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L S Dias

Publications and source records attributed to L S Dias.

At least 19 recordsLinked to original sources
PubMed2001

Describing phytotoxic effects on cumulative germination.

Phytotoxic studies strongly depend on evaluation of germination responses, which implies the need for adequate procedures to account for distinct aspects of the germinative process. For this, indices, comparisons among treatments at various times, and model fitting have been proposed. The objective of this work is to compare the three approaches and select the one providing the greatest insight and precision. Speed of germination, speed of accumulated germination, the coefficient of the rate of germination, comparisons at each determination time, including final germination, and the parameters of the Weibull function were examined. The Weibull function proved the best approach to describe the germination process, providing not only the same type of information about the speed of germination, with greater precision, but also additional information about the initiation and shape of the germination response curve.

Biological Assay↗
PubMed2000

Strategies for studies of neurotoxic mechanisms involving deficient transport of L-glutamate: antisense knockout in rat brain in vivo and changes in the neurotransmitter metabolism following inhibition of glutamate transport in guinea pig brain slices.

This communication briefly reviews characteristics of glutamate transport in the central nervous system and is involved in the aetiology of slow neurodegenerative diseases. Data in the literature suggest that antisense oligonucleotides targeted against glutamate transporters and administered in vivo over a period of days could be used to test the hypothesis. Data from our laboratory have indicated that single intraventricular doses of antisense oligonucleotides can also results in significant reductions in the numbers of substrate binding sites associated with glutamate transporters and may even cause subtle changes in their characteristics. In order to study metabolism in brain tissue, we have used 13C-nuclear magnetic resonance spectroscopy to analyse extracts of slices of guinea pig cerebral cortex exposed to glutamate transport inhibitor L-anti,endo-methanopyrrolidine dicarboxylate (L-a,e-MPDC). The results have shown-for the first time in an experimental model that preserves the relationship between glia and neurones within the context of brain tissue-that inhibition of L-glutamate transport can exert a significant influence on neurotransmitter-related metabolism. These findings suggest that metabolic disturbances caused by deficient glutamate transport could play a significant role in the death of neurones under pathological conditions in vivo.

ATP-Binding Cassette Transporters↗
PubMed2000

Binding characteristics of endothelin ET(A) receptors in normal and post-mortem rat lung.

In control lung homogenates, optimal specific binding of [(125)I]endothelin-1 and minimal filter binding was achieved using 50 microg/ml bacitracin, 30 microM phenylmethylsulphonyl fluoride (PMSF) and 10 mM EDTA. In post-mortem tissue (8, 16, and 32 h), no significant changes were seen in ET(A) receptor affinity (K(d)) or number (B(max)): control and 32 h K(d) = 309 +/- 75, 225 +/- 32 pM and B(max) = 173 +/- 42, 185 +/- 17 fmol/mg protein, respectively. Autoradiographic binding sites for [(125)I]endothelin-1 were densely expressed on bronchiolar smooth muscle and parenchyma with moderate binding on epithelium and blood vessels. Histologic sections of post-mortem lung showed minimal deterioration of structures expressing ET(A) binding sites. Hence the ET(A) receptor is stable in the rat lung for up to 32 h post-mortem.

Animals↗
PubMed2000

Quantitative autoradiography of Na+-dependent [3H]L-aspartate binding to L-glutamate transporters in rat brain: structure-activity studies using L-trans-pyrrolidine-2,4-dicarboxylate (L-t-PDC) and 2-(carboxycyclopropyl)-glycine (CCG).

