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Biomedical subjects

O L Ramos

Publications and source records attributed to O L Ramos.

At least 55 records · Page 3Linked to original sources

Characterization of circulating immune complexes detected by monoclonal rheumatoid factor and conglutinin radioimmunoassays in SLE nephritis.

By utilizing a monoclonal rheumatoid factor (mRF) and bovine conglutinin (K) in radioimmunoassays, ICs detected in sera of patients with lupus nephritis were partially characterized. The mRF-RIA detected high levels of ICs in 86.9% of patients with active SLE and in only 22.7% of patients with inactive disease. Positive association was observed with clinical scores and significant negative correlation was found with serum levels of C1q, C3 and C4. The mRF-reactive ICs were shown to be cryoprecipitable and analysis by gel filtration through Sephacryl S-300 disclosed a material eluting between IgM and IgG, being dissociated in acidic pH. On the other hand, no association could be demonstrated between levels of ICs detected by K-RIA and clinical activity. Positivity in this assay was only 8.7% and 31.8% for active and inactive groups. Differently from the ICs detected by mRF-RIA, the K-reactive material was not precipitated by 3.5% PEG, nor by centrifugation in the cold, and EDTA did not reduce the binding of IgG to K in positive sera. The reactive IgG in Sephacryl S-300 chromatography eluted in the same position as monomeric IgG both in neutral and dissociating conditions. No C3 could be detected in ICs reactive in both assays.

Antibodies, Monoclonal↗

Glomerular hematuria in diabetics.

Three hundred and twenty outpatients with diabetes mellitus (DM) were studied to evaluate the prevalence, origin (glomerular or nonglomerular), significance and possible association of glomerular hematuria (GH) with other clinical and laboratory features. In patients with 24 h proteinuria equal or superior to 500 mg, hematuria was seen in 16 out of 22 (72.7%); for those with 24 h proteinuria between 150 and 500 mg 5 out of 23 (21.7%) had hematuria, and in the general population of diabetics studied hematuria was present in 47 patients (14.7%). It was glomerular in 43 (13.4%) patients and nonglomerular in 4 (1.3%). Red blood cell casts were observed in 15 (34.9%) out of the 43 patients with GH. Ten out of 31 patients (32.3%) with GH, for whom 24 h proteinuria was available, had negative proteinuria in a 24 h urine when analyzed by routine methods. In 18 patients with GH, clinical and laboratory findings that could suggest a second form of glomerulopathy--nondiabetic--were negative. Renal biopsy in 9 of them showed only diabetic glomerulosclerosis. We have observed a significant association between GH and the male sex (p less than 0.001), high serum creatinine levels (p = 0.0002) and 24 h proteinuria greater than 150 mg (p less than 0.001). GH was more frequent among males with DM lasting more than 10 years (p less than 0.001) and among those with retinopathy (p less than 0.001). There was no association between GH and age, type of DM, insulin requirement or hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Glomerular hemodynamics and hormonal participation on cyclosporine nephrotoxicity.

