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Biomedical subjects

A Casacó

Publications and source records attributed to A Casacó.

At least 19 recordsLinked to original sources

Effect of an EGF-cancer vaccine on wound healing and inflammation models.

BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGF-R) are attractive targets for cancer immunotherapy. Tolerance has been broken with an EGF-vaccine and antibodies against EGF have been produced in animals and in cancer patients. EGF also plays an important role in the inflammation stage of wound healing. Because this therapeutic approach may be of importance after surgery procedures in cancer patients, we decided to investigate the possible role of the EGF-vaccine in the croton-oil-induced ear edema and in the wound healing experimental animal models. MATERIALS AND METHODS: Mice were immunized with an EGF-vaccine by intramuscular injections and serum titers against EGF were measured through ELISA techniques. Control animals received saline. RESULTS: Immunized mice produced antibodies against EGF while no antibody titers could be measured in control animals. Croton oil applied to the inner ear surface of EGF-vaccine treated mice caused a 61.3% lower ear punch weight and a 60.2% lower myeloperoxidase activity than control mice. In the EGF-vaccine treated animals, planimetry measurements and histological analysis did not led to significant impairment in tissue repair. CONCLUSIONS: The EGF-vaccination in mice decreased the normal croton-oil-induced inflammation response, without apparent impairment in tissue healing.

Animals↗

Multiple dose toxicity study of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 intravenously administered to Cercopithecus aethiops sabaeus monkeys.

The h-R3 is a humanized growth factor receptor monoclonal antibody (mAb) in development for the treatment of head and neck tumours in which malignant cells overexpress the Epidermal Growth Factor receptor. The present study was designed to evaluate the toxicity of repeated intravenous doses of the h-R3 mAb in a relevant species demonstrated by the avidin-biotin-peroxidase immunohistochemical (IHC) technique in skin biopsy samples from three Cercopithecus aethiops sabaeus monkeys (green monkeys). Additionally, 18 green monkeys were daily intravenously treated during 14 consecutive days. Monkeys were distributed into three experimental groups with three animals of each sex in each group. Group I received saline solution and served as control group; group II received 2.85 mg/kg of h-R3 mAb; and group III received 11.4 mg/kg of the h-R3 mAb. During the study there were no deaths, neither pathological clinical signs, or variations in the corporal weight curve. The electroneurophysiological and sanguine chemistry results did not evidence alterations related to the assay substance. Areas of haematomas, haemorrhages and inflammation, probably related with the administration procedure, were observed at the administration zones of all animals; this fact could also explain the increase in the neutrophil count of all animals at the end of the study. The electrocardiography study showed that in the 14 days of the study one female monkey, from the higher dose group, shifted its cardiac axis from +60 degrees to + 120 degrees; this finding could be interpreted as a right ventricular elongation due to the relative high daily administered volume. It is concluded that doses up to 11.4 mg/kg of h-R3, intravenously administered during 14 consecutive days to Cercopithecus aethiops sabaeus monkeys do not produce considerable toxic effects in the studied system.

Animals↗

Anti-inflammatory and analgesic effects of a mixture of fatty acids isolated and purified from sugar cane wax oil.

The anti-inflammatory and analgesic effects of FAM, a defined mixture of fatty acids isolated from sugar cane (Saccharum officinarum L.), was evaluated. Oral administration of this mixture showed anti-inflammatory activity in the cotton pellet granuloma assay and in the carrageenin-induced pleurisy test, both in rats, as well as in the peritoneal capillary permeability test in mice. In addition, FAM showed analgesic properties in the hot-plate model and in the acetic acid-induced writhings test, both in mice. In conclusion, these results provide evidence on the potential usefulness of the mixture of fatty acids from sugar cane wax oil in inflammatory disorders.

Acetic Acid↗

Antipsoriatic, anti-inflammatory, and analgesic effects of an extract of red propolis.

