Saccharum officinarum L.) with which cholesterol-lowering effects have been demonstrated in experimental models, healthy volunteers and hypercholesterolemic patients. The effects of policosanol on experimental venous and arterial thrombosis in rats were investigated. Policosanol (25 mg/kg) significantly decreased the thrombus weight, in the venous thrombosis models, the protective effect persisting until 4 h after its oral administration. Policosanol (25 mg/kg single dose) was able to reduce rectal temperature variation induced by arterial thrombosis. Also at the same dose policosanol increased 6-keto-PGF1 alpha serum levels in rats.

6-Ketoprostaglandin F1 alpha↗

Cholesterol-lowering effects of policosanol in rabbits.

Policosanol is a natural mixture of higher primary aliphatic alcohols isolated and purified from sugar cane (Saccharum officinarum, L.) wax, whose main component is octacosanol. Policosanol (5-200 mg/kg) orally administered for 4 weeks to normocholesterolemic New Zealand rabbits significantly reduced total cholesterol and low density lipoprotein cholesterol (LDL-C) serum levels in a dose dependent manner. Serum triglyceride levels of treated and control animals were significantly different, but the reduction observed was not dose-dependent. High density lipoprotein cholesterol (HDL-C) levels remained unchanged. Results indicate that the reduction in total cholesterol values induced by policosanol is mainly mediated through a decrease in LDL-C levels.

Animals↗

Seven-day variable-stress regime alters cortical beta-adrenoceptor binding and immunologic responses: reversal by imipramine.

Rats were submitted daily to a variable stressor for 1 week with or without concurrent imipramine (IMI) administration. One day after the last injection or stressful event, binding of cortical beta-adrenoceptors was determined in all experimental groups. Another group of chronically stressed animals with or without concurrent IMI administration were sacrificed 24 h following the last stress or injection treatment, and several immunologic parameters were evaluated. Chronically stressed rats showed an enhanced number of cortical beta-adrenergic sites without changes in their affinity. This effect was not present following concurrent administration with the antidepressant. In addition, a decreased percentage of T lymphocytes and a reduced delayed-type hypersensitivity reaction was also observed in stressed animals. Both responses were no longer evident when stressed rats were previously administered IMI. A possible link between behavioral, neurochemical, and immunologic alterations due to the stress regime is discussed.

Animals↗

Effect of policosanol on cerebral ischemia in Mongolian gerbils: role of prostacyclin and thromboxane A2.

Policosanol is a mixture of higher primary aliphatic alcohols, isolated from sugar cane wax, whose main component is octacosanol. Policosanol (25, 50 and 200 mg/kg) administered by the oral route not only significantly reduced serum thromboxane B2 (TXB2) levels but also, at 200 mg/kg significantly increased 6-keto-PGF1 alpha in Mongolian gerbils. Policosanol at 200 mg/kg significantly protected against cerebral ischemia induced by unilateral ligation of common carotid artery in Mongolian gerbils. In this experimental model, combined administration of ineffective doses of policosanol (25 mg/kg) and aspirin (ASA) (30 mg/kg) significantly protected animals indicating a synergism between them.

6-Ketoprostaglandin F1 alpha↗

On the analysis of viability data: an example with Drosophila.

Larval competition experiments involving two wild type and eight mutant strains of Drosophila melanogaster have been carried out following the substitution procedure proposed by Mather and Caligari (1981). Our main goal has been to compare the competitive abilities of two phenotypically indistinguishable strains (wild and Oregon-R) by means of their responses with eight different mutants. Prior to the analyses of viability data, we have studied the normalizing effect of several transformations in order to determine which was best suited for the analyses. The differences found among the five transformations tested and the untransformed data were not very great. The folded power transformation (Mosteller and Tukey, 1977) was finally chosen. No constant pattern in the responses of the two wild type strains to the mutant competitors was detected. This leads us to conclude that the nature of the competition between the two wild type strains cannot be predicted from a knowledge of their competition with other strains.

Animals↗

Unmasking frequency-dependent selection in tri-cultures of Drosophila melanogaster.

Larval-to-adult viability was measured for three strains of Drosophila melanogaster: a wild strain and two eye colour mutant strains (cardinal and sepia) starting from seventy different genotypic compositions. Analyses of a sub-set of the data (not considering all genotypic frequencies) demonstrate frequency-dependence in the three strains. These results suggest that in this experiment, frequency-dependent selection may be masked by other selective forces, only being apparent when specific analyses are carried out.

Animals↗

Alterations of serotonin neurotransmission and inhibition of mouse killing behavior: II. Effects of selective and reversible monoamine oxidase inhibitors of type A.

Three groups of rats were tested for mouse killing behavior after IP injection of selective and reversible type A monoamine oxidase inhibitors. The rats were either spontaneous killers, or non-killers which acquired killing behavior following para-chlorophenylalanine treatment or electrolytical destruction of dorsal and median raphe nuclei. Moclobemide (para-chloro-N-(2-morpholinoethyl)-benzamide), cimoxatone (3-(4-(3-cyanophenyl-methoxy)phenyl)-5-(methoxy-methyl)-2-oxazo lid inone, MD 780515), toloxatone (5-(hydroxymethyl)-3-(3-methylphenyl)-2-oxazolidinone) and amiflamine ((+)-4-dimethylamino-2, alpha-dimethylphenethyl amine, FLA 336 (+)) were used as selective and reversible monoamine oxidase inhibitors of type A. Cimoxatone, toloxatone and amiflamine inhibited mouse killing behavior of spontaneous killer rats without apparent sedation, whereas moclobemide was not efficient at doses which did not decrease locomotor activity. A similar inhibition of mouse killing behavior was obtained in spontaneous and serotonin depleted killer rats. The results are discussed in relation to the behavioral expression of serotoninergic supersensitivity in the three groups of killer rats described earlier using serotonin agonist and uptake inhibitors.

Aggression↗

Influence of adrenocorticotrophic hormone on the behaviour in the swim test of rats treated chronically with desipramine.

Chronic desipramine (DMI) administration induced a dose-dependent reduction in the immobility time of the swim test in rats. A combined treatment of ACTH (50 iu kg-1 s.c.) and DMI (5 or 10 mg kg-1 i.p.) for 7 days potentiated the anti-immobility effect of DMI. ACTH 4-10, a fragment peptide with little corticotrophic activity, mimicked ACTH-induced potentiation. No stimulating effect on locomotor activity was observed following seven daily co-administrations of ACTH or ACTH 4-10 and DMI (10 mg kg-1). This behavioural evidence indicates that ACTH potentiation involves a central mechanism and demonstrates a functional interaction between ACTH and DMI at the behavioural level.

Adrenocorticotropic Hormone↗