[Characteristics of the clinical picture and course in IgA glomerulonephritis].
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Glomerulonephritis↗
Biomedical subjects
H Brasch
Publications and source records attributed to H Brasch.
Caerulein and morphine in a model of visceral pain. Effects on the hypotensive response to renal pelvis distension in the rat.
In pentobarbital-anaesthetized rats (60 mg/kg, i.p.) renal pelvis distension with a pressure of 80 cm H2O caused a decline in mean arterial blood pressure. This pressure response, which disappeared rapidly after cessation of the distension, was used to study the effects of analgesic drugs known to be effective in renal colic pain in man. Morphine (0.75 and 1 mg/kg, s.c.) and the decapeptide caerulein (1.6, 4 and 8 microgram/kg, s.c.) abolished the pressure response. The effects of the largest doses lasted for at least 30 min. Ineffective in this respect were (a) desulphated caerulein (40 microgram/kg, s.c.) and (b) additional doses of pentobarbital (20 and 40 mg/kg, s.c.). This shows (a) the importance of the sulphated tyrosine (known from previous studies on central effects) and (b) the missing influence of the depth of anaesthesia. Naloxone (0.5 mg/kg, s.c.) abolished the effect of morphine (1 mg/kg, s.c.) but failed to influence that of caerulein (8 microgram/kg, s.c.). Even a fourfold dose of naloxone (2 mg/kg, s.c.) did not weaken the effect of caerulein. Naloxone, per se, was ineffective. These results suggest different mechanisms of the present effects of morphine and caerulein. It appears that renal pelvis distension in the anaesthetized rat can serve as a model of renal colic.
Animals↗
Pharmacokinetics of TRIS (hydroxymethyl-)aminomethane in healthy subjects and in patients with metabolic acidosis.
To investigate the pharmacokinetics of TRIS, an infusion of the buffer was given to 6 healthy volunteers (121 mg/kg = 1 mmol/kg;pH 7.4) and to 20 patients suffering from metabolic acidosis (109--376 mg/kg; pH 10.9). The drug exhibited two-compartment characteristics in volunteers (t0.5,beta = 5.6 h) and patients with intact renal function (t0.5,beta = 16.3--45.6 h). The final volume of distribution (V beta) indicated uptake into tissues, but equilibration between body compartments was slow. Mainly unchanged TRIS was eliminated by the kidney; 82% of the administered dose was recovered from 24 h-urine of healthy subjects. In the patients a linear correlation between creatinine-clearance and TRIS-clearance was observed, the latter always being somewhat greater than the former. Only insignificant amounts of the drug were found in bile and gastric juice. In anuric patients the plasma concentration of TRIS declined monoexponentially, with a half-life between 10 and 58 h. Haemodialysis or haemofiltration did not influence this process. From the data it seems questionable whether cellular uptake of TRIS is an important factor in the therapy of intracellular acidosis, but the possibility of drug accumulation must be borne in mind if repeated doses are given to the same patient.
Acidosis↗
[Light microscopic and immunohistologic studies of IgA glomerulonephritis].
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Adolescent↗
Clinical features and course of IgA glomerulonephritis.
A review of the clinical features, laboratory findings and course in 50 cases of IgA glomerulonephritis confirmed by biopsy is presented. The onset and clinical course of the process was oligosymptomatic in the majority of the cases with a predominance of microhematuria and persistent proteinuria. By the end of the observation period more than 50 per cent of the patients became hypertensive and in 16 cases serum creatinine levels attained 132 mumol/l (1.5 mg per 100 ml) or more. Proteinuria in excess of 1 g/24h, hypertension and an impaired concentration capacity at the onset heralded early progression.
Adolescent↗
Pharmacokinetics of TRIS (hydroxymethyl-)aminomethane in the rabbit.
Pharmacokinetics of TRIS were investigated in rabbits after infusion of 1 mmol/kg. The drug exhibited three-compartment characteristics with long terminal half-life (13 hr). The final volume of distribution V beta (3700 ml/kg) indicated drug accumulation inside cells, but equilibration between compartments was slow compared to drug elimination. From these data is seems questionable whether cellular uptake of TRIS is an important factor in the therapy of intracellular acidosis.
Acidosis↗
IgA glomerulonephritis. Mesangial IgA deposition without systemic signs (Berger's disease).
