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Biomedical subjects

A Quintana

Publications and source records attributed to A Quintana.

At least 19 recordsLinked to original sources

TRP channels in lymphocytes.

TRP proteins form ion channels that are activated following receptor stimulation. Several members of the TRP family are likely to be expressed in lymphocytes. However, in many studies, messenger RNA (mRNA) but not protein expression was analyzed and cell lines but not primary human or murine lymphocytes were used. Among the expressed TRP mRNAs are TRPC1, TRPC3, TRPM2, TRPM4, TRPM7, TRPV1, and TRPV2. Regulation of Ca2+ entry is a key process for lymphocyte activation, and TRP channels may both increase Ca2+ influx (such as TRPC3) or decrease Ca2+ influx through membrane depolarization (such as TRPM4). In the future, linking endogenous Ca2+/cation channels in lymphocytes with TRP proteins should lead to a better molecular understanding of lymphocyte activation.

Animals↗

Metallothionein-I and -III expression in animal models of Alzheimer disease.

Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta) deposition within the brain. We have evaluated the expression of MT-I and MT-III mRNA by in situ hybridization in three different transgenic mice models of AD: Tg2576 (carrying AbetaPP harboring the Swedish K670N/M671L mutations), TgCRND8 (Swedish and the Indiana V717F mutations), and Tg-SwDI (Swedish and Dutch/Iowa E693Q/D694N mutations). MT-I mRNA levels were induced in all transgenic lines studied, although the pattern of induction differed between the models. In the Tg2576 mice MT-I was weakly upregulated in cells surrounding Congo Red-positive plaques in the cortex and hippocampus. A more potent induction of MT-I was observed in the cortex and hippocampus of the TgCRND8 mice, likely reflecting their higher amyloid plaques content. MT-I upregulation was also more significant in Tg-SwDI mice, especially in the subiculum and hippocampus CA1 area. Immunofluorescence stainings demonstrate that astrocytes and microglia/macrophages surrounding the plaques express MT-I&II. In general, MT-I regulation follows a similar but less potent response than glial fibrillary acidic protein (GFAP) expression. In contrast to MT-I, MT-III mRNA expression was not significantly altered in any of the models examined suggesting that the various MT isoforms may have different roles in these experimental systems, and perhaps also in human AD.

Alzheimer Disease↗

Association of broad-spectrum antibiotic use with faecal carriage of oxyiminocephalosporin-resistant enterobacteriaceae in an intensive care unit.

The link between administration of antibiotics and detection of third-generation-cephalosporin-resistant (TGCR) enterobacteriaceae in faeces was studied in patients in a burns intensive care unit (ICU). The presence of extended-spectrum beta-lactamase producers was also determined in these isolates. At least two rectal swab samples were taken from 43 of 72 patients admitted to the ICU from January 1998 to June 1999. Antibiotic resistance tests were performed for all isolated enterobacteriaceae using the methods of the National Committee for Clinical Laboratory Standards. Only 10 out of 30 antibiotic-treated patients showed TGCR enterobacteriaceae in faeces. Fisher's exact test showed a relationship between the administration of oxyiminocephalosporins (third-generation cephalosporins) (P=0.002) or carbapenems (P=0.003) and the isolation of TGCR enterobacteriaceae from faeces. The administration of oxyiminocephalosporins led to the selection of resistant strains in the faecal flora.

Anti-Bacterial Agents↗

Altered disposition and effect of lerisetron in rats with elevated alpha 1-acid glycoprotein levels.

