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C G Duarte

Publications and source records attributed to C G Duarte.

At least 19 recordsLinked to original sources
PubMed2003

Effect of the period of treatment with a single dose of propylthiouracil on the antibody response in rats.

Propylthiouracil (PTU) was employed in a fixed quantity to evaluate the effect of the period of treatment with this drug on the antibody response to sheep red blood cells in Wistar rats. Animals were treated for 8, 16, 30 and 90 days by intragastric route with 5 mg/day, and immunized 24 h following the end of treatment; other groups were treated for 21 days, and immunized on the 17th day of treatment. Animals were sacrificed 5 or 6 days following immunization; the primary response was evaluated by the number of plaque-forming spleen cells and in some cases also by enzyme-linked immunosorbent assay (ELISA). Secondary response of PTU-treated rats, immunized and boostered after 15 days, was evaluated by ELISA 3 days following the booster. RIA performed the measurement of T3 in animals treated for 16 days, immunized, and sacrificed after 1, 2, 3, 4 and 5 days following immunization. Results showed that treatment for 8 and 16 days increased production of antibodies, and for 30 and 90 days decreased this response. Thus, according to the period of treatment, the same dose of PTU stimulates or suppresses the antibody response. This biphasic effect of a single dose of PTU was independent of alterations of serum levels of T3 during the buildup of the immune response. These results contributes towards the understanding of the literature controversy regarding the effects of this drug on the immune response, and could be of interest for studies involving autoimmune processes in thyroid.

Administration, Oral↗
PubMed2001

Review of studies establishing the aging male spontaneously hypertensive rat as a detector and quantifier of the kidney toxicity of radiocontrast media and other chemicals.

RATIONALE AND OBJECTIVES: There is a need for practical and sensitive preclinical tests for detecting the kidney toxicity of chemicals. The spontaneously hypertensive rat (SHR), as it ages, develops renal and cardiovascular changes similar to those considered as human risk factors for radiocontrast-induced renal damage. Age, male gender, and uncontrolled hypertension make these animals susceptible to the volume and osmolality of the administered contrast agent and the effect of repeated contrast administration after a brief interval. This article reviews studies in which the role of these and other factors were evaluated to validate the male SHR as a small animal model for renal damage induced by contrast and other agents. METHODS: Systolic blood pressure was measured with a tail cuff before and after the administration of the experimental substances, and the left kidney and heart were studied histologically to determine the influence of age, dose of contrast repeated at a short interval, gender and strain, the role of the sympathetic adrenergic nervous system, osmolality, and apoptosis. RESULTS: As the animals aged and the systolic blood pressure remained elevated, the animals developed progressive renal lesions that worsened after the administration of contrast. The most advanced renal lesions occurred in adult male SHRs that received two doses of contrast 6 hours apart. Female SHR rats and male Wistar Kyoto rats showed no effect or only minimal changes in heart and kidneys after the administration of contrast compared with age-matched male SHRs. Adrenergic blockade allowed only a small elevation in systolic blood pressure after contrast administration but did not protect the kidneys against renal damage by contrast. Hypaque, Omnipaque, and mannitol caused renal damage in proportion to their osmolality. Apoptosis with Hypaque, Omnipaque, and mannitol was observed in the kidney and heart. CONCLUSION: The results indicate that the aging male SHR develops spontaneous renal lesions that progress with age, increasing the susceptibility to the renal-damaging effects of contrast. Thus, the aging male SHR provides a laboratory tool for detecting the risk of renal damage of new contrast media as well as other pharmaceuticals and assessing methods to protect the kidneys and possible mechanisms of renal damage.

Age Factors↗
PubMed2000

The effect of the antithyroid drug propylthiouracil on the alternative pathway of complement in rats.

The effect of propylthiouracil (PTU) on the lytic activity of complement in rat serum was investigated in vivo. Rats (180+/-10 g) were treated daily by gavage with PTU doses of 1-50 mg/200 g body weight for time intervals ranging from 1 to 30 days. Serum classical pathway (CP) and alternative pathway (AP) activities were determined 24 h after the last dose. A single dose of 50 mg/200 g body weight was administered to additional groups and the animals were sacrificed after periods of 1-48 h. The results showed a relatively small reduction ( approximately 30%) in CP activity, evident only in animals treated with 50 mg of PTU for three weeks. However, a clear and opposite effect of PTU, an increase in lytic activity reaching values up to 180% of controls, was observed on AP activity. This effect was seen at all PTU doses used, and occurred within 4 days of treatment with the highest dose. Maximum activity was observed at intermediate intervals, depending on the PTU dose, with a return to control levels occurring after the longer periods of treatment. The lytic activity of serum from animals treated with a single PTU dose of 50 mg/200 g body weight and sacrificed 1-48 h after dosing did not differ from controls. Serum levels of thyroid hormone (triiodo L-thyronine, T3, and thyroxine, T4) were determined in representative groups of treated animals (injected with 5 mg of PTU/200 g body weight/day). These were either undetectable or considerably lower than those of controls. The serum PTU levels of these rats increased for up to 22 days, reaching values of 2-4 microg/ml.PTU is described in the literature as a modulator of both cellular immune responses and antibody production. Upon complement activation fragments of complement components bind to immune complexes and to specific receptors on cells of the immune system. Thus, alteration in AP activity caused by PTU treatment suggests a possible mechanism by which the drug exerts its modulatory effect. Increased complement AP activity might affect events as antigen presentation and hence the onset and course of the immune response.

