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Biomedical subjects

S Nunez

Publications and source records attributed to S Nunez.

12 recordsLinked to original sources
PubMed2002

Sex pheromone of South American tortricid moth Argyrotaenia sphaleropa.

By means of electroantennographic detection and gas chromatography-mass spectrometry, the sex pheromone of Argyrotaenia sphaleropa was identified as a mixture of (Z)-11-tetradecenal, (Z)-11,13-tetradecadienal, (Z)-11-tetradecenyl acetate, and (Z)-11,13-tetradecadienyl acetate in the ratio of 1:4:10:40. Best trap catches were obtained with mixtures of (Z)-11-tetradecenal and (Z)-11,13-tetradecadienal in the ratio of 1:4 to 1:9.

Aldehydes↗
PubMed2001

Comparison of TNK with wild-type tissue plasminogen activator in a rabbit embolic stroke model.

BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) is an effective treatment for stroke, but its utility is limited by fear of cerebral hemorrhage. Tenecteplase (TNK), a genetically modified form of wild-type tPA, exhibits a longer biological half-life and greater fibrin specificity, features that could lead to fewer cerebral hemorrhages than wild-type tPA in stroke patients. METHODS: We injected radiolabeled blood clots into the cerebral circulation of New Zealand White rabbits. One hour later, we administered tPA (n=57), 0.6 mg/kg TNK (n=43), 1.5 mg/kg TNK (n=27), or vehicle control (n=37). A blinded observer examined the brains for macroscopic hemorrhage using a semiquantitative score. We estimated thrombolysis by assessing the amount of radiolabel remaining in the cerebral vessels postmortem. RESULTS: Both wild-type tPA and TNK caused thrombolysis in most subjects. Hemorrhage was detected in 26% (6/23) of the control group, 66% (27/41) of the wild-type tPA group, 55% (16/29) in the 0.6-mg/kg TNK group, and 53% (9/17) in the 1.5-mg/kg TNK group (P:<0.05, chi(2) test). The tPA group was statistically significantly different from the control group, but the TNK and tPA groups did not differ from each other. Neither TNK nor tPA affected the size of the hemorrhages. CONCLUSIONS: TNK shows comparable rates of recanalization compared with wild-type tPA in a model of embolic stroke. While tPA increases hemorrhage rate, the hemorrhage associated with TNK treatment is not statistically different compared with controls or the tPA group. These findings suggest that TNK shows promise as an alternative thrombolytic treatment for stroke, but we could not demonstrate improved safety compared with wild-type tPA.

Animals↗
PubMed1999

Regulation of interrenal gland steroidogenesis in the Atlantic stingray (Dasyatis sabina).

The interrenal gland (the homologue of the mammalian adrenal cortex) of elasmobranchs (sharks, skates, and rays) produces 1alpha-hydroxycorticosterone (1alpha-B), which has been reported to function both as a gluco- and mineralocorticosteroid. In vitro synthesis of 1alpha-B by Atlantic stingray (Dasyatis sabina) interrenal glands was stimulated by short-term (2 hr) and long-term (24 hr) treatment with porcine adrenocorticotropic hormone (pACTH). Cycloheximide blocked the pACTH-induced effect on 1alpha-B synthesis, thus demonstrating that the mechanism for the short-term induction of steroidogenesis involved protein synthesis. However, gene transcription did not play a role in the short-term induction of 1alpha-B synthesis, as indicated by the lack of an effect with actinomycin D treatment. Long-term in vitro exposure to pACTH (but not short-term exposure) stimulated the synthesis of another steroid, 11-dehydrocorticosterone (A). This induction was partially blocked by cycloheximide and actinomycin D, which suggests enhanced expression of the 11beta-hydroxysteroid dehydrogenase gene. In addition, the 24-hr treatment with pACTH enhanced the activity of cytochrome P450 side chain cleavage several fold and doubled the activity of 3beta-hydroxysteroid dehydrogenase and cytochrome P450 21-hydroxylase in D. sabina interrenals, again suggesting the induction of steroidogenic genes. In contrast to other elasmobranch species, the salmon and human forms of angiotensin II had no effect on D. sabina interrenal steroidogenesis. J. Exp. Zool. 284:517-525, 1999.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

[Diagnosis of hypothyroidism in the adult].

