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Biomedical subjects

J Botella

Publications and source records attributed to J Botella.

At least 19 recordsLinked to original sources
PubMed1992

Intrusion patterns in rapid serial visual presentation tasks with two response dimensions.

A rapid serial visual presentation (RSVP) paradigm using both one and two response dimensions was used to test parallel processing models of stimulus dimensions. Fifty subjects were asked to report the identity and/or color of a target uppercase word inserted in a series of lowercase words. The results produced a predominance of posttarget intrusions for color responses and a predominance of pretarget intrusions for identity responses. The requirement of a response to a second dimension impaired hit rates but did not change the pattern of intrusions. An examination of the distributions of intrusions in each response dimension as a function of the response given to the other dimension showed an unexpectedly high percentage of simultaneous hits, a moderate covariation between both responses, and the same patterns of intrusions when compared with the general distributions. While these results seem to be compatible with parallel models of processing for stimulus dimensions, two modifications to this model are suggested. First, the processing of response dimension(s) needs some attentional resources. Second, provision for a mixed model is indicated, which would include trials where no illusory conjunctions are formed.

Adult↗
PubMed1992

Filtering versus parallel processing in RSVP tasks.

An experiment of McLean, D. E. Broadbent, and M. H. P. Broadbent (1983) using rapid serial visual presentation (RSVP) was replicated. A series of letters in one of 5 colors was presented, and the subject was asked to identify the letter that appeared in a designated color. There were several innovations in our procedure, the most important of which was the use of a response menu. After each trial, the subject was presented with 7 candidate letters from which to choose his/her response. In three experimental conditions, the target, the letter following the target, and all letters other than the target were, respectively, eliminated from the menu. In other conditions, the stimulus list was manipulated by repeating items in the series, repeating the color of successive items, or even eliminating the target color. By means of these manipulations, we were able to determine more precisely the information that subjects had obtained from the presentation of the stimulus series. Although we replicated the results of McLean et al. (1983), the more extensive information that our procedure produced was incompatible with the serial filter model that McLean et al. had used to describe their data. Overall, our results were more compatible with a parallel-processing account. Furthermore, intrusion errors are apparently not only a perceptual phenomenon but a memory problem as well.

Adult↗
PubMed1991

Interaction of [3H]nomegestrol acetate with cytosolic progesterone receptors from the rat uterus.

The binding characteristics of the progestin 17 alpha-acetoxy-6-methyl-19-[3H]norpregna-4,6-diene-3,20-dione, nomegestrol acetate ([3H]NOM-Ac) to progesterone receptors (PgRs) of uterus were determined in the rat. Scatchard plot analysis of the equilibrium binding data showed that [3H]NOM-Ac binds to uterine PgR with a Kd of 5.44 +/- 1.27 nM and a Bmax of 1.51 +/- 0.11 pmol/mg protein. Analysis of dissociation kinetics showed that [3H]NOM-Ac dissociates slowly from the PgR, k - 1 = 4.9 +/- 0.5 10(-5) s-1. Competition experiments against [3H]NOM-Ac showed the specificity of the binding with a sequence in relative affinity as follows: ORG 2058 greater than P greater than NOM-Ac greater than medroxyprogesterone acetate greater than megestrol acetate greater than cyproterone acetone greater than NOM.

Animals↗
PubMed1991

Multicentric study on paired filtration dialysis as a short, highly efficient dialysis technique.

Paired filtration dialysis (two-chamber haemodiafiltration) was evaluated as a short, highly efficient renal replacement therapy in 35 uraemic subjects belonging to three different dialysis centres. The study period was 1 year. Patients were divided into two groups according to their body-weight and drinking habits. The smaller patients underwent 150-min dialysis sessions three times weekly. The larger patients underwent 3-h treatments thrice weekly. The treatment was adequate in all patients according to the KT/V criteria of adequacy. The intradialytic symptomatology was remarkably low and the treatments were well tolerated in all patients. The study confirms the reliability of paired filtration dialysis as a short dialysis technique. In some patients 150 min may be insufficient to achieve an adequate dialysis efficiency and 180 min may be required for the majority of the population.

Adult↗
PubMed1991

Use of the ultrafiltrate obtained in two-chamber (PFD) hemodiafiltration as replacement fluid. Experimental ex vivo and in vitro study.

