Search PubMed⌕ Search

Biomedical subjects

C Castillo

Publications and source records attributed to C Castillo.

At least 91 records · Page 5Linked to original sources
PubMed1996

Interactions between anemone toxin II and veratridine on single neuronal sodium channels.

The nature of the known positive cooperativity between alkaloid and alpha-polypeptide toxins on macroscopic sodium currents was studied at the single-channel level. We have previously characterized the single-channel function of veratridine (VTD)-modified and anemone toxin II (ATX)-modified channels from lobster leg nerve. VTD and ATX are known to potentiate each other's effects in stimulating 22Na flux into vesicles containing sodium channels from lobster leg nerve. These channels, therefore, provided an excellent model for further investigation of the interactions between the toxins. A variety of such interactions were found, some of which would contribute to the positive cooperativity between these toxins. These included first, a decrease in the frequency of occurrence, but not in the lifetime, of the long channel closed state (minute range). This effect resulted in a hyperpolarization shift of the voltage dependence of the overall channel fractional open time. The second effect was a decrease in the apparent-unbinding rate of ATX at -60 mV. These interactions, which could not have been predicted by the effects of the individual toxins, were observed at negative but not at positive potentials, and led to increases in sodium channel currents. Some of the observed interactions could not contribute to the positive cooperativity between these toxins. These included the elimination of the high-conductance state of ATX-modified channels, the predominance of the VTD effect on the voltage dependence of the fast-process, the predominance of the ATX effect on the rate of decay of sodium currents at +60 mV, and the resulting intermediate toxin effect on the level of the noisy open state.

Animals↗
PubMed1996

Anemone toxin II unmasks two conductance states in neuronal sodium channels.

Anemone toxin II (ATX)-modified voltage-dependent neuronal sodium channels were studied in planar lipid bilayers. ATX-modified channels displayed two predominant conducting states: a short-lived (ms-s) high-conductance (approximately 65 pS) state and a long-lived (s-min) low-conductance (approximately 10 pS) state. The high-conductance state underwent brief closures (ms) and the low-conductance state underwent long closures (s). The probability of detecting these states was time- and voltage-dependent. The channel's fractional open time (fo) due to the high-conductance state increased with depolarization and had a midpoint potential (Va) of -36 mV and an apparent gating charge (Za) of 2.8. The channel's fo due to the low-conductance state increased with depolarization and had a Va of +13 mV and a Za of 1.4. At positive potentials, ATX-modified channels slowly (minutes) entered an absorbing non-conducting state. The permeability ratio of Na+/K+ was 2 and 4 for the low- and high-conductance states, respectively. The saxitoxin analog C3 blocked ATX-modified sodium channels with high affinity (Kd(60-90 mV) = 410 nM, 0.5 M NaCl). The data suggest that upon a depolarization step, ATX-modified channels enter rapidly (ms) into a high-conductance state and more slowly (s-min) into a low-conductance state. Also as the membrane potential becomes more positive, the equilibrium is shifted from the high- to the low-conductance state and from the conducting states to an absorbing non-conducting state.

Animals↗
PubMed1996

Papillary thyroid carcinoma in Mexican patients: clinical aspects and prognostic factors.

The present study characterizes papillary thyroid carcinoma (PTC) in a Mexican patient sample and evaluates potential prognostic factors for recurrence. Clinical records of 229 patients with PTC were analyzed. Surgical specimens were rereviewed and DNA ploidy determined. Cox logistic regression was used to explore prognostic factors. Mean age +/- SD of the patients was 42 +/- 16 years, with a male/female ratio of 24:205. A thyroid mass was the initial manifestation in 99%. Extrathyroid invasion occurred in 45% and nodal metastases in 38%. Mean size +/- SD of the tumors was 3 +/- 2 cm. By flow cytometry 88% of the tumors were DNA euploid and 12% aneuploid. Complete tumor resection was achieved in 83% with an operative mortality of 0.4%. Postoperative hormone suppression was administered in 65% and remnant 131I thyroid ablation in 84%. The 10-year recurrence-free survival was 85%. In the group of patients with tumors totally removed and without distant metastases, none of the 14 evaluated variables demonstrated statistical significance as an independent prognostic factor for recurrence. However, the group of patients in whom a combination of the following factors was present--age > or = 40 years, tumor size > or = 3 cm, local invasion, and lymph node metastases--showed a higher incidence of tumor recurrence.

Adult↗
PubMed1996

Retention in a low-threshold methadone maintenance program.

