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G Fraile

Publications and source records attributed to G Fraile.

At least 19 recordsLinked to original sources
PubMed2005

Clozapine prevents apoptosis and enhances receptor-dependent respiratory burst in human neutrophils.

The present study was undertaken to determine if the antipsychotic drug clozapine (CLZ) in the concentration range 2-50 microM can rescue polymorphonuclear cells (PMNs) from undergoing apoptosis. Our results indicate that 20 microM CLZ can rescue PMNs both from UVB-accelerated (28.0% vs. 45.9% for control without CLZ; P < 0.05) and from spontaneous (35.8% vs. 57.6%; P < 0.05) apoptosis whereas 50 microM CLZ could rescue PMNs from spontaneous (34.3% vs. 57.6%; P < 0.05) apoptosis only. Furthermore, since apoptosis has been reported to involve the impairment of PMN function, we evaluated the effects of CLZ on respiratory burst in UVB-irradiated and in unirradiated PMNs. When 20 or 50 microM CLZ-pretreated PMNs were aged in a culture during 4 h, the luminol-dependent chemiluminescence (CL) response was 3-fold (P < 0.01) and 2.5-fold (P < 0.05) increased, respectively, by subsequent exposure to serum opsonized zymosan (OZ). When 50 microM-pretreated PMNs were either UVB-irradiated or unirradiated, the CL response was 2.6-fold (P < 0.05) and 3.3-fold (P < 0.05) increased, respectively, after subsequent exposure to formyl-methionyl-leucyl-phenylalanine (fMLP). In contrast, the degree of enhancement was negligible upon subsequent exposure to ionomycin or phorbol myristate acetate (PMA). When incubation times were extended up to 22 h, the CL response induced by OZ in 20 microM CLZ-treated PMNs had a 4.9-fold increase (P < 0.001). This priming effect could be reverted when 20 microM CLZ-treated PMNs (aged 4 h in culture) were coincubated for 5 min with the protein tyrosine kinase inhibitor genistein as well as with the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin. These findings suggest that CLZ primes respiratory burst and prevents PMN apoptosis as a consequence of tyrosine phosphorylation- and PI3-K activation-dependent signal transduction pathways.

Androstadienes↗
PubMed2003

Antioxidant properties of dipyridamole as assessed by chemiluminescence.

The ability of dipyridamole (DIP) to scavenge oxygen metabolites generated by either activated human neutrophils (PMNs) or cell-free systems using luminol(s)- and lucigenin-enhanced chemiluminescence was investigated. In the presence of DIP (15-50 microM) a dose-dependent inhibition period was seen in phorbol myristate acetate (PMA)-stimulated PMNs as assayed by isoluminol-enhanced chemiluminescence (ILCL) with horseradish peroxidase (HRP). Although such a lag period was not observed in the absence of HRP, 50 microM DIP inhibited extracellular ILCL by more than 50%. Intracellular luminol-enhanced chemiluminescence (LCL) as assayed in either PMA- or in ionomycin-activated PMNs was not affected by dipyridamole (15-50 microM). In cell-free systems, DIP produced concentration-dependent inhibition in H2O2-(45% at 50 microM), OH- (40%, at 0.1 microM) and HOCl-(20% at 10 microM). Both absorbance and fluorescence scans revealed that DIP is able to react with equimolar quantities of either H202 or HOCl. These results suggest that DIP scavenges reactive oxygen species (ROS) presumably secreted by activated human PMNs in the following decreasing order: *OH > HOCl > H2O2 >> O2-.

Acridines↗
PubMed2002

Studies on the photostability and phototoxicity of aloe-emodin, emodin and rhein.

