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Biomedical subjects

C Vergara

Publications and source records attributed to C Vergara.

At least 19 recordsLinked to original sources
PubMed2003

Three-year effectiveness of intravenous pamidronate versus pamidronate plus slow-release sodium fluoride for postmenopausal osteoporosis.

All currently available and approved therapies for osteoporosis inhibit bone resorption. But, despite their great value, antiresorptive agents are generally not associated with dramatic increases in bone mass. In light of these data, the aim of our prospective, placebo-controlled, randomized clinical trial, with a 3-year follow up, was to examine the effects of cyclic intravenous pamidronate and fluoride in combination, versus pamidronate alone, on bone mineral density (BMD) at vertebral and femoral levels, biochemical markers of bone turnover, IGF-1 serum levels, and safety and tolerability in 40 postmenopausal women with osteoporosis. During the treatment period, pamidronate alone reduced both markers of bone formation and bone resorption, resulting in an increase of BMD, after 3 years, of 7.07% at the lumbar level and of 6.76% at the femoral level. In the group treated with pamidronate and fluoride, markers of bone turnover had a different trend: after 3 years, there was a lower reduction of bone resorption and an increase of bone formation markers, with a concomitant increase in IGF-1 levels. This resulted, after 3 years of treatment, in a marked variation of BMD at the lumbar level (+12.74%) and a reduced, but still significant, increase at the femoral level (3.89%). Spine radiography and clinical evaluation did not reveal any vertebral fractures in either treatment group. In conclusion, the combined use of pamidronate and fluoride produced somewhat larger, continuous increases in BMD, at the lumbar level, than pamidronate alone.

Alkaline Phosphatase↗
PubMed2003

External copper inhibits the activity of the large-conductance calcium- and voltage-sensitive potassium channel from skeletal muscle.

We have characterized the effect of external copper on the gating properties of the large-conductance calcium- and voltage-sensitive potassium channel from skeletal muscle, incorporated into artificial bilayers. The effect of Cu2+ was evaluated as changes in the gating kinetic properties of the channel after the addition of this ion. We found that, from concentrations of 20 microM and up, copper induced a concentration- and time-dependent decrease in channel open probability. The inhibition of channel activity by Cu2+ could not be reversed by washing or by addition of the copper chelator, bathocuproinedisulfonic acid. However, channel activity was appreciably restored by the sulfhydryl reducing agent dithiothreitol. The effect of copper was specific since other transition metal divalent cations such as Ni2+, Zn2+ or Cd2+ did not affect BK(Ca) channel activity in the same concentration range. These results suggest that external Cu2+-induced inhibition of channel activity was due to direct or indirect oxidation of key amino-acid sulfhydryl groups that might have a role in channel gating.

Animals↗
PubMed2001

Properties of St I and St II, two isotoxins isolated from Stichodactyla helianthus: a comparison.

Sticholysins I and II are two highly hemolytic polypeptides purified from the Caribbean Sea anemone Stichodactyla helianthus. Their high sequence homology (93%) indicates that they correspond to isoforms of the same hemolysin. The spectroscopic measurements show a close similarity in the secondary structure content, conformation and stability of both toxins. Exposure of the toxins to high pHs (>11), a free radical source (AAPH), urea or temperature produce permanent changes in the toxin that lead to a significant loss of HA. It is significant to note that this loss of hemolytic activity occurs when other indicators, probably with the only exception of near-UV CD spectra, barely detect changes in the protein structure. This emphasizes the sensitivity of the protein function to changes in the macromolecule conformation. The most noticeable difference between both toxins is the considerably higher activity of St II, both measured in terms of erythrocyte internal K(+) exit or hemolysis; which is related to enthalpic factors. This difference is not due to an incomplete association of St I to the membrane. We consider then that the different pore forming capacity of both toxins in erythrocytes can be explained in terms of the difference in charge of the N-terminal fragment, than can considerably reduce the St I insertion rate in the membrane probably due to the negatively charged outer leaflet of the red blood cell, without a significant reduction of its capacity to bind to the cell membrane. This electrostatic effect, together with a slightly more relaxed structure in St II, could explain the higher pore forming capacity of St II in the red blood cell membrane.

Amidines↗
PubMed2001

Structure, organization and characterization of the gene cluster involved in the production of microcin E492, a channel-forming bacteriocin.

