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Biomedical subjects

G Colombo

Publications and source records attributed to G Colombo.

At least 253 records · Page 14Linked to original sources

ESBRA-Nordmann 1996 Award Lecture: ethanol drinking behaviour in Sardinian alcohol-preferring rats.

Sardinian alcohol-preferring (sP) rats have been selectively bred for high ethanol preference and consumption over 16 years and 39 generations. The present paper briefly reviews some recent studies from this laboratory characterizing ethanol drinking behaviour in this rat line. Under the two-bottle regimen of free choice between 10% (v/v) ethanol and water, sP rats consume daily >4 g of ethanol/kg and avoid water almost completely. Relevant features of ethanol drinking behaviour in sP rats are: (a) attainment of high ethanol intake from the first day of exposure to ethanol, suggestive of an immediate disclosure and acquisition of ethanol reinforcement; (b) titration of daily ethanol intake in distinct binges during the nocturnal phase of the light/dark cycle, indicative of their ability to regularize both ethanol dose and administration time; (c) achievement of pharmacologically relevant blood ethanol levels at each drinking episode; (d) substitution of the calories provided by ethanol for a part of those taken from food; (e) maintenance of constant ethanol intake (in g/kg/day) in the presence of ethanol concentrations varying from 7 to 30% (v/v). These results suggest that voluntary ethanol intake in sP rats is sustained by the search for specific pharmacological effects of ethanol. Anxiolysis is likely to be one of these effects; indeed, voluntarily consumed ethanol reversed the innate, high levels of anxiety in sP rats. These results portray sP rats as a valid model for investigating the association between ethanol drinking and anxiety. Finally, the breeding programme as well as results of neurochemical studies are also described.

Alcohol Drinking↗

High sensitivity to gamma-hydroxybutyric acid in ethanol-preferring sP rats.

Sensitivity to the sedative effect of gamma-hydroxybutyric acid (GHB), an endogenous constituent of mammalian brain as well as an effective drug in the pharmacotherapy of alcoholism, was evaluated in rats of the selectively bred, ethanol-preferring sP and non-preferring sNP lines. GHB (0.75 and 1.0 g/kg) was administered i.p. to ethanol-naive sP and sNP rats. Times to lose (onset) and recover (sleep time) the righting reflex following GHB injection were measured. At both doses, sP rats showed a greater sensitivity to the effects of GHB than did sNP rats, as evidenced by significantly shorter onset and longer sleep time. The results of the present study indicate that genetically controlled sensitivity to the sedative effect of GHB is positively correlated to ethanol preference in sP and sNP rats and suggest a possible involvement of the brain GHB system in predisposition to ethanol preference.

Alcohol Drinking↗

Reduction of voluntary ethanol intake in ethanol-preferring sP rats by the cannabinoid antagonist SR-141716.

The present study assessed the efficacy of the cannabinoid CB1 receptor antagonist, SR-141716, in reducing voluntary ethanol intake in selectively bred Sardinian alcohol-preferring (sP) rats. Ethanol (10%, v/v) and food were available in daily 4 h scheduled access periods; water was present 24 h/day. The acute administration of a 2.5 and a 5 mg/kg dose of SR-141716 selectively reduced ethanol intake, whereas a 10 mg/kg dose of SR-141716 reduced to a similar extent both ethanol and food intake. These results suggest that the cannabinoid CB1 receptor is involved in the mediation of the ethanol-reinforcing effects in sP rats.

Alcohol Drinking↗

Tryptophan metabolism in male Sardinian alcohol-preferring (sP) and -non-preferring (sNP) rats.

