Biomedical subjects
Publications and source records attributed to A M Soares.
The authors present a case of a two-year-old boy with stridor since birth, and also recurrent episodes of pulmonary infections, due to mechanical compression of distal trachea by a left pulmonary artery sling. They discussed diagnostic approach, surgical management and review of the literature. To our knowledge, it is the first case of sling of the pulmonary artery reported in Brazil and the fifth in a latin language country.
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In this work we investigated the possibility of using the enzyme acetylcholinesterase (AChE) activity in Daphnia magna homogenates, both in vivo and in vitro conditions, as a specific method for rapid toxicity evaluations. The results from in vivo and in vitro AChE inhibition tests were compared with 48 hours EC50 values obtained in conventional acute bioassays. EC50 values from in vivo AChE inhibition tests were: 2.4 micrograms/l for parathion, 0.2 microgram/l for paraoxon; DCA and cadmium at the concentrations tested had no effects on enzyme activity. I50 values were 764 micrograms/l for parathion, 0.08 micrograms/l for paraoxon and 3367 micrograms/l for cadmium; DCA did not affect AChE activity measured in in vitro conditions. EC50 values from conventional acute tests were: 2.2 micrograms/l for parathion, 0.2 microgram/l for paraoxon, 163 micrograms/l for DCA and 9.5 micrograms/l for cadmium. Our results indicated that the in vivo AChE inhibition test is selective, being very sensitive to detect toxicity of the organophosphates tested. The in vitro AChE inhibition assay is less time consuming, requires less human effort and produces less toxic waste than conventional acute bioassays and the in vivo AChE inhibition test. However, it does not take into account the effect of the metabolization of the toxicants inside live organisms; since the organophosphate metabolism may be activative or degradative, the toxic potential of the parent compound may be under or over evaluated in in vitro conditions.
In this work we compared the effects of medium renewal and use of a carrier (ethanol) in the lethal toxicity of parathion to Daphnia magna Straus. Actual concentrations measured in test solutions with and without ethanol were not significantly different, indicating that there is no need for a carrier solution to assist dissolution of parathion, up to a concentration of 5 mg litre(-1). LC50 values at 48 h from bioassays with and without medium renewal were identical, indicating that in our experimental conditions, degradation of parathion was not a significant consideration. Similar 48-h LC50 values were obtained in all tests, with or without ethanol present. Thus, potential interactions between carrier and toxicant had no effect on the lethal toxicity of parathion to D. magna.
Guanylin is an endogenous peptide synthesized by several mammalian species that mimics the effects of a thermostable enterotoxin of Escherichia coli (STa: NTFYCCELCCNPACAGCY) in the gut. We have cloned a lysine-1 derivative of rat guanylin (Lys-1-NTCEICAYAACTGC) and tested its effects on ileal tissue membranes in Ussing chambers and in the isolated perfused rat kidney. Rabbit ileal mucosa membranes were mounted into a Ussing chamber and the effects of Lys-1 guanylin (Lys-1 G) and STa enterotoxin peptide on chloride secretion were determined by changes in short-circuit current (Isc). Lys-1 G (10 to 100 nM) showed a dose-dependent effect on chloride secretion with a maximal response estimated to be 52 microA/cm2. Lys-1 G mimics the effect of STa peptide, but the enterotoxin elicited a greater maximal effect of 120 microA/cm2 (P < 0.01). Lys-1 G (2.5 micrograms/ml) promoted an increase in both urine flow (from 0.13 +/- 0.07 to 0.40 +/- 0.01 ml g-1 min-1, N = 4; P < 0.05) and glomerular filtration rate (from 0.68 +/- 0.02 to 0.85 +/- 0.00 ml g-1 min-1, N = 4; P < 0.01) in the isolated perfused kidney and a reduction of the fractional reabsorption of sodium (from 76.0 +/- 0.03 to 59.5 +/- 0.85%, N = 4; P < 0.01). These maximal effects were accompanied by intense natriuretic effect observed 30 and 60 min after drug administration. The Lys-1 G analog similar to STa enterotoxin elicited intestinal chloride secretion and a natriuretic effect. These data demonstrate that the cloned peptide analog retains the biological activity of the native hormone and presents activity similar to STa. The properties of Lys-1 G resemble those of a factor formed during perfusion of the hypoxic rabbit kidney and named by us factor natriureticus similis (FNS).