Microcin E492 is a low-molecular-weight, channel-forming bacteriocin produced and excreted by Klebsiella pneumoniae RYC492. A 13 kb chromosomal DNA fragment from K. pneumoniae RYC492 was sequenced, and it was demonstrated by random Tn5 mutagenesis that most of this segment, which has at least 10 cistrons, is needed for the production of active microcin and its immunity protein. Genes mceG and mceH correspond to an ABC exporter and its accessory protein, respectively, and they are closely related to the colicin V ABC export system. The microcin E492 system also requires the product of gene mceF as an additional factor for export. Despite the fact that this bacteriocin lacks post-translational modifications, genes mceC, mceI and mceJ are needed for the production of active microcin. Genes mceC and mceI are homologous to a glycosyl transferase and acyltransferase, respectively, whereas mceJ has no known homologue. Mutants in these three genes secrete an inactive form of microcin, able to form ion channels in a phospholipidic bilayer, indicating that the mutation of these microcin genes does not alter the process of membrane insertion. On the other hand, microcin isolated from mutants in genes mceC and mceJ has a lethal effect when incubated with spheroplasts of sensitive cells, indicating that the microcin defects in these mutants are likely to alter receptor recognition at the outer membrane. A model for synthesis and export is proposed as well as a novel maturation pathway that would involve conformational changes to explain the production of active microcin E492.

Amino Acid Sequence↗
PubMed2000

Coordinated gating of TRP-dependent channels in rhabdomeral membranes from Drosophila retinas.

Using a newly developed dissociation procedure, we isolated the specialized rhabdomeral membranes from Drosophila retinal photoreceptors. From these membranes, we have recorded spontaneous active currents in excised patch, voltage-clamp recordings. We observed rapid opening events that closely resembled those ascribed to one class of light-activated channels, TRP. All activity exhibited Ba(2+) permeability, little voltage dependence, and sensitivity to La(3+) block. Mutational analysis indicated that the spontaneous activity present in these membranes was TRP-dependent. Excised patches from wild-type rhabdomeral membranes exhibited a wide range of conductance amplitudes. In addition, large conductance events exhibited many conductance levels in the open state. Block of activity by La(3+) both developed and recovered in a stepwise manner. Our results indicate that TRP-dependent channels have a small unitary conductance and that many channels can be gated coordinately.

Animals↗
PubMed1999

Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit.

Maxi-K channels consist of a pore-forming alpha subunit and a regulatory beta subunit, which confers the channel with a higher Ca(2+) sensitivity. Estradiol bound to the beta subunit and activated the Maxi-K channel (hSlo) only when both alpha and beta subunits were present. This activation was independent of the generation of intracellular signals and could be triggered by estradiol conjugated to a membrane-impenetrable carrier protein. This study documents the direct interaction of a hormone with a voltage-gated channel subunit and provides the molecular mechanism for the modulation of vascular smooth muscle Maxi-K channels by estrogens.

Animals↗
PubMed1999

Kinetics and mechanism of St I modification by peroxyl radicals.

St I is a toxin present in the Caribbean Sea anemone Stichodactyla helianthus which is highly hemolytic in the nanomolar concentration range. Exposure of the toxin to free radicals produced in the pyrolysis of 2,2'-azobis(2-amidinopropane) hydrochloride leads to a progressive loss of hemolytic activity. This loss of hemolytic activity is accompanied by extensive modification of tryptophan residues. On the average, three tryptophan residues are modified by each inactivated toxin. The loss of hemolytic activity of St I takes place without significant changes in the protein structure, as evidenced by the similarity of the fluorescence and CD spectra of native and modified proteins. Also, the native and modified ensembles present a similar resistance to their denaturation by guanidinium chloride. The hemolytic behavior and the performance of the toxin at the single-channel level when incorporated to black lipid membranes suggest that the modified ensemble can be considered as composed of inactive toxins and active toxins whose behavior is similar to that of the native proteins. These results, together with the lack of induction time in the activity loss, suggest that the fall of hemolytic activity takes place by an all-or-nothing inactivation mechanism in which the molecules become inactive when a critical amino acid residue is modified.

Amino Acids↗
PubMed1999

Localization of the K+ lock-In and the Ba2+ binding sites in a voltage-gated calcium-modulated channel. Implications for survival of K+ permeability.