Sodium-dependent binding of [3H]L-aspartate was studied in thaw-mounted horizontal sections of fresh-frozen (i.e. not fixed) rat brain. After the incubation with [3H]L-aspartate, the sections were exposed against a 3H-sensitive film and the resulting autoradiograms were evaluated by quantitative densitometry. Effects of several inhibitors were examined and their potency expressed as IC50 and nH. Together with previously published data, the present study supports the view that [3H]L-aspartate binding to fresh-frozen sections of rat brain represents interaction of the radioligand with the substrate-binding sites on glutamate transporters. The most potent inhibitors were (2S,3S,4R)-2-(carboxycyclopropyl)-glycine (L-CCG III) and (2S,4R)-4-methylglutamate. In contrast, L-anti,endo-3,4-methanopyrrolidine dicarboxylate (L-a,e-MPDC) was about an order of magnitude less potent. Only subtle regional variations in the characteristics of inhibitors of [3H]L-aspartate binding were detected. It is not certain whether these differences reflect regional variations in the distribution of individual glutamate transporters or regional peculiarities in their pharmacological characteristics. In particular, (2S,4R)-4-methylglutamate, shown previously to differentiate between GLT-1 (principal glutamate transporter in the forebrain) and GLAST (expressed mainly in the cerebellum), did not strongly differentiate between the binding of [3H]L-aspartate in forebrain and cerebellum. Computer-assisted molecular modelling using selected glutamate analogues with restricted conformation (L-trans-pyrrolidine-2,4-dicarboxylate and four isomers of 2-(carboxycyclopropyl)-glycine: L- and D-CCG I, L-CCG III and L-CCG IV) identified at least one area of unfavourable steric interaction. We conclude that the quantitative autoradiographic studies using [3H]L-aspartate or other transporter-specific ligands, will be a useful tool to study the pharmacology of substrate binding sites on glutamate transporters in the mammalian brain in situ.

ATP-Binding Cassette Transporters↗
PubMed2000

Angiotensin II in child urinary bladder: functional and autoradiographic studies.

OBJECTIVES: To investigate the receptors for angiotensin II (AII, reported to be a potent contractile agent in human urinary bladder), using functional and autoradiographic techniques in child and adult bladder specimens. Materials and methods Bladder specimens were obtained from 61 children (aged 4 months to 12 years) undergoing ureteric reimplantation for vesico-ureteric reflux, and from 10 adults undergoing cystectomy. After overnight storage, the mucosa was removed and isometric contractions obtained from detrusor muscle strips in the presence of phosphoramidon (10 micromol/L). Only one concentration of AII was added to each preparation because of tachyphylaxis. The response to KCl (124 mmol/L) was 43% of that to carbachol (100 micromol/L). Sections of child bladder were radio-labelled with the ligand [125I]Sar1,Ile8-AII and binding sites visualized using emulsion autoradio- graphy. RESULTS: The potency of AII was similar in child and adult detrusor strips, with mean (SEM) pD2 values of 6.9 (1.0) (n = 25) and 6.7 (0.2) (n = 9) respectively, and the maximum responses (to 10 micromol/L AII) rather low (39% and 49%, respectively, P > 0.05), compared with carbachol (100 micromol/L). There were no age- or gender-related differences. Responses to AII in strips from children under 3 years old were antagonized by the AT1 receptor antagonist losartan (1 micromol/L) but not by the AT2 receptor antagonist PD 123319 (1 micromol/L), indicating interaction with the AT1 receptor. Sections of child bladder radiolabelled with [125I]Sar1,Ile8-AII showed moderate specific binding over detrusor muscle and arterioles, with denser specific binding over subepithelial blood vessels. Specific binding was inhibited by co-incubation with losartan (10 micromol/L) but not with PD 123319 (10 micromol/L). CONCLUSION: AII was a weak contractile agent of detrusor strips, with no significant differences in potency between child and adult bladder samples. These data show the presence of functional AT1 but not AT2 receptors in child detrusor smooth muscle.

Adult↗
PubMed1998

Effect of post-mortem delay on density of tachykinin receptors in rat peripheral tissues.

