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Biomedical subjects

J Alvarez

Publications and source records attributed to J Alvarez.

At least 55 records · Page 3Linked to original sources
PubMed2001

Epidural washout with high volumes of saline to accelerate recovery from epidural anaesthesia.

BACKGROUND: Prolonged postoperative blockade can follow neuraxial blocks for short surgical procedures. We investigated whether washout with a high volume of saline through an epidural catheter could provide a faster recovery after epidural anaesthesia. METHODS: Thirty patients were randomly assigned to a control group (no washout), to group 2x (epidural washout with twice the volume of 2% mepivacaine) and group 4x (epidural washout with four times that volume). RESULTS: Recovery times from sensory blockade at L2 were 151+/-24, 122+/-29 and 116+/-24 min for control, 2x and 4x groups respectively. Significant differences were found in both saline groups when compared with control group, but not between group 2x and group 4x. No differences were found concerning motor blockade. One patient in group 4x demonstrated signs of intracranial hypertension. Mepivacaine plasma concentrations were increased by saline washout in group 4x. CONCLUSIONS: Epidural washout with a high volume of saline can not be recommended since no clinically significant reduction in the recovery time can be achieved without risk.

Anesthesia Recovery Period↗
PubMed2001

Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels.

1. Two sodium channel toxins, BgII and BgIII, have been isolated and purified from the sea anemone Bunodosoma granulifera. Combining different techniques, we have investigated the electrophysiological properties of these toxins. 2. We examined the effect of BgII and BgIII on rat ventricular strips. These toxins prolong action potentials with EC50 values of 60 and 660 nM and modify the resting potentials. 3. The effect on Na+ currents in rat cardiomyocytes was studied using the patch-clamp technique. BgII and BgIII slow the rapid inactivation process and increase the current density with EC50 values of 58 and 78 nM, respectively. 4. On the cloned hH1 cardiac Na+ channel expressed in Xenopus laevis oocytes, BgII and BgIII slow the inactivation process of Na+ currents (respective EC50 values of 0.38 and 7.8 microM), shift the steady-state activation and inactivation parameters to more positive potentials and the reversal potential to more negative potentials. 5. The amino acid sequences of these toxins are almost identical except for an asparagine at position 16 in BgII which is replaced by an aspartic acid in BgIII. In all experiments, BgII was more potent than BgIII suggesting that this conservative residue is important for the toxicity of sea anemone toxins. 6. We conclude that BgII and BgIII, generally known as neurotoxins, are also cardiotoxic and combine the classical effects of sea anemone Na+ channels toxins (slowing of inactivation kinetics, shift of steady-state activation and inactivation parameters) with a striking decrease on the ionic selectivity of Na+ channels.

Action Potentials↗
PubMed2001

High doses of mepivacaine for brachial plexus block in patients with end-stage chronic renal failure. A pilot study.

BACKGROUND AND OBJECTIVE: Patients with end-stage chronic renal failure are at risk of developing several serious postanaesthetic complications. Many anaesthesiologists perform brachial plexus anaesthesia with high doses of local anaesthetic in order to achieve an extensive blockade of the upper limb. Brachial plexus block is a suitable technique for anaesthesia for creation, repair or removal of vascular access for haemodialysis. The aim of this study was to measure mepivacaine plasma concentrations after axillary block with 650 mg plain mepivacaine in patients with end-stage chronic renal failure. METHODS: Mepivacaine plasma concentrations were assessed throughout a 150-min period, in 10 patients after axillary block with 650 mg plain mepivacaine (600 mg for axillary block and 50 mg for supplementation). RESULTS: Mepivacaine plasma concentrations expressed in microg mL(-1) as medians and their ranges were: 1.69 (1.23--7.78) at 5 min, 5.61 (4.36--8.19) at 30 min, 8.28 (3.83--11.21) at 60 min, 7.93 (5.63--11.1) at 90 min and 6.49 (5.56--8.35) at 150 min without any symptoms of toxicity. CONCLUSIONS: Brachial plexus anaesthesia with 650 mg plain mepivacaine did not result in serious systemic toxicity in these patients despite the high mepivacaine plasma concentrations found.

