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Biomedical subjects

D Carbajal

Publications and source records attributed to D Carbajal.

36 records · Page 2Linked to original sources

Effect of policosanol on platelet aggregation and serum levels of arachidonic acid metabolites in healthy volunteers.

Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and patients with type II hypercholesterolemia. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. This study reports the results of a 2-week, randomized, double-blind, placebo-controlled trial investigating the effects of policosanol on platelet aggregation and thromboxane B2 and prostacyclin (6 keto PGF1alpha) production after stimulation with collagen in healthy volunteers. The volunteers were on a placebo-baseline period for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10 mg/day) for 15 days. Platelet aggregation was determined at baseline and after 15 days of treatment. Significant reductions of arachidonic acid and collagen-induced platelet aggregation were observed. Thromboxane, but not prostacyclin, generation induced by collagen was also inhibited by policosanol.

6-Ketoprostaglandin F1 alpha↗

Anti-inflammatory activity of D-002: an active product isolated from beeswax.

D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results.

Administration, Oral↗

Effect of policosanol on platelet aggregation in type II hypercholesterolemic patients.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects proved in experimental models and healthy volunteers. This study reports the results of a 4-week, randomized, double-blind, placebo-controlled trial investigating the effects of policosanol on platelet aggregation in type II hypercholesterolemic patients. Patients started or continued on a step-one cholesterol-lowering therapy for 4 weeks and those with total cholesterol > 5.0 mmol/L despite dietary conditions were randomized to receive under double-blind conditions placebo or policosanol (10 mg/day) for 30 days. Both groups were similar at randomization. Effects of policosanol on platelet aggregation induced by arachidonic acid (3.2 mM), collagen (0.5-1 microgram/ml) and ADP (0.5-1 uM) were determined at baseline and after 30 days of treatment. Policosanol significantly reduced platelet aggregation induced by arachidonic acid and collagen, meanwhile it only inhibited significantly the platelet aggregation induced by the lowest doses of ADP (0.5 uM). No adverse events occurred during the trial. Only one patient (placebo) discontinued from the study because of arthralgia.

Adenosine Diphosphate↗

Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers.

A randomized, double-blind, placebo-controlled study was conducted in 43 healthy volunteers to compare the effects of policosanol (20 mg day-1), aspirin (ASA) (100 mg day-1) and combination therapy (policosanol 20 mg day-1 plus ASA 100 mg day-1) on platelet aggregation. The healthy volunteers were randomly treated for 7 days. Both, platelet aggregation and coagulation time were measured at baseline and after therapy. When policosanol was administered platelet aggregation induced by ADP (37.3%), epinephrine (32.6%) and collagen (40.5%) were significantly reduced. Meanwhile, aspirin significantly reduced platelet aggregation induced by collagen (61.4%) and epinephrine (21.9%) but not ADP-induced aggregation. Combined therapy significantly inhibited aggregation induced by all the agonists reaching the highest reductions of platelet aggregation induced by collagen (71.3%) and epinephrine (57.5%). Coagulation time did not change significantly in any group. No subject withdrew from the trial. Four volunteers reported mild adverse experiences during the study: three ASA-treated cases referred headache, epigastralgia and nose bleeding, meanwhile one patient receiving combination therapy reported gum bleeding. The present results demonstrate that policosanol (20 mg day-1) is as effective as ASA (100 mg day-1). Moreover, combination therapy shows some advantages compared with the respective monotherapies.

Adult↗

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↗

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↗

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↗

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↗

Effects of Policosanol on platelet aggregation in rats.

