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Biomedical subjects

R Alonso

Publications and source records attributed to R Alonso.

At least 199 records · Page 11Linked to original sources

Sorbitol dehydrogenase deficiency in several pig tissues: potential implications for studies of experimental diabetes.

Screening for red blood cell sorbitol dehydrogenase deficiency in 12 different mammalian species was performed. A wide inter-species variability in red cell sorbitol dehydrogenase with a virtually complete deficiency in pigs was observed. Aldose reductase and sorbitol dehydrogenase activities in 12 different pig tissues also were measured. Aldose reductase activity was present in all the tissues studied, whereas organ specificity for sorbitol dehydrogenase was observed. Sorbitol dehydrogenase activity was not detectable in lenses, among other tissues, making the pig a potential model for studies in experimental diabetes, particularly for the investigation of sorbitol dehydrogenase deficiency as a risk factor in the development of cataracts.

Aldehyde Reductase↗

Paramethasone acetate (PA): corticosteroid potency vs hypothalamic pituitary-gonadal axis.

Because paramethasone acetate (PA) suppresses basal and midcycle LH surge and blocks estrogen synthesis in the female, its possible effect upon testicular physiology was evaluated in 13 healthy men by measuring the circulating levels of FSH, LH, prolactin (PRL), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), estradiol (E2) and cortisol (C) every 4 h throughout the day, before (control) and after PA (6 mg/d/7 d). The total concentrations of each hormone, as well as the PA-induced suppressibility (measured as percent decrease in the mean 24 h plasma level) were analyzed. PA suppressed neither the basal nor circadian rhythm of T and had no effect on LH, FSH or PRL output. DHT, A, E2 were significantly reduced and the basal concentrations and circadian variations of C were abolished. PA showed a dual control on the pituitary gonadal axis and while causing a maximal suppressed adrenocortical activity it had no interference in testosterone synthesis.

Adult↗

A fluorimetric method for red blood cell sorbitol dehydrogenase activity.

A new fluorimetric method for the quantification of red blood cell (RBC) sorbitol dehydrogenase is described. It is based on the oxidation of sorbitol to fructose, in presence of NAD+, catalysed by the RBC-sorbitol dehydrogenase. The quantity of NADH formed is then measured in a filter fluorimeter. Comparison with an indirect spectrophotometric assay yielded good correlation; however, the present method offers several advantages: it is more rapid, simple and inexpensive. It should be useful to screen for sorbitol dehydrogenase deficiency in large numbers of individuals, particularly patients with diabetes or cataracts.

Erythrocytes↗

Diurnal variations of pituitary and testicular hormones in paraplegic men.

The effect of the neuro-spinal cord injury upon testicular physiology was evaluated in six adult paraplegic (PPG) men by measuring the circulating levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), androstenedione, testosterone, and dihydrotestosterone every 4 hr throughout a 24-hr period. Three PPG men were studied within the first 3 months (acute period) and the other three patients 39-79 months (stabilized period) after trauma. Hormonal values were compared with eight age-matched normal adult males. Plasma FSH and LH were constantly above normal concentrations regardless of the sampling time and period of observation, whereas prolactin was higher than normal only during the first two months after trauma, returning to normal afterwards. Plasma androgens were consistently below normal during the first 3 months after injury, and returned toward normal thereafter. There may be a direct relationship between the time elapsed after the spinal cord injury and the plasma androgens concentrations. A possible role of PRL in testicular steroidogenesis is suggested.

Adult↗

[Synthesis, cytostatic activity and mechanism of action of N-glycosylhalomethylazoles. A new class of alkylating agents].

A model to produce a new type of alkylating agents having anti-cancer activity is described. They consist of a halomethyl-azol group of the benzyl type as alkylating center, and a sugar moiety as a carrier fragment. Alkylating nucleosides were produced as halomethyl-pyrazole, -imidazole, 1.2.3-triazole, and 1.2.4-triazole derivatives following the model, and tested upon Ehrlich ascites cancer and P-388 lymphocytic leukemia.

Alkylating Agents↗

Effect of paramethasone acetate upon estrogen action.