Aged↗
PubMed2001

Control of secretion by mitochondria depends on the size of the local [Ca2+] after chromaffin cell stimulation.

In chromaffin cells, plasma membrane calcium (Ca2+) channels and mitochondria constitute defined functional units controlling the availability of Ca2+ nearby exocytotic sites. We show here that, when L-/N-type Ca2+ channels were inhibited with nisoldipine and omega-conotoxin GVIA, cytosolic [Ca2+] ([Ca2+]c) peaks measured in fura-4F-loaded cells were reduced by 36%; however, mitochondrial Ca2+ uptake was unaffected and secretion was potentiated by protonophores as in control cells. By contrast, when non L-type Ca2+ channels were inhibited with omega-conotoxin MVIIC, [Ca2+]c peaks induced by high K+ were reduced by 73%, mitochondrial Ca2+ uptake was abolished, and secretion was not modified by protonophores. However, if Ca2+ entered only through L-type channels activated by FPL64176, high K+ stimulation induced fast mitochondrial Ca2+ uptake and catecholamine secretion was strongly increased and potentiated by protonophores. These results confirm the close association of catecholamine secretion to mitochondrial Ca2+ uptake, and indicate the sharp threshold of local [Ca2+]c (about 5 microM) required for triggering fast mitochondrial Ca2+ uptake that is able to modulate secretion. The entry of Ca2+ through L-type channels generated local [Ca2+]c increases just below that, inducing little mitochondrial Ca2+ uptake unless FPL64176 was present. By contrast, Ca2+ entry through P/Q-type channels fully activated mitochondrial Ca2+ uptake. Control of secretion by mitochondria therefore depends critically on the ability of the stimulus to create large local [Ca2+]c microdomains.

Adrenal Medulla↗
PubMed2001

Stimulation by thimerosal of histamine-induced Ca(2+) release in intact HeLa cells seen with aequorin targeted to the endoplasmic reticulum.

The oxidizing thiol reagent, thimerosal, has been shown to activate reversibly the inositol 1,4,5-trisphosphate (InsP(3)) receptor in several cell types. We have studied here the effects of thimerosal by monitoring the [Ca(2+)] inside the endoplasmic reticulum (ER) of intact HeLa cells with targeted aequorin. We show that thimerosal produced little effects on the ER-Ca(2+)-pump and only slightly increased the ER-Ca(2+)-leak in intact cells. Instead, thimerosal increased the sensitivity to histamine of ER-Ca(2+)-release by about two orders of magnitude, made the response much more prolonged at saturating histamine concentrations and enhanced both cytosolic and mitochondrial [Ca(2+)] responses to histamine. Moreover, inhibition of ER-Ca(2+)release by cytosolic [Ca(2+)] microdomains was fully preserved and sensitive to BAPTA-loading, and histamine-induced Ca(2+) release remained quantal in the presence of both thimerosal and intracellular BAPTA. The effects of thimerosal were reversible in the presence of dithiotreitol, suggesting the possible presence of a physiological redox regulatory mechanism. However, in permeabilized cells thimerosal potentiated InsP(3)-induced Ca(2+) release but oxidized glutathione had no effect. In addition, thimerosal increased the [Ca(2+)](ER) steady-state level in permeabilized cells. Thimerosal partially inhibited also plasma membrane Ca(2+)extrusion and increased Ca(2+)(Mn(2+)) entry through the plasma membrane, both phenomena contributing to increase the steady-state cytosolic [Ca(2+)]. Thimerosal-induced Ca(2+) entry was additive to that induced by emptying of the ER, suggesting that store-operated Ca(2+) channels may not be involved. These results provide new insights on the mechanisms of activation and inactivation of InsP(3) receptors.

Aequorin↗
PubMed2001

Neuronal hypersynchronization, creativity and endogenous psychoses.

