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L C Silva

Publications and source records attributed to L C Silva.

At least 37 records · Page 2Linked to original sources

Highly sulfated dermatan sulfates from Ascidians. Structure versus anticoagulant activity of these glycosaminoglycans.

Dermatan sulfates with the same backbone structure [4-alpha-L-IdceA-1-->3-beta-D-GalNAc-1]n but with different patterns of sulfation substitutions have been isolated from the ascidian body. All the ascidian dermatan sulfates have a high content of 2-O-sulfated alpha-L-iduronic acid residues but differ in the pattern of sulfation of the N-acetyl-beta-D-galactosamine units. Styela plicata and Halocynthia pyriformis have 4-O-sulfated units, but in Ascidian nigra they are 6-O-sulfated. This collection of ascidian dermatan sulfates (together with native and oversulfated mammalian dermatan sulfate), where the extent and position of sulfate substitution have been fully characterized, were tested in anticoagulant assays. Dermatan sulfate from A. nigra has no discernible anticoagulant activity, which indicates that 4-O-sulfation of the N-acetyl-beta-D-galactosamine is essential for the anticoagulant activity of this glycosaminoglycan. In contrast dermatan sulfates from S. plicata and H. pyriformis are potent anticoagulants due to potentiation of thrombin inhibition by heparin cofactor II. These ascidian dermatan sulfates have approximately 10-fold and approximately 6-fold higher activity with heparin cofactor II than native and an oversulfated mammalian dermatan sulfate, respectively. They have no effect on thrombin or factor Xa inhibition by antithrombin. These naturally oversulfated ascidian dermatan sulfates are sulfated at selected sites required for interaction with heparin cofactor II and thus have specific and potent anticoagulant activity.

Acetylgalactosamine↗

Evaluation of an aspartame loading test for the detection of heterozygotes for classical phenylketonuria.

Classical phenylketonuria (PKU) is an inborn error of metabolism of autosomal recessive inheritance characterized by the accumulation of phenylalanine (Phe) in tissues due to Phe-4-hydroxylase deficiency. Several methods have been developed for the detection of PKU heterozygotes based on the determination of plasma Phe and tyrosine (Tyr) levels, on the analysis of the Phe/Tyr and Phe2/Tyr ratios and on the use of discriminant functions. The objective of the present study was to test the value of loading with aspartame (a sweetener consisting of Phe, aspartate and methanol) for the identification of PKU carriers. The study was conducted on 22 obligate heterozygotes and 27 controls. Two blood samples were collected (under fasting conditions and 30 min after the loading) for fluorometric determination of Phe and Tyr. Phe, Phe/Tyr and Phe2/Tyr values were higher in heterozygotes, whereas Tyr was higher in controls in both situations investigated. Linear discriminant function was considered to be the best parameter for differentiation of the individuals in the two groups. Under the conditions employed in the present study, aspartame loading did not show any advantages in discriminating between PKU carriers and normal individuals when compared to the same analysis performed under fasting conditions.

Aspartame↗

Compartmental distribution of sulfated glycosaminoglycans in lateral and medial midbrain astroglial cultures.

Sulfated glycosaminoglycans (S-GAGs) were isolated from the pericellular (P), intracellular (I), and extracellular (E) compartments of astrocytes cultures from lateral (L) and medial (M) sectors of embryonic mouse midbrain; these sectors differ in their ability to support neurite growth (L, permissive, M, non-permissive for growth) and laminin deposition patterns (L, fibrillar; M, punctate pattern). The total amount of S-GAGs in M cultures was twice that in L cultures and was particularly high in the P compartment of M glia. Both glial cultures showed heparan sulfate (HS) in the three cellular compartments but chondroitin sulfate (CS) GAGs were vestigial in I and P compartments of L glia. Our results suggest that M and L astrocytes are heterogeneous concerning the ability to synthesize GAGs and distribute them among the different cellular compartments. Together with other data (Garcia-Abreu et al: J Neurosci Res 40:471, 1995; Garcia-Abreu et al: Neuroreport 6:761, 1995), the present results suggest that this heterogeneous features might be at least partially responsible for the differential effects of L and M glial cultures on the growth of midbrain neurons and may also be involved in complex ways in the guidance of axons at the brain midline.