In 370 opioid-dependent patients included consecutively in a low-threshold methadone maintenance program, the effect of different variables on the retention rate was assessed. The variables included the patients' age, sex, family situation, employment status, length of heroin use, current route of drug consumption, previous treatments, current consumption of cocaine, alcohol and benzodiazepines, needle sharing, HIV serostatus and methadone dose. The retention rate after 2 years of methadone maintenance was 72%. Dose of methadone > 80 mg/day, age > 30 years, living with family or stable partner and non-current use of alcohol were significant predictive variables for retention.

Adult↗
PubMed1996

Multiple open channel states revealed by lidocaine and QX-314 on rat brain voltage-dependent sodium channels.

We have recently reported that brain sodium channels display periods with high (low-Kd) and low (high-Kd) levels of lidocaine-induced open channel block (Salazar, B.C., D.O. Flash, J.L. Walewski, and E. Recio-Pinto. 1995. Brain Res. 699:305-314). In the present study, we further characterize this phenomenon by studying the effects of the permanently charged lidocaine analogue, QX-314. We found that the detection of high- and low-Kd periods does not require the presence of the uncharged form of lidocaine. The level of block, for either period, at various QX-314 concentrations indicated the presence of a single local anesthetic binding site. Increasing the concentration of QX-314 decreased the lifetime of the high-Kd periods while it increased the lifetime of the low-Kd periods. These results could be best fitted to a model with two open channel conformations that display different local anesthetic Kd values (low and high Kd), and in which the channel area defining the local anesthetic Kd consists of multiple interacting regions. Amplitude distribution analysis showed that changes in the Kd values reflected changes in the kon rates, without changes in the koff rates. Both lidocaine and QX-314 were found to be incapable of blocking small-channel subconductance states (5-6 pS). Changes in the local anesthetic kon rates for blocking the fully open state and the lack of local anesthetic block of the small subconductance state are consistent with the presence of channel conformational changes involving the intracellular permeation pathway leading to the local anesthetic binding site.

Anesthetics, Local↗
PubMed1996

Breast-feeding and the nutritional status of nursing children in Chile.

The work reported here sought to describe the feeding patterns of Chilean children up to 18 months old and their relation to nutritional status. To this end, a survey was conducted in 1993 of 9330 Chilean children under 18 months old who were receiving care through the National Health Service System-which provides care for 75% of all children under age 6. The children, whose mothers or caretakers were interviewed, constituted 94% of a sample selected at random from 102 of the 320 urban health clinics located throughout the country. The interview served to identify the type of feeding (exclusive breast-feeding, breast-feeding plus bottle-feeding, breast-feeding plus solid food, exclusive bottle-feeding, or bottle-feeding plus solid food) and to determine the nutritional status of the participants in terms of standards used by the United States National Center for Health Statistics and the World Health Organization. Children were deemed at risk of malnutrition if they had z scores on the weight-for-age distribution between 1.0 and 2.0 standard deviations below the US/WHO standard and as actually malnourished if they had z scores of over 2.0 standard deviations below the standard. The survey found exclusive breast-feeding prevalences of 86.5%, 66.7%, and 25.3% among infants 1, 3, and 6 months old. Some 12.1% of the participants were found to have a weight-for-age deficiency, 30.7% exhibited a height-for-age deficiency, and 35.7% were found to be over-weight. The prevalence of weight-for-age and height-for-age deficiencies were found to be considerably higher among bottle-fed children than among breast-fed children. In general, the results demonstrated the benefits of exclusive breast-feeding through the first 6 months of life, the need to complement exclusive breast-feeding with solid food after that time, and the superior nutritional status of breast-fed children within the age groups studied.

Age Factors↗
PubMed1996

Effects of aging and hypertension on learning, memory, and activity in rats.

A comparison between behavioral alterations induced by hypertension and aging was made in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) of different ages (3-24 months old), trained to perform autoshaping learning and activity tasks. Food-deprived rats received autoshaping training sessions during 6 days; the animals were retrained 1 month later. Two weeks after autoshaping training, the animals were evaluated in the spontaneous activity task during 2 consecutive days. The results show an age-related decrease in learning, memory, and spontaneous activity. Independently of the age group compared, WKY, though showing lower activity, learned and retrieved more than SHR. Accordingly, the reductions in learning and memory were correlated with both aging and hypertension. The combined influence of these two factors had synergistic detrimental effects on cognitive functions.

Aging↗
PubMed1996

Influence of 5-hydroxytryptamine on the pressor responses induced by norepinephrine and electrical sympathetic stimulation in the pithed rat.