I have investigated a neuronal hypersynchronism, currently included under the general subject of epilepsy, and termed interictal activity. I suggest that it is a physiological activity of the mammalian brain and propose it be termed Hyperia. After a thorough study of the extraordinary psychic manifestations of this neuronal hypersynchronism shown by mystics and artists, I have reviewed several scientific publications bearing on my hypothesis. I conclude by elaborating on a variety of cerebral hypersynchronous functions whose cause I consider to be physiological. Such behaviour is a common basis for extraordinary psychic manifestations found not only in mystics and artists, but also in patients suffering from endogenous psychoses, especially Bipolar Disorder.

Creativity↗
PubMed2001

Mitochondrial Ca(2+)-induced Ca(2+) release mediated by the Ca(2+) uniporter.

We have reported that a population of chromaffin cell mitochondria takes up large amounts of Ca(2+) during cell stimulation. The present study focuses on the pathways for mitochondrial Ca(2+) efflux. Treatment with protonophores before cell stimulation abolished mitochondrial Ca(2+) uptake and increased the cytosolic [Ca(2+)] ([Ca(2+)](c)) peak induced by the stimulus. Instead, when protonophores were added after cell stimulation, they did not modify [Ca(2+)](c) kinetics and inhibited Ca(2+) release from Ca(2+)-loaded mitochondria. This effect was due to inhibition of mitochondrial Na(+)/Ca(2+) exchange, because blocking this system with CGP37157 produced no further effect. Increasing extramitochondrial [Ca(2+)](c) triggered fast Ca(2+) release from these depolarized Ca(2+)-loaded mitochondria, both in intact or permeabilized cells. These effects of protonophores were mimicked by valinomycin, but not by nigericin. The observed mitochondrial Ca(2+)-induced Ca(2+) release response was insensitive to cyclosporin A and CGP37157 but fully blocked by ruthenium red, suggesting that it may be mediated by reversal of the Ca(2+) uniporter. This novel kind of mitochondrial Ca(2+)-induced Ca(2+) release might contribute to Ca(2+) clearance from mitochondria that become depolarized during Ca(2+) overload.

Aequorin↗
PubMed2001

Ambulatory blood pressure after renal transplantation.

Renal transplantation has been a usual medical practice in developed countries for several decades. A large number of studies report the excellent results obtained with such a practice. The survival of the graft, although able to be improved, is excellent and gives a great deal of hope to patients with renal insufficiency. The high level of investigation into immunosuppressor drugs offers, almost continuously, more efficient and better tolerated products. Paradoxically, the usual problems of patients with a renal transplant are not immunological but cardiovascular. Elevated serum cholesterol levels, obesity, diabetes and other cardiovascular risk factors (CVRFs) are usual in these patients, arterial hypertension (AHT) being the most frequent. Nephrologists are increasingly using ambulatory blood pressure monitoring (ABPM) on a daily basis. In the last 10 years, we have obtained highly valuable and interesting results with this technique which have allowed us to study and understand with greater precision the relationship of AHT to the kidney. Here we analyse and review the most relevant aspects of ABPM in the different stages of kidney disease, with special emphasis on renal transplantation.

Blood Pressure↗
PubMed2001

Collagen metabolism is markedly altered in the hypertrophic cartilage of growth plates from rats with growth impairment secondary to chronic renal failure.

Skeletal growth depends on growth plate cartilage activity, in which matrix synthesis by chondrocytes is one of the major processes contributing to the final length of a bone. On this basis, the present work was undertaken to ascertain if growth impairment secondary to chronic renal insufficiency is associated with disturbances of the extracellular matrix (ECM) of the growth plate. By combining stereological and in situ hybridization techniques, we examined the expression patterns of types II and X collagens and collagenase-3 in tibial growth plates of rats made uremic by subtotal nephrectomy (NX) in comparison with those of sham-operated rats fed ad libitum (SAL) and sham-operated rats pair-fed with NX (SPF). NX rats were severely uremic, as shown by markedly elevated serum concentrations of urea nitrogen, and growth retarded, as shown by significantly decreased longitudinal bone growth rates. NX rats showed disturbances in the normal pattern of chondrocyte differentiation and in the rates and degree of substitution of hypertrophic cartilage with bone, which resulted in accumulation of cartilage at the hypertrophic zone. These changes were associated with an overall decrease in the expression of types II and X collagens, which was especially marked in the abnormally extended zone of the hypertrophic cartilage. Unlike collagen, the expression of collagenase-3 was not disturbed severely. Electron microscopic analysis proved that changes in gene expression were coupled to alterations in the mineralization as well as in the collagen fibril architecture at the hypertrophic cartilage. Because the composition and structure of the ECM have a critical role in regulating the behavior of the growth plate chondrocytes, results obtained are consistent with the hypothesis that alteration of collagen metabolism in these cells could be a key process underlying growth retardation in uremia.