Parameters of tryptophan (Trp) and related metabolism were compared in male Sardinian alcohol-preferring (sP) and -non-preferring (sNP) rats. Liver Trp pyrrolase activity was 38-58% higher in sP than in sNP rats, and this was associated with a greater expression of the enzyme mRNA as measured by multiprobe oligonucleotide solution hybridization. Moderately (about 10-19%), but significantly, lower concentrations of free serum, total serum, and brain Trp were also observed in sP compared with sNP rats. Concentrations of whole brain 5-hydroxytryptamine (5-HT) and its major metabolite 5-hydroxyindol-3-yl-acetic acid (5-HIAA) were, however, 14-21% higher in sP rats. Serum corticosterone concentration was 18% higher in sP rats. We conclude that alcohol preference in Sardinian rats is associated with increased liver Trp pyrrolase activity and mRNA expression leading to a decrease in Trp availability to the brain. Although a simple serotonin deficiency could not be demonstrated in the whole brain, the possibility could not be ruled out that a deficiency may be present in discrete areas of the brain of the sP rat.

Alcoholism↗

Serotonin is reduced in the frontal cortex of Sardinian ethanol-preferring rats.

Ethanol-naive Sardinian alcohol-preferring (sP) and Sardinian alcohol-non-preferring (sNP) rats were tested to evaluate the levels of serotonin (5-HT) and 5-hydroxyindol-3-yl-acetic acid (5-HIAA) in the frontal cortex, hypothalamus, and nucleus accumbens, and the levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hypothalamus and nucleus accumbens. Compared with the sNP line, the sP rats had lower 5-HT and 5-HIAA concentrations in the frontal cortex, whereas no differences were found in the other brain areas tested, neither for neurotransmitters nor their metabolites. As the decreased 5-HT function is a feature shared by different alcohol-preferring strains, it could be linked to the genetic predisposition to voluntary ethanol consumption.

3,4-Dihydroxyphenylacetic Acid↗

In vitro and in vivo study of 5-methoxypsoralen skin concentration after topical application.

The aim of this work was to study the skin distribution of 5-methoxypsoralen (5-MOP) after application of topical gels, in vitro and in vivo, in both healthy and psoriatic skin sites of 6 psoriatic patients. Drug skin distribution was determined using the thin slicing technique and subsequent HPLC analysis. In the presence of dermatological disease, i.e. psoriasis, the permeability of the tissue changed considerably, leading to an important increase in the cumulative amount of 5-MOP recovered in the skin after topical application. The amount of 5-MOP found in vitro in the human skin was intermediate between those cumulated in healthy and psoriatic skin sites during an in vivo experiment. The gel formulation is an efficacious carrier for the topical photochemotherapy of psoriasis with 5-MOP, since it allows drug penetration in psoriatic skin.

5-Methoxypsoralen↗

A case of carcinoid of Meckel's diverticulum associated with gastric adenocarcinoma.

Meckel's diverticulum is an uncommon gastrointestinal congenital anomaly that occurs in 1-3% of the population. It is sometimes associated with complications related to the presence of ectopic tissue (obstruction, ulceration, hemmorhage, inflammation, perforation, fistula and tumors). Neoplastic degeneration of Meckel's diverticulum mucosa is rare, developing in only 1-5% of all diverticula, usually asymptomatic and occasionally discovered. Disease is metastatic, usually to the liver, in 25% of cases. We report a case of asymptomatic unsuspected carcinoid of Meckel's diverticulum with ileal, hepatic and mesenteric metastasis discovered during a gastrectomy performed for gastric adenocarcinoma. The patient underwent ileal and Meckel diverticulum resection, excision of mesenterial metastasis and liver bisegmentectomy. Furthermore, total gastrectomy with esophago-jejunal anastomosis was performed. After an 18-month follow-up period, the patient is alive and disease free. Owing to possible neoplastic degeneration, Meckel's diverticulum should be resected when occasionally discovered. In the presence of a carcinoid tumor, even if associated with metastatic disease, extended resection is recommended.

Adenocarcinoma↗

Treadmill training of paraplegic patients using a robotic orthosis.