AIM: To study the antipsoriatic, anti-inflammatory, and analgesic effects of ethanolic extract of red propolis. METHODS AND RESULTS: This extract induced the formation of granular layer in the mouse tail test used as a model of psoriasis. Propolis 50 mg.kg-1 i.g. showed anti-inflammatory activity in the cotton-pellet granuloma assay in rats, in croton oil-induced edema in mice at a dose of 25% (2.5 microL), and in the peritoneal capillary permeability test in mice at a dose of 10 mg.kg-1. The extract (25 mg.kg-1 i.g.) showed analgesic effect in the model of acetic acid-induced writhings, whereas 40 mg.kg-1 was effective in the hot plate test in mice. CONCLUSION: Anti-inflammatory, analgesic, and antipsoriatric properties of Cuban red propolis were evident.

Animals↗

Is bronchial asthma a pancreatic disease?

Bronchial asthma and diabetes mellitus seldom occur in the same patient. The exact mechanism of this mutual exclusion is still unknown and its elucidation can make clear the physiopathology of both diseases. Clinical and experimental evidences suggest that insulin is a proinflammatory hormone and glucagon an antiinflammatory and a bronchodilator one. We hypothesize that the relationship between plasma insulin and glucagon may play an important role in bronchial asthma.

Anti-Asthmatic Agents↗

Diabetes-induced rat hyposensitivity to compound 48/80.

Rat mortality and contractile responses of isolated tracheas to compound 48/80 from rats made diabetic 4 days before by a single intravenous injection of alloxan and from diabetic rats that had been treated with insulin 6 h before were compared with control animals. Diabetic animals and tracheal segments from diabetic rats were significantly less responsive to compound 48/80 than control and insulin-treated diabetic animals. On the other hand, diabetic animals have a lower quantity of peritoneal mast cells than control rats, and insulin restored the normal quantity of cells in diabetic animals. These data indicate that diabetes elicits an hyposensitivity to compound 48/80, possibly related to a diabetes-induced decrease in the mast cell count.

Animals↗

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↗

Interference of levamisole with cerebral edema.

The anthelmintic and immunomodulator drug levamisole is also a thromboxane synthetase inhibitor. The effect of levamisole on cerebral edema in Mongolian gerbils and in rat models of stroke was evaluated. Cerebral ischemia was produced in gerbils by right carotid ligation and in rats by right carotid ligation and anoxia. Mortality and right hemisphere edema were evaluated 24 hours after induction of cerebral anoxia in levamisole treated animals. Levamisole failed to protect gerbils from death or cerebral edema but decreased dose-dependently the cerebral edema in rats. The fact that levamisole inhibits thromboxane synthetase and decrease cerebral swelling in rats supports further tests against human stroke.

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↗

Kerosene aerosol induces guinea-pig airway hyperreactivity to acetylcholine.

Kerosene aerosol (32.5 mg/l; 20 min), when administered to guinea pigs 1 h before exposure to acetylcholine (Ach), induced potentiation of cumulative dose-response curve of this agonist on isolated tracheal strips as well as a decrease of the lethal doses of Ach. This enhanced response was absent or greatly reduced when kerosene aerosol was administered to guinea pigs 24 h previously or just before Ach challenge. This airway hyperreactivity was also lacking when carbachol or histamine were used as spasmogens instead of Ach. Possible explanations of these results are discussed.

Acetylcholine↗

Induction of acetylcholinesterase inhibition in the guinea pig trachea by kerosene.

The effect of kerosene on in vivo and in vitro tracheal acetylcholinesterase (CHE) activity of guinea pigs has been investigated. Kerosene aerosol administered to guinea pigs during 20 min at a mean concentration of 20.4 mg/l elicited immediately, 1 h and 24 h later tracheal CHE inhibition by 30, 48.8, and 32.3% of control values (p less than 0.05). Kerosene at 1% concentration inhibited significantly, after 1 h of incubation in vitro, the CHE activity by 44.9% of control values. The tracheal CHE inhibition induced by kerosene could actually increase the acetylcholine concentration acting on smooth muscle of airways, and this partially explains the respiratory symptoms which are frequently observed after kerosene intoxication.

Animals↗

Topical anti-inflammatory activity of human recombinant epidermal growth factor.