Animals↗

Maternal hyperphenylalaninaemia as a cause of microcephaly and mental retardation.

We attempted to evaluate the role of maternal hyperphenylalaninaemia (HPA) as an isolated cause of mental retardation and microcephaly in children. This transversal study observed the plasma phenylalanine from mothers of 161 children with mental retardation and/or microcephaly of unknown origin. In this sample, we found two women with previously undiagnosed HPA, a frequency (2/161) higher than expected for our general population (1:12 500) (p < 0.001). We concluded that the plasma phenylalanine levels should be determined during preconceptional evaluation of every woman of reproductive age that already has had a child affected either by mental retardation or microcephaly of unknown cause. It is particularly significant where women currently having their pregnancies have not been screened for phenylketonuria as newborns, as happens in most developing countries.

Adult↗

Heterogeneity of median and lateral midbrain radial glia and astrocytes.

In the developing mammalian midbrain, radial glial cells are divided into median formations and lateral radial systems with differential properties including rate and timing of cell proliferation, expression of cytoskeletal and calcium-binding proteins, storage of glycogen and relations to afferent fiber systems. To test the hypothesis that radial glial cells of median and lateral midbrain sectors and/or their derivatives are heterogeneous in their relations with local neurons, an in vitro system has been developed and has also been characterized in terms of extracellular matrix (ECM) components. Confluent astrocyte cultures, derived from median (M) or lateral (L) embryonic mouse midbrain sectors, were used as substrates for culturing dissociated cells from median (m) or lateral (l) sectors of embryonic midbrains. In spite of the morphological invariance of glial substrates at confluency, cells that were plated onto these substrates and that were immunoreactive for neuronal markers (MAP2, polysialylated N-CAM or beta III tubulin) showed differences in the aggregation of somata and in the length, caliber and branching of neurites. These differences, which depend mostly on the sector of origin of astrocytes (L: permissive, M: non-permissive for neuronal growth), suggest that the substrates may differ in adhesiveness and/or their carrying of growth-promoting vs. growth-interfering molecules. Indeed, L and M cultures differ in laminin deposition patterns (L: fibrillar, M: punctate pattern). Furthermore, sulfated glycosaminoglycans (s-GAGs) isolated from the pericellular (P), intracellular (I) and extracellular (E) compartments of these sectoral cultures also showed correlations with the ability to support neurite growth. The total amount of s-GAGs in M cultures was twice that in L cultures and was particularly high in the P compartment, with about 3 times as much heparan sulfate (HS) and about 15 times as much chondroitin sulfate (CS) in this fraction of M than in the corresponding compartment of L glia. Our results indicate that cultured astrocytes have heterogeneous properties including different organization of their extracellular matrix that reflect the roles played by their parent radial glia in regions favorable to axonal growth or barrier regions of the developing brain.

Animals↗

Discontinuity indices: a tool for epidemiological studies on breastfeeding.

BACKGROUND: The Discontinuity Index (DI), which measures the percentage of infants who were exclusively breastfed (EBF) at the beginning of a given age interval and had abandoned this mode of feeding at its end, and the relative weight of this discontinuation, was introduced and employed in the National Survey on Breast Feeding and Infant Feeding Practices carried out in Cuba in 1990. The aim of this article is to illustrate, through a specific example, the quality of DI as a simple procedure for assessing breastfeeding trends. METHODS: The prevalence of EBF in the 14 provinces of Cuba at discharge from the maternity services and at 30, 60, 120, and 180 days of age, was obtained using data from a national sample of 6661 infants (4820 urban and 1791 rural) which were processed by means of a logistic regression model. Cumulative DI were calculated for the intervals 0-30, 0-60, 0-120 and 0-180 days, and partial DI for the terms 30-60, 60-120 and 120-180 days, for each province and for the whole country. RESULTS: Cumulative DI show the progress of cessation of breastfeeding and are strongly influenced by previous intervals. The Eastern provinces showed the lowest figures at most of the terms. Discontinuation during the first month of life was particularly high in two Western provinces. Partial DI are more specific and allow discrimination of the intervals at which EBF discontinuation is more frequent. The highest values were observed between 4 and 6 months. CONCLUSIONS: Discontinuity indices are useful complements to prevalence rates in epidemiological studies of breastfeeding. The separate analysis of discontinuation in different periods can be highly useful when comparing trends and in the study of the impact of breastfeeding promotion programmes focused on different age intervals.