Recent studies have confirmed that regular treadmill training can improve walking capabilities in incomplete spinal cord-injured subjects. At the beginning of this training the leg movements of the patients have to be assisted by physiotherapists during gait on the moving treadmill. The physical capabilities and the individual experience of the therapists usually limit this training. A driven gait orthosis (DGO) has been developed that can move the legs of a patient in a physiological way on the moving treadmill. The orthosis is adjustable in size so different patients can use it. Actuators at the knee and hip joints are controlled by a position controller. With the DGO the legs of patients with different degrees of paresis and spasticity could be trained for more than half an hour, and physiological gait patterns were obtained.

Exercise Therapy↗

[Wet oxidation of toxic industrial waste with oxygenated water].

The industrial toxic waste streams hot treatment technology with hydrogen peroxide and catalysts, developed by the research laboratories of Montefluos in Bollate, allows the abatement of many organic and bio-toxic pollutants. Some treatment examples are here reported. The examples, performed on a laboratory scale, relate to industrial waste streams with a high COD (100000-200000 mg/l) in which it was possible to obtain an abatement over the 90% of pollutants like phenols, formaldehyde, dimethylformamide and phenyl acetate. The application range of this technology is similar to that of oxygen or air wet oxidation, but it has remarkable advantages due to the lower plant, maintenance and energy costs, because the treatment is performed using much more bland conditions (atmospheric pressure and 90-100 degrees C of temperature). The aim of the bio-toxic pollutants abatement and COD reduction (70-80%) is to allow the final bio-digestion waste streams with high organic content, but too diluted to be directly incenerated at a suitable cost.

Hazardous Waste↗

[Earthenware and lead poisoning. Description of a case].

A case of acute lead poisoning caused by drinking wine that had been kept in a decorative amphora is reported. Chomico-physical analysis of the internal surface of the recipient evidenced a layer of lead paint very soluble in wine. It is hoped that this report will draw the attention of the practising physician and Preventive Medicine Departments to this unusual cause of saturnism. The craft production of earthenware recipients that have been inadequately glazed and their improper use as containers of drings of foods could be commoner than might be thought on the basis of the sporadic reporting of such cases of lead poisoning.

Adult↗

[Clinical evaluation of clotiazepam in the ambulatory treatment of anxiety states].

To assess the therapeutic efficacy and tolerability of Clotiazepam in the treatment of anxiety, the drug was administered to 20 subjects suffering from anxiety (12 cases) or from nervous depression (8 cases), all of whom were without psychopharmacological drugs for at least one month prior to the trial. Treatment with Clotiazepam improved the anxiety and brought about a statistically significant reduction in both groups of patients regards the total score in the Hamilton Scale and in the two sub-scale scores (somatic and psychological symptoms). Tolerability to the drug was very satisfactory.

Adult↗

Modulation of receptor levels in canine breast tumors by administration of tamoxifen and etretinate either alone or in combination.

Steroid receptors were measured in a series of 30 operable canine mammary gland tumors; both cytoplasmic estrogen (ERc) and progesterone (PgRc) receptor mean concentrations were very low with respect to the mean levels found in humans. Therefore a study was designed to modulate receptor levels by administration of Tamoxifen and Etretinate, either alone or in combination. Forty dogs with resectable, histologically documented mammary gland tumors were subdivided into the following treatment groups: a. Etretinate (1 mg/kg/d) p.o. for 7 days followed by Tamoxifen (0.7 mg/kg/d) p.o. for 7 days; b. Tamoxifen (0.7 mg/kg/d) p.o. for 14 days; c. Etretinate (1 mg/kg/d) p.o. for 14 days; d. 14 days placebo, and cytoplasmic ERc and PgRc and nuclear ER (ERn) were measured before and after the treatment. An increase of ERc and ERn was observed after administration of Tamoxifen, while an increase of ERc only was seen after treatment with Etretinate. We conclude that canine mammary tumors are indeed hormone sensitive despite their very low receptor concentrations and a suitable treatment can in fact modulate receptor levels. However, further studies are needed better to define the optimal treatment regimen in order to achieve maximal steroid receptor induction.

Animals↗