Using Ba2+ as a probe, we performed a detailed characterization of an external K+ binding site located in the pore of a large conductance Ca2+-activated K+ (BKCa) channel from skeletal muscle incorporated into planar lipid bilayers. Internal Ba2+ blocks BKCa channels and decreasing external K+ using a K+ chelator, (+)-18-Crown-6-tetracarboxylic acid, dramatically reduces the duration of the Ba2+-blocked events. Average Ba2+ dwell time changes from 10 s at 10 mM external K+ to 100 ms in the limit of very low [K+]. Using a model where external K+ binds to a site hindering the exit of Ba2+ toward the external side (Neyton, J., and C. Miller. 1988. J. Gen. Physiol. 92:549-568), we calculated a dissociation constant of 2.7 mircoM for K) at this lock-in site. We also found that BK(Ca) channels enter into a long-lasting nonconductive state when the external [K+] is reduced below 4 microM using the crown ether. Channel activity can be recovered by adding K+, Rb+, Cs+, or NH4+ to the external solution. These results suggest that the BK(Ca) channel stability in solutions of very low [K+] is due to K+ binding to a site having a very high affinity. Occupancy of this site by K+ avoids the channel conductance collapse and the exit of Ba2+ toward the external side. External tetraethylammonium also reduced the Ba2+ off rate and impeded the channel from entering into the long-lasting nonconductive state. This effect requires the presence of external K+. It is explained in terms of a model in which the conduction pore contains Ba2+, K+, and tetraethylammonium simultaneously, with the K+ binding site located internal to the tetraethylammonium site. Altogether, these results and the known potassium channel structure (Doyle, D.A., J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, and R. MacKinnon. 1998. Science. 280:69-77) imply that the lock-in site and the Ba2+ sites are the external and internal ion sites of the selectivity filter, respectively.

Algorithms↗
PubMed1999

[Multiple mononeuropathy and vasculitis].

BACKGROUND: Seventy percent of vasculitis are neurologically expressed as multiple mononeuropathy (MM) or asymmetrical neuropathy (AN). Concurrent nerve and muscle biopsy increases the diagnostic accuracy of the disease. AIM: To define the pathological features of vascular damage in nerve and muscle in patients with MM or AN. PATIENTS AND METHODS: Between 1980 and 1997, 50 patients with a MM or AN diagnosis, based on neurological and neurophysiological findings, were studied at the Neurology Department of Hospital del Salvador. All underwent nerve and muscle biopsy (of the superficial peroneal nerve and the short peroneal muscle). Slices were stained with hematoxylin eosin, luxol fast blue and Gomori staining. RESULTS: Forty two patients, aged 52 +/- 15 years old (29 female) had a vasculitis. These subjects with MM or AN associated to vasculitis, corresponded to 22% of neuropathies subjected to nerve biopsy at the Department in the study period. Thirty two cases (76%) had necrotizing arteritis, characterized by wall fibrinoid necrosis and lumen occlusion in large vessels (> 100 microns), with lymphoplasmocytic and macrophage infiltration. Ten cases showed an inflammatory reaction and endothelial proliferation without wall necrosis, specially in small epineural arteries. Vascular recanalization was found in 33% of cases. Diagnostic vascular changes were found in 87% of nerve biopsies and 53% of muscle biopsies. No definitive relationship between the intensity of vascular and nerve lesions was found. All muscle biopsies showed some degree of neurogenic atrophy and 5 had micro infarcts. CONCLUSIONS: Superficial peroneal nerve biopsy is diagnostic in most patients with MM or AN associated with vasculitis. Nerve and muscle biopsies are complementary in the diagnostic work up.

Adult↗
PubMed1999

[Cerebral hemorrhage and angiopathy amyloid].

