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Biomedical subjects

M Sala

Publications and source records attributed to M Sala.

At least 19 recordsLinked to original sources

Dose-dependent conditioned place preference produced by etonitazene and morphine.

The conditioned place preference (CPP) paradigm was used to study the reinforcing properties of etonitazene in comparison with those of morphine. Increasing doses of etonitazene (2.5-15 micrograms/kg i.p.) and morphine (1-80 mg/kg i.p.) induced a dose-dependent CPP. High doses of etonitazene (25-40 micrograms/kg) did not elicit CPP. In addition, these reinforcing properties were related to behavioral modifications such as analgesia, assessed with the tail-flick method, and increased catalepsy, evaluated by a scoring system. It is concluded that neither the strong behavioral effects induced by etonitazene nor tolerance to such effects account for the results. These findings are discussed with regard to the possibility that etonitazene could interfere with associative learning motivated by reward.

Analgesia

Quality control of cathepsin-D measurement by the EORTC Receptor Study Group.

Cathepsin-D is a lysosomal protease that can serve as an important prognostic cytosolic factor in breast cancer. To evaluate the performance of a commercially available immunoradiometric assay kit, 15 lyophilised cytosol participating EORTC laboratories for preparations containing various levels of cathepsin-D have been sent to 13 participating EORTC laboratories for quality control purposes. The between-laboratory variation, when expressed as coefficient of variation, did not exceed 24%. The within-laboratory variation was assessed by analysing five samples of the 15 specimens containing lyophilised material from a homogeneous cytosol pool. The mean within-laboratory coefficient of variation was 7%. Analysis of human breast tumour cytosols in one of the participating EORTC laboratories resulted in a median within-assay variation between duplicate measurements of 2.1% (n = 408), with a between-assay variation of a pooled human breast tumour cytosol of 4.6% (n = 11).

Breast Neoplasms

LAV revisited: origins of the early HIV-1 isolates from Institut Pasteur.

Two of the first human immunodeficiency virus type-1 (HIV-1) strains isolated were authenticated by reanalyzing original cultured samples stored at the Collection Nationale de Culture des Microorganismes as well as uncultured primary material. Cloned polymerase chain reaction products were used to analyze coding sequences of the V3 loop in the gp120 glycoprotein. The original isolate HIV-1 Bru, formerly called LAV, was derived from patient BRU. HIV-1 Lai was derived from patient LAI and contaminated a HIV-1 Bru culture between 20 July and 3 August 1983. The culture became, in effect, HIV-1 Lai, identifiable by a unique motif in the V3 loop. Because of this contamination two, rather than one, HIV-1 isolates were sent to the Laboratory of Tumor Cell Biology at the National Cancer Institute on 23 September 1983. Original HIV-1 Bru was indeed present in the sample marked JBB/LAV. However the M2T-/B sample harbored HIV-1 Lai, a strain capable of growing on established cell lines. The striking similarity between HIV-1 Lai (formerly LAV-Bru) and HTLV-3B sequences remains.

Academies and Institutes

Effect of centrally administered atropine and pirenzepine on radial arm maze performance in the rat.

The effect of two anticholinergic drugs administered intracerebroventricularly on acquisition of an 8-arm radial maze task was examined in the rat. Increasing doses of atropine (1, 4.5, 22.5, 45 micrograms/rat) and pirenzepine (4.5, 15, 60, 90 micrograms/rat) significantly impaired performance in the working-memory components of the task. For both drugs this impairment was linearly related to the log of the administered doses and log-dose-response relationship were parallel. The regression lines calculated for each parameter for both drugs were parallel to each other, thus allowing us to calculate the potency of atropine versus pirenzepine: atropine was 5.4 times more potent than pirenzepine for correct arm entries, 10 times more potent for the number of errors and 4 times more potent for the total time taken to complete the task. The relevance of M1 and M2 subtype central acetylcholine receptors in cognitive processes is discussed.

Animals

Prevention of necrotizing enterocolitis in neonates at risk by oral administration of monomeric IgG.

Necrotizing enterocolitis (NEC) represents one of the major causes of morbidity in low-birth-weight (LBW) preterm infants. This randomized clinical trial evaluated the efficacy of an oral immunoglobulin preparation (containing monomeric IgG in a concentration of 90%) in reducing the incidence of NEC in infants of LBW for whom maternal breast milk was not available. One hundred and thirty-two formula-fed newborns with a birth weight less than or equal to 1,500 g or a gestational age less than or equal to 34 weeks were randomly studied. Five hundred mg of IgG pro die, subdivided into 5 doses, were given orally to the test group of 65 neonates during the first 2 weeks of life. Although the number of infants included in this group is limited, the results of this study are encouraging: during the first 15 days after birth, none of the subjects developed NEC, while 4 cases were confirmed in the untreated control group. It, therefore, seems possible that oral monomeric IgG administration may prevent the development of NEC in LBW infants.