Alkaline Phosphatase↗
PubMed2001

The autonomous axon: a model based on local synthesis of proteins.

In the current understanding of axons, axoplasmic synthesis of proteins is negated, and it is asserted that proteins are transported from perikarya to axons. This 'transport model' in which axons are fully dependent of perikarya is seriously flawed. The 'autonomous axon' proposed here negates in turn transport of proteins, and asserts (i) local synthesis of axoplasmic proteins, corner stone of this model, (ii) existence of internal programs in axon and terminals, (iii) external control of programs resulting in local regulation of phenotype of axons and terminals, hence they are autonomous from perikarya; (iv) participation of perikarya through the fast transport in setting up the axonal programs but not in their immediate regulation. The word merotrophism (meros meaning part) denotes post-transcriptional regulation of phenotype of restricted regions of a cell. We surmise that merotrophism is at the base of many plastic phenomena.

Animals↗
PubMed2001

Molecular cloning, expression, and regulation of hippocampal amyloid precursor protein of senescence accelerated mouse (SAMP8).

Alzheimer's disease (AD) is associated with increased expression of amyloid precursor protein (APP) with a consequent deposition of amyloid beta peptide (Abeta) which forms characteristic senile plaques. We have noticed that the senescence accelerated mouse (SAMP8), a strain of mouse that exhibits age-dependent defects such as loss of memory and retention at an early age of 8-12 months, also produces increased amounts of APP and Abeta similar to those observed in Alzheimer's disease (AD). In order to investigate if this is due to mutations in APP similar to those observed in AD, and to develop molecular probes that regulate its expression, APP cDNA was cloned from the hippocampus of 8-month-old SAMP8 mouse. The nucleotide sequence is 99.7% homologous with that of mouse and rat, 88.7% with monkey, and 89.2% with human homologues. At the amino acid level, the homology was 99.2% and 97.6% with rodent and primate sequences, respectively. A single amino acid substitution of Alanine instead of Valine at position 300 was unique to SAMP8 mouse APP. However, no mutations similar to those reported in human familial AD were observed. When the cDNA was expressed in HeLa cells, glycosylated mature APP could be detected by immunoblotting technique. The expression could be regulated in a time- and concentration-dependent manner by using an antisense oligonucleotide specific to APP mRNA. Such regulation of APP expression may have a therapeutic application in vivo.

Aging↗
PubMed2001

Treatment of tuberculosis in a rural area of Haiti: directly observed and non-observed regimens. The experience of H pital Albert Schweitzer.

SETTING: Artibonite Valley, a rural area in Haiti. OBJECTIVE: To evaluate a tuberculosis control program in rural Haiti and to compare two strategies for treatment implemented in two areas that were not chosen at random: treatment delivered at the patients' homes observed by former tuberculosis patients (DOT), and non observed treatment (non-DOT). DESIGN: Retrospective analysis of the clinical records of adult patients diagnosed with tuberculosis at H pital Albert Schweitzer in Deschapelles, Haiti, during 1994-1995. RESULTS: There were 143 patients in the non-DOT group and 138 patients in the DOT group. The results of treatment were significantly different: in the non-DOT group 29% defaulted, 12% died and 58% had a successful outcome; in the DOT group 7% defaulted (P < 0.01), 4% died (P = 0.01) and 87% had a successful outcome (P < 0.01). These differences are also significant when considering only human immunodeficiency virus (HIV) infected patients (defaulted P < 0.01; died P = 0.09; successful outcome P < 0.01). CONCLUSION: Delivering treatment in patients' homes with direct observation by former tuberculosis patients can achieve good results, even in an area of extreme poverty and high rates of HIV infection. In this population the number of patients who are able to complete their treatment without observed administration is far from optimal.