The effect of post-mortem delay on the affinity and density of tachykinin NK1 and NK2 receptors was examined in the rat submandibular gland and gastric fundus, respectively, using saturation binding studies with the radioligands [125I]Bolton-Hunter [Sar9, Met(O2)11]SP and [125I][Lys5, Tyr(I2)7, MeLeu9, Nle10]NKA(4-10). For NK1 receptors, no significant changes were seen in either Kd (control 375 +/- 35 pM, n = 5; 32 h post-mortem 390 +/- 59 pM, n = 5) or Bmax (control 96 +/- 16 fmol/mg protein, n = 5; 32 h post-mortem 62 +/- 10 fmol/mg protein, n = 5). For NK2 receptors, no alterations were seen up to 16 h post-mortem. However, significant (p < 0.001) changes were seen at 32 h post-mortem (n = 4), where values for Kd were increased (3.0 +/- 0.2 nM) and those for Bmax were reduced (42 +/- 5.9 fmol/mg protein), relative to control (Kd = 1.3 +/- 0.2 nM; Bmax = 208 +/- 30 fmol/mg protein, n = 5). These changes are probably related to observed histological deterioration. This study demonstrates the stability of tachykinin receptors in these peripheral tissues and indicates the suitability of post-mortem tissue as a valid control in future tachykinin receptor studies.

Animals↗
PubMed1997

P2 purinoceptor blocker suramin antagonises NMDA receptors and protects against excitatory behaviour caused by NMDA receptor agonist (RS)-(tetrazol-5-yl)-glycine in rats.

It has been reported that suramin, an anthelminthic, trypanocidal agent and an inhibitor of P2 receptors, may antagonise N-methyl-D-aspartate (NMDA) subtype of the excitatory amino acid receptors. Both NMDA receptors and P2X subclass of P2 receptors are ligand-gated Ca2+-selective channels and, since the increased influx of Ca2+ into neurons has been linked to neurotoxicity, simultaneous inhibition of P2X and NMDA receptors in vivo by suramin could represent an effective neuroprotective treatment. We have found that suramin inhibited the binding of [3H]CGP 39653 to NMDA receptor binding sites in vitro and reduced the frequency of NMDA channel openings in patch-clamp studies. Suramin (1 mM) had no effect on [3H]kainate binding in vitro. In vivo, intracerebroventricular (I.C.V.) injections of suramin (70 nmol/brain) antagonised convulsive effects of the NMDA agonist (RS)-(tetrazol-5-yl)-glycine (TZG, LY 285265). Suramin, however, did not prevent neurotoxic lesions in the hippocampus caused by I.C.V. administration of TZG. Increasing the dose of suramin resulted in death from severe respiratory depression.

Animals↗
PubMed1997

Gait electromyography in children with myelomeningocele at the sacral level.

OBJECTIVE: Patients with sacral level myelomeningocele can be expected to maintain a high level of ambulatory status long into adulthood. Gait deterioration and knee pain reported in this population may be attributed to compensatory movements and increased recruitment of less affected muscle groups to achieve this desired level of ambulation. The objective of this study was to analyze the effect of the solid ankle-foot-orthoses (AFOs) on the muscular activity of selected muscles during walking. DESIGN: Cohort/outcome. SETTING: Laboratory. PATIENTS: Twenty four patients with sacral level myelomeningocele between 4 to 17 years of age. INTERVENTION: Electromyographic activity of selected muscle groups were studied during barefoot walking and walking with solid AFOs at a self-selected walking velocity. MAIN OUTCOME MEASURES: Timing of electromyographic activity and sagittal plane knee kinematics. Comparison to normal electromyographic patterns and changes between barefoot and AFO walking conditions. RESULTS: With the AFOs there was significantly less prolonged stance phase quadriceps activity compared with barefoot walking, although greater than normal activity persisted. There was no change between conditions for the other monitored muscle groups. All muscles elicited greater duration of activity over the course of the gait cycle. CONCLUSIONS: Our results show that solid AFOs improve the prolonged knee extensor activity evident for barefoot walking. This is clinically relevant to the gait deterioration and knee pain sometimes seen in this patient population. We espouse early and persistent orthotic intervention to reduce compensatory muscular overactivity and maintain gait quality.