Administration, Oral

Immunoradiometric assay of pS2 protein in breast cancer cytosols.

We studied the ELSA-pS2 immunoradiometric kit (CIS Bio International) for pS2 protein assay in breast cancer cytosols according to classic validation methods. In addition, we studied correlations between pS2, steroid receptors, and cathepsin-D assays. Repeatability (CV = 1.5% to 4.8%) and reproducibility (CV = 1.6% to 4.9%) were good. The results were linearly related to pS2 concentrations between 205 and 2200 ng/L; the detection limit was 40 ng/L. The accuracy of the assay was measured by assessing recovery; analytical recoveries were near 100% throughout the standard curve. The use of different compounds for cytosol preparation (Tris 10 mmol/L or phosphate 25 mmol/L, KCl 0.4 mol/L, bovine serum albumin 1 g/L) had no effect on pS2 results. pS2 was assayed in breast tumor cytosols from 197 postmenopausal and 92 premenopausal patients. The mean value was 24 micrograms/g of protein; the median and 25th and 75th percentiles were 6, 1, and 23 micrograms/g protein, respectively. We observed a relation between concentrations of pS2 and those of estrogen and progesterone receptors, but there was no relationship between the concentrations of pS2 and cathepsin-D.

Breast Neoplasms

Central effect of yohimbine on sexual behavior in the rat.

A large range of doses of yohimbine (Y) was administered intracerebroventricularly (ICV) (5-100 micrograms/rat) or intraperitoneally (IP) (0.35-10 mg/kg) to male rats and the effects on sexual, locomotor and general behavior were evaluated. For both routes there was a clear-cut inverted-U effect (stimulating/depressing), calculable as parabolic regressions on the log of administered doses. The maximal stimulating doses (15 micrograms/rat ICV and 1 mg/kg IP) significantly shortened mount, intromission and ejaculation latencies and the mean interintromission interval. These data indicate the importance of CNS mechanisms in the sexual effect of Y.

Animals

Ischemic optic neuropathies.

Primary or secondary impairment of blood supply to the optic nerve results in a spectrum of ischemic optic neuropathies with multiple etiopathogenesis. Among these the clinical features of traumatic and radiation optic neuropathy are outlined. Diagnostic criteria, associated conditions, risk factors and functional prognosis of anterior ischemic optic neuropathy are reviewed and discussed in the light of the contribution of recent literature.

Humans

Dexamethasone in the treatment of bronchopulmonary dysplasia.

Sixteen chronically ventilator-dependent newborns with BPD were treated with one or more cycles of dexamethasone (0.5 mg/kg/day). In 11 cases extubation was possible during the therapy period. Ventilatory parameters were lowered in 3 other newborns. FIO2, respiratory rate, PIP, and PEEP, assessed before and after dexamethasone administration, decreased in a statistically significant way. Our data confirm the utility of dexamethasone in the extubation in chronically ventilated infants with BPD.

Bronchopulmonary Dysplasia

Histamine as a central modulator of rat intestinal transit.

Histamine (HA) injected i.c.v. to rats inhibited intestinal propulsion in linear relation to the log of the administered doses (in the range from 20-100 micrograms/rat). In the same dose range HA also induced a dose-related analgesic effect (tail-flick test). The dose of HA maximally active by the i.c.v. route (100 micrograms/rat) showed neither of these effects when injected i.v. or i.p. HA-induced intestinal inhibition and analgesia were antagonized competitively by i.c.v. mepyramine (10 micrograms/rat), an H1 receptor antagonist, whereas cimetidine (10 micrograms/rat), an H2 receptor antagonist, had no effect. Repeated i.c.v. injections of HA resulted in tachyphylaxis of both intestinal inhibition and analgesia. Pretreatment with i.c.v. naloxone (20 micrograms/rat) antagonized the antipropulsive effect of HA in a noncompetitive fashion, but did not affect its antinociceptive action. The relevance of the central histaminergic system in the modulation of gastrointestinal motility and its relationship with the opioid system are discussed.