PFD (Paired Filtration Dialysis) is the only hemodiafiltration (HDF) technique in which the ultrafiltrate (UF) is continuously available not mixed with the dialysate. As with all convective or prevailingly convective techniques, a replacement fluid is necessary in an amount equal to the difference between the UF and the desired weight loss. This replacement fluid (R) must have an adequate electrolytic balance (Na+, Ca++, and buffer), and must be sterile and pyrogen-free. Using an uncoated adsorbent charcoal cartridge, we "regenerated" the UF obtained in PFD, eliminating the small (except for urea, which was later eliminated by diffusion in the dialyzing section of the PFD system) and the medium-to-large molecules (vit B12 and myoglobin in vitro and beta-2-microglobulin (B2m) and (hANP) in vivo), but not the electrolytes and the endogenous bicarbonate, so as to verify its possible use as R. This technique, experimentally performed in 12 patients under HDF treatment with standard PFD, with a total mean UF of 9650 +/- 875 ml and the use of 130 g of uncoated charcoal, produced a solution with the following composition: Na+ 135.4 +/- 2.4 mmol/l, K+ 3.4 +/- 1.23 mmol/l, Ca++ 1.18 +/- 0.14 mmol/l, HCO3- 26.7 +/- 2.3 mmol/l, phosphates 2.88 +/- 0.81 mg/dl, urea 63 +/- 14 mg/dl, creatinine 0.08 +/- 0.02 mg/dl, uric acid 0.05 +/- 0.0 mg/dl, beta-2 microglobulin 0.5 +/- 0.5 mg/l, and hANP 4.15 +/- 5 pg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellulose↗
PubMed1990

Structure-activity and structure-affinity relationships of 19-nor-progesterone derivatives in rat uterus.

19-nor-progesterone (19NP) is a potent progestagen which possesses a high affinity for the progesterone receptor (PgR). In contrast, 17 alpha-hydroxylated-progesterone (17OHP) shows no hormonal activity and does not compete with progesterone (P) for the PgR. The aim of the present work was to analyse in parallel the structure-affinity and the structure-activity relationships for new molecules obtained by modifications of 19NP and 17OHP. The attachment of a 17 alpha-hydroxyl group on 19NP led to a dramatic decrease in both affinity and activity for the end-product, 17 alpha-hydroxylated-19-nor-progesterone (17OH-19NP). The further addition of a methyl group combined with the formation of a double-bound at C6 on 17OH-19NP results in nomegestrol (NOM), the relative affinity of which remained low. Negligible activity was also associated with this affinity in comparison to the parent 19NP. Strikingly, the protection of the free 17 alpha-hydroxyl group of NOM by an acetate led to a potent progestin with high affinity for PgR. It is concluded that the sum of the modifications brought into the 17OHP-19NP molecule reestablishes both affinity and activity of the original 19NP molecule. The same conclusion holds if P is considered as the parent compound, as already stated in the literature.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Kinetic analysis of the binding of nomegestrol acetate to the progesterone receptors in rat uterus by competition studies.

The characteristics of binding (Kinetic and equilibrium binding analysis) of nomegestrol acetate (NOM, 17 alpha-acetoxy-6 alpha-methyl-19-nor-pregna-4.6-diene-3.20-dione) to the progesterone receptor (PgR) in rat uterine cytosolic fraction were determined in comparison to progesterone (P), to fully appreciate the amplitude and specificity of the induced biological response. Since an appropriate radio-labelled form of this steroid molecule was not available, competition studies were performed against the synthetic progestin: [3H]-Organon 2058 [( 3H]-ORG). This allowed a direct comparison between the unlabelled forms of NOM and P, the kinetic constants of which were respectively: Inhibition constant (Ki): 22.8 and 34.3 nM; Association rate constant (k1): 0.39 X 10(3) and 0.21 X 10(3) M-1.s-1; Dissociation rate constant (k-1): 1.81 X 10(-5) and 2.16 X 10(-5) s-1. These results are much more informative than the mere determination of relative binding affinities which only reflect the specificity of the PgR. It was concluded that NOM behaves like the natural hormone in the cytosol of rat uterus.