Aloe-emodin (1), emodin (2) and rhein (3) were found to be photolabile by visible (390-500 nm) light under aerobic conditions. The drugs 1, 2 and 3 were phototoxic in vitro when examined by the photohemolysis test under both oxygen and argon atmospheres, although the photohemolysis rate was markedly lower under anaerobic conditions. The experiments were also carried out in the presence of butylated hydroxyanisole (BHA), reduced glutathione (GSH), sodium azide (NaN3) and superoxide dismutase (SOD). Based on the inhibition of this process on addition of BHA, GSH, SOD and NaN3, there would seem to be involvement of free radicals (type I mechanism) and singlet oxygen in the process (type II mechanism). The in vitro phototoxicity of this anthraquinone series was also verified in a lipid-photoperoxidation test with linoleic acid. In summary, this anthraquinone series is phototoxic in vitro. This behavior can be explained through the involvement of singlet oxygen and stable photoproducts.

Acetylcholinesterase↗
PubMed2001

Photosensitizing activity of thiocolchicoside: photochemical and in vitro phototoxicity studies.

The phototoxic drug thiocolchicoside (2-dimethoxy-2-glucosidoxythiocolchicine, 1), is photolabile under irradiation with UV-A light from TL 100 W-P Philips bulbs (at lambda max 355 nm) light and also with a N2 laser (at 337 nm) in aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 produces two photoproducts without a glucoside group. One of these lost the methylthio-group, while the other is oxidized (only under aerobic conditions) to sulfoxide. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-MS), furfuryl alcohol, 1,3-cyclohexadiene-1,4-diethanoate (HPLC) and by the histidine test as 1O2 scavengers. Thiocolchicoside has been shown to photosensitize the reduction of nitro blue tetrazolium by direct electron transfer mechanism, when irradiated under the same conditions as for photolysis. Oxygen may also be involved in this electron transfer reaction to form the superoxide anion radical. Thiocolchicoside was screened in vitro in different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and superoxide radical quenchers. In addition, 1 photosensitized the peroxidation of linoleic acid, monitored by the UV-detection of dienic hydroperoxides. Studies on peripheral blood mononuclear cells (lymphocytes) demonstrated phototoxic effects on them. Protection by GSH, DABCO, sodium azide and SOD are indicative of both Type I and II photosensitization pathways mediated by free radicals and singlet molecular oxygen.

Colchicine↗
PubMed2000

Photochemistry and phototoxicity studies of flutamide, a phototoxic anti-cancer drug.

The phototoxic anti-cancer drug flutamide is photolabile under UV-B light in either aerobic or anaerobic conditions. Irradiation of a methanol solution of this drug produces several photoproducts, one by photoreduction of the nitro group, one by rupture of the aromatic-NO2 bond of the parent compound, two as a result of the rupture of the CO-NH bond and one derived from the photoreduction product by scission of the aromatic-NH2 bond. Flutamide shows a photohemolytic effect on human erythrocytes and photoinduces lipid peroxidation. Studies on peripheral blood polymorphonuclear cells (neutrophils) demonstrated the phototoxicity of flutamide as well as inhibition of the cytotoxicity respiratory burst by the photoproduct derived from its photoreduction. The results suggest that the inhibition of the respiratory burst observed in phorbol myristate acetate (PMA)-activated cells is mediated by photosensitization and concomitant singlet oxygen production and/or formation of toxic photoproducts.

Antineoplastic Agents, Hormonal↗
PubMed2000

Studies on the in vitro phototoxicity of the antidiabetes drug glipizide.

The phototoxic antidiabetes drug glipizide (1) is photolabile under aerobic conditions and UV-B light. Irradiation of a phosphate-buffered solution of 1 under oxygen atmosphere produces 4 photoproducts as well as singlet oxygen, which was detected by trapping it with 2,5-dimethylfuran and by the histidine test. The photochemistry of 1 involves cleavage of the sulfonamine and the sulfonamine-R bonds. Red blood cell lysis, photosensitized by glipizide and the products of its aerobic photolysis were demonstrated. The photohemolysis rate was lower for 1 than for its photoproducts. Inhibition of this process on addition of 1, 4-diazabicyclo[2.2.2]octane (DABCO), reduced glutathione (GSH), Vitamin C, sodium azide, superoxide dismutase, and a-tocopherol confirmed the possibility of singlet oxygen, superoxide ion and free radicals participation. Furthermore, in a lipid-photoperoxidation test with linoleic acid the in vitro phototoxicity of glipizide was also verified. A low decreasing cell viability of lymphocytes and neutrophils was observed.