Policosanol is the trivial name of a mixture of high molecular weight alcohols isolated from sugar cane, wherein octacosanol is the main component. The effects of Policosanol treatment on rat platelet aggregation were studied. Depending on the dose, Policosanol (5-20 mg/kg, perorally) inhibited the decrease in circulating platelet counts and collagen-induced malondialdehyde concentration in plasma. In rat clotted whole blood thromboxane B2 formation was inhibited by Policosanol (25 mg/kg). Policosanol (50-200 mg/kg, single doses) inhibited ADP-induced platelet aggregation in platelet-rich plasma, while lower doses (25 mg/kg) did not change responses to ADP significantly. However, rats treated with this dose (25 mg/kg) for 4 weeks showed a significant inhibition of platelet aggregation in PRP when a submaximal ADP concentrations was administered.

Adenosine Diphosphate↗

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↗

The effect of disodium 4-chloro-2-iminodibenzoate (CCA) on IgE levels and anaphylactic shock.

The effect of disodium 4-chloro-2,2-iminodibenzoate (CCA) on IgE antibody response was examined in C3H/A and (BALB/c x C57BL/6J) F1 hybrid mice immunized with low doses of ovalbumin (OA) adsorbed on aluminium hydroxide gel. CCA administered orally at the doses of 5 and 50 mg/kg/day reduced IgE antibody production in these mice as determined by PCA test. High doses of CCA (100 mg/kg/day) given from day 7 before immunization of C57BL mice and during 1 week after immunization of mice with OA and Bordetella Pertussis Vaccine reduced the mortality of these mice subjected to anaphylactic shock on day 7 of immunization. CCA treatment was ineffective in anaphylactic shock of C57BL mice immunized with very high dose of OA, known to elicit little or no IgE antibody production but high IgG antibody response. The treatment of OA-immunized Guinea pigs with one oral dose of CCA (100 mg/kg) did not reduce mortality in protracted anaphylactic shock. Our results demonstrate that CCA inhibits IgE production as well as IgE mediated hypersensitivity reactions in mice.

Anaphylaxis↗

Pharmacological study of Cymbopogon citratus leaves.

Cymbopogon citratus leaves are employed by the Cuban population as an antihypertensive and anti-inflammatory folk medicine. A 10% or 20% decoction of leaves was tested using arterial pressure in rats, urine production and carrageenan-induced edema in rats. The decoction showed some dose-related hypotensive effects given intravenously and some weak diuretic and anti-inflammatory effect when given orally.

Animals↗

Infant oxygen administration by modified nasal cannula.

In both pediatric and neonatal intensive care settings, and occasionally at home, there exists the need to deliver chronic low dose oxygen therapy to small, uncooperative patients. To be effective, a method of oxygen delivery must be both reliable and comfortable, and, at the same time, inexpensive and safe. We believe that this may be achieved by a simple modification of existing pediatric nasal cannulae.

Equipment Design↗

Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers.

Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10 mg day-1) for 7 days. After this period dosage was doubled to 20 mg day-1 for the next 7 days and then again doubled to 40 mg day-1, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.

Adenosine Diphosphate↗

Pharmacological screening of plant decoctions commonly used in Cuban folk medicine.

Pharmacological screening for cardiotonic, hypotensive or bronchodilator activities was performed on 50 plant species depending on their traditional medical use by the Cuban population. Eleven of these species may have promise as therapeutic agents, but additional preclinical pharmacological and toxicological studies are needed to establish their therapeutic effectiveness and safety in human disease.

Animals↗

Bronchial asthma and diabetes mellitus. Experimental evidences of mutual exclusion.

The reasons for the frequent mutual exclusion in the same patient of asthma and diabetes and the fact that dextran anaphylactoid reaction does not occur in diabetic rats remain unknown. The mortality induced by the compound 48/80 and its histamine releasing effect from peritoneal mast cells have been tested in alloxan diabetic rats. The effect of acetylcholine on isolated airways from these animals has also been investigated. It is suggested that the lower quantity of peritoneal mast cells found in diabetic animals (and not the histamine released from its mast cells or airway hyporeactivity to acetylcholine) contributes to the protective effect of diabetes mellitus to the anaphylactoid reaction consequences.

Acetylcholine↗