The mechanism of cyclosporine A (CyA) nephrotoxicity is unclear. In order to evaluate renal microcirculation seven euvolemic Munich-Wistar (MW) rats were studied after acute CyA treatment (50 mg/kg, i.v.). Both total glomerular filtration rate (GFR, 0.96 +/- 0.04 vs. 0.47 +/- 0.07 ml/min) and single nephron GFR (27.90 +/- 3.39 vs. 14.02 +/- 3.49 nl/min) declined significantly (P less than 0.001). It was observed an increase in afferent (RA, increases 188%) and efferent (RE, increases 360%) arteriolar resistances that caused a decrease on glomerular plasma flow rate (QA) from 100.99 +/- 17.09 to 44.37 +/- 13.37 nl/min (P less than 0.001). Mean glomerular capillary hydraulic pressure (PGC) increased from 45 +/- 1 to 55 +/- 4 mm Hg (P less than 0.05) and the glomerular ultrafiltration coefficient (Kf) decreased by 70% (0.096 +/- 0.030 to 0.031 +/- 0.010 nl/sec X mm Hg, P less than 0.05). Additionally, in order to study hormonal participation in this nephrotoxicity, other three groups of MW rats were previously treated with captopril (2 mg/kg, i.v.), verapamil (20 micrograms/kg/min, i.v.) or indomethacin (2 mg/kg, i.v.). Both captopril and verapamil minimized the renal effects of CyA, with a decline of approximately 25% instead of approximately 50% on GFR and RPF. Moreover, two groups of Brattleboro rats were studied. Acute CyA administration in homozygote Brattleboro rats produced a decline of only approximately 22% and approximately 31%, respectively, in GFR and renal plasma flow (RPF), when compared with MW rats (P less than 0.05). Similar results were observed in heterozygote Brattleboro rats when compared with MW rats, disclosing differences due to a different strain of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Consequences of reversal of hypertensive cardiac hypertrophy by captopril on left ventricular pumping ability and performance.

Left ventricular hypertrophy can be reversed by treatment of hypertension with captopril but the consequences of this regression are not yet fully described. We studied the maximal capacity of the hypertrophied and hypertrophy-reversed ventricle to generate pressure during transient total occlusion of the aorta, and also the left ventricular end-diastolic pressure required to meet this maximal effort. Two-kidney, one clip Goldblatt (renal hypertensive rats; RHR) hypertension was induced in 17 Wistar rats, eight of which were treated with captopril (RHR-C: 50 mg/kg given orally) from the fourth to the eighth week. Sham-operated controls (SC) remained untreated, or were treated with similar doses of captopril (SC-C). Significantly lower heart weights were found in RHR-C than in RHR (2.88 +/- 0.15 versus 2.38 +/- 0.04; P less than 0.001). During transient total occlusion of the aorta, the maximal intraventricular pressure developed in RHR-C was not significantly different from that in RHR, but left ventricular end-diastolic pressure was significantly less in RHR-C than in RHR (21.4 +/- 2.2 versus 34.3 +/- 3.8; P less than 0.01). The analysis of pressure-volume characteristics of the hypertrophied left ventricles and those in which hypertrophy was reversed revealed similar compliances between these two groups. Our data suggest that there was a mechanical improvement in the heart function after reversal of left ventricular hypertrophy.

Animals↗

Effects of cyclosporin on renal microcirculation.

To evaluate renal microcirculation during acute cyclosporin (CsA) administration (50 mg/kg, i.v.), seven euvolaemic Munich-Wistar rats were studied. CsA infusion caused a significant decrease in total glomerular filtration rate (GFR) (0.96 +/- 0.04 vs 0.47 +/- 0.07 ml/min) and in single-nephron GFR (SNGFR) (27.90 +/- 3.4 vs 14.02 +/- 3.5 nl/min). The efferent arteriolar resistance increased substantially (P less than 0.05) while the afferent resistance rose moderately. Consequently, there was an increase (P less than 0.05) in mean glomerular capillary hydraulic pressure (PGC), from 45 +/- 1 to 55 +/- 4 mmHg, together with an important decrease in mean glomerular plasma flow rate (QA), from 100 +/- 17 to 44 +/- 13 nl/min. Since tubular hydraulic pressure was maintained unaltered, an elevated transglomerular hydraulic pressure difference was observed (P less than 0.05). The lower values of SNGFR were accounted for by both the decrease in QA and in the glomerular ultrafiltration coefficient (Kf). The latter was reduced from 0.096 +/- 0.03 to 0.031 +/- 0.010 nl/sec per mmHg (P less than 0.05) by CsA. Additionally, three groups of Munich-Wistar rats were previously treated with captopril (2 mg/kg per h, i.v.), verapamil (20 micrograms/kg per min, i.v.) or indomethacin (2 mg/kg, i.v.). Both captopril and verapamil minimised the renal effects of CsA, with a decline of approximately 25% instead of approximately 50% on GFR and RPF. Thus CsA infusion caused a decline on SNGFR due to an important reduction in QA and Kf with an impressive increase on arteriolar resistance, a mark of angiotensin II stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute hemodynamic action of captopril in congestive heart failure: contrasts between refractory and untreated patients.