Cell Survival↗
PubMed1998

Photodegradation and phototoxicity studies of furosemide. Involvement of singlet oxygen in the photoinduced hemolysis and lipid peroxidation.

The phototoxic diuretic drug furosemide (1), a 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)-amino] benzoic acid is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 under oxygen produces photoproducts 2, 3, 4 and singlet oxygen, while under argon the photoproducts 2 and 4 were isolated. A peroxidic unstable photoproduct was detected during the photolysis under oxygen atmosphere. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-mass), furfuryl alcohol and 1,3-cyclohexadiene-1,4-diethanoate (HPLC) as 1O2 scavengers and by the histidine test. Furosemide was screened in vitro at different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and hydroxyl radical quenchers. However, furosemide photosensitized the peroxidation of linoleic acid, as monitored by the UV-detection of dienic hydroperoxides and it also photosensitized the oxidation of histidine. The photodegradation was catalyzed in the presence of human serum albumin. Studies on peripheral blood mononuclear and polymorphonuclear cells (lymphocytes and neutrophils) demonstrated no phototoxicity on these cell lines.

Dermatitis, Phototoxic↗
PubMed1997

Involvement of a 50-kDa mRNP protein from Saccharomyces cerevisiae in mRNA binding to ribosomes.

A yeast 50-kDa mRNA-binding protein (50mRNP) is found selectively associated with the 48S and 80S initiation complexes. This protein is structurally related to the translational elongation factor EF-1alpha. The protein reacts with antibodies directed against EF-1alpha and, similarly, EF-1alpha recognizes antibodies against the 50mRNP protein. This is evidence that they share at least one epitope which allows a similar antigenic behavior. In addition, both proteins show similar cleavage patterns upon treatment with the endoproteinase Lys-C. A murine antibody raised against 50mRNP inhibits both 48S and 80S initiation complex formation. The inhibitory effect is relieved by preincubating anti-50mRNP with EF-1alpha. Antibody to EF-1alpha manifests a similar inhibitory pattern for the formation of 48S and 80S complexes. These data strongly suggest that 50mRNP is an EF-1alpha-like polypeptide essential for the formation of the above complexes.

Antibodies↗
PubMed1997

Cytotoxicity of a low molecular weight fraction from Aloe vera (Aloe barbadensis Miller) gel.

The cytotoxicity of a low mol. wt fraction (LMWF) obtained from Aloe vera gel was determined by two different assays. Firstly, exposure of monolayers of chicken fibroblasts to LMWF induced disruption of intercellular junctions and detachment of individual cells from the bottom of the flask, with formation of cell-free gaps in the monolayer. Secondly, LMWF inhibited the production of reactive oxygen species by human polymorphonuclear leukocytes stimulated by zymosan, as followed by luminol-dependent chemiluminescence. The toxic activity of LMWF was compared to that of sodium dodecyl sulfate (a well-known toxic substance), aloe-emodin and aloin (an anthraquinone and its precursor present in Aloe vera cortex) using the chemilumescence assay, and was found to be of similar potency to these toxic substances on a weight-to-weight basis. These results confirm that Aloe vera gel contains toxic low mol. wt compounds, and every effort must be made to limit the amount of these toxins in the commercially prepared Aloe vera gel products.

Aloe↗
PubMed1997

Gliomatosis cerebri mimicking a metastatic breast cancer: fatal outcome.

Gliomatosis cerebri (GC) is defined by the World Health Organization as a neoplasm of the glial cells. It is extremely rare, and there exists only 160 documented cases since 1897. There is no known treatment and the median survival rate is one year. The association of extracranial and CNS tumors is unusual, only three cases of breast cancer have been associated with gliomas and meningiomas but none with GC. Below we describe a case of breast cancer associated with GC and review the anatomoclinical and radiological manifestations of Gliomatosis Cerebri.

