Monoaminoguanidine prevents sorbitol accumulation,nonenzymatic protein glycosylation and development of kidney lesions in diabetic rats

Summary Monoaminoguanidine administration (25 mg/kg b.wt, i.p. for 14 weeks) to alloxan diabetic rats (blood glucose 250 mg/dl) decreased the nonenzymatic protein glycosylation and sorbitol levels. It prevented development of Armanni-Ebstein tubular lesions, pathological changes in the glomerular capillary tufts and glomerular basement membrane thickening in the kidney.CDRI Communication no. 4694.     

Renal polycystosis in the rat induced by prednisolone tertiary butyl acetate

Summary A single i.m. injection of 66 mg/kg prednisolone tertiary butyl acetate given on the 1st day of life produced glomerular degeneration and collecting duct and proximal tubule cysts in rat kidneys. There was evidence of delayed nephrogenesis leading to persistance of the neogenic zone.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Summary Low i.v. doses of cadmium chloride (15 g Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed.It is suggested that the renal changes following the i. v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

A2 adenosine receptors in human glomerular mesangial cells

A₂ adenosine receptors were characterized in human glomerular mesangial cells using [³H] 5-N-ethylcarboxamidoadenosine (NECA) as a tracer. There was a single group of receptor sites with a K_D of 184 nM, and a number of sites of 317 fmol/mg of cell protein. Adenosine agonists increased 5-nucleotidase activity via A₂ receptor stimulation. The specific A₂ agonist-NECA, at 0.1 and 1 m, was a potent inhibitor of DNA synthesis.     

Hypoaldosteronism in piglets induced by carbadox

An exploratory study was made of the mechanisms underlying the toxic action of carbadox in young pigs: dehydration, loss of appetite and at autopsy seemingly specific and selective structural alterations of the glomerular zone of the adrenal cortex. Administration of carbadox in the feed, in dosages of 150 ppm (approximately 6 mg X kg-1 b. wt X day-1) caused a rapid decline in the plasma aldosterone levels (to 10% of control) followed by significant changes in the sodium and potassium levels in blood. Characteristic for the toxic action of carbadox are the rapid and seemingly selective and specific alterations in the aldosterone-releasing zona glomerulosa of the adrenals. Our results indicate that with carbadox a functional and possibly reversible extirpation of the adrenal zona glomerulosa can be achieved in pigs.     

Cadmium-induced changes in avian renal morphology

Summary The effects of i.m. administered cadmium on growth rate and nephromorphology were studied in young pullets. The growth rate of pullets treated with 0.6 mg Cd²⁺/kg at 48-h intervals was severely retarded, reaching only 50% of normal growth by 21 days. Such a decrease in growth rate was prevented when cadmium was given with either ferric or magnesium EDTA chelate. Electron micrographs of kidney tissue from cadmium intoxicated birds revealed massive intracellular disorganisation of proximal tubular cells, showing increased vacuolation and dilated endoplasmic reticulum. Mitochondria were few and swollen with reduced cristae. Some disorganisation was noted in the group treated with MgEDTA in conjunction with cadmium, with normal morphology observed in the group treated FeEDTA plus cadmium.In general, glomerular morphology of intoxicated pullets appeared normal, except that a 25% increase in thickness of the glomerular basement membrane was evident. No such membrane thickening was observed in any of the chelate treated groups.These findings indicate that both chelates can provide certain levels of protection, in terms of growth rate and morphology, from cadmium intoxication. The possible mechanisms by which chelates offer protection have been discussed, but many questions remain unanswered.     

Immune-mediated glomerulonephritis induced by mercuric chloride in mice

Summary The BALB/c mouse developed mesangial deposits of immune constituents and light microscopical changes characteristic of immune complex glomerulonephritis after 8 weeks' treatment with mercuric chloride given by s.c. injection. There were no signs of linear of granular immune deposits along the glomerular capillary basement membrane after 2 or 8 weeks. The antigen could not be identified. No antibodies to nuclear or renal structures were found. Using a histochemical method (silver amplification) mercury was detected by light and electron microscopy in tubular and glomerular structures. Mercury was present in secondary lysosomes of the mesangial cells after eight weeks of mercury poisoning.We are deeply indebted to Dr. Gorm Danscher, Institute of Anatomy, B., University of Aarhus, Denmark, for valuable discussions and technical advice. This work was supported by the Swedish Medical Research Council, project no 6536.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Low i.v. doses of cadmium chloride (15 micrograms Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed. It is suggested that the renal changes following the i.v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

Potentiation of immunologic memory by Corynebacterium parvum and its mechanism]

Immune response to bovine serum albumin (BSA) at dose of 2,50 mg/kg which is rather a weak immunogen in Rabbits, when given intravenous was highly potentiated when the animals received a previous single intravenous infection of 2 mg/kg of C. parvum, followed by subsequent BSA anamnestic challenges for several months. Thus, the antibody amounts synthesized following the 1st anamnestic injection (3 weeks) were 0,260 mg/ml in the control versus, 0,800 mg/ml in the C. parvum pretreated groups; following the 2nd anamnestic challenge (12 weeks afterwards) 1 mg/ml in the control versus, 2,50 mg/ml in the treated groups following the 3rd anamnestic challenge (28 weeks afterwards) 1,3 mg/ml in the control versus 5 mg/ml in the C. parvum pretreated groups; following the 4th anamnestic challenge (52 weeks afterwards) 0,300 mg/ml in the control versus 0,800 mg/ml in the C. parvum treated groups. On the whole for the four first anamnestic challenges the differences at peak levels between the control and C. parvum treated groups were about to 4. Furthermore, the antibody molecules synthesized by the C. parvum treated animals were found to belong to IgG class. The results suggest that the immunological mechanisms mobilized are peculiar to C. parvum since they could not be reproduced either by BCG or by Freun'd adjuvant under similar conditions.     