Renal biopsy specimens from 204 patients with glomerulonephritis or nephrotic syndrome have been studied. In ten of the patients not suffering from acute poststreptococcal glomerulonephritis, systemic lupus erythematosus or Schönlein-Henoch syndrome, diffuse, selective mesangial IgA deposition was observed. Clinically, persistent microscopic haematuria, mild proteinuria and, except in one patient, normal renal function were found. Light microscopically the histological picture was dominated by a diffuse or focal increase in volume of the mesangial matrix, and mild mesangial cell proliferation. Exceptionally, there was also crescent formation. Immunofluorescence revealed large IgA, IgG and C3 deposits, as well as small IgM and fibrinogen deposits in the mesangial glomeruli. The authors' assumption that immunocomplexes containing a secretory component might be implicated in the pathomechanism of Berger's disease, could not be proved.
Adolescent↗
The role of hepatitis B surface antigen in the pathogenesis of glomerulopathies.
The frequency of hepatitis B surface antigen (HBsAg) has been studied in the sera and renal biopsies of 276 patients with various forms of glomerulonephritis (GN), the nephrotic syndrome and other nephropathies. Using a modified Hepanosticon method, HBs antigenemia was detected in 32 of 196 patients (16.3%) with immune complex (IC) GN and the nephrotic syndrome. Indirect immunofluorescence revealed HBsAg in 33 renal biopsy tissue specimens (16.8%). HBsAg was found in the sera of four of the 80 remaining patients with other renal diseases (5%), and in the renal biopsy tissues of another four (5%). Antibody against HBsAg could only be demonstrated in the serum of one glomerulonephritic patient. The sera of 18,799 normal blood donors were used as controls; of these 186 (0.99%) had positive tests for HBsAg. It is concluded that, in some patients with GN and the nephrotic syndrome, HBsAg-containing IC may be implicated in the development and/or progression of the disease.
Adolescent↗
Effects of the local anesthetics brufacain and lidocaine on transmembrane action potentials, refractory period, and reactivation of the sodium system in guinea pig heart muscle.
Lidocaine (3-10(-5) and 10(-4) M) and equimolar concentrations of brufacain dose-dependently reduced the depolarization velocity (dV/dtmax) and the force of contraction of guinea pig atria and papillary muscles. Repolarization time was increased in atria but reduced in papillary muscles. The maximum effects on action potential parameters were identical but developed with brufacain more slowly than with lidocaine. In papillary muscles lidocaine (3-10(-5) M) prolonged the functional refractory period. No such effect but even a shortening was observed with brufacain. As brufacain reduced the duration of the action potential (AP) more than the functional refractory period, the "relative refractory period" (in percent of AP duration) was slightly prolonged. The half-time of the recovery of the Na+ system was increased three to five times the control value after lidocaine but only doubled after brufacain.
Action Potentials↗
Effects of simple indoles, noradrenaline, nicotine, and tyramine on action potential and contractility of the isolated guinea-pig papillary muscle.
1. Simultaneous recordings of both the transmembrane action potential and the contractions were made in isolated electrically driven papillary muscles of the guinea pig in order to compare the effects of 6-methoxyindole (6-MOI), 3-methylindole (3-MI) and 5-methylindole (5-MI) with those of noradrenaline (1.2 - 10(-6) M), nicotine (2 - 10(-5) M), and tyramine (5.8 - 10(-6) M). 2. Noradrenaline, nicotine, tyramine and 6-MOI (5.4 - 10(-4) M) enhanced the contractility whilst 3-MI (3.8 and 7.8 - 10(-4) M) and 5-MI (1.9 and 3.8 - 10(-4) M) had only irregular effects. The active compounds shortened and time-to-peak tension and increased the rate of relaxation. 3. The duration of the action potential was prolonged by noradrenaline, nicotine, and tyramine, but shortened by 3-MI, 5-MI, and 6-MOI. 4. The results showed that the effect of drugs on the action potential are not necessarily linked to those on contractility.
Action Potentials↗
Simple method for in vitro metabolic studies with continuous-flow incubation.
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Animals↗
Influence of phorbol esters on contractile force, action potential and calcium current of isolated guinea-pig heart tissues.
