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Biomedical subjects

L Pinto

Publications and source records attributed to L Pinto.

At least 37 records · Page 2Linked to original sources
PubMed1999

The role of cannabinoid receptors in intestinal motility, defaecation and diarrhoea in rats.

We have studied the effects of the cannabinoid receptor agonists (R)-(+)[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2, 3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN 55,212-2, 0. 3-5 mg/kg, i.p.) and (-)-cis-3-[2-hydroxy-4-(1, 1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) (CP 55,940, 0.03-1 mg/kg, i.p.), the cannabinoid CB(1) receptor antagonist (N-piperidin-1-yl)-5-(4-chlorophenyl)-1-2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A, 0. 3-5 mg/kg, i.p.) and the cannabinoid CB(2) receptor antagonist N-[-(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazo le- 3-carboxamide (SR144528, 1 mg/kg, i.p.) on intestinal motility, defaecation and castor-oil (1 ml/100 g rat, orally)-induced diarrhoea in the rat. SR141716A, but not SR144528, increased defaecation and upper gastrointestinal transit, while WIN 55,212-2 and CP 55,940 decreased upper gastrointestinal transit but not defaecation. WIN 55,212-3 (5 mg/kg), the less active enantiomer of WIN 55,212-2, was without effect. A per se non-effective dose of SR141716A (0.3 mg/kg), but not of SR144528 (1 mg/kg) or the opioid receptor antagonist, naloxone (2 mg/kg i.p.), counteracted the inhibitory effect of both WIN 55,212-2 (1 mg/kg) and CP 55,940 (0.1 mg/kg) on gastrointestinal motility. WIN 55,212-2 did not modify castor-oil-induced diarrhoea, while CP 55,940 produced a transient delay in castor-oil-induced diarrhoea at the highest dose tested (1 mg/kg), an effect counteracted by SR141715A (5 mg/kg). These results suggest that (i) intestinal motility and defaecation could be tonically inhibited by the endogenous cannabinoid system, (ii) exogenous activation of cannabinoid CB(1) receptors produces a reduction in intestinal motility in the upper gastrointestinal tract but not in defaecation, (iii) endogenous or exogenous activation of cannabinoid CB(2) receptors does not affect defaecation or intestinal motility and (iv) the cannabinoid receptor agonist, CP 55, 940, possesses a weak and transient antidiarrhoeal effect while the cannabinoid receptor agonist, WIN 55,212-2, does not possess antidiarrhoeal activity.

Analgesics↗
PubMed1999

Contractile effect of (+)-glaucine in the isolated guinea-pig ileum.

The intestinal effects of (+)-glaucine [(S)-1,2,9,10-tetramethoxyaporphine] were studied using the guinea-pig ileum. (+)-Glaucine (10-300 microM) induced ileal contractions. The contraction was not affected by tetrodotoxin, atropine, hexamethonium, propranolol, naloxone, methysergide, N(G)-nitro-L-arginine methyl ester, SR141716A (a cannabinoid CB1 receptor antagonist) or SR140333 (a tackykinin NK1 receptor antagonist) plus SR48968 (a tackykinin NK2 antagonist). (+)-Glaucine-induced contraction was reduced by indomethacin, nordihydroguaiaretic acid or bisindolylmaleimide I and abolished by verapamil and nifedipine. These results suggest that (+)-glaucine-induced contraction involves activation of voltage-dependent Ca2+ channels and protein kinase C and could be mediated by the release of arachidonic acid metabolites.

Animals↗
PubMed1999

Action of chlorogenic acid on the complement system.

Previous research on plants used in folk medicine as antidotes against snake-bite revealed some constituents responsible for such protection. Chlorogenic acid (3-0-caffeoyl quinic acid) was one of these substances, studied with more attention. It has been shown that this substance binds to proteins through hydrophobic interactions and hydrogen bonds. This paper shows the preliminary results about the anti-complementary action of chlorogenic acid. Human and guinea pig sera, treated with chlorogenic acid, were added to the hemolytic system (sheep erythrocyte sensitized with hemolysin) to study its effect on the activation of the classical complement pathway. The action on the alternative pathway was studied with human serum treated with chlorogenic acid and zymosan. Our results show that chlorogenic acid presents anti-complementary action at the classical pathway, since the sera are not able to lysis the indicator system. The presence of C3b fragments on the surface of the yeast cells demonstrates that the alternative pathway was not affected.