BACKGROUND: Cerebral amyloid angiopathy is considered pathogenic in non traumatic cerebral lobar hemorrhages. AIM: To study the frequency of cerebral amyloid angiopathy in brains of patients dying of non traumatic cerebral hemorrhages. MATERIAL AND METHODS: Thirty seven brains from patients, 25 men and aged 65 +/- 10 years old, with cerebral hemorrhages (14 lobar, 18 in basal ganglia and 5 in cerebellum or brainstem) were studied. As controls, the brains of 30 subjects, 14 men and aged 64 +/- 16 years old, dying of non neurological causes were studied. Deep and cortical vessels were stained with hematoxylin eosin, Gomori, Thioflavin T and Bodian. Definitive cerebral amyloid angiopathy was diagnosed when amyloid deposition was observed in the media of vessels. RESULTS: Twenty six out of 32 patients dying of cerebral hemorrhage and 3 of 21 controls had chronic hypertension. Cerebral amyloid angiopathy was present in 19 of 37 brains of patients with cerebral hemorrhage and 13 of 30 control brains. In patients with hypertension, vascular changes independent of the location and volume of amyloid deposition, were observed. Such changes were dilatation, tortuousness, thickening of walls specially in muscular and adventitia and hyaline degeneration. Thirteen brains with hemorrhage had fibrinoid necrosis and 10 had microaneurysms. CONCLUSIONS: In this series of patients, cerebral amyloid deposition was unspecific and its role in the pathogenesis of cerebral hemorrhages was not confirmed. Hypertension was associated with vascular degenerative changes that can lead to cerebral hemorrhages.

Aged↗
PubMed1998

Calcium-activated potassium channels.

Calcium-activated potassium channels are fundamental regulators of neuronal excitability, participating in interspike interval and spike-frequency adaptation. For large-conductance calcium-activated potassium (BK) channels, recent experiments have illuminated the fundamental biophysical mechanisms of gating, demonstrating that BK channels are voltage gated and calcium modulated. Structurally, BK channels have been shown to possess an extracellular amino-terminal domain, different from other potassium channels. Domains and residues involved in calcium-gating, and perhaps calcium binding itself, have been identified. For small- and intermediate-conductance calcium-activated potassium channels, SK and IK channels, clones have only recently become available, and they show that SK channels are a distinct subfamily of potassium channels. The biophysical properties of SK channels demonstrate that kinetic differences between apamin-sensitive and apamin-insensitive slow afterhyperpolarizations are not attributable to intrinsic gating differences between the two subtypes. Interestingly, SK and IK channels may prove effective drug targets for diseases such as myotonic muscular dystrophy and sickle cell anemia.

Amino Acid Sequence↗
PubMed1998

Asthma mortality in Columbia.

BACKGROUND: Asthma mortality rates have increased in several industrialized countries during the past two decades. In Latin America, there have been reported only a few national studies of asthma mortality. OBJECTIVE: To determine asthma mortality rates in Colombia from 1979 to 1994. METHODS: Death certificates from the National Administrative Statistical Department of Colombia were collected and analyzed. RESULTS: For the entire population we found increasing rates of asthma mortality from 2.15 in 1979 to 3.3 in 1985 followed by a decrease to 1.6 in 1994. Overall, the trend has been to decrease, with a variation coefficient of 1.09% by year. Age-adjusted rates of death from asthma, based on the population distribution of 1973, showed the same decreasing trend. Deaths from asthma were more frequent in subjects older than 35 years as compared with those younger than 5 years of age or the age group ranging from 5 to 34 years. For the latter, rates of death increased from 0.32 in 1980 to 0.37 in 1988, and fell to 0.20 in 1991. From 1992 to 1994 rates for 5 to 34 years of age were higher than previously, increasing to 0.9 in 1992 and decreasing to 0.6 in 1994. There was no significant variation in death rates between men and women. Sixty-two percent of deaths from asthma occurred at home, 31% at hospitals, and 6.7% in other places. Most asthma deaths were in urban areas. CONCLUSIONS: In contrast to that observed in industrialized countries, we found a decreasing trend in asthma mortality in Colombia. Rates of death from asthma, however, are still high in this country.

Adolescent↗
PubMed1998

[Isolated central nervous system demyelinating syndrome as the clinical expression of late multiple sclerosis. Report of one case].

We report a 56 years old male who developed a transverse myelopathy with cuadriparesis, neurogenic bladder and a sensitive level at C4. Cerebral and spinal cord magnetic resonance imaging showed only one demyelinative lesion at the cervical level. Post mortem neuropathological study showed segmental myelin loss without anatomical limits and with axonal preservation in the involved spinal cord segment. This lesion had the classical features of multiple sclerosis. The isolated lesion, the pathological findings and the delayed age of onset allow the definition of this case as an isolated nervous system demyelinative syndrome.

Demyelinating Diseases↗
PubMed1998

Interactions between bradykinin and ANP in rat kidney in vitro: inhibition of natriuresis and modulation of medullary cyclic GMP.

