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Biomedical subjects

A Bäcker

Publications and source records attributed to A Bäcker.

50 records · Page 3Linked to original sources

[Elevated plasma levels and heterogeneity of human atrial natriuretic peptide in patients with progressive chronic renal failure].

The role of human atrial natriuretic peptide (alpha-hANP) in chronic blood pressure (BP) and extracellular fluid volume (ECFV) regulation remains elusive. Hence, the role of alpha-hANP in chronic renal failure is of particular interest since in this pathological condition: (1) increased sodium and water retention plays a major pathogenetic role in the development of hypertension and (2) altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. To evaluate the relationship between the degree of renal insufficiency, BP and circulating alpha-hANP, we determined plasma alpha-hANP concentrations by radioimmunoassay in 16 nondialyzed patients with progressive chronic renal failure (CRF) of various degrees; subsequently analysis of potential molecular heterogeneity of immunoreactive (ir) ANP was performed by means of gel permeation of plasma extracts from patients with CRF without concomitant hypertension. Serum creatinine concentrations ranged from 127 to 1187 (435 +/- 76) mumol/l, systolic BP from 135 to 200 (158 +/- 4) and diastolic BP from 80 to 110 (94 +/- 2) mmHg, respectively. Plasma alpha-hANP concentrations ranged from 5 to 75 (23 +/- 4) pmol/l which was thus significantly higher as compared to 9 +/- 2 pmol/l found in healthy volunteers (p less than 0.05). A highly significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92; p less than 0.01) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66) and serum creatinine concentration (r = 0.59), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Combined treatment of severe essential hypertension with the new angiotensin converting enzyme inhibitor ramipril.

Ramipril is a newly synthesized angiotensin converting enzyme inhibitor without a sulfhydryl group in the molecule but with a prolonged duration of action. Efficacy, tolerance and safety of this drug were evaluated in 10 patients with severe essential hypertension. After a treatment period of at least 4 weeks with the conventional antihypertensive drug combination of a diuretic and a beta-blocking agent with the vasodilator dihydralazine, their systolic and diastolic blood pressures averaged 161 +/- 6 and 111 +/- 2 mm Hg, respectively. Because diastolic blood pressure during this drug regimen was still greater than 105 mm Hg in all patients, the patients received ramipril initially at single daily doses of 5 mg in addition to their previous medication. The first dose of 5 mg ramipril resulted in a moderate but significant decrease in systolic and diastolic blood pressure in 9 of the 10 patients to 142 +/- 5 and 104 +/- 4 mm Hg (p less than 0.01), respectively, between 3 and 6 hours after drug administration. In 1 patient blood pressure was unresponsive to ramipril and 1 patient complained of nausea and vomiting within the first week of treatment with ramipril. Within the following 8-week treatment period with a once-daily intake of 5 or, if necessary, 10 mg of ramipril, diastolic blood pressure normalized in the remaining 8 patients to less than 90 mm Hg. Systolic and diastolic blood pressure averaged 130 +/- 5 and 83 +/- 2 mm Hg, respectively, at the end of the 8-week treatment period with ramipril. Severe hypotension and reflex tachycardia were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship of plasma concentrations of human atrial natriuretic peptide to renal function and blood pressure in patients with progressive chronic renal failure.

Recent experimental and clinical findings indicate that immunoreactive human Atrial Natriuretic Peptide (alpha-hANP) is involved in the regulation of blood volume and arterial blood pressure (BP). Whereas the potential regulatory role of alpha-hANP in acute changes of extracellular fluid volume (ECFV) and in the modulation of BP has been demonstrated in various studies, their involvement in the chronic maintenance of sodium and water homeostasis is still equivocal. Moreover the role of alpha-hANP is of particular interest in chronic renal failure, since in this pathological condition increased sodium and water retention plays a major pathogenetic role in the development of hypertension and altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. To evaluate the relationship between the degree of renal insufficiency, BP and circulating alpha hANP we determined plasma alpha-hANP concentrations in 16 nondialyzed patients with progressive chronic renal failure (CRF) of various degree. Serum creatinine concentrations ranged from 127 to 1187 (435 +/- 76) mumol/l, systolic BP from 135 to 200 (158 +/- 4) and diastolic BP from 80 to 110 (94 +/- 2) mm Hg respectively. Plasma alpha-hANP concentrations ranged from 49 to 753 with a mean of 228 +/- 42 pg/ml which was thus significantly higher as compared to 90.0 +/- 16.2 pg/ml found in healthy volunteers (p less than 0.05). A highly significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66) and serum creatinine concentration (r = 0.59), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Studies on the tubular effects of atrial extract and of atriopeptin III in conscious rats.