Analgesia

Multi-center study of a new technique for measuring free thyroxin in serum.

In a multi-center trial we evaluated the accuracy of a new assay kit for free thyroxin (T4), the Behring free T4 RIAgnost, in 1036 subjects: 379 normal subjects, 536 patients with thyroid dysfunction, and 121 subjects with no thyroid dysfunction but with conditions that potentially could interfere with the assay. The kit combines immunoextraction and the use of a modified tracer. Although some limitations remained in using a direct assay method for free T4 in certain nonthyroid conditions, this test was superior to one based on the use of a T4 analog. This kit seems to be very accurate for the diagnosis of untreated thyroid pathologies.

Adolescent

Differences in the DNA adducts formed in cultured rabbit and rat dermal fibroblasts by benzo(a)pyrene and (-)benzo(a)pyrene-7,8-diol.

Benzo(a)pyrene (BaP) is highly carcinogenic in rats but is without effect in rabbits when administered s.c. The possibility that BaP-DNA adducts could be responsible for this species difference was investigated by comparing BaP-deoxyribonucleoside adducts formed in dermal fibroblast cultures from Wistar rats and New Zealand rabbits. Treatment with [G-3H]BaP (1.2 microM) for 6, 24, and 48 h produced an essentially qualitative species-specific difference. Over 95% of the DNA adducts in the rabbit dermal cell cultures were derived from anti-BaPDE; the major BaP adduct formed (90%) was (+)-anti-BaPDE-deoxyguanosine. This adduct was formed at very low levels in the rat dermal fibroblasts (7%). These cells contained a large proportion of (+/-)-r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (syn-BaPDE)-DNA adducts (45%) and over 48% of other, unidentified, BaP-DNA adducts. Cells treated with (-)-BaP-7,8-diol (1.2 microM) produced almost exclusively (greater than 99%) (+)-anti-BaPDE-deoxyguanosine in rabbit cells, while the rat cells did not form this product. These results suggest that adducts other than anti-BaPDE-deoxyguanosine may be involved in rat s.c. BaP carcinogenesis; the preferential formation of (+)-anti-BaPDE-deoxyguanosine by rabbit dermal fibroblasts does not directly correlate with the resistance of rabbit dermis to tumor formation.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Supraspinal cerebral areas involved in morphine's intestinal inhibition and analgesia.

To explore the neuroanatomical pathways involved in mediating the antipropulsive effect and analgesia of morphine (M) in the periaqueductal gray matter (PAG), we examined the influence of the vagus nerve and the role of serotonergic neurotransmission. M-induced inhibition of intestinal transit was unaffected by subdiaphragmatic vagotomy. In contrast, electrolytic lesions in the raphe magnus nucleus (NRM) and pretreatment with a selective neurotoxin (5,6-DHT, 15 micrograms/rat) in the same region, both significantly reduced M-induced inhibition of intestinal transit. Analgesia was only slightly affected. p-CPA pretreatment (100 mg/kg IP) induced the same results. Finally some other central brain regions were found to be sensitive to M's intestinal inhibition and analgesia such as the mid-line thalamus, the dorsal and lateral hypothalamus, and the bulbar reticular formation. Negative results were obtained for frontal cortex, caudate and amygdala. Some considerations are put forward about the existence in the central nervous system of selective areas involved in intestinal modulation and their relation with those mediating pain transmission.

Analgesia

Splanchnic exchange of amino acids after amino acid ingestion in patients with chronic renal insufficiency.

Splanchnic exchange (net uptake or release) of amino acids (AAs) was evaluated by measuring arterial-hepatic venous differences for AAs and hepatic blood flow in patients with chronic renal insufficiency (CRI) and control subjects before and for 70 min after the ingestion of an AA mixture simulating an animal protein meal. In CRI after AA ingestion, splanchnic exchange area for total nonessential AAs (NEAAs) is increased 135% over control subjects because of an augmented escape of proline, glutamate, serine, glycine, alanine, and cyst(e)ine; contrarily, glutamine shows an increased splanchnic uptake. Splanchnic exchange area for total essential AAs (EAAs) is increased only by 67% over controls because of a higher escape of threonine, isoleucine, phenylalanine, and histidine. Abnormalities in arterial areas for AAs parallel those in splanchnic areas except for glutamine and isoleucine. Data indicate that in CRI, at least for 70 min after an AA meal, splanchnic organs metabolize abnormally ingested AAs and export an increased and unbalanced bulk of AAs, severely affecting postprandial arterial profile of AAs.

Adult