The topical anti-inflammatory activity of epidermal growth factor (EGF) was evaluated in inflammation models induced by 12-Otetradecanoylphorbol-13-acetate, croton oil and arachidonic acid. When EGF (1.5, 3 or 6 microg/ear) was coapplied with each inflammatory agent, there was a dose-related decrease in inflammation as assessed by ear punch weights, myeloperoxidase activity as well as by histopathological studies. The precise anti-inflammatory action of EGF is yet unclear, but we believe that interference with arachidonic acid metabolism may play an important role.

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↗

Effects of kerosene on airway sensitization to egg albumin in guinea pig.

We undertook a study to determine if pre-exposure to kerosene smoke enhances airway sensitization to egg albumin in the guinea pig. Kerosene vapor inhalation for 15 days, 1 hour daily, in similar conditions to which some housewives who use kerosene as cooking fuel are exposed elicited tracheal damage characterized by signs of dysplasia and inflammatory infiltrate. When these animals were exposed to egg albumin aerosol there was an increase in the antialbumin antibody blood titer and an increased response to egg albumin in the isolated tracheal preparation (Schultz-Dale reaction), We conclude that the airway damage elicited by inhalation of kerosene vapor increase antigen absorption and thereby antibody formation.

Aerosols↗

Disodium cromoglycate inhibits bronchoconstriction by kerosine aerosol in rabbits.

To determine whether or not disodium cromoglycate (DSCG) inhibits the bronchoconstriction induced by inhalation of kerosene aerosol in rabbits, we carried out a study in 31 normal rabbits which were divided into four groups. DSCG was administered through the tracheal cannula twenty minutes before exposure to kerosene aerosol. Twenty and forty milligrams of DSCG as total doses inhibited kerosene induced bronchoconstriction in large airways (RL), but 5 mg of drug did not have any effect. DSCG at any tested dose did not inhibit the decreased dynamic lung compliance (CL) which was observed after kerosene aerosol. Our findings suggest that DSCG at high dose inhibit the bronchoconstrictor effect of kerosene in large airways of rabbits.

Aerosols↗

[Effect of several antiasthmatic prophylactic drugs on bronchoconstriction induced by kerosene in rabbits].

Various authors have reported the protective effect of disodium cromoglycate (DSCG) against bronchoconstriction induced by cold air, exercise, sulfurdioxide and other agents. We also found in our experimental work the protective effect of DSCG, ketotifen and oxatomide against the contractile effect of various agonists such as histamine prostaglandin F2, acetylcholine and barium chloride on isolated guinea pig intestine and trachea. This suggests an additional effect of these drugs on cholinergic endings and/or directly on smooth muscle fibers in addition to their membrane stabilizing effects on mast cells as it has been suggested by other authors previously. To offer insight into these mechanisms we decided to evaluate the action of ketotifen, oxatomide, ICI 74917 and BRL 10833 using the model of kerosene-induced bronchoconstriction in rabbits. Here the parasympathetic pathways play an important role as it has been demonstrated by us using atropine or vagal section. Ketotifen (5 mg/kg i.v.) and oxatomide (5 mg/kg i.v.) were administered before kerosene aerosol exposure these significantly inhibited kerosene-induced bronchoconstriction, whereas ICI 74917 (10 mg/kg i.v.) and BRL 10833 (10 mg/kg i.v.) lacked this protective effect. These results support our hypothesis that an additional protective effect on smooth muscle and its innervation is involved in the mode of action of the prophylactic antiasthmatic drugs which have been clinically successful.

Airway Resistance↗

[Morphological changes in the respiratory tract of guinea pigs exposed to kerosene aerosol].

It's well known that there exists a high correlation between daily usage of Kerosene and the appearance of dyspnea in healthy humans and in asthmatic patients. Our aim is to study the histological alterations of the respiratory tract of guinea pigs submitted to Kerosene aerosol. It was administered to male guinea pigs fifteen minutes daily for a month. Fragments of trachea and lungs were processed for histological studies. Erosion of tracheal epithelium and inflammatory infiltration were observed. Lungs presented with thickening of the interalveolar septa. The eosinophilic infiltration may represent an immunological response resembling reactions of immediate hypersensitivity. The morphological alterations may be induced by toxic products of Kerosene such as sulphur impurities that act as mucosal irritants which damage defense mechanisms of the organism.

Aerosols↗