To investigate a tubular action of atrial natriuretic peptide (ANP), in the present study the effects of rat atrial extract (AE) and of synthetic rat atriopeptin III (AP III) were assessed in conscious rats during hypotonic saline infusion. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were estimated by the clearances (C) of PAH and of endogenous creatinine, respectively. CPO4 was used as a marker of proximal tubular function. Distal delivery (DD) and distal fractional absorption of chloride (DFACl), a measure of solute absorption in the diluting segments, were calculated from CH2O and CCl. AE and AP III increased RPF in all groups of animals. Low doses of AP III (40 ng/100 g B.W.) significantly increased urine flow rate and CCl, whereas GFR, CNa, CPO4, and CK remained unaltered. The marked natriuresis at high doses of ANP was associated with a rise in GFR and in absolute and fractional CPO4 as well as an increase in DD and CK. AE and AP III (1 microgram/100 g B.W.) decreased DFACl from 0.94 +/- 0.03 and 0.87 +/- 0.03 to 0.80 +/- 0.07 (p less than 0.05) and 0.54 +/- 0.07 (p less than 0.01), respectively. Some of the effects on tubular reabsorptive capacity probably result from medullary wash-out which thereby contributes to the natriuresis by potentiating the rise in the filtered load of sodium at high ANP levels. In the absence of changes in GFR and CPO4, the tubular action of ANP is more accurately reflected by CCl which may result from decreased absorption in the medullary collecting tubule.

Animals↗

Further characterization of the endogenous natriuretic and digoxin-like immunoreacting activities in human urine: effects of changes in sodium intake.

In the present study natriuretic activity and digoxin-like immunoreacting activity (DLIA) were determined in small molecular weight (MW) fractions of urine from healthy subjects during low (35 mmol/day) and high (greater than 400 mmol/day) sodium intake by bioassay and by a radioimmunoassay for digoxin, respectively. After gel filtration of urine on a Sephadex G-25 column the natriuretic activity appeared in the post-salt fraction SIV, whereas DLIA was present in small amounts in the salt fraction SIII and, with consistently higher activity, in the post-salt fraction SIV. Natriuretic activity significantly increased and DLIA decreased in fraction SIV with high sodium intake, but total urinary excretion of DLIA remained unaltered during changes in sodium intake. In addition, anion-exchange and reverse-phase chromatography revealed that DLIA is not specifically related to the natriuretic activity but also reflects unspecific binding of various urine constituents to this digoxin antibody. Although the antibody binds a natriuretic material, this radioimmunoassay is thus unsuitable to determine the endogenous natriuretic activity in urine fractions. Whereas they elute differently on reverse-phase chromatography, amino acid analyses revealed that both the natriuretic factor directly purified from the post-salt fraction SIV and the natriuretic material bound to the digoxin antibody have in common four amino acids at similar molar ratios. The physicochemical properties as evidenced by chromatographic and electrophoretic studies as well as enzymatic inactivation suggest that the low MW natriuretic factor(s) in human urine may be associated with a small peptide(s) of weak acidic nature.

Adult↗

Effects of inhibition of prostaglandin-synthesis on renal electrolyte excretion and concentrating ability in healthy man.

