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Biomedical subjects

M Noa

Publications and source records attributed to M Noa.

At least 37 records · Page 2Linked to original sources

Tiamulin-nitrovin interaction in pigs: a case report and experimental reproduction.

Tiamulin is a diterpenic veterinary drug widely used in swine for the control of infectious diseases, including swine dysentery and enzootic pneumonia. Tiamulin is well tolerated and only a few drug interactions have been reported with some ionophore antibiotics. A case of tiamulin adverse drug interaction with nitrovin, a nitrofuranic growth promoter, in fattening pigs from a commercial farm is described. To confirm the diagnosis, experimental reproduction was conducted using 20 healthy female pigs. The animals were randomly divided into 4 groups: 1 of them receiving feed medicated with 100 mg tiamulin hydrogen fumarate/kg, another received 20 mg nitrovin/kg to establish the harmlessness of the drugs alone. The other 2 groups received feeds containing both drugs at the previous concentrations, one of which came from the farm. In the last 2 groups clinical signs appeared 72-96 h after initially feeding pigs the tiamulin hydrogen fumarate + nitrovin-containing feed. The animals had uneasiness, anxiety, skin erythema, and rash on snout, vulva and abdomen, and increased body temperatures. No mortality occurred, and there were no characteristic findings during pathological examination. The signs disappeared after 96 h of consuming the medicated feed, leaving a slight skin thickening of the affected regions. All signs disappeared spontaneously 4-5 d after ceasing medication.

Animal Feed↗

Effect of policosanol on cerebral ischemia in Mongolian gerbils.

Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg) administered immediately after unilateral carotid ligation and at 12- or 24-h intervals for 48 h significantly inhibited mortality and clinical symptoms when compared with controls, whereas lower doses (100 mg/kg) were not effective. Control animals showed swelling (tissue vacuolization) and necrosis of neurons in all areas of the brain studied (frontal cortex, hippocampus, striatum and olfactory tubercle), showing a similar injury profile. In the group treated with 200 mg/kg policosanol swelling and necrosis were significantly reduced when compared with the control group. In another experimental model, comparison between groups showed that the brain water content of control gerbils (N = 15) was significantly higher after 15 min of clamping and 4 h of recirculation than in sham-operated animals (N = 13), whereas policosanol (200 mg/kg) (N = 19) significantly reduced the edema compared with the control group, with a cerebral water content identical to that of the sham-operated animals. cAMP levels in the brain of control-ligated Mongolian gerbils (N = 8) were significantly lower than those of sham-operated animals (N = 10). The policosanol-treated group (N = 10) showed significantly higher cAMP levels (2.68 pmol/g of tissue) than the positive control (1.91 pmol/g of tissue) and similar to those of non-ligated gerbils (2.97 pmol/g of tissue). In conclusion, our results show an anti-ischemic effect of policosanol administered after induction of cerebral ischemia, in two different experimental models in Mongolian gerbils, suggesting a possible therapeutic effect in cerebral vascular disorders.

Animals↗

Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients.

This randomized, double-blind study was undertaken to compare the effects of policosanol and pravastatin administered at 10 mg/day on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk. After 6 weeks on a lipid-lowering diet, patients with low-density lipoprotein (LDL) cholesterol levels > 3.4 mmol/l were randomized to receive, under double-blind conditions, policosanol or pravastatin 10 mg tablets that were taken with the evening meal for 8 weeks. Policosanol significantly (p < 0.00001) lowered LDL-cholesterol (19.3%), total cholesterol (13.9%) and the ratios of LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol (28.3%) and total cholesterol/HDL-cholesterol (24.4%). Pravastatin significantly (p < 0.00001) lowered LDL-cholesterol (15.6%), total cholesterol (11.8%) and the ratios (p < 0.0001) of LDL-cholesterol/HDL-cholesterol (18.9%) and total cholesterol/HDL-cholesterol (15.7%). Policosanol, but not pravastatin, significantly increased (p < 0.001) levels of HDL-cholesterol (18.4%) and reduced (p < 0.01) triglycerides (14.1%). Policosanol was more effective (p < 0.05) than pravastatin in inhibiting platelet aggregation induced by all agonists and it significantly reduced (p < 0.0001) platelet aggregation induced by arachidonic acid at 1.5 and 3 mmol/l by 42.2% and 69.5%, respectively, platelet aggregation induced by collagen 0.5 microgram/ml (p < 0.05) (16.6%) and that induced by adenosine diphosphate 1 mumol/l (p < 0.01) (20.3%). Pravastatin significantly reduced (p < 0.001) (27%) only platelet aggregation induced by arachidonic acid 3 mmol/l. Both drugs significantly decreased (p < 0.00001) endothelemia levels but final values were significantly lower (p < 0.001) in the policosanol than in the pravastatin group. Both treatments were safe and well tolerated. Pravastatin significantly (p < 0.01) increased serum levels of alanine amine transferase but individual values remained within normal. Two patients on pravastatin discontinued the study because of adverse experiences (myocardial infarction and jaundice, respectively). In conclusion, the effects of policosanol (10 mg/day) on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk are more favorable than those induced by the same doses of pravastatin.