Serotonin (5-hydroxytryptamine; 5-HT) modifies the responses to several vasoconstrictor stimuli prejunctionally and/or postjunctionally. The present study analyzed the effects of 5-HT on the pressor responses induced by norepinephrine (NE) or electrical sympathetic stimulation in pithed rats. Responses to intravenous (i.v.) NE (0.03-3 micrograms/kg) or electrical stimulation at increasing frequencies (0.1-3 Hz) were evaluated before and during continuous i.v. infusions of physiological saline (0.01 ml/min) or 5-HT (1-10 micrograms/kg x min). The effects of 5-HT on the tachycardic responses to NE and sympathetic stimulation were studied in parallel. The increases in diastolic blood pressure and heart rate produced by NE were not modified by 5-HT. In contrast, 5-HT significantly and dose-dependently inhibited the increases in diastolic blood pressure - but not those in heart rate - produced by stimulation of the appropriate spinal segments. These effects of 5-HT were more pronounced on the responses to lower frequencies of stimulation. It is suggested that 5-HT inhibits the electrically induced pressor responses by a prejunctional mechanism which would lead to a reduction of neurotransmitter release from the sympathetic nerves supplying the systemic vasculature. The selective stimulation of this inhibitory mechanism might represent a new approach for the development of novel antihypertensive agents.

Animals↗
PubMed1995

5-hydroxytryptamine inhibits pressor responses to preganglionic sympathetic nerve stimulation in pithed rats.

5-Hydroxytryptamine (5-HT) inhibits contractile responses to adrenergic nerve stimulation in several blood vessels and organs. We have now investigated the potential ability of 5-HT to inhibit the pressor responses caused by preganglionic sympathetic stimulation (T7-T9) in pithed rats. Sympathetic stimulation (0.03, 0.1, 0.3, 1 and 3 Hz) resulted in frequency-dependent increases in diastolic blood pressure; these effects were augmented after i.v. treatment with desipramine (50 micrograms/kg). During continuous infusions of 5-HT (1.8, 3.1, 5.6 and 10 micrograms/kg.min, i.v.), but not of saline, the pressor responses were dose-dependently inhibited in both control and desipramine-pretreated rats; this inhibitory effect of 5-HT was significantly more pronounced at lower frequencies of stimulation. In contrast, the above infusions of 5-HT did not inhibit the pressor responses induced by i.v. bolus injections of exogenous norepinephrine (up to 3 micrograms/kg). Taken together, the above findings suggest an operative 5-HT-induced prejunctional inhibition of sympathetic nerve activity on the systemic vasculature in vivo.

Animals↗
PubMed1995

Molecular and ultrastructural analysis of a nonchromosomal variegated mutant. Tomato mitochondrial mutants that cause abnormal leaf development.

Mutants were recovered in a population of cybrids formed following protoplast fusion between tomato (Lycopersicon esculentum Mill.) cv UC82 and Lycopersicon pennellii Corr. The cybrids were identified as individuals with recombinant cytoplasmic genomes but only tomato nuclear genomes. The mutants were identified based on two features, a variegated sectoring of light and dark green regions on their leaves, stems, and fruit, and reduced growth in the field. The mutants produced 50% of the shoot fresh weight and 20% of the fruit fresh weight of the parental type, UC82. The variegated sectoring was maternally inherited. The chloroplast genome in the mutants was indistinguishable from the chloroplast genome in UC82, when distribution of restriction endonuclease sites was used as an assay. The mitochondrial genome in the mutants, however, was recombinant, containing genes from UC82 and L. pennellii. Light microscopic analysis of the leaves of the mutants demonstrated an absence of the palisade layer in the variegated sectors. Electron microscopic analysis of these same regions demonstrated an absence of normal inner membranes in the mitochondria of these cells.

Blotting, Southern↗
PubMed1995

Characterization of prejunctional 5-HT receptors mediating inhibition of sympathetic vasopressor responses in the pithed rat.