To compare the hemodynamic mode of action of captopril in patients with Congestive Heart Failure (CHF) with high- or low-plasma renin activity, we studied the systemic and renal hemodynamic changes induced by this drug in patients with refractory CHF (Group I) or untreated CHF (Group II). Plasma Renin Activity (PRA) was 7.46 +/- 3.7 ng/ml/hr in Group I and 1.15 +/- 0.45 ng/ml/hr in Group II. After the administration of captopril, these values increased to 14.35 +/- 6.19 and to 1.99 +/- 0.76 ng/ml/hr respectively (p less than 0.05). We observed that patients of Group I responded with increases in cardiac index and stroke volume and diminutions in total peripheral resistance, but Group II did not show any significant change in these variables. In contrast to this difference in responses between the refractory and untreated patients, both groups showed similar decreases in pulmonary artery and wedge pressures. Both groups also showed similar increases in plasma volume and effective renal plasma flow, and decreases in renal vascular resistance. These results show that captopril has predominantly venodilator effects in patients with CHF with low PRA levels, and it acts as a mixed vasodilator in patients refractory to conventional therapy, receiving high doses of diuretics, and in whom PRA is elevated. Our results also suggest that the venodilator action of captopril is not mediated by the Renin-Angiotensin System.

Adult↗

Kallikrein-kinin system in severe experimental hypertension.

Plasma levels of low and high molecular weight kininogens, prokallikrein and active kallikrein were determined in four models of experimental hypertension and in genetically hypertensive rats. The high molecular weight kininogen remained essentially unaltered in all groups, whereas the low molecular weight kininogen was decreased in the renovascular groups. In the glucocorticoid hypertensive rats low molecular weight kininogen increased, but rats with hypertension induced both by renovascular and glucocorticoid mechanisms had normal kininogen. Genetically hypertensive rats had levels of low molecular weight kininogen similar to the ones observed in control group. The data presented reinforce the hypothesis of a participation of the kallikrein-kinin system in the etiopathogenesis of hypertension, indicating an implication of the low molecular weight kininogen in some types of severe experimental hypertension.

Animals↗

The effect of Collins' solution on the function and structure of isolated proximal convoluted tubules from rabbit kidneys.

Proximal convoluted tubules (PCTs) from rabbit cortical slices were perfused after preservation in Collins' solution with the in vitro microperfusion technique. Under these conditions, after maneuvers of in vitro preservation, the following findings were observed: Tubules were best preserved, functionally and morphologically, when bathed with Collins' solution peritubularly. Tubular preservation was inadequate when the Collins' solution contacted only the luminal or luminal and peritubular sides. These observations indicate a difference in the reactions of various cellular sides to the preservation process, suggesting that during preservation of the whole kidney, there are differences in the preservation of the various tissues of the organ.

Animals↗

Renal haemodynamics in spontaneously hypertensive rats with superficial glomeruli.

Spontaneously hypertensive rats (SHR) were mated with Munich-Wistar rats (MW), and the F1 hybrids were called Escola Paulista de Medicina (EPM) rats. The EPM rats present spontaneous hypertension and superficial glomeruli, allowing a study of glomerular haemodynamics. Mean whole kidney (GFR) and single nephron glomerular filtration rate (SNGFR), and mean total and glomerular plasma flow, were similar in EPM and MW rats. However, a higher glomerular capillary hydraulic pressure and a reduced ultrafiltration coefficient (Kf) of EPM rats were observed. The glomerular hypertension may be the cause of low Kf, a possible initial lesion of glomerular sclerosis. When mean arterial pressure levels were reduced to about 90 mmHg, a maintenance of SNGFR, with a 40% reduction in GFR, in EPM rats were achieved, suggesting an autoregulatory mechanism in the superficial but not in the juxtamedullary nephrons. The decrease on urinary sodium excretion (UNaV) in this condition, which was also lower than in MW rats, showed an impaired sodium handling by EPM kidneys, a possible role in the hypertension genesis. Thus, the data suggest that EPM rats can be a useful model for glomerular haemodynamics and microcirculatory studies in the spontaneously hypertensive state.