Although intercellular junctions have been described between mature lamellar bone cells, little has been known about junctions between osteoblasts in early developing bone. We therefore conducted a freeze-fracture and ultrathin section study on developing calvaria of rat embryos aged 17-19 days to determine what types of intercellular junctions appear between osteoblasts in early osteogenesis. We observed that three main types of junctional structures, i.e., adherens of the macular type, gap, and focal tight junctions, coexist between osteoblasts in early developing bone. Their possible involvement in early morphogenetic events is discussed. Tight junctions are considered to be involved in compartmentalization of the early matrix and final polarization of osteoblasts.
The antibody response against the antigen sheep red blood cells (SRBC) was investigated in mice pre-treated with formalin-killed Paracoccidioides brasiliensis or with cell wall fractions of the fungus. Pre-treatment with P. brasiliensis, as well as with the Fl fraction and beta-glucan significantly increased the anti-SRBC antibody response in the experimental groups as compared to the control group that received only SRBC. This immunomodulatory effect varied with the different doses employed and with pre-treatment time. We conclude that the cell wall fractions of P. brasiliensis might play an important role in the hypergammaglobulinemia associated with Paracoccidioidomycosis.
In adult bone the calcified matrix and enclosed osteocytes are separated from the extracellular space by a continuous layer of bone lining cells. It thus appears that bone matrix is compartmentalised and, as such, may constitute a 'milieu intérieur' which is different from the general extracellular space. Since adult bone matrix is compartmentalised and matrix vesicles also form a microcompartment, it is conceivable that compartmentalisation, in early osteogenesis, may be a requirement for the initial events of the mineralisation process. We have therefore conducted an ultrastructural, tracer, and freeze-fracture study to determine the stage in which bone matrix becomes compartmentalised and also to find out whether there are tight junctions between osteoblasts. The results show that in early nonmineralised stages and in incipient mineralisation, lanthanum penetrates all intercellular spaces and the newly forming bone matrix which is rich in matrix vesicles and collagen. With the progression of mineralisation, when all matrix vesicles appear mineralised and calcification is 'spreading' to the surrounding matrix, lanthanum is restricted to intercellular spaces and conspicuous macular tight junctions are present between osteoblasts. We suggest that matrix vesicles act as microcompartments for calcification when the early bone matrix is in continuity with the surrounding extracellular space. In later stages, when lanthanum fails to penetrate the matrix, matrix vesicles may no longer be necessary because the bone matrix itself is compartmentalised, thus allowing for localised changes in composition that might favour mineral deposition.
To investigate the effect of substrates during oral rehydration therapy, we studied intestinal cation cotransport (ICC) with glutamine (Gln), alanine (Ala) and glucose (Glu). The specific aims were to determine the biological effects of these three different cotransport systems on intestinal function. Isolated rabbit ileal mucosa preparations mounted in Ussing chambers were studied. ICC was determined by measuring short-circuit current (Isc) and potential difference (PD) while monitoring tissue resistance (TR). The data are reported as the mean +/- SEM of 4-6 experiments for each amino acid concentration. Increasing concentrations of Gln (10(-5) to 10(-2) M), Ala (10(-5) to 10(-1) M) and Glu (10(-5) to 10(-2) M) caused a significant (P < 0.05) increase in ICC. Gln (30 mM) and Ala (0.1 M) had a maximal effect (Em(Gln) = 100% and Em(Ala) = 66%, P < 0.05) which was higher than that obtained with 30 mM Glu (Em(Glu) = 35%). When sodium was replaced with choline on the mucosal side, Ringer solution completely abolished the response with Gln, Ala and Glu. The presence of all three substrates (10(-2) M Gln, 10(-1) M Ala, and 10(-2) M Glu) in Ringer solution on the mucosal side caused a significant increase in ICC (delta increase of short circuit current = 111 +/- 43 microA, P < 0.05). These results demonstrate that Gln, Ala and Glu each increased sodium-dependent cation cotransport, and that sodium-dependent intestinal cation cotransport was higher with Gln than with Ala or Glu.