PURPOSE: To examine the effect of changes in plasma alpha1-acid glycoprotein (AAG) levels on the pharmacokinetics (PK) and pharmacodynamics (PD) of lerisetron, a novel serotonin 5-HT3 receptor antagonist, in the rat. METHODS: After subcutaneous administration of turpentine oil, AAG was significantly elevated compared with controls. The PK of unchanged lerisetron (UL; high-performance liquid chromatography with radioactivity monitoring) and total lerisetron (TL; unchanged + changed, scintillation counting) was characterized post intravenous (i.v.) 14C lerisetron (50 microg/kg) in control and turpentine oil pretreated rats. The PK (0-180 min) was described by a two-compartmental model. Protein binding of lerisetron in vitro was measured using an ultrafiltration technique. The effect of lerisetron (5 microg/kg, i.v.) over 180 min was measured in anesthetized rats (control and pretreated) with the Bezold-Jarisch reflex (inhibition of bradycardia after 16 microg/kg serotonin i.v.) as the endpoint. PD parameters were estimated by sigmoid Emax models. RESULTS: The unbound fraction was significantly diminished in pretreated rats (mean +/- SEM) (6.60 +/- 1.23% vs. control 14.4 +/- 1.40%, P < 0.05). Volume of distribution (V) and clearance for UL and TL were significantly decreased when compared to the controls (P < 0.0001 for UL and P < 0.05 for TL). Plasma clearance based on unbound concentration for UL did not differ between groups but the unbound V and steady-state unbound V remained decreased (P < 0.05 and P < 0.0001). Pretreated rats showed a significantly diminished drug effect: the area under the E-t curve over 180 min was (mean +/- SEM) 5,189 +/- 657.7 in control animals vs. 3,486 +/- 464.4 in the pretreated group (P < 0.05). The EC50 (concentration at half maximum effect) for UL and TL were increased in pretreated rats and were not compensated when the unbound concentration was used. CONCLUSIONS: An increase in AAG causes alterations in the PK and PD of lerisetron, and because this is not compensated with the unbound concentration, we suggest that mechanisms not linked to protein binding may be involved.

Animals↗

Effect of S-nitrosoglutathione (GSNO) added to the University of Wisconsin solution (UW): I) Morphological alteration during cold preservation/reperfusion of rat liver.

Cold liver preservation in the University of Wisconsin solution (UW) followed by reperfusion alters hepatic parenchyma and stroma. In this study we demonstrated the benefit of adding S-nitrosoglutathione (GSNO) to the UW solution before cold storage, as an effective Nitric Oxide (NO) donor to prevent hepatic injury. Wistar adult rat livers were stored in UW solution (4 degrees C-48Hs) and then reperfused 60 minutes in the isolated perfused rat liver model (IPRL). Normal untreated livers and perfused livers, but not preserved were used as controls. Parenchymal damages were evaluated with Hematoxylin-Eosin stain and an inmunohistochemistry assay for albumin was used as functional test. To study the stroma, collagen type III and I networks were analyzed using Picro-sirius Red stain and Gordon Sweets' method for reticulin. After 48 Hs of cold preservation in UW solution livers showed few rounded endothelial cells inside sinusoidal lumen and extended areas of cell vacuolation. Albumin distribution was evident only around central veins and middle zones of the hepatic lobule. Collagens III and I networks were disorganized. When preserved with the addition of 100 microM GSNO and then reperfused, the hepatic morphology, in general, was conserved showing little vacuolation, fewer endothelial cells inside sinusoids and good albumin distribution around central veins and middle zones. The stroma had organized networks of collagen III and I. We concluded that the addition of 100 microM GSNO as a NO donor, can improve UW solution properties to preserve rat liver by maintaining the hepatic morphology and avoiding hepatic injury post cold preservation/reperfusion.

Animals↗

Intravascular and endobronchial DNA delivery to murine lung tissue using a novel, nonviral vector.