Adult↗
PubMed2000

Identification and enzymatic characterization of two diverging murine counterparts of human interstitial collagenase (MMP-1) expressed at sites of embryo implantation.

Remodeling of fibrillar collagen in mouse tissues has been widely attributed to the activity of collagenase-3 (matrix metalloproteinase-13 (MMP-13)), the main collagenase identified in this species. This proposal has been largely based on the repeatedly unproductive attempts to detect the presence in murine tissues of interstitial collagenase (MMP-1), a major collagenase in many species, including humans. In this work, we have performed an extensive screening of murine genomic and cDNA libraries using as probe the full-length cDNA for human MMP-1. We report the identification of two novel members of the MMP gene family which are contained within the cluster of MMP genes located at murine chromosome 9. The isolated cDNAs contain open reading frames of 464 and 463 amino acids and are 82% identical, displaying all structural features characteristic of archetypal MMPs. Comparison for sequence similarities revealed that the highest percentage of identities was found with human interstitial collagenase (MMP-1). The new proteins were tentatively called Mcol-A and Mcol-B (Murine collagenase-like A and B). Analysis of the enzymatic activity of the recombinant proteins revealed that both are catalytically autoactivable but only Mcol-A is able to degrade synthetic peptides and type I and II fibrillar collagen. Both Mcol-A and Mcol-B genes are located in the A1-A2 region of mouse chromosome 9, Mcol-A occupying a position syntenic to the human MMP-1 locus at 11q22. Analysis of the expression of these novel MMPs in murine tissues revealed their predominant presence during mouse embryogenesis, particularly in mouse trophoblast giant cells. According to their structural and functional characteristics, we propose that at least one of these novel members of the MMP family, Mcol-A, may play roles as interstitial collagenase in murine tissues and could represent a true orthologue of human MMP-1.

Amino Acid Sequence↗
PubMed2000

Non-heart-beating donors from the streets: an increasing donor pool source.

BACKGROUND: Non-heart-beating donors have become a source for organ donation, especially kidneys. The emergency room and the critical care unit are the two sources for this kind of donor. Three years ago, our hospital began a policy of obtaining organs and tissues successfully from subjects who died in the streets. METHODS: We consider as potential organ donors people who die out-of-hospital, are less than 50 years old, with less than 15 min of asystolia without cardiac massage, with a known etiology of death, and without general contraindications for donating. After death diagnosis, the cadaver is taken to the hospital where an emergency room doctor certifies the death. Afterward, the cadaver is transferred to the operating room where a cardiopulmonary bypass is performed to preserve the organs while the legal aspects of donation go on. RESULTS: Up to now, 111 cadavers have been taken as non-heart-beating donors; 53 of them have been actual donors. The average time before arrival to the hospital was 68+/-2.64 min, and the average interval between cardiac arrest and the beginning of cardiopulmonary bypass was 111.33+/-7.09 min. We have obtained 105 kidneys, 12 livers, 84 corneas, and 31 pancreata for islets isolation as well as 49 long bones. Seventy-two kidneys were transplanted, with a probability of survival of 83% at 36 months. CONCLUSIONS: Our experience indicates that it is possible to obtain organs for transplant from donors who die in the streets and are brought to the hospital under strict selection criteria.

Cadaver↗
PubMed2000

Nerve regeneration in Wld(s) mice is normalized by actinomycin D.

