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Biomedical subjects

C Grönhagen-Riska

Publications and source records attributed to C Grönhagen-Riska.

At least 109 records · Page 6Linked to original sources
PubMed1986

Effects of ACE inhibition on renal regulation of salt and water.

CHF may activate the RAS by various mechanisms. Acute CHF is associated with high PRA, whereas chronic, stable disease is combined with normal values. The response to ACEI is affected by blood pressure, degree of activation of the RAS, salt balance and degree of possible renal failure. It may also be affected by concomitant diuretic or, e.g., digoxin therapy. ACEI improves RPF, GFR may remain normal or may increase, if it was previously impaired due to reduced RPF. Severe hypotension in combination with decreased autoregulatory capacity may decrease GFR. Generally, renal excretion of sodium and water increase. These changes in renal handling of salt and water are primarily caused by decreased AII. They are also augmented by inhibited sympathetic tone and thirst and decreased release of ADH and aldosterone. Increased synthesis of vasodilating and natriuretic PGs is probably also of some importance. Dilutional hyponatremia may be corrected by combined ACE inhibitor and furosemide treatment. Water and sodium excretion increase and sodium is redistributed from the intracellular space. Low serum sodium values increase and azotemia may be corrected, if ACE inhibitor doses are carefully titrated to avoid severe hypotension. These effects are ascribed mainly to a decrease of AII, thirst and ADH release. The effect of furosemide is improved since increased amounts of salt are delivered to the loop of Henle and access of furosemide to its site of action is facilitated by increased RPF. ACEI does not cause any obvious negative effects on renal handling of salt and water.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva.

Angiotensin-converting enzyme (ACE) was studied immunohistochemically in conjunctival biopsies from 6 patients with systemic sarcoidosis, 4 patients with posterior non-sarcoid uveitis and in specimens from 4 patients with chalazion of the eyelid. Specimens with sarcoid granulomas showed intense ACE-positive immunoreactivity in epitheloid cells of the granuloma, whereas chalazion granulomas did not contain ACE-immunoreactivity. There was no difference in staining patterns between specimens without granulomas. Thus immunohistochemical staining for ACE may be of help in differentiating conjunctival granulomatous tissue of a chalazion from sarcoid granuloma.

Conjunctival Diseases↗
PubMed1985

Thyroid hormones affect serum angiotensin I converting enzyme levels.

Serum angiotensin I converting enzyme (ACE) was measured in 10 patients with Graves' disease and 2 with thyroiditis during different stages of the diseases. The effect of thyroxine on serum ACE levels was also recorded in 12 patients with thyroid cancer, who were on thyroxine suppression. Serum ACE levels correlated positively with clinically assessed thyroid function and peripheral thyroid hormone levels, especially during hyper- or hypofunction. ACE was measured both with an enzyme kinetic and a new, quantitative inhibitor binding assay. The methods gave similar results, which indicates that ACE increments during thyroid hyperfunction were quantitative, and not a result of increased enzyme activity. Serum ACE increments associated with high lysozyme concentrations are signs of immunologic activation or proliferation of monocytic cells. In this study there was no correlation between the two enzymes, which may indicate either increased synthesis or possibly shedding of ACE from endothelial cells or delayed metabolic clearance of this enzyme. Serum ACE measurements may provide a useful tool for assessing thyroid function and the effect of thyroxine treatment.

Adolescent↗
PubMed1985

Systemic manifestations and enzyme studies in sarcoidosis with neurologic involvement.

The dissemination and activity of systemic disease was evaluated retrospectively in 50 patients with neurosarcoidosis, 24 of whom presented with neurologic symptoms. During follow-up, five patients never developed detectable systemic disease. In 26 patients, sarcoidosis had previously been diagnosed, but in 11 (42%) of them the neurologic symptoms were initially not connected with this disease. During follow-up, extraneural features were those of sarcoidosis in general. However, 23 patients (46%) had normal chest X-ray on admission to neurologic examinations. Fourteen (35%) of 40 examined patients had ocular changes, 13 (33%) of 39 hypercalciuria and 13 (26%) of 50 skin manifestations. Serum angiotensin converting enzyme (ACE) was elevated in only 31% of the patients. Measureable amounts of ACE were recorded in the cerebrospinal fluid from 13 of 17 examined patients. During follow-up the activity of neurosarcoidosis seemed to be linked to the course of systemic disease in general.

Adolescent↗
PubMed1985

Erythropoietin and renin substrate in cerebellar haemangioblastoma.

We examined eight cerebellar haemangioblastoma tumours from eight patients, aged 16-63 years, 5 females and 3 males. Preoperative haemoglobin values exceeded 180 g/l in four patients, and 150 g/l in four. All high Hb values were normalized upon surgical removal of the tumours. All tumours contained scattered cells which stained positively with antisera against pure human urinary erythropoietin and plasma renin substrate. We conclude that cerebellar haemangioblastomas produce immunoreactive erythropoietin, which shares common antigenic determinants with renin substrate.