Gene transfer to the lung can be achieved via either the airway or the pulmonary vasculature. We evaluated gene transfer and expression by intravascular and endobronchial routes, using DNA complexed with G9 PAMAM dendrimer or naked plasmid DNA. Intravascular tail vein delivery of dendrimer-complexed pCF1CAT plasmid resulted in high levels of transgene expression in the lung at 12 and 24 hr, followed by a second peak of expression 3 to 5 days after administration. After intravenous administration of the complexes, CAT expression was never observed in organs other than the lung. There were only minimal levels of CAT protein expressed in the lung after intravenous administration of naked plasmid DNA. Repeated intravascular doses of the dendrimer-complexed plasmid, administered four times at 4-day intervals, maintained expression at 15-25% of peak concentrations achieved after the initial dose. Endobronchial delivery of naked pCF1CAT plasmid produced significant amounts of CAT protein in the lung. Comparison of intratracheal and intranasal routes resulted in similar expression levels of CAT in the lung and trachea. However, in juxtaposition to vascular delivery, intranasal delivery of dendrimer-complexed plasmid DNA gave lower levels of CAT expression than that observed with naked plasmid DNA. In situ localization of CAT enzymatic activity suggested that vascular administration seemed to achieve expression in the lung parenchyma, mainly within the alveoli, while endobronchial administration primarily targeted bronchial epithelium. Our results show that intravenously administered G9 dendrimer is an effective vector for pulmonary gene transfer and that transgene expression can be prolonged by repeated administration of dendrimer-complexed DNA.

Administration, Intranasal↗

Characterization of cocoa butter extracted from hybrid cultivars of Theobroma cacao L.

Cocoa butter is the most important fat used in the confectionery and chocolate industries. The main objective of the present study was to determine the physical and chemical characteristics of cocoa butter extracted from hybrid cultivars belonging to the germplasm bank of the Fondo Nacional de Investigaciones Agropecuarias (National Foundation for Agricultural Research). AOAC methods were used for the assessment of the proximal composition of the beans, physical and chemical characteristics as well as for the fatty acid profile of the fat. It was found that there were statistical differences in the proximate composition of the cocoa beans among the cultivars studied as well as the iodine and saponification indices of the butter. Saturated fatty acids were present in higher proportions than unsaturated fatty acids, with palmitic and stearic acid as the main fractions. Oleic acid content was higher than linoleic acid. The fatty acid profile found is the main factor that influences the hard texture of the cocoa butter from Venezuelan cocoa hybrids cultivars.

Butter↗

Role of sodium nitroprusside in the improvement of rat liver preservation in University of Wisconsin solution: A study in the isolated perfused liver model.

BACKGROUND: Long-term liver preservation is needed to transform liver transplantation from an emergency operation into an elective procedure and, therefore, to improve the results of liver transplantation. AIMS: We have studied the possibility of extending the period of cold ischemia of the rat liver, maintaining good hemodynamics and functional conditions, by adding the NO donor sodium nitroprusside (NPNa) to the preservation solution. MATERIALS AND METHODS: Rat livers were preserved for 24, 48, and 72 h in University of Wisconsin solution (UW) at 4 degrees C (groups I, II, and III) or UW to which 500 microM NPNa was added (groups IV, V, and VI). Following the preservation time, liver viability was assessed using the isolated perfused liver model. Lactate dehydrogenase (LDH) and K(+) release, bile flow, and portal resistance were evaluated in each group and compared with those of liver controls (group VII) excised and perfused without preservation. RESULTS: Some deleterious effects can be seen during cold storage conditions as assessed by an increment in intrahepatic resistance and a diminution in the capacity of the organ to produce bile. On histological observation, we see vacuolated hepatocytes and free endothelial cells (detached) in the sinusoidal lumen. Addition of 500 microM NPNa to UW significantly moderates these injuries, with an improvement in intrahepatic circulation (less intrahepatic resistance), an increment in bile production, and better histological appearance of the organ. We were also able to determine the capacity of the UW + NPNa to produce NO. CONCLUSION: We assume that the beneficial vascular effects of NPNa are mediated by NO production.

Adenosine↗

Effects of intravenous administration of prostacyclin on regional blood circulation in awake rats.