Animals↗

Radioimmunoassay for IgG and IgM rheumatoid factors.

The present paper describes two solid phase radioimmunoassays for detecting IgG and IgM rheumatoid factors (RF). Basically, serum rheumatoid factors were bound to rabbit IgG previously adsorbed to wells of flexible microtiter plates and quantitated after the addition of 125I-Fab anti-human gamma Fd for the IgG-RF assay or 125I-IgG anti-mu chain for the IgM-RF assay. The IgG and IgM rheumatoid factor assays were tested on 56 and 30 control sera, respectively. The upper normal limits for these assays were taken for cpm test serum/cpm control pool as 1.00 (0.76 + 0.24; X + 2SD) and 1.39 (0.73 + 0.66; X + 2SD) for IgG-RF and IgM-RF, respectively. When applied to sera of patients with rheumatoid arthritis, IgM-rheumatoid factor was detected in 15 of 15 (100%) patients, and IgG-rheumatoid factor in 15 of 17 (88%). The radioimmunoassay results for both rheumatoid factors were significantly higher for these patients than for the normal control sera (P less than 0.01).

Animals↗

Comparison of the hemodynamic effects of sodium acetate in euvolemic dogs and in dogs submitted to hemorrhagic shock.

We determined the dose-response relationship of systemic hemodynamics with graded intravenous infusions of sodium acetate (0.75, 1.50 and 3.00 microEq kg-1 min-1) in a group of dogs in the euvolemic state (N = 10) and in animals submitted to severe hemorrhagic shock (N = 7). Sodium acetate had a marked vasodilator effect on both groups, decreasing total peripheral resistance by 36.6% and 55.1%, respectively. Cardiac index increased simultaneously by 68.4% and 143.0%, respectively. Sodium acetate induced an approximate normalization of cardiac index and peripheral resistance at the highest infusion rate in the animals submitted to hemorrhagic shock. The normalization of cardiac output was due to a marked increase in heart rate in euvolemic dogs and to an increase in stroke volume in shocked animals. The hyperkinetic state of the circulation induced by the drug and a possible inotropic action of sodium acetate either direct or indirect could explain the different patterns of response.

Acetates↗

Detection of IgG-rheumatoid factor in sera of patients with acute poststreptococcal glomerulonephritis and its relationship with circulating immunecomplexes.

Rheumatoid factors (RF) were measured in sera from 75 patients with acute poststreptococcal glomerulonephritis (APSGN) and compared with normal controls, patients with rheumatoid arthritis in activity and acute rheumatic fever. Using two sensitive and specific solid phase radioimmunoassays, IgM-RF and IgG-RF were detected, respectively, in 15% and 32% of the patients with APSGN. A positive correlation (r = 0.37, n = 75, p less than 0.05) was obtained between serum levels of IgG-RF and circulating immune complexes determined by conglutinin assay. Chromatographic studies in serum from two patients with APSGN demonstrated that the circulating IgG-RFs were mainly free, not complexed. It is suggested that RFs, particularly of the IgG class, may participate in the pathogenesis of the renal injury in some patients with APSGN.

Acute Disease↗

Renal accumulation of 99mTc-DMSA in the artificially perfused isolated rat kidney.