Adolescent↗
PubMed1996

Autoradiographic studies indicate regional variations in the characteristics of L-glutamate transporters in the rat brain.

Quantitative autoradiography of [3H]L-aspartate binding in thaw-mounted sections of rat brain has shown that L-trans-pyrrolidine-2,4-dicarboxylate and D-threo-3-hydroxyaspartate but not DL-2 aminoadipate strongly interacted with the binding sites while dihydrokainate, kainate and beta-aminoadipate produced only weak effects. The potency of inhibitors did not vary from one region to another in the telencephalon (neocortex, hippocampus and neostriatum) but, D-threo-3-hydroxyaspartate, L-trans-pyrrolidine-2,4-dicarboxylate, kainate and dihydrokainate inhibited [3H]L-aspartate binding in the cerebellar cortex less potently than that in the forebrain. Characteristics of the known excitatory amino acid transporters can, in part, explain the present results but contributions from additional transporter molecules to the heterogeneity of [3H]L-aspartate binding sites cannot be ruled out.

ATP-Binding Cassette Transporters↗
PubMed1995

Inhibition of [3H]CGP 39653 binding to NMDA receptors by a P2 antagonist, suramin.

Suramin, which has been used for more than 50 years as an anthelmintic in humans, has recently been shown to inhibit P2 purinoceptors in the CNS and to block glutamate-evoked excitatory potentials in hippocampus. We now report that suramin inhibits (IC50 approximately 100 microM) the binding of [3H]CGP 39653, a ligand specific for NMDA-type glutamate receptors in brain. Consequently, suramin at concentrations used sometimes in physiological experiments may act as both P2x and NMDA antagonist. Since both NMDA receptors and P2x-subtype of purinoceptors form Ca(2+)-selective channels, suramin may block Ca2+ entry into neurones depolarized by either ATP, L-glutamate or any other neurotransmitter or drug acting via P2x or NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1995

Selective posterior rhizotomy and soft-tissue procedures for the treatment of cerebral diplegia.

The results of selective posterior rhizotomy in fifty patients (group I) and of soft-tissue procedures in fifty patients (group II), all 100 of whom had cerebral diplegia and were seen in a private office, were reviewed retrospectively. No effort was made to randomize the treatment, as the selection criteria for the two procedures are different. We evaluated the range of motion and the ability and quality of walking preoperatively and postoperatively as well as the need for additional operative intervention in the two groups. The average age of the patients in both groups was five years (range, three to twelve years in group I and one to thirteen years in group II). The average duration of follow-up in both groups was four years (range, one to six years in group I and one to seven years in group II). Thirty-two patients (64 percent) in group I and forty-one patients (82 percent) in group II were able to walk independently at the latest follow-up examination. Both groups had an over-all improvement in the ranges of abduction of the hips and dorsiflexion of the ankles, a decrease in the flexion contractures of the hips, and more normal popliteal angles; however, with the numbers available, there were no significant differences in these measurements between the two groups at the 0.05 percent confidence level. Despite the overall improvement in range of motion, thirty-one patients in the rhizotomy group subsequently had soft-tissue releases, and twenty-two patients in the soft-tissue-release group had additional operative intervention.

Adolescent↗
PubMed1994

Arterial and venous compromise by an osteochondroma.

A 9.5-year-old girl had popliteal arterial and venous compression by a distal femoral osteochondroma. Magnetic resonance imaging demonstrated the relation of the vessels to the osteochondroma and a three-phase bone scintigram showed asymmetry of arterial perfusion and evidence of venous stasis.

Arterial Occlusive Diseases↗
PubMed1994

A convective-diffusion model for dissolution of two non-interacting drug mixtures from co-compressed slabs under laminar hydrodynamic conditions.