Age Factors↗

Dietary factors in epidemic neuropathy on the Isle of Youth, Cuba.

An epidemic neuropathy that broke out in Cuba in late 1991 has exhibited clinical manifestations similar to those of other polyneuropathies of nutritional origin. To investigate its possible association with diet, a study was conducted on the Isle of Youth in 1993, at the start of an outbreak there. Thirty-four subjects with cases and 65 controls were interviewed regarding their diets, measured anthropometrically, and evaluated. As a whole, the subjects with cases demonstrated greater weight loss before the onset of disease, lower body mass indexes (BMI), lower percentages of body fat, and more deficient diets than the control subjects. Analysis of individual variables found associations between occurrence of the disease and the following: weight loss, low BMI, a broad range of specific dietary deficiencies, a sugar intake exceeding 15% of total caloric intake, alcohol consumption, and smoking. Also, protective associations were found between absence of the disease and regular consumption of certain foods at or above specified levels. Multivariate analysis indicated that while smoking and alcohol consumption reinforced the effects of the dietary deficiencies, they did not account for occurrence of the disease by themselves. Overall, the results indicate that diets which are deficient in caloric energy, protein, fat, and the micronutrients included in the study, and which reflect an imbalance resulting from a relative excess of sugar, with consequent effects on body weight, are strongly associated with, and causally related to, the occurrence of epidemic neuropathy in Cuba.

Adult↗

Evidence that angiotensin-(1-7) plays a role in the central control of blood pressure at the ventro-lateral medulla acting through specific receptors.

In this study we determined which angiotensin receptors may mediate the cardiovascular effects elicited by angiotensin-(1-7) [Ang-(1-7)] in the rostral ventrolateral medulla (RVLM) and caudal pressor area (CPA) of the ventrolateral medulla (VLM) of anesthetized rats. Furthermore the role of endogenous angiotensins in these areas was also investigated. The pressor effect produced by unilateral microinjection of Ang-(1-7) into the RVLM or CPA was not modified by either the AT1 receptor antagonist, DuP 753 or by the AT2 receptor antagonist, CGP 42112A, but was completely blocked by the Ang-(1-7) selective antagonist, A-779. In contrast, the pressor effect produced by microinjection of angiotensin II (Ang II) was completely blocked by DuP 753 but was not changed by CGP 42112A or A-779. Bilateral microinjection of A-779 into the RVLM or CPA produced a significant fall in mean arterial pressure and heart rate. Microinjection of DuP 753 produced a pressor effect comparable to bilateral injection of vehicle. These results indicate that, although Ang II acts in the VLM through an AT1 receptor subtype, the cardiovascular effects produced by microinjection of Ang-(1-7) into the RVLM and CPA are mediated by a specific angiotensin receptor (AT5?). Furthermore, our data provide evidence that endogenous Ang-(1-7) participates at the VLM in the neural control of arterial blood pressure.

Analysis of Variance↗

Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors.

In this study we describe a new angiotensin antagonist [Asp1-Arg2-Val3-Tyr4-Ile5-His6-D-Ala7, (A-779)] selective for the heptapeptide angiotensin-(1-7) [Ang-(1-7)]. A-779 blocked the antidiuretic effect of Ang-(1-7) in water-loaded rats and the changes in blood pressure produced by Ang-(1-7) microinjection into the dorsal-medial and ventrolateral medulla. In contrast, A-779 did not change the dipsogenic, pressor, or myotropic effects of angiotensin II (Ang II). Also, A-779 did not affect the antidiuretic effect of vasopressin or the contractile effects of angiotensin III, bradykinin, or substance P on the rat ileum. In the rostral ventrolateral medulla, the pressor effect produced by Ang-(1-7) microinjection was completely blocked by A-779 but not by AT1 or AT2 receptor antagonists (DUP 753 and CGP 42112A, respectively). Conversely, the pressor effect produced by Ang II was not changed by A-779 but was completely blocked by DUP 753. Binding studies substantiated these observations: A-779 did not compete significantly for 125I-Ang II binding to adrenocortical membranes at up to a 1 microM concentration. Low affinity binding was also observed in adrenomedullary membranes with an IC50 greater than 10 microM. Our results show that A-779 is a potent and selective antagonist for Ang-(1-7). More importantly, our data indicate that specific angiotensin receptors mediate the central and peripheral actions of Ang-(1-7).