Injured nerves of Wld(s) mice neither degenerate nor regenerate for several weeks. We have conjectured that Wld(s) axons have the ability to regenerate but its expression is impaired by the Schwann cells of the undegenerated distal stump. To test this conjecture, transcription was locally arrested with actinomycin D (ActD), nerves were crushed, and regrowth was evaluated. In normal CD1 nerves injected with ActD 3 days before the crush, the rate of elongation was not affected but the delay of regrowth was shortened. In sharp contrast, ActD normalized the elongation of Wld(s) axons. When Wld(s) nerves were crushed past the treated segment, axons did not regenerate. After 7, but not 4, days of treatment, intact CD1 and Wld(s) axons presented a local sprouting response. We conclude that Wld(s) axons can regenerate in a normal way but do not do so because the undegenerated Schwann cells of the distal stump repress the regrowth program. We present a model axon that includes a destruction program and a post-transcriptional trophic regulation of its phenotype.

Animals↗
PubMed2000

Fluorinated methyl cation (CF(3)(+), CFH(2)(+))-alkyl nitrile cluster ions.

Ion-molecule reactions of CF(3)(+) or CFH(2)(+) with an acetonitrile-butyronitrile mixture yield product cluster ions in which the two neutral molecules are associated with the cation. The structures of the ion-molecule product ions were investigated by collision-induced dissociation in a multi-quadrupole mass spectrometer. The cluster ions fragment by loss of one neutral alkyl nitrile. The abundance of the fragment ions shows an unexpected inverse correlation with the proton affinity of the alkyl nitrile. This result is inconsistent with the formation of a simple cation-bound dimeric cluster containing two alkyl nitrile molecules and a fluorinated methyl cation; instead, a pair of non-symmetrical dimeric complexes, separated by a large internal barrier, is indicated. This result is analogous to that observed for the putative methyl cation-bound heterodimer of acetonitrile and butyronitrile. Collision energy dependence studies and ab initio calculations suggest that the dimeric complexes are formed in potential energy wells located in an approximately symmetrical potential energy surface. Quasi-equilibrium theory calculations were used in order to obtain additional insights into the experimental data.

Journal Article↗
PubMed2000

Resistance to growth hormone and insulin-like growth factor-I in acidotic rats.

Growth impairment induced by chronic metabolic acidosis is associated with an abnormal growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. To examine the potentially beneficial effects of IGF-I on acidosis-induced growth impairment and the influence of GH and IGF-I treatment on the GH/IGF-I axis, three groups of acidotic young rats (untreated, AC, n=12; treated with recombinant human GH, GH, n=8; treated with recombinant human IGF-I, IGF-I, n=8) were studied, and compared with nonacidotic rats fed ad libitum (C, n=9)) or pair-fed with the AC group (PF, n=12). After 14 days of acidosis and 7 days of treatment, growth rate, hepatic abundance of 4.7-kilobase (kb) and 1.2-kb GH receptor transcripts and 7.5-kb and 1.8- to 0.8-kb IGF-I transcripts, serum GH-binding protein (GHBP), and IGF-I concentrations (mean+/-SEM) were analyzed. Significant decreases of 4.7-kb GH receptor [26+/-2 vs. 49+/-6 arbitrary densitometry units (ADU)] and 7.5 kb IGF-I (41+/-3 vs. 104+/-10 ADU) transcripts and low serum GHBP (25+/-1 vs. 32+/-1 ng/ml) and IGF-I (279+/-50 vs. 366+/-6 nmol/l) levels were found in the AC compared with the C rats. The majority of these alterations were also observed in PF rats. Compared with acidotic untreated rats, GH and IGF-I therapy produced no improvement in growth rate. GH treatment normalized the levels of IGF-I mRNA, aggravated the acidosis-related inhibition of the GH receptor gene, and did not modify the serum levels of GHBP and IGF-I. In contrast, IGF-I administration depressed the hepatic expression of all GH and IGF-I transcripts and normalized serum IGF-I concentrations. Our results confirm that sustained metabolic acidosis alters the GH/IGF-I axis, in part because of associated malnutrition, and induced growth retardation that is resistant to GH therapy. Our study also shows that administration of IGF-I does not accelerate the growth of acidotic rats, suggesting a peripheral mechanism, at the level of target tissues, is responsible for the resistance to the growth-promoting actions of GH and IGF-I.

Acid-Base Equilibrium↗