A numerical convective-diffusion dissolution model has been extended to describe dissolution of two neutral non-interacting drugs co-compressed in a slab geometry. The model predicted the experimental dissolution rates of naproxen/phenytoin mixtures and hydrocortisone/nitrofurantoin mixtures quite accurately, except for phenytoin in the naproxen/phenytoin mixture at low weight proportions. A non-linear dependence of dissolution rate on weight proportion with a positive deviation from linearity was observed. An increase in flow rate increased the dissolution rate and the cube-root dependency of dissolution rate on the flow rate for a given weight proportion of the component in the slab, as proposed earlier by Shah and Nelson for pure compounds, was also observed here, suggesting that the changes in dissolution profile were caused by changes in surface area only. As expected from the model an increase in particle size of the powders used to make the slab decreased the dissolution rate. This was explained by an increase in the average length of the component resulting in a bigger 'carryover' of material from one section of the component in the slab to the next section of the same component, due to convection, and hence lower flux.

Diffusion↗
PubMed1992

Congenital and acquired orthopedic abnormalities in patients with myelomeningocele.

This article presents a radiologic review of the spectrum of acquired and congenital orthopedic abnormalities found in patients with myelomeningocele. These abnormalities are caused predominantly by muscle imbalance, paralysis, and decreased sensation in the lower extremity. Iatrogenic injury, such as a postoperative tethered cord, may also cause bone abnormalities. Selected images were obtained from more than 800 children. Important entities presented include spinal curvatures such as kyphosis, scoliosis, and lordosis; subluxation and dislocation of the hip, coxa valga, contractures of the hip, and femoral torsion; knee deformities; rotational abnormalities of the lower extremity and external and internal torsion; ankle and foot abnormalities such as ankle valgus, calcaneus foot, congenital vertical talus (rocker-bottom deformity), and talipes equinovarus; and metaphyseal, diaphyseal, and physeal fractures. Familiarity with congenital abnormalities and an understanding of the pathogenesis of acquired disorders in patients with myelomeningocele are essential for proper radiologic interpretation and timely therapy.

Child↗
PubMed1991

The natural history of congenital kyphosis in myelomeningocele. A review of 51 children.

The progression of congenital lumbar kyphosis in myelomeningocele is a well-known problem, but rates of progression are not well documented in the literature. Fifty-one children with congenital kyphosis and myelomeningocele were followed for an average of 4.8 years. Minimum follow-up was 1 year. Group I (35 patients) had initial radiographs at 1 year of age or less. Group II (16 patients) had radiographs taken after the age of 1 year. Curves less than or equal to 90 degrees in Group I progressed 7.7 degrees/yr; those greater than 90 degrees progressed 12.1 degrees/yr. Curves less than or equal to 90 degrees and greater than 90 degrees progressed at similar rates, regardless of initial curve magnitude: 6.4 degrees/yr and 6.7 degrees/yr, respectively. No correlation existed among the rate of curve progression, the frequency of shunt revisions, or the presence of vertebral anomalies, aside from the dysraphism.

Child↗
PubMed1991

Musculoskeletal problems in association with cloacal exstrophy.

The records of all thirteen patients for whom a diagnosis of cloacal exstrophy had been recorded in our hospitals were analyzed for evidence of musculoskeletal problems. All thirteen patients had spina bifida, four had congenital scoliosis, two had congenital kyphosis, and three had non-congenital scoliosis. All had a lipomeningocele, and eleven had paralysis of the lower extremities. Hydrocephalus and its associated problems were not found, but tethered-cord syndrome was diagnosed in eleven patients. Persistent diastasis of the symphysis pubis was found in all patients. Abduction and external rotation of the hips were more than normal. Mild dysplasia was seen in six of the twenty-six hips. Deformities of the foot were common, and twelve feet had been operated on for correction. Recurrent equinovarus deformity of the foot was associated with tethered-cord syndrome in two patients.

Abnormalities, Multiple↗
PubMed1991

Myelomeningocele.

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Foot Deformities↗