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Biomedical subjects

A Rubio

Publications and source records attributed to A Rubio.

At least 19 recordsLinked to original sources
PubMed1992

Melatonin potentiates cyclic AMP production stimulated by vasoactive intestinal peptide in human lymphocytes.

The present paper demonstrates the effect of melatonin on cyclic AMP production in human lymphocytes from peripheral blood. Melatonin by itself did not influence cyclic AMP accumulation in these cells at any dose studied; however, the drug potentiated the effect of vasoactive intestinal peptide (VIP) on the cyclic nucleotide production. In the presence of physiological concentrations of VIP (either 1, 10 or 100 pM), melatonin potentiated cyclic AMP production. However, at high doses of VIP (either 1, 10 or 100 nM), melatonin exhibited no such effect. The results suggest that human lymphocytes are a target for melatonin and that it may participate, jointly with VIP, in the regulation of immune function.

Cyclic AMP↗
PubMed1992

Synergistic action of melatonin and vasoactive intestinal peptide in stimulating cyclic AMP production in human lymphocytes.

In the present study we investigated the synergistic effect of melatonin and vasoactive intestinal peptide (VIP) on cyclic AMP production in human blood lymphocytes. As shown by our group previously, VIP alone behaved as a potent activator of cyclic AMP production in human lymphocytes. On the other hand, melatonin alone did not affect the intracellular levels of cyclic nucleotide at any time or dose studied. However, when cells were incubated with melatonin plus VIP, melatonin potentiated the effect of the peptide. This effect can be observed in the presence of physiological doses of both melatonin (10-100 pM) and VIP (1-100 pM). The effect is specific for VIP because with other peptides belonging to the secretin-VIP family the effect was not observed. Results suggest that melatonin, in conjunction with VIP, may directly participate in the regulation of immune function in the human.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Adrenergic regulation of type II 5'-deiodinase circadian rhythm in rat harderian gland.

This paper reports on the regulation of the nyctohemeral profile of type II thyroxine 5'-deiodinase (T45'D) activity in the rat harderian gland. Harderian gland T45'D activity exhibits a nighttime increase with maximal values late in the dark period (0200-0400 h) and basal values during the daytime. The nocturnal rise of the deiodinating activity was prevented by either exposure of animals to light at night, injecting the animals with both alpha- and beta-adrenergic receptor blockers, or bilateral superior cervical ganglionectomy (SCGx). However, adrenalectomy did not affet the enzyme activity in the harderian gland. In brown adipose tissue (BAT), where thyroid hormone metabolism is extremely dependent on alpha 1-adrenergic stimulation by blood-circulating catecholamines, adrenalectomy significantly decreased T45'D activity. Deiodinating activities in brain frontal cortex (BFC) and pituitary gland were unaffected by adrenalectomy. Unlike in the harderian gland, SCGx did not modify the T45'D activity in either BAT, BFC, or the pituitary gland. The results suggest that elevated plasma catecholamines are not required for harderian gland T45'D activation and that the nyctohemeral profile of the enzyme activity in the harderian gland is dependent on the noradrenergic input from the superior cervical ganglia.

Adrenalectomy↗
PubMed1992

Prediction of diltiazem plasma concentration curves from limited measurements using compliance data.

This analysis illustrates the importance of compliance in understanding intrapatient variation in plasma drug concentrations during 2 weeks of repeated (4 times daily) administration. Plasma concentration data are presented from 4 illustrative patients enrolled in a dose-ranging randomised clinical trial comparing diltiazem with placebo for the prevention of painful vaso-occlusive crises in sickle cell disease. Nonlinear regression was used to fit a 1-compartment model (using 1 elimination constant for the first dose and another for subsequent doses) to the observed diltiazem concentration curves for individual patients, taking into account the time of administration of each dose. Actual dosage intervals were obtained from an electronic device (the Medication Event Monitoring System). The parameters estimated from fitting the actual compliance curves were then used to predict the curves obtained if compliance had been as prescribed (perfect compliance curves). Comparison of the actual and perfect compliance curves shows that within-patient variation in plasma diltiazem concentrations over time can only be understood when the timing of drug administration is included in the analysis. We conclude that dynamic compliance data are important in those situations where close monitoring of treatment is required and may be important in population pharmacokinetic modelling when limited data are available from each patient.

Anemia, Sickle Cell↗
PubMed1991

Stimulation of adenosine A2 receptors induces catalepsy.

The central administration of the adenosine A2 agonist CGS 21680 induced catalepsy in the rat. This effect was counteracted by the previous systemic administration of the adenosine antagonist theophylline or the D2 agonist BHT-920. These results are in agreement with the view that adenosine A2 receptors regulate central dopamine D2 transmission and underline the potential antipsychotic activity of A2 agonists.

Adenosine↗
PubMed1991

In vivo activation of pineal N-acetyltransferase but not type II thyroxine 5'-deiodinase by phenylephrine in young rats.

The regulation by alpha- and beta-adrenergic agonists of pineal N-acetyltransferase (NAT) and type II thyroxine 5'-deiodinase (5'-D) in rats at either 2 or 6 weeks of age was studied. The pattern of stimulation was different because NAT activity could be clearly activated by an alpha-adrenergic agonist, phenylephrine, only in 2-week-old rats. However, isoproterenol, a beta-adrenergic agonist, was able to stimulate NAT activity in rats at both 2 and 6 weeks of life. On the other hand, phenylephrine was always ineffective in stimulating 5'-D activity, while isoproterenol clearly activated it at both ages. These results strongly suggest a role for alpha-adrenergic receptors, in addition to beta-adrenergic receptors, in regulating rat pineal NAT activity during development.

Adrenergic alpha-Agonists↗
PubMed1991

Nyctohemeral rhythmicity of type II thyroxine 5'-deiodinase activity in the pineal gland but not in the Harderian gland of the Swiss mouse.

Type II thyroxine 5'-deiodinase (5'-D) activity in both pineal and Harderian glands of the Swiss mouse was studied. Pineal 5'-D activity exhibited a nyctohemeral profile with a maximal peak value at 05.00 h, which coincides with that for pineal melatonin production. However, no rhythm of 5'-D activity in the Harderian gland could be found. In pineal gland, light at night inhibited the nocturnal increase in 5'-D activity, while isoproterenol, a beta-adrenergic agonist, could not stimulate the enzyme. In the Harderian gland, neither darkness, nor light or night, or isoproterenol were capable of modifying basal values of 5'-D activity.

Animals↗
PubMed1991

Beta- and alpha-adrenergic receptors are involved in regulating type II thyroxine 5'-deiodinase activity in the rat Harderian gland.

The role of alpha- and beta-adrenergic receptors in regulation of rat Harderian gland type II thyroxine 5'-deiodinase (5'-D) activity was investigated. Our results show that isoproterenol, a beta-adrenergic agonist, and phenylephrine, an alpha-adrenergic agonist, elicited increases in Harderian gland 5'-D activity. The activation was dependent on the time and the dose of the drug. Other adrenergic agonists, i.e., norepinephrine, methoxamine or terbutaline, also clearly increased the enzyme activity. Moreover, administration of propranolol, a beta-adrenergic blocker, or prazosin, an alpha-adrenergic blocker, completely prevented the activation of the enzyme induced by norepinephrine. Results show a clear regulation by adrenergic mechanisms of 5'-D activity in the rat Harderian gland, where alpha- and beta-adrenergic receptors appear to be involved.

Animals↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

[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↗
PubMed1988

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↗