Hyperbolic and allosteric mathematical equations are used extensively to describe cumulative dose-response curves in pharmacology. In 1954, using an axiom described by Clark, Ariëns suggested the following equation for cumulative dose-response curves: Em/E-1 = Kd/[D], where Em = maximum effect, E = effect, Kd = dissociation constant of the drug-receptor complex and [D] = drug concentration. To evaluate the validity of the modified Ariëns equation on the dose-response curves with a Hill coefficient statistically different from one, we used sodium intestinal cotransport (SIC) with glutamine (Gln) and glucose (Glu). Increasing doses (10 microM to 0.1 M) of Gln and Glu were added to the mucosal side of the isolated rabbit ileum mucosal membrane mounted on Ussing chambers. Sodium cotransport was recorded by measuring short-circuit current (Isc), potential difference (PD) and tissue resistance (TR) at 20-min intervals for 2 h. The Em and ED50 for SIC with glucose were 25% and 150 microM, respectively, using the method proposed by Lineweaver-Burk. The same method could not be used to estimate the Em and ED50 in SIC with glutamine, suggesting a specific limitation of the Gln cotransport kinetic curve in the equation. Therefore, we modified the Ariëns equation to Em/E-1 = (Kd/[D])p. With p = Log (S), Log (Kd) = -pD2 and Log[D] = -pDx, we obtain E = Em/(1 + S(pD x -pD2)), where S is a hyperbolic constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic life-cycle tests using the freshwater cladoceran Daphnia magna aim to measure the effect of toxic chemicals on adult reproduction, in terms of the number of viable offspring produced. A tacit assumption is made that the primary effect of toxicants in these tests is a sublethal effect on the parent, reducing egg production and hence fecundity. The authors' observations on two chemicals, sodium bromide and 3,4-dichloroaniline, demonstrate that this assumption is at least partly false. In these experiments, the primary toxic effect of these compounds was to kill developing eggs in the brood chamber. Total egg output was unaffected, whereas output of viable eggs was severely impaired--an acute lethal effect. A further experiment demonstrated that the effect was limited to those eggs developing in the brood chamber, with eggs in the ovary remaining unaffected. It was suggested that these observations may provide the basis for the development of a short, sensitive early life-stage test with this species.
The genetic typing of laboratory strains of Daphnia magna revealed that although there are genetic differences between different testing laboratory strains, most laboratories culture single genotypes as clones. A comparative study was made of the performance of five of the more common clones in terms of neonate mortality under acute exposure to nine toxic chemicals. The range in clonal EC50 response was from less than one to more than two orders of magnitude in terms of concentration. Surprisingly, there was little pattern in rank order of response of clones exposed to different toxicants, thus suggesting that genotype-environment interactions were predominating. Nevertheless, it was suggested that specifying the genotype used in D. magna toxicity tests will result in increased test repeatability. Evidence indicating that culture environment may also significantly affect the performance of neonates in acute toxicity tests was also presented.
The number and activity of natural killer (NK) cells were studied in 34 untreated patients with paracoccidioidomycosis, 20 with the chronic form of the disease and 14 with the acute form. NK cells were detected with monoclonal antibody Leu-11c and the cytotoxic activity was measured using a single cell assay against K562 target cells. Both groups of patients had an increased number of circulating NK cells, their cytotoxic activity being significantly lower than in the healthy controls. These findings may be of importance in the immunological disturbances associated with paracoccidioidomycosis since NK cells exert important immune effector functions and may play a role in resistance against Paracoccidiodes brasiliensis.
Malnutrition and dehydration are the immediate consequences of diarrheal diseases. To investigate the biological significance of glutamine, alanine and glucose in the intestinal mucosa, we have used Ussing chambers to determine electrolyte transport by measuring short-circuit current (Isc), potential difference (PD) and tissue resistance (TR) in rabbit intestinal mucosa. Increasing doses (10(-5) M to 10(-1) M) of glutamine, alanine and glucose cause a significant increase in intestinal cation cotransport. Although glucose had a slightly earlier effect, 30 mM glutamine and 0.1 M alanine had a maximal effect which was more than two times that caused by 30 mM glucose. The pD2 values for glucose, glutamine and alanine were 3.0, 2.5, and 2.0, respectively. The dose-response curves of these substrates suggest that the intestinal cotransport kinetics for glutamine is different from that of glucose and alanine. Our results demonstrate that all three substrates cause a significant increase in Isc or PD, suggesting an increase in the intestinal mucosa cation cotransport. Glutamine has a larger effect on cation cotransport than alanine and glucose. These combinations should be studied further for the development of an oral rehydrating solution for diarrhea treatment which could prevent the resulting malnutrition, especially in those cases of prolonged diarrheal diseases.