Animals↗
PubMed1998

Inactivation of the gene coding for the 30.4-kDa subunit of respiratory chain NADH dehydrogenase: is the enzyme essential for Neurospora?

We have isolated and characterised the nuclear gene that codes for the 30.4-kDa subunit of the peripheral arm of complex I from Neurospora crassa. The single-copy gene was localised on chromosome VI of the fungal genome by restriction fragment length polymorphism mapping. An extra copy of the gene was introduced into a strain of N. crassa by transformation. This strain was crossed with another strain in order to inactivate, by repeat-induced point mutations, both copies of the duplication carried by the parental transformant. Ascospore progeny from the cross were analysed and a mutant strain lacking the 30.4-kDa protein, nuo30.4, was isolated and further characterised. The mutant appears to assemble the membrane arm of complex I, while formation of the peripheral arm is prevented. Nevertheless, the mutant grows reasonably well--indicating that this well conserved protein is not essential for vegetative growth--and is able to mate with other strains both as male or female. Strains with multiple mutations are readily obtained from heterozygous crosses between different complex I mutants of N. crassa. On the other hand, homozygous crosses between several mutants, including nuo30.4, fail to produce ascospores. These results suggest that complex I plays an essential role during the sexual phase of the life cycle of the fungus.

Fungal Proteins↗
PubMed1998

[Endoscopic sphincterotomy in acute biliary pancreatitis. A multicenter study].

BACKGROUND: Severe acute pancreatitis are still dangerous, as can be seen from the high mortality rate (around 30%). It's commonly known that in the last years diagnostic ability, precise stadiation and control over the disease development were increased. Surgical therapy is directed mainly to achieve the control over septic evolution, and in biliary pancreatitis to resolve hypertension and infection inside the biliary tree (now widely accepted as the real cause of this disease). Recently, some authors demonstrated that the prognosis of a pancreatitis can be greatly improved by stopping the evolution toward a severe phase with necrosis and multiple organ failure without any surgical operation. They believe that's possible to achieve this result performing an early endoscopic sphincterotomy in all biliary pancreatitis (recognised by means of echography and CT scan), before the development of necrosis. METHODS: In our department, following this address, very good results have been obtained: that's why a multicentric trial has been carried out to appraise the results obtained by endoscopic sphincterotomy within 48 hours from the disease onset. Answers from 114 hospitals were received, with a total survey of more than 10,000 pancreatitis. Endoscopic sphincterotomy was performed in 55% of billiary pancreatitis, which were estimated at the onset, on second or third degree of Balthazar classification. RESULTS: In 86% of patients, endoscopic sphincterotomy was performed within 48 hours from symptoms onset. Complications related to this treatment are reported in less than 4% of patients. CONCLUSIONS: The procedure, avoiding the evolution toward necrosis and sepsis, allowed the reduction of surgical operations to 6.7%, and of the mortality amongst all cases gathered to 2.5%.

Acute Disease↗
PubMed1996

[Nationally produced 153SmEDTMP in the palliative treatment of metastatic bone cancer pain].

153SmEDTMP was obtained from enriched 152Sm irradiated at the 5 MW Chilean Research Reactor and labelled at a molar ratio of 15:1 pH 7.5. Biodistribution, autoradiography, radiochemical purity tests were done for evaluation. 40 patients were treated with 37-55 MBq/kg weight. Bone scans using 99mTcHMDP were obtained prior and after treatment. Bone marrow depression was observed in 37% of them and normal liver function in all of them. In 45% the pain dissapear completely, in 22.5% significantly decreased and partially in 30%. In 17 patients more than one dosis was injected. Our preliminary results indicate that 153SmEDTMP is a promising radiotherapeutic agent for palliative treatment of metastatic bone cancer pain and encourage its use specially because it can be produced in countries with low economic resources, thus a large number of patients can get the benefits of this new procedure.