1. The effects of intravenous infusion of prostacyclin (PGI2, 0.1, 0.2, 0.3 and 1.0 microg kg(-1) min(-1) lasting 5 min) on regional blood flow and regional vascular resistance have been studied in awake rats using the radioactive microsphere method. 2. The control values of blood flow to the heart, kidney, small intestine, hind limb muscle, pericranial skin and brain as well as the corresponding vascular resistance were not modified by an i.v. infusion (0.1 ml min(-1)) of Tris-buffer (the vehicle of PGI2). 3. The i.v. infusion of PGI2 produced graded dose-dependent decreases of MAP (r=0.87, P<0.001; ED20=0.73 [0.13-2.55] microg kg(-1) min(-1)) as well as decreases of vascular resistance in the heart (r=0.83, P<0.001; ED30=0.17 [0.09-0.31] microg kg(-1) min(-1)), pericranial skin (r=0.88, P<0.001; ED30=0.28 [0.18-0.43] microg kg(-1) min(-1)) and small intestine (r=0.74, P<0.001; ED30=0.21 [0.11-0.39] microg kg(-1) min(-1)), which led to dose-related increases of blood flow to these territories. 4. On the contrary, PGI2 increased vascular resistance in skeletal muscle (r=0.73, P<0.001; ED30=0.20 [0.10-0.39] microg kg(-1) min(-1)) with corresponding reductions in blood flow. The low doses reduced renal blood flow but there were no significant changes during the high ones. Cerebral vessels did not dilate during any infusion of PGI2 and cerebral blood flow decreased as MAP fell (r=0.56, P<0.01). 5. We conclude that, in awake rats, the coronary vessels are extremely sensitive to the vasodilating effect of PGI2 and that the mesenteric vessels and those of the pericranial skin are very responsive too. Moreover, autoregulation is inefficient to maintain cerebral blood flow during infusion of PGI2.

Animals↗

[Trends in human immunodeficiency virus infection prevalence in homosexual/bisexual men in Madrid (1986-1995)].

BACKGROUND: We analysed the trend in seroprevalence for human immunodeficiency virus (HIV) in homosexual or bisexual men who voluntary requested the test in a sexually transmitted disease/HIV clinic in Madrid. PATIENTS AND METHODS: We studied 5,424 homo/bisexual non-injecting drug user (non-IDU) men, who came for the first time since 1986 to 1995. We analysed the HIV seroprevalence taken into account the year, age and exchange of sex by money. A hundred and thirty-six IDU homo/bisexual men were also attended during the same period and they were compared with non-IDU. RESULTS: HIV seroprevalence among the 5,424 non-IDU homo/bisexual men were 20.2%, rising from 19.6% in 1986 to 29.6% in 1990. After then, the trend decreased to 15.3% in 1995 (chi 2 for trend, 66.8; p < 0.0001). Average age was three years higher among seropositives (p < 0.0001), and showed an upward trend from 29.9 in 1986 to 34.6 in 1995 (p = 0.0059). Seroprevalence among homosexuals younger than 25 fell in the last years. One percent of individuals had ever practiced the prostitution. They were younger (average age, 27.6), and their HIV seroprevalence were 25.9%. A hundred and thirty-six IDU homo/bisexual men were also attended for the first time, being 2.4% of overall homo/bisexual men. They had a higher seroprevalence (48.5%) than non-IDU (p < 0.0001), and did not show any significative time-trend. CONCLUSIONS: A favourable evolution can be observed in HIV seroprevalence among homo/bisexual from Madrid, Spain, men who came to be tested, especially among the youngest. Prevention programs should make an effort to maintain this trend.

Adult↗

Indomethacin and piroxicam inhibit Na+-adenosine transport in rat renal brush-border membranes.

The effects of the cyclooxygenase inhibitors, indomethacin and piroxicam, were evaluated on Na+-dependent [3H]adenosine transport in rat renal brush-border membranes of the outer renal cortex of the rat. Adenosine co-transport (1-10 microM) was estimated in the presence of 0.001-10 microM indomethacin and piroxicam. Both drugs inhibited the Na+-dependent transport in a dose-dependent manner with IC50 of 3.5 microM and 0.1 microM, respectively. The Na+-independent transport was not modified. Preincubations carried out on the vesicles with 10-50 microM arachidonic acid increased transport in a dose-dependent manner up to 1.7 times. Whereas 50 pM to 5 microM prostaglandin E2 in the presence of indomethacin did not change carrier activity, 5 microM prostaglandin E2 increased the Na+-dependent transport 1.5 times. Other prostanoid synthesis pathways were investigated with 10 microM nordihydroguaiaretic acid (lipoxygenase inhibitor), and 17-octadecynoic acid and clotrimazole (leukotriene and cytochrome P450 inhibitors). Our results demonstrated that the Na+-dependent adenosine transport in brush-border membranes was inhibited by indomethacin and piroxicam, suggesting that cyclooxygenase activity might modulate this co-transport.