Aged↗

Effect of policosanol on intimal thickening in rabbit cuffed carotid artery.

We studied the effect of policosanol on smooth muscle cell proliferation in the cuffed carotid artery of the rabbit. Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, with cholesterol lowering effects proved in experimental models and patients with type II hypercholesterolemia. It acts by inhibiting cholesterol biosynthesis. The positioning of a nonocclusive silicone collar around the rabbit carotid artery results in the formation of a neointima. We wished to determine whether policosanol orally administered prevented intimal thickening. Collars were placed around the left carotid for 15 days. The contralateral artery was sham operated. We included three experimental groups: a control received vehicle and two others policosanol at 5 and 25 mg Kg until sacrificed. Samples of arteries were examined by light and electron microscopy. To evaluate intimal thickening the cross-sectional area of intima and media were measured. Neointima was significantly reduced in policosanol-treated animals compared with controls. The smooth muscle cell proliferation was studied by the immunohistochemical detection of proliferating cell nuclear antigen and a significant reduction was observed in policosanol treated rabbits. It is concluded that policosanol has a protective effect on the neointima formation in this experimental model.

Animals↗

Effect of D-002 on the pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig.

D-002 is a natural mixture of higher aliphatic primary alcohols, isolated and purified from beeswax which has anti-inflammatory properties, reduces leukotrienes (LTB4) and thromboxane B2 (TXB2) in exudated carrageenan-induced pleurisy, and has anti-ulcer activity in different experimental models. This study was conducted to determine the effect of D-002 on the pre-ulcerative phase of carrageenan-induced colonic ulceration in guinea-pigs. Animals were randomly distributed among a negative control, a positive control group treated with the vehicle Tween 20 in H2O and two experimental groups receiving D-002 at 25 and 50 mg kg(-1). All treated animals received degraded carrageenan for three days for induction of colonic ulceration. Significant reductions in wet weight, wall thickness, counts of infiltrating polymorphonuclear neutrophils and of macrophages, and histological index were observed in colonic mucosa of D-002-treated animals compared with controls. It is concluded that D-002 has a protective effect on the pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig.

Animals↗

Preclinical oral toxicology in rats of D-002, a natural drug with antiulcer effects.

D-002 is a mixture of higher aliphatic primary alcohol isolated from bees wax (Apis mellifera) with effective antiulcer effects demonstrated in different experimental models. Oral toxicity of D-002 (5-5000 mg/kg) was evaluated in sub-acute (14 days), subchronic (90 days) and chronic (1 year) studies in Sprague-Dawley rats from both sexes. There was no treatment-related toxicity. Thus, effects on body weight, food consumption, clinical observations, blood parameters, organ weight ratios and histopathological findings were similar in control and treated groups. These short and long-term studies support a wide safety margin for this product.

Administration, Oral↗

Effect of policosanol on circulating endothelial cells in experimental models in Sprague-Dawley rats and in rabbits.

The effect of policosanol on circulating endothelial cells has been studied in different experimental models with endothelium damage. Oral administration of 25 mg kg-1 policosanol to Sprague-Dawley rats resulted in significant protection of the endothelial lining against the desquamating effect of citrate. Oral administration of 5 mg kg-1 policosanol to spontaneously hypertensive rats (SHR) resulted in a significant reduction of circulating endothelial cells compared with controls. Moreover, comparison between groups revealed a lower frequency of aortic lesions in policosanol-treated animals than in controls. On the other hand, administration of 5 mg kg-1 policosanol to rabbits with intimal hyperplasia induced by cuff placement in the carotid artery resulted in levels of circulating endothelial cells significantly lower than in controls. These results demonstrate the protective effect of policosanol in different experimental models and suggest its potential for endothelial protection.

Animals↗

Effect of policosanol on foam-cell formation in carrageenan-induced granulomas in rats.

Policosanol is a new cholesterol-lowering drug isolated and purified from sugar-cane wax, which prevents the development of lipofundin-induced lesions and foam-cell formation in New Zealand rabbits and Wistar rats. This study was conducted to examine the effects of policosanol on foam-cell formation in carrageenan-induced granulomas in rats. Eighteen Wistar rats were randomly distributed in three experimental groups which received orally for 20 days Tween 20 H2O as vehicle (control group) or policosanol at 2.5 or 25 mg kg-1. At the 11th day, lipofundin was injected intraperitoneally for 8 days to induce formation of foam cells in the granuloma. At day 13, carrageenan was injected subcutaneously for granuloma induction and seven days later animals were killed. A significant reduction of the foam-cell formation in granulomas of policosanol-treated rats was observed. It is concluded that policosanol prevents the development of foam cells in carrageenan-induced granulomas (extravascular medium) in rats.

Animals↗

Effect of policosanol on lipofundin-induced atherosclerotic lesions in rats.