Animals↗
PubMed1999

Effects of radiocontrast, mannitol, and endothelin on blood pressure and renal damage in the aging male spontaneously hypertensive rat.

RATIONALE AND OBJECTIVES: The purpose of this research was to study the effects of the radiocontrast medium (CM) Hypaque-76 (diatrizoate meglumine sodium), equiosmolar mannitol, and endothelin on blood pressure and renal damage in a aging male spontaneously hypertensive rat, a small animal model for CM-induced renal damage. The importance of the pressor effect and the high osmolality of CM in producing renal damage was investigated by first reducing the blood pressure with pentobarbital anesthesia, which suppresses sympathetic nervous system activity, then testing the effects of CM, saline, mannitol, and the potent vasoconstrictor endothelin alone and in combination with CM. METHODS: Systolic blood pressure was measured in 14-month-old male rats (1) when awake, (2) after pentobarbital anesthesia, (3) after the administration of saline, CM, mannitol, endothelin, or CM plus endothelin, (4) after awakening the same day, and (5) the following day while awake. Renal damage was quantified by evaluating histopathologically the left kidney removed the day after administration of test substances. RESULTS: The pentobarbital-lowered blood pressure remained depressed after saline and mannitol but rose dramatically after CM, endothelin, and CM plus endothelin. Renal damage, compared with the saline controls, occurred with CM, mannitol, endothelin, and endothelin plus CM. The order of increasing severity was mannitol = CM < endothelin < endothelin plus CM. CONCLUSIONS: The effect of CM on systolic blood pressure is not related to its osmolality. High osmolality, however, appears to be a factor in CM-induced renal damage. Ischemia and direct nephrotoxicity are factors contributing to the renal-damaging effects of CM, mannitol, and endothelin.

Aging↗
PubMed1998

Effects of radiocontrast and endothelin administration on systolic blood pressure and renal damage in male spontaneously hypertensive and Wistar Kyoto rats with phentolamine-induced adrenergic blockade.

RATIONALE AND OBJECTIVES: The systemic administration of hypertonic solutions may activate the adrenergic system, thus triggering vasomotor reactions that may result in renal failure. In this study, the effects of diatrizoate meglumine sodium radiocontrast agent Hypaque-76 on systolic blood pressure (BP) and renal damage were determined in male spontaneously hypertensive (SH) rats and Wistar Kyoto (WKY) rats under adrenergic blockade. METHODS: The systolic BP was measured in ketamine-anesthetized male SH and WKY rats after administration of saline solution, radiocontrast, or endothelin during adrenergic blockade with phentolamine. Then the left kidney was removed and examined histologically. RESULTS: The fall in systolic BP after phentolamine was not influenced by saline solution or radiocontrast in WKY rats but was restored partially by radiocontrast in SH rats. Endothelin produced an elevation in BP toward baseline levels in both strains. Only moderate renal damage was observed in the kidneys of WKY rats given radiocontrast or endothelin, but very severe damage was produced by these agents in SH rats. CONCLUSIONS: Adrenergic blockade with phentolamine did not prevent the elevation in systolic BP in SH rats by radiocontrast or by endothelin in SH and WKY rats, nor did it protect against renal damage by radiocontrast or by endothelin in SH rats.

Adrenergic alpha-Antagonists↗
PubMed1997

The SHR as a small animal model for radiocontrast renal failure. Relation of nephrotoxicity to animal's age, gender, strain, and dose of radiocontrast.

The male spontaneously hypertensive rat (SHR), as it ages, suffers many of the renal and cardiovascular complications that are recognized in humans as risk factors for radiocontrast (RC) agent induced renal failure (RF). Knowledge of this led us to test this strain of rats as a small animal model for RC-induced renal failure (RC-RF). Functional studies demonstrated a significant fall in GFR in the recovery period after RC administration. In addition, histopathologic evaluation of the kidneys was done in this study. Our results are based on assigning separate scale values to the histopathological evaluation of the (a) glomeruli, (b) tubules, (c) interstitium, and (d) arteries and arterioles of the kidneys. Saline (S) was administered to one group and the RC agent Hypaque-76 (diatrizoate meglumine sodium) to paired groups of 5-, 8-, 10-, 12-, and 14-month-old male SHR. The results indicated that younger animals (5 and 8 months old) were resistant to the nephrotoxic effects of the RC, but developed susceptibility at 10 months of age, when spontaneous renal pathology became manifest. Both spontaneous renal pathology and RC-induced renal damage (RC-RD) increased as the animals aged. In addition, when the administered dose of RC was repeated after a short interval of only 6 h, the degree of RC-RD increased greatly. In parallel control studies of the influence of gender and strain on the response to RC in 12-month-old rats, neither hypertensive female SHR nor male normotensive Wistar-Kyoto (WKY) rats demonstrated significant spontaneous renal pathology or the marked susceptibility to RC nephrotoxicity shown by their male SHR counterparts. This small animal model for RC-RD, the mature male SHR, has the distinct advantage that risk factors for RC-RD, similar to those characterized in humans for RC-RF, develop spontaneously without requiring any special treatment or surgical intervention.