Adult↗
PubMed1995

Juvenile chronic myelogenous leukemia: in vitro characterization before and after allogeneic bone marrow transplantation.

In previously published studies on patients with juvenile chronic myelogenous leukemia (JCML), excessive proliferation of malignant monocyte-macrophage elements and impaired growth of normal hematopoietic progenitors were demonstrated. A selective hypersentivity of granulocyte-macrophage progenitors (CFU-GM) to granulocyte-macrophage colony stimulating factor (GM-CSF) seems to represent the main pathogenetic mechanism. Allogeneic bone marrow transplantation (BMT) has been demonstrated to be the only curative strategy for patients with JCML. In this study, we evaluated the growth of peripheral blood hematopoietic progenitors in semisolid cultures in two children with JCML before and after allogeneic BMT. Serum levels of GM-CSF, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) were also assessed. IL-1-beta, GM-CSF and TNF-alpha serum levels of the patients before and after BMT did not differ significantly from those obtained in 45 healthy controls. After marrow transplant, the engraftment of donor hematopoietic stem cell was associated with the disappearance of both pretransplant GM-CSF hypersensitivity and CFU-GM spontaneous growth. The inhibitory effect on the growth of normal hematopoietic progenitors also resolved. This confirms that the substitution of the pathological hematopoietic progenitors represents the basis for the curvative effect of allogeneic BMT in the treatment of JCML, abolishing both the excessive responsiveness of JCML progenitor cells even to very low concentrations of GM-CSF and the growth-inhibitory effect on normal hematopoiesis.

Bone Marrow Transplantation↗
PubMed1995

Transferable clastogenic activity in plasma from patients with Fanconi anemia.

The present study was conducted on 13 patients with Fanconi anemia. 25 parents and 12 siblings. The chromosomal instability characteristic of this congenital breakage syndrome was associated with the presence of transferable clastogenic material in the plasma, as also reported previously for ataxia telangiectasia and Bloom's syndrome. While all plasma ultrafiltrates from homozygotes had chromosome damaging properties, the clastogenic material had to be concentrated in most heterozygotes to reach detectable levels. The clastogenic effect was exerted via the intermediacy of superoxide radicals, since it was regularly inhibited by superoxide dismutase (SOD). This adds further evidence for a prooxidant state in this hereditary disease. The autosustained clastogenic activity possibly plays a role in the progressive impairment of blood cell-producing bone marrow and may predispose patients to develop cancer and leukemia. Prophylactic use of antioxidants may be recommended, using clastogenic plasma activity as a guide.

Adolescent↗
PubMed1995

In vivo accumulation of 8-hydroxy-2'-deoxyguanosine in DNA correlates with release of reactive oxygen species in Fanconi's anaemia families.

The present study was aimed at verifying the occurrence, if any, of in vivo oxidative DNA damage in FA homozygotes, their parents and siblings. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured, by HPLC/EC, in DNA from circulating blood leucocytes from FA homozygotes and their relatives and compared with a group of paediatric and adult healthy subjects. The population studied consisted of: (i) 15 FA homozygotes; (ii) 24 FA heterozygotes; (iii) 11 siblings. The 8-OHdG level in FA homozygotes was significantly higher with respect to age-matched controls, with a mean level of 33.3 +/- 6.8 (mean +/- SE) and 3.9 +/- 0.26 8-OHdG/10(5) dG respectively. The FA parents (heterozygotes) also displayed higher 8-OHdG levels relative to controls. The release of hydroxyl (.OH) and .OH-like radicals from leucocytes was determined by luminol-dependent chemiluminescence (LDCL) in a subgroup of FA homo- and heterozygotes, showing a very large in vivo formation of non-superoxide radicals. Chromosomal instability was also measured in the FA population. When relating either 8-OHdG or LDCL levels to spontaneous or diepoxybutane-induced chromosomal instability (S-CI and DEB-CI respectively), a significant correlation was observed between the 8-OHdG, LDCL and S-CI data. Within families a positive association was found between 8-OHdG levels in homozygotes and their related heterozygotes, suggesting segregation of the genetic defect(s) underlying the abnormal oxidative metabolism. The present study provides evidence for an in vivo pro-oxidant state in FA, in terms of excess formation of .OH and .OH-like radicals, and of DNA hydroxyl adducts. This finding appears to be shared by homozygotes and, to a lesser extent, by heterozygotes.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