Hypothyroidism is a common endocrine disease, specially in women after the age of fourty. The clinical manifestations may be insensitive, aspecific or absent, which may impair diagnosis. Clinical, anamnestical and biological features may lead to a diagnostical suspicion that needs to be confirmed by a determination of serum TSH. Serum TSH determination allows the early recognition of subclinical hypothyroidism. However the signification of this moderate increase in TSH level is controversial, and uncertainty remains over the benefits of treating such patients yielding slightly elevated TSH concentration. Hypothyroidism is usually caused by a primary autoimmune thyroid disease, and seldom due to central hypothalamic or pituitary disorder.

Adult↗
PubMed1997

Isolation of the putative cDNA encoding cholesterol side chain cleavage cytochrome P450 (CYP11A) of the southern stingray (Dasyatis americana).

Cholesterol side chain cleavage cytochrome P450 (P450scc; CYP11A) catalyzes the first step in the production of steroid hormones. By utilizing degenerate oligonucleotide primers in a reverse transcriptase-coupled polymerase chain reaction (RT-PCR), a specific 252 bp fragment of the putative P450scc was amplified from RNA of interrenal tissue (the adrenal cortex homolog) from the southern stingray (Dasyatis americana), blacktip shark (Carcharhinus limbatus), and the spiny dogfish shark (Squalus acanthias). The amino-acid sequences predicted by these PCR products were 73-90% identical to each other. Using the homologous PCR-generated probe, five positive clones were isolated from a cDNA library constructed from interrenal mRNA of the southern stingray. The longest clone (4619 bp) contained the 3'-untranslated region, including four putative polyadenylation signals. Northern blot analysis of stingray interrenal RNA revealed a single transcript of 4.2 kb in length. The incomplete amino-acid sequence predicted by the open reading frame of the cDNA (514 residues in length) is 48% homologous to the trout form and 39-40% homologous to mammalian forms. Even though the stingray P450scc contains an amino terminus longer than the other forms of P450scc, no translation initiation signal (ATG) was evident within the open reading frame. This report presents the first sequence of cytochrome P450scc from this evolutionary unique taxon of vertebrates.

Amino Acid Sequence↗
PubMed1997

High dose baclofen is neuroprotective but also causes intracerebral hemorrhage: a quantal bioassay study using the intraluminal suture occlusion method.

Agonists of the GABA-A receptor are neuroprotective after experimental stroke, but studies of GABA-B agonists have contradicted each other. To further investigate whether GABA-B agonists may be neuroprotective, we devised a quantal bioassay using the intraluminal occlusion method of inducing reversible cerebral ischemia. Subjects underwent middle cerebral artery occlusion for varying amounts of time, ranging from 5 to 90 min. Behavioral outcome was measured 48 h later with a quantal observational scale: score of abnormal given for any one of asymmetric forepaw flexion on tail lift, asymmetric grip, circling, reduced exploration, seizures, or death. To the grouped response data the logistic equation was used to find the ED50, the duration of occlusion that caused one-half of the subjects to be abnormal. To find the potency ratio for each drug, we divided the ED50 for treatment by that for vehicle. We administered baclofen, a GABA-B agonist, intraperitoneally 5 min after the onset ofischemia. Baclofen (20 mg/kg) was neuroprotective (potency ratio of 3.0, P < 0.05), but a lower dose (10 mg/kg) was not. However, both doses of baclofen caused significantly more intracerebral hemorrhages than control. In awake animals, both baclofen doses caused significant increases in mean arterial pressure, but no changes in other cardiorespiratory variables. The glutamate antagonist MK-801, the GABA-A agonist muscimol, and hypothermia were all protective using the bioassay (potency ratios ranging from 1.5 to 3.0). We conclude that although baclofen (20 mg/kg) may be neuroprotective, its utility is complicated by postischemic hypertension and cerebral hemorrhages.

Animals↗
PubMed1997

Expression of cytochrome P450 aromatase in the channel catfish, Ictalurus punctatus.