Adolescent↗
PubMed1985

Angiotensin converting enzyme in cerebrospinal fluid: a new assay.

Serum and CSF angiotensin converting enzyme (ACE) were measured by a new inhibitor binding assay in 32 patients with sarcoidosis, 49 with neurologic diseases, and 38 controls. In neurosarcoidosis, 11 of 20 patients had high levels of CSF ACE. In systemic sarcoidosis without neurologic abnormality, only 1 of 12 patients had elevated CSF ACE. The highest value was observed in a patient with widespread meningeal sarcoidosis. High values were also observed in patients with bacterial meningitis or malignant tumors of the CNS. Fluctuation in successive analyses correlated to clinical course of neurosarcoidosis. CSF ACE analysis seems useful in diagnosis and follow-up of neurosarcoidosis.

Adolescent↗
PubMed1985

Radioimmunoassay of haemoglobin F in K 562 cells following induction with renin substrate and erythropoietin.

To test the hypothesis of renin substrate (RS; angiotensinogen) being a precursor of erythropoietin (EP), the capacity of RS and EP to induce Hb synthesis was compared in cultured human erythroid leukaemia cells of the K 562 line after prestimulation with haemin. For this purpose a radioimmunoassay for haemoglobin F (HbF) was developed. This assay was shown to be specific for HbF, reproducible, and sensitive for 0.1 ng of HbF. The cells were induced by RS and EP to increased HbF production. Cells stimulated with RS or EP showed increased benzidine staining. This data, corroborating our earlier observations on immunological similarities between RS and EP, supports the hypothesis that renin substrate is a likely precursor of erythropoietin.

Angiotensinogen↗
PubMed1985

Fine-needle aspiration biopsy at various stages of induction of Heymann nephritis.

Fine-needle aspiration biopsy (FNAB) has been successfully used for the monitoring of the in situ inflammatory response of rejection. We have evaluated FNAB as a technique for the quantification and cytological classification of infiltrating leukocytes during the induction of and manifest Heymann nephritis (HN). FNAB results were compared and supplemented with results of conventional histopathological and immunofluorescence (IFL) studies and with immunohistochemical studies to classify infiltrating T-lymphocyte subsets with immunoperoxidase (IP) technique. Rats (8/group) were killed three weeks after immunisation, and two and ten weeks after a booster. FNAB proved more sensitive than histopathological examination for the evaluation of interstitial infiltration in HN. Plasmablasts dominated the inflammatory picture three weeks after immunisation, when no glomerular or interstitial changes were observed histopathologically. The intensity and number of plasmablast reactions reached their peak two weeks after the booster, although disease was still not apparent. When membranous glomerulonephritis (MGN) was established, FNAB indicated plasmablasts in 4/7 rats, the reaction was strong in two. These rats had the most severe histopathological changes, too. FNAB indicated modest lymphocyte infiltration three weeks after immunisation. Immunohistochemical subtyping of T-lymphocytes showed initial T-helper infiltration, which gradually decreased after the booster, and had disappeared when MGN was manifest. At this stage T-suppressor infiltration was observed in the same two rats which had strong plasmablast reactions and severe HN with interstitial changes, as well. These observations suggest a role for cell-bound immunity in the induction of HN. Plasmablast reaction may initially be supported by the infiltrating T-helper lymphocytes, and it may imply local antibody production. Severe manifest disease was associated with both plasmablast and suppressor cell infiltration.

Animals↗
PubMed1985

Evidence that renin substrate (angiotensinogen) may be a precursor of erythropoietin.

We suggested a role for renin substrate (RS, angiotensinogen) in the biogenesis of erythropoietin (EP) (Nature 308:649-652, 1984). Purified RS was prepared from pooled plasma of healthy adult subjects, or from plasma of pregnant, healthy females. Antisera against human RS were shown to cross-react with purified human urinary EP, using a haemagglutination technique. On the other hand, antisera generated against highly purified human urinary EP showed strong cross-reaction with purified human plasma RS, by agglutinating erythrocytes covered with glutaraldehyde-coupled human RS. Moreover, using antisera generated against RS or EP, we have demonstrated monocytoid cells staining positive for both EP and RS in cerebellar haemangioblastoma tumors from 8 patients. Taken together, these observations point to a close relation between RS and EP. One interesting explanation is that renin substrate may be a precursor of erythropoietin.

Adult↗
PubMed1984

Enalapril and lisinopril in renovascular hypertension--antihypertensive and hormonal effects of two new angiotensin-converting-enzyme (ACE) inhibitors. A preliminary report.