To test the antiestrogenic action of paramethasone acetate (PA), a group of five postmenopausal women were treated in two ways. For phase I, PA + mestranol, 6 mg + 80 micrograms per day for 10 days, was administered. Ten days were allowed for withdrawal of medication. For phase II, mestranol, 80 micrograms per day for 10 days, free of the glucocorticoid was administered. Daily samples of cervical mucus, vaginal cells, and peripheral blood were obtained to analyze fernlike crystallization (%), cornified pyknotic nuclei cells (%), and concentrations of ethynyl-estradiol (EE-2, pg/ml) during both phases. The fernlike crystallization pattern had a mean value of 8 +/- 0.9% for phase I, while for phase II it was 85 +/- 8% (P less than 0.05). The percentage mean value of cornified pyknotic nuclei cells of phase I was 28 +/- 5% in comparison with 53 +/- 7% observed in phase II (P less than 0.05). EE-2 mean value concentrations for phase I were 85 +/- 90 pg/ml, while for phase II they were 724 +/- 418 pg/ml (P less than 0.05). These results demonstrate that 6 mg of PA is able to compete against the estrogenic action in the parameters of the study selected.

Cervix Mucus↗

Elevation of urinary catecholamines and their metabolites following tyrosine administration in humans.

A single oral dose of tyrosine (100 or 150 mg/kg) caused significant increases in urinary levels of norepinephrine (NE), epinephrine (E), dopamine (DA), 3-methoxy-4-hydroxyphenylglycol (MHPG), vanilmandelic acid (VMA), and homovanillic acid (HVA) during the first 2 hr after its ingestion; water administration failed to produce such changes. The temporal patterns of these increases paralleled those of previously described increases in plasma tyrosine. Since urinary catecholamines derive from peripheral sources, while the catecholamine metabolites in urine may reflect both CNS and peripheral catecholamine turnover, these findings indicate that tyrosine administration may accelerate catecholamine synthesis in and release from cells throughout the human body. Tyrosine may thus constitute a useful agent for treating central or peripheral disorders associated with insufficient release of catecholamines.

Adolescent↗

Changes in catecholamine excretion after short-term tyrosine ingestion in normally fed human subjects.

The effects of ingesting the aromatic amino acid L-tyrosine on excretion of unconjugated catecholamines (dopamine, norepinephrine, and epinephrine) and tyrosine were studied. (Tyrosine is the circulating precursor for the catecholamines, but only a small fraction of the tyrosine in the body is utilized for catecholamine synthesis.) In 10 of 11 normal volunteer subjects, ingestion of 100 mg/kg tyrosine (in three divided doses, preceding each meal, between 8 AM and 5 PM) for 1 day increased the 24-h excretions of total catecholamines by 25%. Only 0.42% of the tyrosine dose was excreted unchanged, but this was sufficient to increase urinary tyrosine by 138%. Both tyrosine and catecholamine excretions varied diurnally; 60% or more of the total output occurred during the day. Since urinary catecholamines reflect molecules synthesized outside the central nervous system, these findings indicate that tyrosine administration can accelerate catecholamine synthesis in the human sympathoadrenal system, probably by enhancing saturation of tyrosine hydroxylase. Therefore, tyrosine may be useful therapeutically in diseases characterized by peripheral catecholamine deficiencies.

Adolescent↗

Tyrosine loading enhances catecholamine excretion by rats.

Tyrosine administration to rats causes dose-related increases in urinary catecholamine levels without reducing tissue catecholamines. Pretreatment with carbidopa, a peripheral inhibitor of aromatic-L-amino acid decarboxylase, reduces basal urinary catecholamine levels and blocks of urinary catecholamine increases caused by tyrosine administration or cold exposure. DOPA excretion, which is usually undetectable by our methods, becomes significant after carbidopa, and rises a further four-fold when rats are also given tyrosine. These observations suggest that tyrosine availability can affect both catecholamine synthesis in and release from the sympathoadrenal apparatus.

Adrenal Glands↗

Alkylating nucleosides 1. Synthesis and cytostatic activity of N-glycosyl(halomethyl)-1,2,3-triazoles. A new type of alkylating agent.