Adenosine↗

Sodium-dependent adenosine transport is diminished in brush border membrane vesicles from hypothyroid rat kidney.

Studies of the uptake of [3H]adenosine ([3H]ADO) were performed using brush border membrane vesicles (BBMV) from normal (N) and hypothyroid (Tx) rat kidneys, to test if decreased Na+ reabsorption in hypothyroidism might be associated with abnormalities in ADO transport. [3H]ADO uptake (1-10 micromol) for both conditions was measured in the presence of Na+ (10-150 mmol/l); the effects of dipyridamole (10 micromol/l) and 1, 3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX, 10 micromol/l) were also studied. Na+-stimulated ADO uptake was decreased in Tx BBMV. Michaelis-Menten constants showed a decreased ADO carrier affinity (Km 2.46 +/- 0.14 in N, vs Km 4.46 +/- 0.88 micromol/l in Tx, P<0.05), with no change in the number of carriers (Vmax 295 +/- 25 in N, vs 229.2 +/- 56 pmol.min-1.mg protein in Tx). Na+ affinity remained unchanged (K Na+ 11.5 +/- 3.5 in N, vs K Na+ 12.72 +/- 0.7 mmol/l in Tx). Inhibition of Na+-dependent ADO transport was 50% in N as opposed to 58% in Tx with dipyridamole, and 72% in N versus 47% in Tx with PACPX. These results suggest that decreased Na+-dependent ADO cotransport contributes to the diminished tubular reabsorption that occurs in hypothyroidism.

Adenosine↗

Ca 15.3 in breast cancer: comparison of two assays and validation in a Mexican population.

Ca 15.3 is a tumor marker used for breast carcinoma, since one epitope is an antigen present in milk fat globules. Serum from 171 patients with breast cancer upon initial presentation was studied for Ca 15.3. In the first 72 cases, the authors compared RIA vs. ELISA using a simple linear regression. On the following 99, only ELISA was performed. With all 171 patients, a clinical association between Ca 15.3 measurement and age, stage and hormone receptors was carried out. Correlation coefficient between RIA and ELISA was 0.85. Of 104 patients below 50 years of age, 88 had normal Ca 15.3 and 16, elevated; 67 were older than 50 years, 46 had normal Ca 15.3 and 21, elevated (p=0.022). Ca 15.3 was elevated in 11% of patients with clinical stages I/II, and 89% in stages III/IV (p=0.0001). The association of Ca 15.3 with hormone receptors was not significant. In conclusion, ELISA and RIA measure Ca 15.3 with comparable results, the first method has the advantage of not using radioactivity. The authors found higher probability of elevated Ca 15.3 in older patients and in those with advanced disease.

Biomarkers, Tumor↗

Nucleotide sequence of the genomic region encompassing Adh and Adh-dup genes of D. lebanonensis (Scaptodrosophila): gene expression and evolutionary relationships.