The cDNA encoding the catfish ovarian aromatase has previously been isolated and described (accession number S75715). As demonstrated previously, the predicted amino acid sequence and enzymatic activity of the encoded protein share a significant degree of similarity to the forms of aromatase found in other vertebrates. Analyses utilizing reverse transcription coupled with the polymerase chain reaction (RT-PCR) demonstrate the expression of aromatase mRNA in catfish brain, testis and ovary. In spite of the evidence provided by Northern blot analysis for a single transcript encoding ovarian aromatase, RT-PCR analysis indicated transcript heterogeneity within the ovary, but not the testis or the brain. Although not characterized, PCR analysis indicated that the transcript complexity of ovarian aromatase was within the encoding region. Until this study, the expression of aromatase and its correlation with the reproductive physiology of fish had not been studied at the molecular level. In the catfish, significant changes in ovarian development were evident following elevation of plasma estradiol titers during October and again in February. Seasonal changes in the expression of ovarian aromatase and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNA was reflected in estradiol plasma titers. Ovarian expression of 3beta-HSD mRNA commenced a month before the message for aromatase was detected. Both transcripts were present from October to April. As the female approached the time of spawning (in May), the abundance of both aromatase and 3beta-HSD transcripts decreased. The aromatase message was not detected in post-spawning females but 3beta-HSD transcripts were evident. These data indicate that the timely synthesis of estradiol in catfish is caused by the regulation of both 3beta-HSD and aromatase.

Animals↗
PubMed1996

Relationships between plasma thyrotropin receptor antibodies and lipid or lipoprotein parameters in Graves' disease.

Functional thyrotropin receptors (TSH-R) have recently been detected in fat cells but not in liver cells from rat, and it seems that in infant adipocytes stimulatory TSH-R antibodies (TSH-R-ab) act through this receptor pathway, resulting in increased triglyceride catabolism. We investigated the relationships between plasma TSH-R-ab and free thyroxine (FT4) levels and plasma lipid or lipoprotein values in 49 untreated adult women with Graves' disease, all positive for these antibodies. A simple positive correlation (p < 0.01) was found between TSH-R-ab levels and FT4 values (r = 0.40). Simple positive correlations (p < 0.001) were found between triglyceride levels and FT4 (r = 0.51) or TSH-R-ab (r = 0.52) values. Multiple regression analysis confirmed that both FT4 and TSH-R-ab are strong (p < 0.005) predictors of triglyceride (FT4: partial r = 0.40; TSH: partial r = 0.39). Simple negative correlations (p < 0.05, at least) were found between FT4 levels and total cholesterol (TC) (r = -0.45), low-density lipoprotein (LDL)-C (r = -0.46), apoprotein (apo)-B (r = -0.31) or high-density lipoprotein (HDL)-C (r = -0.55) values. Among these lipid parameters, only HDL-C levels (r = -0.31, p < 0.05) correlated to TSH-R-ab values. However, multiple regression analysis revealed that while FT4 is a strong predictor (p < 0.005) of TC (partial r = -0.42), LDL-C (partial r = -0.43) or HDL-C (partial r = 0.47), TSH-R-ab are not. Thus, the apparent positive relationship between TSH-R-ab and HDL-C results from the positive correlation between TSH-R-ab and FT4. In conclusion, this study suggests that stimulating TSH-R-ab are involved in triglyceride metabolism. In contrast to thyroid hormones, these antibodies seem not to be related to cholesterol metabolism.

Adult↗
PubMed1995

Combination chemotherapy extends the therapeutic window to 60 minutes after stroke.

We sought to extend the therapeutic window for acute stroke therapy using the combination of a glutamate antagonist and a GABA agonist, which in prior studies was effective if given 5 min after stroke. We used a quantal bioassay to measure neuroprotective potency after injection of several thousand microspheres into the cerebral circulation of rats. The GABA-A agonist muscimol, but not MK-801, was effective if given 30, 45, or 60 min after embolization (potency ratio compared with saline of 3.0, 2.3, 1.8, respectively). If muscimol was combined with MK-801 at lower doses of each drug, the combination was neuroprotective (potency ratio of 4.2). Agonists of GABA-A, but not GABA-B, receptors blocked the toxic vacuolization seen in the cingulate and retrosplenial cortex after MK-801 treatment. Combination chemotherapy appears to extend the time window for acute stroke therapy in rats to 1 h and to result in fewer side effects.

Animals↗