1,3-Dipolar cycloaddition of benzyl azide or peracetylated glucopyranosyl azides to propargyl halides or 1,4-dihalobutynes yielded 1-benzyl- or 1-glycosyl(halomethyl)-1,2,3-triazoles. Alkylating chloromethyl- bromomethyl- and iodomethyl-1,2,3-triazoles were also obtained from the corresponding hydroxymethyl derivatives by treatment with (C6H5)3P/CCl4, (C6H5O)3P/Br2, and (C6H5O)3P/I2, respectively. 1-Benzyl-4-(fluoromethyl)-1,2,3-triazole was obtained from 1-benzyl-4-(bromomethyl)-1,2,3-triazole by treatment with KF and 18-crown-6. Chloromethyl-, bromomethyl-, and iodomethyl-1,2,3-triazole derivatives inhibited the "in vitro" growth of HeLa cells. Some of these compounds increased the life span of mice bearing tumors.

Alkylating Agents↗

Lactate dehydrogenase isoenzymes of the hypothalamus, limbic structures, and the anterior pituitary during the estrous cycle.

Lactate dehydrogenase (LDH) and its isoenzyme (ISO) pattern were measured in the hypothalamus (HYP), amygdala (AMYG), hippocampus (HIP), cerebral cortex and anterior pituitary (PIT) of adult female rats sacrificed at different estrous cycle phases. The HYP, the AMYG and the PIT showed their maximal LDH values at proestrus and the lowest at diestrus. Those of the HIP showed the opposite pattern. The study of the ISO distribution pattern indicated that the cyclic variations of pituitary LDH activity were mainly due to changes of the ISO rich in A subunits, while in the B type they remained constant. By contrast, the cyclic changes of total LDH activity of all the brain structures studied were due to well balanced variations of both A and B subunits.

Amygdala↗

Melatonin secretion decreases during the proestrous stage of the rat estrous cycle.

Urine was collected from rats during 12 consecutive daily dark periods and assayed for melatonin and norepinephrine; the phase of the vaginal estrous cycle associated with each urine sample was determined from daily vaginal smears. The proestrous phase of the estrous cycle was consistently associated with significant reductions in the excretions of both compounds. The level of melatonin in any urine sample tended to vary as a function of its norepinephrine content; however, the slope of the curve relating these two compounds in metestrous-diestrous samples differed from that for proestrous-estrous specimens. This difference suggests that factors other than the catecholamine (e.g., gonadal hormones) also affect melatonin secretion. Oophorectomy elevated the melatonin concentration of serum but not that of the pineal; this rise was suppressed by the administration of estrogen plus progesterone. The fate of circulating melatonin (as indicated by the proportion of an exogenous dose excreted into the urine) was not affected by the state of the estrous cycle.

Animals↗

Increase in pituitary levels of luteinizing hormone and follicle-stimulating hormone after pinealectomy in both intact and castrated male rats.

Twenty-eight-day-old male Wistar rats were pinealectomized and/or castrated. Animals were killed 26 days later and anterior pituitaries were dissected out, weighed, and their content of LH and FSH measured by RIA. Pinealectomized rats showed higher body weights than sham-operated animals, which suggests an inhibitory influence of the pineal on growth. The weights of pituitaries were increased by both pinealectomy and castration. However, in pinealectomized rats, but not in castrated, the elevated pituitary weights seemed to be due to the high body weights of those animals. The pituitary content and concentration of LH and the content of FSH were increased by pinealectomy in both intact and castrated rats. This finding may suggest that the pineal gland exerts an inhibitory action on the hypothalamic-pituitary axis that seems to be independent of the testicular function.

Animals↗

Antiandrogenic effects of the pineal gland and melatonin in castrated and intact prepubertal male rats.

In castrated prepubertal rats, pinealectomy enhanced the testosterone-induced growth response of the seminal vesicles and melatonin inhibited this effect in a dose-related manner. In entire animals, the serum concentration of LH was increased after pinealectomy with no significant changes in other parameters. Administration of melatonin to intact, pinealectomized rats did not affect the serum concentrations of LH or testosterone but caused a dose-related decrease in the weight of the seminal vesicles. The highest dose of melatonin tested reduced the weight of the ventral prostate gland and the uptake of radioactivity by both the ventral prostate gland and the testes after injection of [5-3H]uridine. It is suggested that the pineal gland and melatonin may exert an antagonistic effect on the biological activity of androgens administered to castrated rats and that melatonin can reduce the growth of the accessory sex organs of intact, pinealectomized rats, in spite of a high concentration of LH in the serum. The well-known inhibitory influence of systemically administered melatonin on the accessory sex organs in male rats may be due to its antagonistic effect at a peripheral level.

Animals↗