The region of the genome of D. lebanonensis that contains the Adh gene and the downstream Adh-dup gene was sequenced. The structure of the two genes is the same as has been described for D. melanogaster. Adh has two promoters and Adh-dup has only one putative promoter. The levels of expression of the two genes in this species are dramatically different. Hybridizing the same Northern blots with a specific probe for Adh-dup, we did not find transcripts for this gene in D. lebanonensis. The level of Adh distal transcript in adults of D. lebanonensis is five times greater than that of D. melanogaster adults. The maximum levels of proximal transcript are attained at different larval stages in the two species, being three times higher in D. melanogaster late-second-instar larvae than in D. lebanonensis first-instar larvae. The level of Adh transcripts allowed us to determine distal and proximal initiation transcription sites, the position of the first intron, the use of two polyadenylation signals, and the heterogeneity of polyadenylation sites. Temporal and spatial expression profiles of the Adh gene of D. lebanonensis show qualitative differences compared with D. melanogaster. Adh and Adh-dup evolve differently as shown by the synonymous and nonsynonymous substitution rates for the coding region of both genes when compared across two species of the melanogaster group, two of the obscura group of the subgenus Sophophora and D. lebanonensis of the victoria group of the subgenus Scaptodrsophila. Synonymous rates for Adh are approximately half those for Adh-dup, while nonsynonymous rates for Adh are generally higher than those for Adh-dup. Adh shows 76.8% identities at the protein level and 70.2% identities at the nucleotide level while Adh-dup shows 83.7% identities at the protein level and 67.5% identities at the nucleotide level. Codon usage for Adh-dup is shown to be less biased than for Adh, which could explain the higher synonymous rates and the generally lower nonsynonymous substitution rates in Adh-dup compared with Adh. Phylogenetic trees reconstructed by distance matrix and parsimony methods show that Sophophora and Scaptodrosophila subgenera diverged shortly after the separation from the Drosophila subgenus.

Alcohol Dehydrogenase↗

Genetic and environmental factors in the resistance of Drosophila subobscura adults to high temperature shock. III. Chromosomal-inversion and enzymatic polymorphism variation in lines selected for heat shock resistance.

Two replicate selection experiments to increase and decrease heat shock resistance of Drosophila subobscura adults were carried out maintaining control lines. In the present paper, the chromosomal-inversion and enzymatic polymorphism variation with selection is analyzed. The results indicate an erratic variation of chromosomal arrangement frequencies for practically all the chromosomes in the selected lines, showing a loss of the less frequent arrangements especially in sensitive lines. Only the A chromosome and the O + 4 arrangement show a behaviour that may not be due to random effects, which points to the possible existence of heat shock factor(s) in these chromosomes. Similarly, an erratic variation of allele frequencies is observed for all the enzymes studied (Aph, Pept-1) except for the Hk-1 enzyme. We cannot establish the possible participation of this locus in heat shock resistance from the results obtained up to now. A significant decrease in heterozygosity is detected in sensitive lines from chromosomal-inversion polymorphism.

Animals↗

The CHARGE association and athyreosis.

We report on a male infant with congenital hypothyroidism owing to athyreosis occurring with the CHARGE association (bilateral papillary coloboma, congenital heart disease, dysmorphic ears, sensorineural deafness, psychomotor retardation, cryptorchidism, facial palsy, and vesicoureteral reflux). The coexistence of these two disorders has not been described previously.

Abnormalities, Multiple↗

Evaluation of bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of decasilate in experimental models.

The bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of 8-(2-phenylethyl)-1-oxa-diazaspiro[4,5]decan-2-one 2-tiophenecarboxylate (decasilate, CAS 76652-72-7) have been evaluated using different experimental models. 1. Decasilate showed a remarkable spasmolytic activity against histamine-induced contractions in the isolated guinea-pig tracheal preparation with an IC50 of 2.7 x 10(-6) mol/l. In addition, the oral administration of decasilate (5-30 mg.kg-1) significantly reduced the histamine aerosol-induced bronchospasm in guinea-pigs. 2. Decasilate had a preventive effect against antigen-induced contractions of ileum segments from sensitized guinea-pigs (EC50 8.0 x 10(-6) mol/l) and relaxed them when added after the antigen challenge (IC50 9.5 x 10(-7) mol/l). 3. Both carrageenin- and dextran-induced rat hind paw oedemas were significantly reduced by the oral administration of decasilate with ED50 values of 169.5 and 34.5 mg.kg-1, respectively. However, it was ineffective against the cotton pellet-induced granuloma in the rat. 4. Furthermore, decasilate had a significant mucolytic activity in rabbits and reduced the number of tussive seizures induced by an aerosol of citric acid in guinea-pigs. The pharmacological profile of decasilate suggests that it might be useful in the management of chronic bronchitis.

Animals↗