Animals↗
PubMed1990

Paired filtration dialysis: optimizing depurative efficiency with separate convection and diffusion processes.

To overcome reciprocal interaction between convection and diffusion occurring in hemodiafiltration, we separated the two processes in a new dialysis technique called paired filtration dialysis (PFD). In this technique, convection and diffusion take place separately on two capillary membranes: a polysulfone hemofilter and a hemophan dialyzer. The depurative effectiveness of PFD with respect to small (blood urea nitrogen, creatinine, uric acid, phosphate) and large (beta 2-microglobulin) molecules was acutely assessed in 6 patients on maintenance acetate hemodialysis. Despite a 3-hour treatment time, a high mass removal of small and large solutes was found in PFD without high ultrafiltration rates or blood flows in excess of 300 ml/min. There was no significant difference in solute removal between the two different depurative sequences adopted in PFD, i.e., convection followed by diffusion or vice versa. A significant reduction in beta 2-microglobulin serum levels was observed in both PFD modes. Twenty patients, on a 12-month period of 3-hour PFD treatment, maintained an unaltered metabolic, clinical, and acid-base status, and cardiovascular stability was not affected. PFD thus provides excellent depurative results, along with simple technical features that are particularly useful in treating patients with high depurative needs and yet are unable to tolerate high-flux techniques.

Adult↗
PubMed1990

Evaluation of dialysis treatment in uremic patients by gel filtration of serum.

A group of substances of molecular masses between 300 and 1500 Da have been found to be toxic metabolites in patients with uremia. We determined the concentration in serum of these molecules in the following groups of patients: two hemodialyzed groups (one with cuprophane and the other with polyacrylonitrile dialyzers), one group treated with continuous ambulatory peritoneal dialysis, one group of nondialyzed azotemic patients, and one control group of healthy persons. Ultrafiltrates of the subjects' sera were fractionated on Sephadex G-15 followed by ion-exchange chromatography. Eluates were monitored by absorbance at 254 and 206 nm. Partially characterized peaks P1 and P2, obtained by gel filtration, correlated with the concentration of creatinine in serum; their concentrations were significantly (P less than 0.01) larger in hemodialyzed groups than in peritoneal dialyzed or in nondialyzed azotemic patients. After ion-exchange chromatography, two peaks (P'5 and P'6) correlated with serum creatinine and also were larger in hemodialyzed patients than in the other groups. Apparently, adequate discrimination is obtained by gel-filtration analysis and further analysis by ion-exchange chromatography does not provide additional information in most of the affected patients.

Chromatography, Gel↗
PubMed1989

Regulation of rat uterine steroid receptors by nomegestrol acetate, a new 19-nor-progesterone derivative.

The regulatory effects of nomegestrol acetate (NOM-Ac: 17 alpha-acetoxy-6 alpha-methyl-19-nor-pregna-4,6-diene-3,20-dione), a new 19-nor-progesterone derivative, active p.o. progestin, were studied on rat uterine estrogen (ER) and progestogen receptor (PgR) levels. The actions of estradiol (E2), progesterone (P) and various progestins were investigated. The effects of E2 were reproduced with 5 micrograms/animal: a 2-fold increase in activated ER level in the nucleus at 30 min, 2-fold stimulation of cytosolic ER replenishment at 48 hr and a 4-fold induction of PgR synthesis at 48 hr. The negative regulatory effects of P were also reproduced at doses ranging from 0.25 to 2 mg/animal: inhibition of basal and E2-stimulated cytosolic ER replenishment and inhibition of E2-induced PgR synthesis. NOM-Ac reproduced these negative regulatory effects. The 50% effective doses in reducing estrogen receptor levels and the corresponding potencies relative to P showed NOM-Ac to be 2.4-fold more active than P and to present, when compared to the other progestins, the highest antiestrogenic capacity. Furthermore, in contrast with norethisterone acetate, a 19-nor-testosterone derivative, it was completely devoid of estrogenic potency.

Animals↗
PubMed1987

The cellular mechanism of the antiandrogenic action of nomegestrol acetate, a new 19-nor progestagen, on the rat prostate.