We assessed the antihypertensive and hormonal effects of two new angiotensin converting enzyme (ACE) inhibitors, enalapril (MK-421) and lisinopril (MK-521) in 22 patients with renovascular hypertension. All patients had angiographically verified renal artery lesions, 3 had bilateral renal artery stenosis and one a stenosis in a single kidney, and the rest had unilateral renal artery stenosis. After placebo treatment for 3 days in hospital, increasing doses from 5 to 40 mg daily, of both ACE-inhibitors were given. Both drugs induced a significant fall in blood pressure (BP). Significant BP reductions were seen after 2 h with a maximum fall for the enalapril group at a dose of 40 mg 4 h after drug intake (mean supine BP decrease - 31/24 mm Hg, standing - 29/16 mmHg). The corresponding maximal BP reductions were for the lisinopril group at a dose of 40 mg o.d. at 6 h: mean supine BP fall - 25/28 mmHg and standing - 33/31 mm Hg. Both drugs significantly inhibited serum ACE to about 5 to 10% of initial values and with a duration for more than 24 h. Both drugs also caused a decrease in plasma-AII levels and also in plasma aldosterone concentrations. There were not toxic effects and no serious side effects. Careful monitoring of biochemical variables showed no significant changes. We conclude that both enalapril and lisinopril are effective and very safe agents for the treatment of renovascular hypertension and with a long duration of action and with very good tolerance.

Adult↗
PubMed1984

Competitive inhibitor binding assay (IBA) of captopril and other inhibitors of angiotensin converting enzyme.

We developed a novel assay method for the determination of captopril and enalapril serum concentrations. This method is based on a new principle of enzyme assay, inhibitor binding assay (IBA), recently introduced by us for the measurement of serum angiotensin converting enzyme (ACE). The assay principle is based on binding of 125I-labelled ACE inhibitor (351A, p-hydroxy-benzamidine derivative of N-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline) to ACE. A competitive IBA was established using captopril as a standard and human serum ACE as a binder. For the assay of captive captopril, 0.1 ml of venous blood was taken into 9.9 ml of ice-cold buffer. Following separation of cells, the supernatant was stored at -20 degrees C until assayed. Tubes containing added serum ACE as a binder, labelled inhibitor, and unknown samples, were incubated for 1 hour at 37 degrees C. Following separation of bound label the content of captopril was read from a standard curve. Results in healthy subjects showed peak blood concentrations ranging from 220 to 1300 ng/ml within 30-60 minutes after a single oral dose of 50 mg captopril, and virtual disappearence of active drug from the blood within 3 hours. About 50% of the measurable active captopril was lost during storage of diluted plasma for one month at -20 degrees C. The assay method is simple and sensitive, and measures active drug only. The present new assay principle may prove convenient and feasible for the assay of captopril and other ACE inhibitors in biological fluids.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Angiotensin I-converting enzyme inhibition after renal transplantation.

The angiotensin I-converting enzyme inhibitor captopril was administrated to 15 renal transplant patients for a minimum period of 14 weeks after transplantation. The object was to decrease ischaemic damage caused by secondary activation of the renal renin-angiotensin system after rejection and associated vascular damage. Captopril patients had lower s-creatinine values than controls in the immediate phase after rejection. On the other hand, after 14 weeks renal perfusion was better, but glomerular filtration rate lower in the captopril group than in the control group. However, none of the differences were significant. Renal function was examined during captopril administration, which may have affected the results. Final evaluation of this trial requires extended follow-up. Captopril was well tolerated in the low doses used (37.5-75 mg daily) in spite of varying degrees of renal failure and concomitant azathioprine administration. Only one case of mild leukopenia was recorded, which improved immediately after captopril interruption. No other serious side effects were observed. Captopril may be safely administered to renal transplant patients, if monitoring of renal function and possible side effects is carried through.

Adult↗
PubMed1984

Inhibitor binding assay for angiotensin-converting enzyme.

We describe a new principle for the determination of enzymes, here applied to angiotensin-converting enzyme (ACE, EC 3.4.15.1) in human serum. The enzyme inhibitor binding assay is based on specific binding of labeled inhibitor to the active center of the enzyme. Serum (10-15 microL) is incubated with 125I-labeled ACE inhibitor (" 351A ," a p- hydroxybenzamidine derivative of N-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline) at pH 7.0 at 37 degrees C for 2 h in a non-equilibrated system. Inhibitor bound to ACE is separated by adsorption to coated charcoal, the radioactivity remaining in the supernate is counted, and the ACE value is calculated from a standard curve. Sensitivity for ACE in serum is 200 U/L, corresponding to 5.0 ng of ACE purified from human lung. The coefficient of variation was 3.9% within assay, and 6.4% between assays for normal ACE activities. Correlation with a comparison spectrophotometric method (Am J Med 59: 363-372, 1975) for ACE assay was excellent (r = 0.98) in 59 samples from healthy subjects and from patients with various diseases including active sarcoidosis. The novel assay principle presented here is simple and specific, and can be extended to use with various biological fluids and tissues, and to other enzymes as well.

Angiotensin-Converting Enzyme Inhibitors↗