Adrenal Glands↗

Proteoglycans and glycosaminoglycans synthesized by the hepatic granulomas isolated from schistosome-infected mice and by a granuloma-derived connective tissue cell line.

1. This paper summarizes our studies on proteoglycans and glycosaminoglycans in the hepatic fibrosis occurring in schistosomiasis. 2. We have compared proteoglycans and glycosaminoglycans isolated from schistosomal fibrotic granulomas with those obtained from the cellular and extracellular compartments of a murine cell line derived from schistosome-induced granulomas, the primary cell line "GR". 3. Our results have shown some biochemical and structural similarities between proteoglycans and glycosaminoglycans extracted from granulomas and those synthesized and secreted by GR cells, suggesting that these cells may be the major cell population involved in synthesis and accumulation of these molecules in the schistosomal periovular granulomas in liver. Furthermore, we have shown that GR cells can function as an extramedullary myelopoietic stroma that mediates a long-term myeloid proliferation through an autocrine mechanism where the interaction between myelopoietic growth factors and cell-surface heparan sulfate proteoglycans was characterized.

Animals↗

[Dietetic factors in epidemic neuropathy on Isla de la Juventud, Cuba].

The epidemic of neuropathy that arose in Cuba in late 1991 has clinical manifestations similar to those of other neuropathies that are nutritional in origin. In an effort to identify its possible association with the diet, a case-control study was conducted at the beginning of the epidemic in Isla de la Juventud. Dietary intake was assessed through a semi-quantitative survey of consumption frequency obtained by direct personal interviews, and measurements were taken of the weight, height and skin fold thickness of 34 cases and 65 controls. As compared to controls, cases showed more pronounced weight loss prior to becoming ill, a lower body mass index (BMI), a lower percentage of body fat, and a poorer diet. According to odds ratios (OR) resulting from the separate analysis of each variable, factors associated with illness were weight loss, low BMI, low weight for height, a lower consumption of bread and rice, a less balanced diet, lack of milk intake, an intake of sugar greater than 15% of total energy consumed, consumption of alcohol, and smoking. The association was protective in the case of beans, tubercles, starchy roots, oil, and meat substitutes made from soy. Multifactorial analysis revealed higher OR values, adjusted for smoking and alcohol consumption, for intakes of less than 50% of the recommended daily allowance of protein, pyridoxine, thiamine, energy, vitamin E, niacin, folic acid, fat, riboflavin, and vitamin A. The results of this analysis show that tobacco and alcohol promote the effects of a deficient diet, but do not in and of themselves explain the association. A global analysis of these results leads to the conclusion that a diet poor in energy, calories, fats, and those micronutrients that have come under study, and that is unbalanced because of a relative excess of sugars, with its resulting effect on body weight, is strongly associated with and causally related to epidemic neuropathy.

Adult↗

Breast-feeding trends in Cuba and the Americas.