The oxidation of pyrene and benzo[a]pyrene by nonbasidiomycete soil fungi.

The purpose of this study was to determine the ability of nonbasidiomycete soil fungi to oxidize pyrene (four rings) and benzo[a]pyrene (BaP) (five rings). Fungi were isolated from five different soils in which the polycyclic aromatic hydrocarbon content ranged from 0.8 to 80 micrograms/g dry soil. Approximately 50% of the isolates in all sites were able to oxidize pyrene. The pyrene-oxidizing species belonged to all fungal divisions except basidiomycetes. The most common were Penicillium spp. of the subgenus Furcatum and these dominated the more contaminated soils. Penicillium janthinellum and Syncephalastrum racemosum exhibited the most rapid rates of pyrene oxidation. The major pyrene metabolites were identified by proton NMR and mass spectrometry as 1-pyrenol, 1,6- and 1,8-pyrenediol, and the 1,6-and 1,8-pyrenequinones. A high correlation was found between the ability to oxidize pyrene and BaP. As with pyrene, approximately 50% of the fungal isolates tested oxidized BaP to 9-hydroxy-BaP. Eighty percent of the pyrene-oxidizing strains were also able to metabolize BaP.

Benzo(a)pyrene↗
PubMed1994

Mild elliptocytosis associated with the alpha 34 Arg-->Trp mutation in spectrin Genova (alpha I/74).

We report a new mutation responsible for nonhemolytic hereditary elliptocytosis (HE). The proband displayed an impaired spectrin self-association and an increase of the alpha I 74-kD fragment (alpha I/74 abnormality). The responsible mutation occurred in exon 2 of spectrin alpha-gene: alpha 34 Arg-->Trp (CGG-->TGG), defining spectrin Genova. In Trans to allele alpha Genova, the proband disclosed allele alpha LELY, a common low-expression allele of spectrin alpha-gene. It was recognized through particular peptide maps as well as characteristic mutations in exon 40 and intron 45, respectively. The father, who carried allele alpha Genova, but not allele alpha LELY, had a milder presentation. The sensitization of allele alpha Genova by allele alpha LELY was noticeable in the proband as compared with his father. Nevertheless, it was not as sharp as that observed with many other alpha I/74 HE alleles. Therefore, each alpha I/74 HE allele has a distinct intrinsic severity.

Alleles↗
PubMed1994

Lymphocyte reactivity to ex-vivo drug antigens in drug-induced hepatitis.

The diagnosis of drug-induced hepatitis is usually based on clinical criteria, with emphasis on both the temporal relationship between drug intake and liver injury and the exclusion of alternative causes. In vitro tests of lymphocyte sensitization to drugs are considered to have a low sensitivity. We investigated the possibility of detecting lymphocyte reactivity to drugs in drug-induced hepatitis by analyzing the lymphocyte proliferative responses to ex-vivo drug or metabolite antigens to improve the sensitivity of the in vitro test. Lymphocyte proliferative responses to five different concentrations of the drug and to ex-vivo drug antigens (serum collected from normal subjects after the ingestion of the drugs) were analyzed in 25 patients with a clinical diagnosis of drug-induced hepatitis, 27 healthy subjects and 10 individuals with a recent exposure to the same drugs without development of adverse drug reactions. In seven of the 25 patients, lymphocyte reactivity to drugs was detected (28%). The use of sera collected from healthy volunteers after drug intake (ex-vivo drug antigens) and the addition of a prostaglandin inhibitor to the cultures allowed the detection of lymphocyte sensitization in seven additional cases, increasing the detection ability from 28% to 56%. We suggest that the use of ex-vivo drug antigens may represent a significant contribution to the identification of the drug involved in cases of drug-induced hepatitis.