In anesthetized rats, the renal excretory actions of atrial natriuretic peptide (ANP) are inhibited by intravenous or intraperitoneal injections of bradykinin. To elucidate the mechanisms underlying this inhibition, we evaluated bradykinin effects on: i- ANP-induced natriuresis and diuresis in isolated perfused rat kidneys, and ii- ANP-induced cGMP production in rat renal medulla in vitro. In perfused kidneys, 1 microgram bradykinin completely inhibited the diuretic and natriuretic responses elicited by 0.5 microgram ANP, without changes in perfusion pressure. The inhibitory effects of bradykinin were abolished by HOE-140, a kinin-B2 receptor antagonist. Bradykinin alone had no effect on urinary excretion or perfusion pressure. Incubation with ANP (0.1 nM to 1 microM) increased renal medullary cGMP content up to 30-fold, in a concentration-dependent fashion. Medullary cGMP was moderately increased by the nitric oxide donor, sodium nitroprusside (1 microM), but it was unchanged by bradykinin (0.1 nM-0.1 microM). Despite this, ANP-induced cGMP production was significantly enhanced by co-incubation with low concentrations of bradykinin (up to 0.1 nM). In contrast, ANP-induced cGMP accumulation was unchanged by concentrations of 1 nM bradykinin or higher. In the presence of 100 nM HOE-140, bradykinin (0.1-1 nM) did not affect ANP-induced cGMP production. These results demonstrate that bradykinin counteracts ANP-stimulated sodium and water excretion, by acting directly on the kidney. The interaction between both peptides is complex; our data suggest that renal medullary ANP receptors are subjected to an on/off modulation by fluctuating bradykinin concentrations.

Animals↗
PubMed1997

Current issues in invertebrate phototransduction. Second messengers and ion conductances.

Investigation of phototransduction in invertebrate photoreceptors has revealed many physiological and biochemical features of fundamental biological importance. Nonetheless, no complete picture of phototransduction has yet emerged. In most known cases, invertebrate phototransduction involves polyphosphoinositide and cyclic GMP (cGMP) intracellular biochemical signaling pathways leading to opening of plasma membrane ion channels. Excitation is Ca(2+)-dependent, as are adaptive feedback processes that regulate sensitivity to light. Transduction takes place in specialized subcellular regions, rich in microvilli and closely apposed to submicrovillar membrane systems. Thus, excitation is a highly localized process. This article focuses on the intracellular biochemical signaling pathways and the ion channels involved in invertebrate phototransduction. The coupling of signaling cascades with channel activation is not understood for any invertebrate species. Although photoreceptors have features that are common to most or all known invertebrate species, each species exhibits unique characteristics. Comparative electrophysiological, biochemical, morphological, and molecular biological approaches to studying phototransduction in these species lead to fundamental insights into cellular signaling. Several current controversies and proposed phototransduction models are evaluated.

Animals↗
PubMed1997

Clinical and neuropathological study of six patients with spastic paraparesis associated with HTLV-I: an axomyelinic degeneration of the central nervous system.

Between 1990 to 1994, 6 TSP/HAM patients, 3 women and 3 men with an average age of 57.1 years (39 to 76 years old), who died in the Salvador Hospital were submitted to postmortem examination. The mean time of paraparesis was 7 years (3 to 17 years), and 2 patients had pseudobulbar signs. Three cases had macroscopic atrophy of the spinal cord. Histologically, all cases had lesions in the pyramidal tracts and 4 cases showed somatotopic lesions of the Goll's tracts which followed a "dying back" ascendant and descendant distribution, respectively. In 2 cases, both of which had intellectual impairment, demyelination of the subcortical and parathalamic areas was observed without U fiber involvement. Abnormal vessels with gross thickening of the adventitia, many of them with lymphocytic cuffs, were seen everywhere, especially in the spinal cord, brain stem, midbrain and meninges, but no relation between these findings and the parenchymal lesions was observed. Also, in the cases with posterior column involvement, neuronal changes and proliferation of satellite cells in the dorsal ganglia were found. All cases showed histological sialoadenitis and none had inflammatory muscle changes. We conclude that the lesions affected the neuraxis in a systemic axial fashion as in degenerative diseases, and did not seem to be secondary to vascular or inflammatory abnormalities.

Adult↗