Aged↗
PubMed1994

Localized eosinophilic gastroenteritis with necrotizing granulomas presenting as acute abdomen.

Eosinophilic gastroenteritis is a condition of unknown aetiology that has been frequently reported involving the stomach and bowel. The colon is rarely cited as a site for the condition. We report a patient suffering from allergic symptoms (asthma, atopic dermatitis, elevated serum IgE levels) who presented with colonic perforation due to eosinophilic colitis with necrotizing granulomas.

Abdomen, Acute↗
PubMed1993

Detection of Epstein-Barr genome in the lymph nodes of Hodgkin's disease.

We have used the enzymatic in situ hybridization method to investigate the presence of Epstein-Barr virus (EBV) genome in lymph node tissues from patients with Hodgkin's disease. Also, 11 patients with persistent human immuno-deficiency virus-associated generalized lymphadenopathy as well as seven autopsy cases with no Hodgkin's disease, formed part of these studies. EBV DNA-positive reaction was demonstrated in Reed-Sternberg cells and variants in seven of 16 cases and in the small accompanying lymphocyte cell population in 14 of the 16 cases. It was also found in eight of the 11 cases with persistent generalized lymphadenopathy but in none of the lymph nodes from negative selective autopsy cases. Our results indicate that the colorimetric in situ hybridization technique is useful in EBV nucleic acid detection and cell-type localization in Hodgkin's disease. Additionally, the detection of EBV genome, not only in the diagnostic cells but in the small lymphocyte cell components, could provide new insights into the potential role of this agent in the pathogenesis of Hodgkin's disease.

AIDS-Related Complex↗
PubMed1992

Thymic cyst presenting as Horner's syndrome.

We describe a case of Horner's syndrome secondary to a thymic cyst. Following successful surgical removal of the cyst, the patient's symptoms resolved. To the best of our knowledge, a similar case has not been reported.

Horner Syndrome↗
PubMed1991

Association of ribosomal subunits. A new functional role for yeast EF-1 alpha in protein biosynthesis.

A yeast ribosomal subunit association factor (AF) has been purified from a high-salt ribosomal wash. The purified enzyme is a thermostable protein that associates ribosomal subunits at low Mg2+ concentration without requiring energy. It appears to be an aggregate of trimers or dimers (molecular mass 125 or 79 kDa) which on sodium dodecyl sulfate gels shows the presence of a major protein band whose estimated molecular mass is 43 kDa. Evidence also indicates the existence of a 50-kDa polypeptide which seems to be unstable since with freezing and thawing it gives rise to the 43-kDa polypeptide. It was shown that the labelled factor interacts with 80S ribosomes and with 40S ribosomal subunits. The purified polypeptide reacts with antibodies directed against EF-1 alpha, this last protein recognizing the antibodies raised against AF. Likewise, both EF-1 alpha and AF associate ribosomal subunits in the same way. When EF-1 is heated, it not only maintains its association activity, but also behaves like a 43-kDa polypeptide in an SDS electrophoresis run. These observations strongly suggest that AF originates from EF-1 alpha, which implies that the well-known elongation factor may also play a role in the initiation step of protein synthesis.

Blotting, Western↗
PubMed1991

Primary sclerosing cholangitis associated with systemic sclerosis.

Primary sclerosing cholangitis is a chronic inflammatory fibrotic disorder strongly associated with inflammatory bowel disease. Although an association between some inflammatory fibrotic conditions, such as Riedel's thyroiditis and retroperitoneal fibrosis and primary sclerosing cholangitis has been described, to our knowledge there are no reports of primary sclerosing cholangitis in patients with systemic sclerosis. A patient with this combination of conditions is presented and the possible significance of the association discussed.

Biliary Tract↗