In order to investigate aspects of the renal handling of 99mTc-DMSA, 68 isolated rat kidneys were artificially perfused. The experimental groups were: Group 1 (no. = 32)-oxygenated filtering kidneys; Group 2 (no. = 29)-oxygenated non-filtering kidneys; Group 3 (no. = 7)-anaerobic non-filtering kidneys. We conclude that the 99mTc-DMSA complex is strongly bound to albumin, is not filtered and is removed from perfusion fluid through the renal peritubular capillary route and that this occurs by an active process which depends upon aerobic metabolism. This process has a high capacity and is not inhibited by probenecid.

Animals↗

The renin-angiotensin system in the control of systemic arterial pressure.

The renin-angiotensin system through its active octapeptide, angiotensin II, has an important role in systemic arterial pressure control. Angiotensin II is a potent direct vasoconstrictor and is also the main regulator of aldosterone secretion. The complete analysis of the role of angiotensin II has to take into account the prevailing sodium balance for a given level of angiotensin II and also its indirect action upon the sympathetic nervous system as well as other hormonal systems. A number of studies have provided evidence for an important role for the renin-angiotensin system in renovascular hypertension, malignant and severe hypertension, as well as in mild to moderate forms of essential hypertension.

Angiotensin II↗

Role of the prostaglandin and kallikrein-kinin systems in aminoglycoside-induced acute renal failure.

The role of humoral factors in the pathogenesis of gentamicin and tobramycin aminoglycoside-induced acute renal failure was studied in rats. Renal function was evaluated after inhibition of prostaglandin synthesis with indomethacin and inhibition of the kallikrein-kinin system with aprotinin. Plasma and urinary kallikrein levels were measured in aminoglycoside-treated rats, as was in vitro effect of of these antibiotics on plasma kallikrein activity and prekallikrein activation by dextran sulfate. Indomethacin treatment (2 mg kg-1 day-1, ip, for 13 days) of rats which received gentamicin or tobramycin (40 mg kg-1 day-1, ip, for 10 days) caused a further fall in glomerular filtration rate (GFR) and renal blood flow and an impressive increase in renal resistance. The effect of indomethacin on GFR was more evident for gentamicin- than tobramycin-treated animals. Aprotinin administration had no additional effects on the renal function of antibiotic-treated rats. Plasma and urinary kallikrein levels in aminoglycoside-treated rats were significantly lower than in untreated controls. Both aminoglycosides at concentrations of 0.1 mg/ml inhibited dextran sulfate activation of plasma prekallikrein, and 2.0 micrograms/ml tobramycin, but not gentamicin, inhibited the hydrolysis of H-D-Pro-Phe-Arg-p-nitroanilide by rat plasma. These data suggest that prostaglandins may protect against aminoglycoside nephrotoxicity.

Acute Kidney Injury↗

Characteristics of spontaneously hypertensive, Wistar Kyoto and Munich Wistar rats bred in Brazil.

The breeding of imported strains of isogenic rats was started in 1981 because of the lack of experimental rat models in Brazil. The imported strains were: Spontaneously Hypertensive Rats (SHR) and their normotensive controls Wistar Kyoto Rats (WKY) from the National Institutes of Health, Bethesda, MD, and Munich Wistar (MW) rats which present superficial renal glomeruli, from Simonsen Laboratories, Gilroy, CA. Breeding of these strains was carried out without strict barriers (conventional breeding), under Standard Operating Procedures and strict inbreeding. Environmental factors such as ration, light, temperature, type of shavings and bedding, size of cages and their population were constant. Body weight growth curves were constructed for the three strains. The productivity of imported rats and local breeding colonies in 1981, 1982 and 1983 was compared on the basis of the following parameters: mean litter size, productivity of the females, pre- and post-weaning mortality, and effective yield. Systolic blood pressure was also measured for SHR and WKY rats. MW rats showed a high and relatively stable reproduction performance. The productivity of SHR and especially WKY animals declined progressively during the first three years, making the breeding of these strains of isogenic rats very difficult.

Animals↗