Age Factors↗
PubMed1993

Assessment of renal function--glomerular and tubular.

The tests most commonly used to estimate the status of renal function via alterations in glomerular filtration rate (GFR) are plasma creatinine concentration (PCr), blood, urea, nitrogen (BUN), and creatinine clearance (CCr). Unfortunately, these tests have some drawbacks. Nevertheless, they are quite useful to clinicians aware of their limitations, especially in many instances when it may be unnecessary or impractical to have precise measurements. Accordingly, serial measurements of PCr, especially when related to simultaneous BUN determinations, or CCr, may suffice. However, the functional status of the kidneys often needs to be corroborated by more precise methods when subtle changes in renal function are detected or when clinically indicated.

Animals↗
PubMed1984

Effects of desoxycorticosterone acetate on magnesium metabolism in potassium-depleted rats.

Metabolic balance studies were performed in two groups of 6 rats each, pair-fed a diet deficient in potassium. While one group was injected with desoxycorticosterone acetate (DOCA) for 11 days, the other group, used as a control, was injected with oil. The administration of DOCA suppressed or reversed the thirst, natriuresis, diuresis, calciuria and magnesiuria that developed in the potassium-deficient control group. Potassium-depleted DOCA-treated rats had a more positive water and sodium balance, experienced a significant expansion in plasma volume, had a more negative potassium balance and had a lower plasma potassium concentration. Magnesium balance decreased in the group fed the diet deficient in potassium and injected with oil but it rose towards control levels in the group fed the same diet and treated with DOCA. As the content of potassium in muscle decreased in rats fed the diet deficient in potassium and injected with oil, the concentration of magnesium in muscle also fell and the plasma concentration of magnesium increased. Thus, the hypermagnesemia of potassium depletion could be explained by the shifting of magnesium from tissue into the extracellular space. The partial compensation of the hypermagnesemia observed in the potassium-deficient group injected with DOCA may be the result of the hemodilution secondary to plasma expansion.

Animals↗
PubMed1978

Magnesium metabolism in potassium-depleted rats.

In rats, a diet depleted of potassium caused a significant hypokalemia and hypermagnesemia, a diuresis and natriuresis, a decrease in urinary and fecal excretion of potassium, a magnesiuria, and a decrease in fecal excretion of magnesium. Balance studies revealed that potassium metabolism was negative in potassium-depleted rats and that magnesium metabolism was positive and higher than in control rats. In potassium-depleted rats, potassium and magnesium contents in muscle were reduced, whereas the sodium level was increased and plasma aldosterone was significantly lower. Therefore, the elevation in plasma concentration of magnesium induced by a diet poor in potassium is the result of a more positive metabolic balance of magnesium and of shifting of magnesium from the tissue into the plasma compartment. Results of additional preliminary studies support the possibility that the hypermagnesemia may be mediated through the depression in mineralocorticoid activity induced by the depletion of potassium.

Animals↗
PubMed1976

Effect of colchicine on urinary phosphate and regulation by parathyroid hormone.

The possible role of cytoplasmic microtubules in the renal handling of phosphate and its regulation by parathyroid hormone (PTH) was evaluated with colchicine, a microtubule-disrupting agent. Colchicine-treated rats were thyroparathyroidectomized (TPTX) and subsequently infused with PTH. Treatment with a total dose of 1 mg colchicine had no effect on glomerular filtration rate or fractional excretions of sodium and potassium. Fractional excretion of phosphate in colchicine-treated TPTX rats was significantly higher compared with TPTX controls. After PTH infusion, control rats responded with increases in fractional excretion of phosphate and urinary cyclic AMP but colchicine-treated rats had variable and insignificant changes in both parameters. Fractional excretion of sodium and potassium did not change significantly after PTH. Renal cortical activities of cyclic AMP phosphodiesterase, soluble alkaline phosphatase, cytochrome oxidase, leucine aminopeptidase, or basal adenylate cyclase were not significantly affected by colchicine treatment. On the other hand, stimulation of adenylate cyclase by a submaximal dose of PTH was markedly decreased in colchicine-treated rats, and the activity of membrane-bound alkaline phosphatase was also significantly decreased. The binding of radioactive colchicine in renal cortical extracts from rats treated with colchicine was significantly diminished. These results suggest that disruption of cytoplasmic microtubules in renal cortical cells interferes with phosphate transport and its regulation by PTH.

Alkaline Phosphatase↗