In five healthy subjects inhibition of prostaglandin (PG)-synthesis with indomethacin did not significantly alter glomerular filtration, urinary flow rate or sodium and potassium excretion during control urine collection periods or i.v. hypertonic saline infusion. Saline administration was accompanied by a fall in urinary PGEI-excretion from 0.58 +/- 0.14 to 0.26 +/- 0.09 ng/min (p less than 0.05). While indomethacin had no effect on basal urinary osmolality (Uosm), renal concentrating ability following hypertonic saline or i.v. administration of 100 mU lysine-vasopressin significantly increased in the presence of indomethacin with Uosm rising from 805 +/- 25 to 970 +/- 53 mosm/L (p less than 0.01) and from 839 +/- 47 to 996 +/- 62 mosm/L (p less than 0.01), resp. Since this was not accompanied by respective changes in urinary excretion of cyclic adenosine monophosphate (cAMP) mechanisms other than PG-antagonism of vasopressin, such as decreased medullary washout of solute, may contribute to enhanced renal concentrating ability following inhibition of PG-synthesis with indomethacin.

Adult↗

Ouabain-like factors in human urine: identification of a Na-K-ATPase inhibitor as vanadium-diascorbate adduct.

We investigated endogenous Na-K-ATPase inhibitors, i.e. ouabain-like factors(OLFs), in the urine of salt-loaded healthy subjects. During an intake of > 30g NaCl/day 24h-urines were collected, lyophilized, redissolved and acidified to pH 3.5. With gelchromatography the inhibitory activity eluted in a post-salt fraction FIV from Sephadex G-25. When this fraction was again passed through Sephadex G-10, one of three OLFs eluted in the early subfractions FIV/1-2 close to H-ouabain and cross-reacted strongly with a ouabain antibody (NEN). Two additional OLFs with Mr around 400 eluted in a late subfraction FIV/8 which resolved after reverse-phase HPLC into a more polar OLF- (water phase) and a more apolar OLF-2 (20% acetonitrile). Only the more apolar OLF-2 cross-reacted with digoxin and ouabain antibodies. OLF-1 and OLF-2 purified to single compounds by preparative thin layer chromatography inhibited Na-K-ATPase with IC50 of around 1.5 x 10(-5) M and 1.5 x 10(-4) M, respectively. Identification of OLF-2 was first attempted because most material was available for further processing. Data from mass-spectroscopy, nuclear magnetic resonance (1H-NMR) and infrared spectroscopy characterized OLF-2 as structurally unrelated to ouabain but resembling ascorbic acid derivatives, i.e. vanadium (V) diascorbates (Mr 403) with similar elution times from RP-HPLC as OLF-2. They inhibited the enzyme in its E2-configuration with IC50 of 9 x 10(-5) M and 2 x 10(-6) M for V(IV)- and V(V)-diascorbate, respectively. OLF-1, OLF-2 and V-diascorbate raise intracellular free calcium in inner medullary collecting duct and vascular smooth muscle cells which also contract in vitro. V-diascorbate was also natriuretic in a bioassay. We suggest that V-diascorbates represent one of several OLFs excreted in human urine.

Adult↗

[Effects of significantly increased perinatal risks on developmental status in adolescence].

In a 13-years-catamnesis a sample of 50 children with severe perinatal risks was assessed with regard to their physical, cognitive and behavioral development; selective drop-outs were analysed. In accordance with the results of other prospective studies there are deficits in visual-motor functioning, higher rates of somatic complaints, social withdrawal and attention deficits; a large number of these children attend special schools. The study presents predicative relations between risk factors of birth-time and the developmental status at youth. In comparison with typical single risks (e.g. gestational age or respiratory distress syndrome) a complex index for the perinatal risk, the so-called birth-optimality offers no substantial advantage. A significant influence of social factors is shown for school achievement. Children of fathers with higher educational level are attending schools of a higher grade. The combination of biological and social factors improves the reliability of developmental prognosis; the Mental Developmental Index of the Bayley Scales of Infant Development provides additional prognostic accuracy. For compensating developmental disadvantages especially parents with lower educational level should be informed about beneficial care. Even children of these families, who scored low in early cognitive assessments should receive early intervention or therapeutic support.

Adolescent↗