1. It has recently been shown that continuous infusions of 5-hydroxytryptamine (5-HT) are able to inhibit, in a dose-dependent manner, the pressor responses induced by preganglionic (T7-T9) sympathetic stimulation in pithed rats pretreated with desipramine (50 micrograms kg-1, i.v.). This inhibitory effect, besides being significantly more pronounced at lower frequencies of stimulation (0.03-I Hz) and devoid of tachyphylaxis, is reversible after interrupting the infusions of 5-HT (up to 5.6 micrograms kg-1 min-1). In the present study we have characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-HT. 2. The inhibition induced by 5.6 micrograms kg-1 min-1 of 5-HT on sympathetically-induced pressor responses was not blocked after i.v. treatment with physiological saline (1 ml kg-1), ritanserin (0.1 mg kg-1), MDL 72222 (0.15 mg kg-1) or tropisetron (3 mg kg-1), which did not modify the sympathetically-induced pressor responses per se, but was significantly antagonized by the 5-HT1-like and 5-HT2 receptor antagonist, methysergide (0.3 mg kg-1), which also produced a slight attenuation of the pressor responses to 0.03 and 0.1 Hz per se. 3. Unexpectedly and contrasting with methysergide, the 5-HT1-like and 5-HT2 receptor antagonists, methiothepin (0.01, 0.03 and 0.1 mg kg-1) and metergoline (1 and 3 mg kg-1), apparently failed to block the above 5-HT-induced inhibition. Nevertheless, it is noteworthy that these antagonists also blocked the electrically-induced pressor responses per se, presumably by blockade of vascular alpha 1-adrenoceptors and, indeed, this property might have masked their potential antagonism at the inhibitory 5-HT1-like receptors. 4. Consistent with the above findings, 5-carboxamidotryptamine (5-CT, a potent 5-HT1-like receptor agonist), metergoline and methysergide mimicked the inhibitory action of 5-HT with the following rank order of agonist potency: 5CT > > 5-HT > metergoline > or = methysergide. 5. Taken together, the above results suggest that the inhibitory action of 5-HT on the electrically-induced pressor responses is primarily mediated by an action on inhibitory prejunctional 5-HT1-like receptors leading to a decrease in the sympathetic nerve discharge. Interestingly, 5-HT-induced excitatory mechanisms could be made manifest once the inhibitory action of 5-HT had been antagonized.

Animals↗
PubMed1995

Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5-HT in vagosympathectomized dogs.

1. 5-Hydroxytryptamine (5-HT) can produce vasodilatation or vasoconstriction of the canine external carotid bed depending upon the degree of carotid sympathetic tone. Hence, external carotid vasodilatation to 5-HT in dogs with intact sympathetic tone is primarily mediated by prejunctional 5-HT1-like receptors similar to the 5-HT1D subtype, which inhibit the carotid sympathetic outflow. The present investigation is devoted to the pharmacological analysis of the receptors mediating external carotid vasoconstriction by 5-HT in vagosympathectomized dogs. 2. Intracarotid (i.c.) infusions for 1 min of 5-HT (0.3, 1, 3, 10, 30 and 100 micrograms) resulted in dose-dependent decreases in both external carotid blood flow and the corresponding conductance; both mean arterial blood pressure and heart rate remained unchanged during the infusions of 5-HT. These responses to 5-HT were resistant to blockade by antagonists at 5-HT2 (ritanserin) and 5-HT3/5-HT4 (tropisetron) receptors, but were partly blocked by the 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (0.3 mg kg-1); higher doses of methiothepin (1 and 3 mg kg-1) caused little, if any, further blockade. These methiothepin (3 mg kg-1)-resistant responses to 5-HT were not significantly antagonized by MDL 72222 (0.3 mg kg-1) or tropisetron (3 mg kg-1). 3. The external carotid vasoconstrictor effects of 5-HT were mimicked by the selective 5-HT1-like receptor agonist, sumatriptan (3, 10, 30 and 100 micrograms during 1 min, i.c.), which produced dose-dependent decreases in external carotid blood flow and the corresponding conductance; these effects of sumatriptan were dose-dependently antagonized by methiothepin (0.3, 1 and 3 mg kg-1), but not by 5-HT1D-like receptor blocking doses of metergoline (0.1 mg kg-1). 4. The above vasoconstrictor effects of 5-HT remained unaltered after administration of phentolamine, propranolol, atropine, hexamethonium, brompheniramine, cimetidine and haloperidol, thus excluding the involvement of alpha- and beta-adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors. Likewise, inhibition of either 5-HT-uptake (with fluoxetine) or cyclo-oxygenase (with indomethacin), depletion of biogenic amines (with reserpine) or blockade of calcium channels (with verapamil) did not modify the effects of 5-HT. 5. Taken together, the above results support our contention that the external carotid vasoconstrictor responses to 5-HT in vagosympathectomized dogs are mainly mediated by activation of sumatriptan-sensitive 5-HT1-like receptors. It must be emphasized, notwithstanding, that other mechanisms of 5-HT, including an interaction with a novel 5-HT receptor (sub)type and/or an indirect action that may lead to the release of a known (or even unknown) neurotransmitter substance cannot be categorically excluded.

Animals↗