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Biomedical subjects

A Rubio

Publications and source records attributed to A Rubio.

At least 163 records · Page 9Linked to original sources

Characterization of melatonin binding sites in the harderian gland and median eminence of the rat.

The characterization of specific melatonin binding sites in the Harderian gland (HG) and median eminence (ME) of the rat was studied using [125I]melatonin. Binding of melatonin to membrane crude preparations of both tissues was dependent on time and temperature. Thus, maximal binding was obtained at 37 degrees C after 30-60 min incubation. Binding was also dependent on protein concentration (up to 1.5 mg/ml). The specific binding of [125I]melatonin was saturable, exhibiting only one class of binding sites in both tissues. The dissociation constants (Kd) were 170 and 190 pM for ME and HG, respectively. The concentration of the binding sites in ME was 8 fmol/mg protein, and in the HG 4 fmol/mg protein. In competition studies, binding of [125I]melatonin to ME or HG was inhibited by increasing concentration of native melatonin; 50% inhibition was observed at about 702 and 422 nM for ME and HG, respectively. Additionally, the [125I]melatonin binding to the crude membranes was not affected by the addition of different drugs such as norepinephrine, isoproterenol, phenylephrine, propranolol, or prazosin. The results confirm the presence of melatonin binding sites in median eminence and show, for the first time, the existence of melatonin binding sites in the Harderian gland.

Animals↗

Sibutramine in weight control: a dose-ranging, efficacy study.

We tested the safety and efficacy of sibutramine, 5 and 20 mg, and placebo on weight loss. Medication was added to caloric restriction, behavior modification, and exercise in a parallel-group, double-blind clinical trial. Participants were 130% to 180% of ideal body weight and in good health. The study lasted 12 weeks over Thanksgiving, Christmas, and New Year's Day. Weight loss during 8 weeks of study medication was: placebo, 1.4 +/- 2.1 kg (n = 19); 5 mg sibutramine, 2.9 +/- 2.3 kg (n = 18); and 20 mg sibutramine, 5.0 +/- 2.7 kg (n = 18) (p less than 0.05 sibutramine, 5 and 20 mg, versus placebo; p less than 0.05 sibutramine, 20 mg versus 5 mg). There is a significant dose-effect relationship. Five participants left the study before completion, all because of adverse events; placebo (one patient), 5 mg sibutramine (one patient), and 20 mg sibutramine (three patients). Sleep difficulties were noted by eight participants (20 mg sibutramine, seven patients; 5 mg, one patient; and placebo, no patients). Six of 21 participants receiving 20 mg complained of irritability, unusual impatience, or "excitation." Sibutramine, 5 and 20 mg, added to a multimodal program assisted participants in losing weight.

Adult↗

Beta- and alpha-adrenergic mechanisms are involved in regulation of rat pineal type II thyroxine 5'-deiodinase activity during development.

Adrenergic regulation of type II T4 5'-deiodinase (5'-D) activity has been studied in the rat pineal gland during development. Nocturnal increases in 5'-D activity gradually rose from the second week of age until the sixth week. Isoproterenol, a beta-adrenergic agonist, stimulated 5'-D activity during the daytime; however, the pattern of stimulation during development was slightly different from nocturnal activation of the enzyme, since pineal 5'-D activity could be clearly activated by isoproterenol from the first week of age. Isoproterenol activation of the enzyme always reached more than 70% of nocturnal values at all ages studied. Phenylephrine, an alpha-adrenergic agonist, did not increase the enzyme activity. Another selective alpha-adrenergic agonist, methoxamine, as well as clonidine, an alpha 2-adrenergic agonist, were ineffective in stimulating the enzyme, while norepinephrine or terbutaline, a beta-adrenergic agonist, clearly activated it. Additional results showing a role for alpha-adrenergic receptors on pineal 5-D activity were obtained when alpha- and beta-adrenergic receptor blockers were used. Thus, propranolol, a beta-adrenergic blocker, clearly prevented pineal 5'-D activation in both 2- and 6-week-old rats when the gland was stimulated by either norepinephrine or darkness at night. However, prazosin, a selective alpha 1-adrenergic receptor blocker, also prevented the norepinephrine-induced or darkness-induced activation of the enzyme in 2-week-old rats, although it was ineffective when used in 6-week-old rats. Moreover, at night and after 3 h of exposure to darkness, phenylephrine was able to activate the enzyme. Results strongly suggest a role for alpha-adrenergic receptors, in addition to beta-adrenergic receptors, in regulating rat pineal 5'-D activity during development.

Animals↗

Elevated serum liver enzymes in obesity: a dilemma during clinical trials.