Phorbol-12, 13-dibutyrate (PDB) reduced concentration-dependently the contractile force of guinea-pig papillary muscles (EC50 1.07 mumol/l) while phorbol-12-myristate-13-acetate (PMA) was ineffective. The protein kinase C inhibitors staurosporine (0.1 mumol/l) and polymyxin B (70 mumol/l) did not antagonize the negative inotropic effect of PDB. Neither PMA nor PDB, in concentrations up to 30 mumol/l, caused significant changes of the maximum depolarization velocity, the action potential duration or the functional refractory period in intact papillary muscles. In isolated ventricular cardiomyocytes the inward calcium current was halved by either 1 mumol/l PDB or 10 mumol/1 PMA. PKC inhibitors attenuated, but could not completely abolish this effect of the phorboles. It is concluded that the negative inotropic effect of PDB is caused by a reduction of the slow inward calcium current and that this inhibition is, for the greater part, not mediated by an activation of protein kinase C.
Action Potentials↗
Field stimulation-induced noradrenaline release from guinea-pig atria is modulated by prejunctional alpha 2-adrenoceptors and protein kinase C.
Guinea-pig left atria were loaded with 10 microCi 7-[3H]noradrenaline, and noradrenaline release from sympathetic nerve endings was then elicited by refractory period field stimulation. When one pulse of 0.2 ms duration was applied during each refractory period, the resulting transmitter release was halved by 3 x 10(-7) mol/l of the alpha 2-adrenoceptor agonist clonidine and increased about 2.5-fold by either 3 x 10(-7) mol/l of the alpha 2-adrenoceptor antagonist idazoxan, 5 x 10(-3) mol/l of the potassium channel blocker tetraethylammonium chloride (TEA) or 3 x 10(-7) mol/l phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C (PKC). Phorbol-12-myristate-13-acetate-4-O-methylether, a compound which does not stimulate PKC, was ineffective. The stimulatory effect of PMA was antagonized by 7 x 10(-5) mol/l of the PKC inhibitor polymyxin B. No significant transmitter release was observed when either PMA or TEA was applied together with 10(-7) mol/l of the sodium channel blocker tetrodotoxin. Combinations of either idazoxan and TEA or PMA and TEA caused greater increases of the noradrenaline release than any individual drug given alone. Thus, different mechanisms of action seem to mediate the increase of noradrenaline release by action potential prolongation on the hand and activation of PKC or inhibition of alpha 2-adrenoceptors on the other hand. In contrast, the effects of idazoxan and PMA were not additive, which suggests a common mechanism of action. In atria pretreated for 10 min with 10(-4) mol/l N-ethylmaleimide, an alkylating agent which inactivates Gi-proteins neither idazoxan nor PMA caused a significant increase of the stimulation-induced transmitter release, while TEA was still effective. When a train of four pulses, lasting 0.05 ms each, was applied during each refractory period, the resulting transmitter release was not modified by idazoxan or PMA, but was significantly increased by TEA. From these results, a scheme is proposed which links the regulation of noradrenaline release by prejunctional alpha 2-adrenoceptors and protein kinase C via an influence on a common inhibitory Gi-protein.
Animals↗
Influence of phorbol esters on stimulation-induced noradrenaline release and contractile force of isolated guinea-pig atria.
Phorbol-12,13-dibutyrate (PDB) and phorbol-12-myristate-13-acetate (PMA) increased the field-stimulation-induced efflux of radioactivity from guinea-pig atria preloaded with 7-[3H]-noradrenaline. The efflux was more than doubled by 10(-7) mol/l of either compound. Phorbol-12-myristate-13-acetate-4-O-methylether (PME), which has no effect on the protein kinase C (PKC), did not modify the stimulation-induced efflux of radioactivity, while a slight reduction was seen with 70 microM of the PKC inhibitor polymyxin B. In the presence of polymyxin B, the effects of PMA and PDB were greatly attenuated. In addition, PDB had a concentration-dependent negative inotropic effect (EC50 7.0 x 10(-10) mol/l). Pretreatment with polymyxin B shifted the concentration-response curve for PDB to the right (EC50 4.6 x 10(-9) mol/l). No negative inotropic effect was seen with PMA or PME. The results suggest that all effects of the phorbol esters were mediated by a stimulation of PKC. The different lipophilicity of PMA and PDB or a different influence on the various isozymes of PKC may account for the diverging postjunctional effects of the two compounds.
Animals↗