Adult↗
PubMed1994

Erythrocyte membrane protein alterations underlying clinical heterogeneity in hereditary spherocytosis.

Hereditary spherocytosis (HS) is a very heterogenous condition both at clinical and biochemical level. To establish the relationship between these aspects we performed a clinical and biochemical study in 87 Italian HS subjects. Patients were divided into three groups based on clinical severity (mild, typical and severe) and into five subgroups based on specific membrane abnormalities identified by polyacrylamide gel electrophoresis (isolated spectrin deficiency, spectrin deficiency combined with mild ankyrin reduction, spectrin deficiency combined with severe ankyrin reduction, band 3 reduction and isolated protein 4.2 reduction). We were not able to assess any alteration in six HS patients. A good correlation between clinical HS forms and membrane protein defects is shown. We conclude that erythrocyte membrane analysis should be carried out after diagnosis of HS in order to predict the clinical course of the disease.

Adolescent↗
PubMed1994

[Posterior cranial fossa hemorrhage in term newborn infants: clinical and ultrasonographic aspects in 2 cases].

Haemorrhages of the posterior cranial fossa were diagnosed by cerebral sonography, sometimes these lesions were misinterpreted by the examination. We report two cases of posterior fossa haemorrhages in the term newborn without ultrasonography signs of this pathology. In a case some days after haemorrhagical damage, the signs of past haemorrhage were demonstrated.

Cerebral Hemorrhage↗
PubMed1993

M-07e cell bioassay detects stromal cell production of granulocyte-macrophage colony stimulating factor and stem cell factor in normal and in Diamond-Blackfan anemia bone marrow.

Ten healthy donors and four patients with Diamond-Blackfan anemia (DBA) have been investigated for granulocyte-macrophage colony stimulating factor (GM-CSF) and stem cell factor (SCF) production by bone marrow-enriched fibroblasts (BMEF) in a highly sensitive biological assay on growth factor-dependent M-07e cells. M-07e cells detected active soluble kit-ligand from normal bone marrow fibroblasts as well as from DBA BMEF which produce constitutively significant amounts of SCF. Interleukin 1 beta (IL-1 beta) induced a significant increase of soluble SCF from both normal and DBA BMEF. GM-CSF was undetectable in unstimulated cultures, while its production by bone marrow microenvironmental cells was documented for both normal and DBA patients after IL-1 beta stimulation in vitro.

Adult↗
PubMed1993

Coexistence of hereditary spherocytosis (HS) due to band 3 deficiency and beta-thalassaemia trait: partial correction of HS phenotype.

A kindred with hereditary spherocytosis and beta-thalassaemia trait was identified. Detailed studies of the red cell membrane proteins on polyacrylamide gels with sodium dodecyl sulphate (SDS-PAGE) demonstrated the presence of band 3 (anion transporter) deficiency in all HS subjects (20-25% reduction) whereas spectrin content was in the normal range. The molecular defect of beta thalassaemia in this kindred was due to a beta(0) codon 39 (C-T) mutation, as assessed by beta globin gene amplification and ASO-probe hybridization. Seven subjects of this family were studied: two were normal, two had HS alone, two co-inherited HS and beta-thalassaemia trait, and one had beta-thalassaemia trait only. The two subjects with HS alone had a typical clinical form of spherocytosis with anaemia, reticulocytosis and increased red cell osmotic fragility. The two with both HS and beta-thalassaemia trait were not anaemic and showed a small, well-compensated haemolysis. Hence the finding of red cells with abnormalities of both HS and beta-thalassaemia indicates that beta-thalassaemic trait 'silences' HS caused by band 3 deficiency.

Adult↗