Policosanol is a mixture of higher aliphatic alcohols isolated from sugar cane wax, showing cholesterol-lowering effects and preventing the development of lipofundin-induced lesions in New Zealand rabbits. This study was conducted to determine whether policosanol orally administered to rats also protects against the development of lipofundin-induced atherosclerotic lesions. Fifty four male Wistar rats were randomly distributed amongst a negative control group, a positive control group intravenously injected with lipofundin for eight days, and four experimental groups also injected with lipofundin, but orally receiving policosanol at 0.5, 2.5, 5 and 25 mg kg-1, respectively. Policosanol treatment was orally administered once-a-day for eight days, while control groups similarly received equivalent amounts of vehicle. A significant reduction of the atherosclerotic lesions in the treated animals was observed. It is concluded that policosanol has a protective effect on lipofundin-induced aortic lesions in Wistar rats.

Animals↗

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↗

Toxicity of policosanol in beagle dogs: one-year study.

Policosanol is a new chemical entity composed of 8 higher aliphatic alcohols obtained from sugar cane (Saccharum officinarum), L. wax, whose cholesterol-lowering effects have been demonstrated in experimental models, healthy volunteers and patients with type II hypercholesterolemia. This study investigated the oral toxicity of policosanol administered for 52 weeks to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in 3 experimental groups (4 animals/group): a control and 2 treated groups receiving policosanol at 30 and 180 mg/kg daily (7 days/week) by gavage. No mortality was observed in any group. Overall, policosanol was well tolerated throughout the study and no toxic symptoms were observed. All groups showed similar weight gain and food consumption. Lipid profile determinations showed that policosanol decreased total cholesterol by 20% approximately from 8 to 52 weeks. Cholesterol-lowering effects did not wear off during the study, thus demonstrating the persistence of the effectiveness. Triglycerides and high density lipoprotein-cholesterol (HDL-C) were not changed significantly. No blood biochemistry or histopathological disturbances attributable to treatment were observed. This study has shown that no drug-related toxicity was induced by policosanol administered up to 180 mg/kg/day for 52 weeks to beagle dogs. Since this dose is approximately 620 times higher than the maximal recommended therapeutic dose (20 mg/day) it indicates a good safety margin of this product.

Administration, Oral↗

A 12-month study of policosanol oral toxicity in Sprague Dawley rats.

Policosanol is a natural mixture of higher aliphatic primary alcohols. Oral toxicity of policosanol was evaluated in a 12-month study in which doses from 0.5 to 500 mg/kg were given orally to Sprague Dawley (SD) rats (20/sex/group) daily. There was no treatment-related toxicity. Thus, effects on body weight gain, food consumption, clinical observations, blood biochemistry, hematology, organ weight ratios and histopathological findings were similar in control and treated groups. This study supports the wide safety margin of policosanol when administered chronically.

Administration, Oral↗

Effect of policosanol on isoprenaline-induced myocardial necrosis in rats.

Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) and octacosanol represents its main component. This study was conducted to examine the effects of policosanol on myocardial necrosis induced by subcutaneous injection of isoprenaline in rats. A significant reduction (P < 0.01) of infarct size, polymorphonuclear cells and mast cells was observed in animals treated with policosanol at 5 or 25 mg kg-1, while animals receiving only acetysalicylic acid pretreatment showed a significant decrease in the infarct area (P < 0.05). No significant differences in polymorphonuclear and mast cells were obtained when compared with positive control data. It is concluded that policosanol delays the evolution of infarction, showing a protective effect on the myocardial necrosis induced by isoprenaline in this experimental model.

Administration, Oral↗

Interference of levamisole with Forssman shock.

The anti-helminthic drug levamisole has been used as an adjunct in the treatment of some immunologic defects including cancer. Recently, it has been shown that this drug inhibits thromboxane synthetase as well. Since Forssman shock in guinea pig is used as a model for pulmonary thromboembolism involving thromboxane A2, we studied the interference of levamisole with bronchoconstriction, thrombocytopenia, endothelial cells and pulmonary damage induced by Forssman antiserum. Levamisole inhibited dose-dependently the pathological changes produced by Forssman antiserum raising the possibility that levamisole may be effective for the treatment of pulmonary thromboembolism in man.

Animals↗

Kerosene-induced asthma.

Clinical evaluation of 286 asthmatic women showed 15.5% of those who improved clinically had contact with kerosene, while 43.9% of those who failed to improve used kerosene as fuel for cooking. In 16 women the onset of asthma occurred soon after they began to use kerosene. Kerosene can cause and aggravate asthma.

Asthma↗

Changes in the aorta of guinea pigs exposed to kerosene.

Guinea pigs were exposed to kerosene aerosols or to smoke produced from kerosene under conditions approximating those in a kitchen. They were compared to controls exposed to saline aerosols or to atmospheric air. Both types of kerosene exposure engendered aortic plaques, resembling those seen in atherosclerosis, and changes in levels of blood lipids. The results suggest that chronic exposure to kerosene, a domestic fuel widely used in many countries, may have important toxic effects in addition to the pulmonary effects that have been reported by others.

Animals↗