Nomegestrol acetate, like other synthetic progestins such as medroxyprogesterone acetate (MPA), chlormadinone acetate, megestrol acetate and cyproterone acetate, is able to modify the physiological actions of androgens. In the present study, the effects of nomegestrol acetate and other antiandrogens on the binding of androgen to the androgen receptor (AR) and on the 'activation' of this receptor were investigated, using rat ventral prostate as target model. Relative binding affinities (RBA) for AR were first estimated in vitro with respect to [3H]testosterone for a series of structurally-related compounds. The values obtained ranged as follows: dihydrotestosterone (DHT) much greater than megestrol acetate greater than or equal to testosterone (T) greater than nomegestrol acetate greater than 19-nor progesterone (19NP) greater than progesterone (P). An assay was established, using two different incubation times (3 h and 24 h) to further investigate relationships between binding affinity and androgenic, or antiandrogenic, activity. The following order (as %) was obtained for progestins as against [3H]mibolerone (DMNT): 1) DMNT (100) much greater than nomegestrol acetate (42) greater than megestrol acetate (29) greater than chlormadinone acetate (9) greater than MPA (8) greater than cyproterone acetate (6) after 3 h and 2) DMNT (100) much greater than MPA (53) much greater than nomegestrol acetate (19) greater than megestrol acetate (12) greater than chlormadinone acetate (14) and cyproterone acetate (8) after 24 h. Since the RBA of nomegestrol acetate declined with time, these results indicate that this substance may act like an antiandrogen rather than an androgen, while the contrary prevails concerning MPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists↗
PubMed1987

Extinction of mineralocorticoid effects in 19-norprogesterone derivatives: structure-activity relationships.

19-Norprogesterone (19-NOR-P) is a potent progestagen in mammals by s.c. injection, but is almost inactive when given p.o. In the rat, 19-NOR-P also shows marked salt-retaining and hypertensive effects, consistent with its high affinity for mineralocorticoid receptors (MR). We synthetized recently some p.o. active 19-NOR-P derivatives, and have examined the extent to which the structural changes made on the parent compound can modify the affinity for MR and the salt-retaining potency. Compared with aldosterone, 19-NOR-P has a 47% affinity for rat renal cytosolic MR, decreasing to 13% with alpha-hydroxylation on C-17 (17 alpha-OH-19-NOR-P). The addition of a methyl group combined with the formation of a double bond at C-6 led to nomegestrol, the relative affinity of which was 1.2%. Binding was almost abolished completely (0.23%) by acetylation of the 17 alpha-OH group (nomegestrol-acetate). A single s.c. injection of 19-NOR-P, 20 micrograms/animal, induced a marked decline of [Na+]/[K+] ratio in urine of adrenalectomized male rats. The antinatriuretic effect was still observed after a 11-day period of daily administrations of the same dosage. 17 alpha-OH-19-NOR-P decreased the [Na+]/[K+] ratio only at a high p.o. dose (2500 micrograms/animal). NOM-Ac did not affect the [Na+]/[K+] ratio after a single s.c. or p.o. administration, but increased it at the end of a 11-day p.o. treatment. Thus, the chemical modifications that lead to potent p.o. active progestins derived from 19-NOR-P induce stepwise reductions in the affinity for MR and of the mineralocorticoid effects of the parent compound.

Adrenalectomy↗
PubMed1986

Steroid regulation of Na+/K+-ATPase activity in the rat kidney: effect of a new 19-nor-progestagen.

The effects of Nomegestrol acetate (17 alpha-acetoxy-6-methyl-19-nor-4,6-pregnadiene-3,20-dione), a new 19-nor-progesterone derivative, on renal Na+/K+-ATPase activity were assessed in normal and adrenalectomized rats, and compared with the stimulatory or inhibitory actions produced by other steroids. This compound displayed an inhibitory effect which was similar to, but smaller than, that induced by progesterone and quite distinct from the stimulation produced by 19-nor-progesterone and corticosteroids. In addition, unlike progesterone, it did not antagonize the effect of aldosterone in adrenalectomized rats. This result, together with previous in-vivo and in-vitro observations on this compound indicates that additional modifications introduced in the molecular structure of 19-nor-progesterone produces a potent progestagenic substance virtually devoid of effects on renal Na+/K+-ATPase activity and sodium loss in urine.

Adrenalectomy↗