Dialysable leukocyte extracts (DLE) were obtained from lymph nodes and spleen cells of hamsters immunized with Paracoccidioides brasiliensis (immune DLE) or from non-immunized hamsters (non-immune DLE). Sensitivity to P. brasiliensis antigen (PbAg) was transferred by immune DLE to normal recipient hamsters and could be detected by the macrophage migration inhibition (MIF) assay on day three and by a positive skin test to PbAg on day seven after DLE inoculation. This reactivity persisted for 120 days. The specificity of DLE was studied by inoculation of immune or non-immune DLE into normal hamsters and transfer was evaluated 7 days later by the MIF assay and by skin tests to PbAg, Candida albicans antigen (CaAg), sonically treated bacille Calmette-Guérin (BCG) (SBCG) and ovalbumin (OVA). The immune DLE recipients showed a reactivity to PbAg that was significantly stronger than that of the nonimmune DLE recipients although both groups of recipient animals showed reactivity to CaAg and SBCG. The results suggest that both DLE preparations contain a non-specific antigen augmenting factor. This factor may stimulate the minimal background response to the antigens in nonimmunized recipient hamsters.
Seventy untreated paracoccidioidomycosis patients, 15 with the acute or subacute form of the disease and 55 with the chronic form, were compared with two normal control groups of the same age range. Peripheral blood mononuclear cell subsets were defined by monoclonal antibodies directed at total T cells, helper/inducer and suppressor/cytotoxic T cell subpopulations; B cells, cortical thymocytes and monocyte/null cells. Both groups of patients showed an increased number of monocyte/null cells, a low helper/suppressor ratio and a reduced percentage of total T cells and their helper/inducer subsets. In addition patients with the acute form of the disease exhibited high levels of suppressor/cytotoxic T cells and B cells. These findings are of importance in our attempts to understand the pathogenesis of this mycosis and also to evaluate its prognosis in individual patients.
Severe blood loss can be reverted to normal circulatory function and indefinite survival by a small volume of 2,400 mOsm/liter NaCl (7.5%). This response requires functioning cervical vagal trunks at the time of hypertonic injection. Other equally hypertonic solutes (glucose, mannitol) are ineffective. This paper examines the effects of hypertonic (2,400 mOsm/liter) NaCl (7.5%) and glucose (50%) on femoral, mesenteric, splanchnic, renal, and coronary circulations. Hypertonic NaCl was given to dogs with intact or blocked vagi. Femoral flow was measured in innervated or denervated hindlimbs. Hemorrhage severely restricted both innervated and denervated femoral flows. Hypertonic glucose and NaCl, vagi blocked, redilated both femoral territories. Hypertonic NaCl, intact vagi, redilated denervated femoral vasculature but severely restricted innervated flow. Renal, mesenteric, total splanchnic, and coronary flows were restricted by hemorrhage and undistinguishable redilated by glucose or NaCl, blocked or intact vagi. It appears therefore that hypertonic NaCl induces permanent survival, partly because of its ability to elicit a pulmonary reflex, which induces muscular/cutaneous precapillary constriction. This shunts essentially required flow into the viscera, which are unspecifically vasodilated by hypertonicity.
The effect of Ketoconazole (KTZ) on the hamster experimental intratesticular paracoccidioidomycosis was studied employing different treatment schedules. KTZ long course treatment beginning at an early stage of the infection was effective in preventing fungal proliferation, dissemination to lymph nodes, spleen and kidneys, and in maintaining low levels of humoral and cellular specific immune responses. KTZ short course treatment starting at an advanced stage of disease resulted in a more severe histopathological picture without significant changes in the immunological profile. The drug prolonged the life span of hamsters infected with Paracoccidioides brasiliensis, but did not prevent mortality. Toxic necrosis of the bone marrow occurred in normal animals receiving 120 mg/kg/day of KTZ but with lower doses no morphologic alterations were observed in heart, lungs, kidneys, adrenals, spleen, liver, intestine or bone marrow.