We found that 17 out of 60 (28.3 percent) obese, otherwise healthy volunteers had elevated serum alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) or alkaline phosphatase (AP) at least once in the course of a 12 week clinical trial. ALAT was the most commonly elevated serum aminotransferase occurring in 16 out of the 17 participants. Its range of elevation, as a percentage of the upper limit of normal (ULN) at screening was 102-164 percent (mean +/- s.d.; 127 percent +/- 18.4). Three participants had slight elevations of AP (112 percent, 113 percent, 119 percent of ULN). One participant had a minor elevation of ASAT (107 percent of ULN at screening). Of the 17 participants with elevated aminotransferases and AP, six were randomized to placebo, seven were treated with the low dose and four with the high dose of the new medication. Study participants having elevated enzymes had higher ideal body weight (IBW) than the group with normal values at screening (162 +/- 10 percent IBW, 152 +/- 11 percent IBW respectively), and at week 8 (152 +/- 3 percent IBW, 146 +/- 2 percent respectively) (P less than 0.05). The corresponding body mass index (BMI) values are 36.8 +/- 2.8 for the participants with elevated liver enzymes vs 34.2 +/- 2.6 (P less than 0.001) for the participants with normal values at screening and 34.9 +/- 3.1 and 32.8 +/- 2.8 (P = 0.02) respectively at week 8. Males (46 percent) were more likely than females (21 percent) to have elevated aminotransferases. We found no evidence for hepatic disease during the study period. Slightly elevated and fluctuating serum aminotransferases and alkaline phosphatase concentrations are a more frequent finding in healthy obese populations than previously established. In studies of anti-obesity agents investigators should broaden the entry criteria since elevated aminotransferase levels rarely interfere with the safe conduct of clinical trials in obesity.

Adult↗

Ontogeny of type II thyroxine 5'-deiodinase, N-acetyltransferase, and hydroxyindole-O-methyltransferase activities in the rat Harderian gland.

The ontogeny and regulation by isoproterenol of type II thyroxine 5'-deiodinase, N-acetyltransferase, and hydroxyindole-O-methyltransferase activities were studied in the rat Harderian gland. Both 5'-deiodinase and N-acetyltransferase activities exhibited maximal values at the first week of age. These activities gradually decreased till the fourth week. However, hydroxyindole-O-methyltransferase activity did not change during the period of time studied. Neither the different killing times (1600 or 0200 h) nor the photoperiod regimens (darkness or light exposure at night) modified the enzyme activities. On the other hand, isoproterenol, a beta-adrenergic agonist, could not to stimulate 5'-deiodinase at first week of life. Nevertheless, while basal 5'-deiodinase activity was diminishing during development, the enzyme was becoming sensitive to the action of isoproterenol. Thus, isoproterenol elicited increases in Harderian gland 5'-deiodinase activity in rats older than two weeks. However, both N-acetyltransferase and hydroxyindole-O-methyltransferase activities were not affected by isoproterenol treatment in either week studied.

Acetylserotonin O-Methyltransferase↗

Fractionated total body irradiation for bone marrow transplantation: clinical results on 66 patients.

Short term clinical results of bone marrow transplantation on 66 patients conditioned with fractionated total body irradiation (12 Gy in 6 fractions and 3 days) are presented here. An acute toxic effects incident, similar to that obtained previously, a 27.6% interstitial pneumonitis associated with acute severe graft versus host disease in 77% of cases, 19.2% relapses, and 41% total crude survival with an actuarial probability of surviving for more than two years of 46% for ALL, 64% for AML and 28% for CML, are the results obtained since now.

Adolescent↗

[Clinical experience with a new fluoroquinolone: ciprofloxacin].

Twenty one adult patients, both males and females, with 32 bacterial infections of several localizations and moderate to severe prognosis were treated with ciprofloxacin (200 mg every 12 hours), initially intravenously and then with 500 mg every 12 hours orally during 25 +/- 11 days. At the end of the evolution period it was found that 28 infections (87.5%) were cured in 24 of the 28 patients (85.7%), in three patients there was a definite clinical improvement and the treatment failed in the remaining patient. Adverse reactions were suspected in 2 patients, but their relation with the administration of ciprofloxacin was considered to be remote. In 3 patients mild leukopenia without clinical relevance was detected.

Adult↗

Solubility behavior of enzymes after addition of polyethylene glycol to erythrocyte hemolysates.

The addition of polyethylene glycol to a hemolysate of rat erythrocytes reduces the solubility of phosphofructokinase and glucose-6-phosphate and 6-phosphogluconate dehydrogenases in an exponential manner with respect to polymer concentration. Analyses of the solubility curves (log solubility versus polymer concentration) obtained at different pH values suggest that the solubility can be related to both the aggregation state and the intrinsic solubility of the proteins promoted by solution conditions. These findings suggest the possibility of using polyethylene glycol in a rational way for the fractional precipitation of a mixture.

Animals↗

Selective precipitation of phosphofructokinase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from rat erythrocyte hemolysates by polyethylene glycol.

Precipitation profiles of phosphofructokinase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase have been established in the range of 0-16% PEG at different pH values. Precipitation generally occurred between narrow limits of polyethylene glycol. The polymer concentration needed to reach any level of enzyme precipitation is dependent on pH. Particular conditions (% PEG and pH) for the selective enzyme enrichment have been determined.

Animals↗