In order to analyze breast-feeding trends in the Region of the Americas vis-à-vis trends observed in Cuba, information was culled from a selection of national surveys on the prevalence and duration of breast-feeding conducted in the 1970s and compared with the results of a national survey carried out in Cuba in 1973. Similarly, information from PAHO Document HPN/92.7, which contains reports from countries of the Americas for the period 1986-1991, was compared with the results of the National Survey carried out in Cuba in 1990. A cessation index (CI) was calculated with a view to comparing the relative extent to which the cessation of breast-feeding occurred at different ages in the two time periods. The study revealed a consistent pattern: typically, a relatively high percentage of newborns were initially breast-fed, but the prevalence of exclusive breast-feeding was low and the percentage of breast-fed infants declined quickly. However, the more recent data showed improvements in most of the countries involved with respect to both the prevalence and duration of breast-feeding. Cuba was found to have intermediate values relative to the other countries. Although a slight decline in the initial prevalence of breast-feeding was observed in 1990 (as compared to 1973), notably higher percentages of infants were being breast-fed at 30, 60, 90, and 120 days, and the CI values for the corresponding intervals up to 90 days were lower. These results suggest that positive changes have taken place in factors promoting a longer duration of breast-feeding.

Adult↗

[Breast-feeding trends in Cuba and the Americas].

To determine breast-feeding trends in the Region of the Americas and compare them with those observed in Cuba in the last decade, information was complied from a select group of national surveys conducted in the 1970s on the prevalence and duration of breast-feeding and then compared with information from a survey carried out in Cuba in 1973. In addition, data were taken from document HPN/92.7 of the Pan American Health Organization, which contains reports corresponding to the period 1986-1991, and these were compared to the results of the national study carried out in Cuba in 1990. The discontinuation rate (DR) was also calculated. The study found a sustained pattern of initial breast-feeding of a relatively high proportion of babies, with rapid declines in subsequent days and low prevalence of exclusive breast-feeding. In most countries, prevalence and duration showed a tendency to increase. In Cuba intermediate values were observed with a discrete decline in initial prevalence, increases up to 180 days, and lower DR values up to 90 days in 1990 as compared to 1973. This suggests that there have been favorable changes in the factors that help to prolong the duration of breast-feeding. Calculation and analysis of the DR at various intervals proved useful for comparing the trends observed in the different countries.

Adult↗

Cardiovascular effects produced by micro-injection of angiotensin-(1-7) on vasopressor and vasodepressor sites of the ventrolateral medulla.

In this study, we determined the cardiovascular effects produced by micro-injection of the heptapeptide Angiotensin-(1-7) [Ang-(1-7)] into the rat ventrolateral medulla (VLM). Micro-injection of Ang-(1-7) into the rostral VLM and the caudal pressor area of the VLM produced significant increases in arterial pressure, comparable to that observed with micro-injection of Ang II. The changes in arterial pressure were associated with more variable changes in heart rate (HR) (usually tachycardia). On the other hand, micro-injection of Ang-(1-7) into the caudal depressor area induced decreases in arterial pressure and HR. The results suggest that, besides Ang II, Ang-(1-7) is involved in the mediation of the cardiovascular actions of the renin-angiotensin system in the VLM.

Angiotensin I↗

[Hemodynamic study with Swan-Ganz catheterization, concomitant to endomyocardial biopsy in heart transplantation patients. Importance in the early diagnosis of rejection].

PURPOSE: To evaluate the role of hemodynamic parameters in the diagnosis of acute rejection who underwent orthotopic cardiac transplantation. METHODS: A protocol was carried out in 19 patients who underwent heart transplantation and in whom Swan-Ganz hemodynamics was performed immediately prior to routine endomyocardial biopsy in the first few months postoperatively. The results of 28 biopsies were divided in group I--severe rejection who needed pulse-therapy (n = 10) and group II--No or mild/moderate rejection who did not need any pulse (n = 18). Hemodynamic parameters were compared between both groups. RESULTS: There were significant differences among hemodynamic parameters in groups I and II. Group I had higher mean right atrial pressures (13.0 x 7.3 mmHg), mean pulmonary pressure (26.3 x 20.4 mmHg), mean wedge pressure (14.4 x 10.9 mmHg) and lower cardiac index (2.57 x 3.10 l/min/m2). CONCLUSION: In a routine situation, hemodynamic measurements, as obtained with Swan-Ganz catheter, simultaneously with endomyocardial biopsies, show significant alterations in transplanted patients who develop acute rejection. This information, obtained earlier than the biopsy results, could shorten the time to initiate pulse-therapy in patients with severe rejection.

Adult↗