Cadmium-induced changes in avian renal morphology

The effects of i.m. administered cadmium on growth rate and nephromorphology were studied in young pullets. The growth rate of pullets treated with 0.6 mg Cd2+/kg at 48-h intervals was severely retarded, reaching only 50% of normal growth by 21 days. Such a decrease in growth rate was prevented when cadmium was given with either ferric or magnesium EDTA chelate. Electron micrographs of kidney tissue from cadmium intoxicated birds revealed massive intracellular disorganisation of proximal tubular cells, showing increased vacuolation and dilated endoplasmic reticulum. Mitochondria were few and swollen with reduced cristae. Some disorganisation was noted in the group treated with MgEDTA in conjunction with cadmium, with normal morphology observed in the group treated with FeEDTA plus cadmium. In general, glomerular morphology of intoxicated pullets appeared normal, except that a 25% increase in thickness of the glomerular basement membrane was evident. No such membrane thickening was observed in any of the chelate treated groups. These findings indicate that both chelates can provide certain levels of protection, in terms of growth rate and morphology, from cadmium intoxication. The possible mechanisms by which chelates offer protection have been discussed, but many questions remain unanswered.     

Effects of bicuculline and chlordiazepoxide on locomotor activity and avoidance performance in rats

Summary Bicuculline, at a dose of 1 mg/kg which, per se, failed to change locomotor activity in rats, counteracts the facilitating effect induced by chlordiazepoxide (10 mg/kg). Conversely, bicuculline (1 mg/kg) does not modify the decrease of motor activity and the disruption of avoidance performance induced by this benzodiazepine derivative (20 mg/kg).     

Effect of progesterone on male and female sex behavior induced by steroid hormones in adult ovariectomized ewes]

Ovariectomized adult Ewes daily treated with I/M injections of testosterone propionate (10 mg/day) or oestradiol benzoate (200 microgram/day) show male-like sexual behaviour and simultaneously a permanent female receptivity. Additional daily treatment with 100 mg of progresterone results in a rapid decrease in male sexual responses both when Ewes are treated with testosterone and with oestradiol. No effect is observed on the female receptivity. Cyproterone acetate (100 mg/day) given to Ewes in addition to daily injection of testosterone propionate (10 mg/day) has effects similar to those of progesterone. These results show that progesterone has antiandrogen and antioestrogen properties and that this hormone administered at high doses is able to inhibit male activity.     

Effects of inflammatory mediators on the glomerular localization of intravenously administered ferritins

Summary Effects of inflammatory mediators such as serotonin, histamine, and bradykinin upon glomerular localization of i.v. administered ferritins have been investigated. These mediators appear to enhance accumulation of the i.v. injected ferritins in the glomerular capillary walls of rats.     

The angiotensin converting enzyme inhibitor enalapril in acute ischemic renal failure in rats

The influence of the renin-angiotensin system on renal hemodynamics, tubular pressure and tubulo-glomerular feedback was investigated with the angiotensin converting enzyme inhibitor MK 421 (enalapril), in uninephrectomized rats with and without ischemia-induced acute renal failure. In animals with normal renal function proximal tubular pressure and tubulo-glomerular feedback response were lowered by enalapril long-term treatment, whereas glomerular filtration rate and renal blood flow were not influenced by the drug. After 45 and 70 minutes ischemia there was no difference between treated and untreated animals in the severely impaired glomerular filtration rate. Renal blood flow remained unaffected by the treatment. The histological damage due to ischemia (tubular casts, tubular necrosis and medullary capillary congestion) was not influenced by enalapril. As tubulo-glomerular feedback had been significantly inhibited during renin-angiotensin inhibition, its importance in mediating acute renal failure remains doubtful; other factors such as tubular obstruction and medullary congestion may be crucial.     

Neural map formation in the mouse olfactory system

In the mouse olfactory system, odorants are detected by ~1,000 different odorant receptors (ORs) produced by olfactory sensory neurons (OSNs). Each OSN expresses only one functional OR species, which is referred to as the “one neuron–one receptor” rule. Furthermore, OSN axons bearing the same OR converge to a specific projection site in the olfactory bulb (OB) forming a glomerular structure, i.e., the “one glomerulus–one receptor” rule. Based on these basic rules, binding signals of odorants detected by OSNs are converted to topographic information of activated glomeruli in the OB. During development, the glomerular map is formed by the combination of two genetically programmed processes: one is OR-independent projection along the dorsal–ventral axis, and the other is OR-dependent projection along the anterior-posterior axis. The map is further refined in an activity-dependent manner during the neonatal period. Here, we summarize recent progress of neural map formation in the mouse olfactory system.     

Influence of flupirtine, a novel nonopioid analgesic agent on somatosensory evoked potentials in rats.

The effect of flupirtine, a novel nonopioid analgesic, on somatosensory evoked potentials (SEP) was investigated in anesthetized rats. Primary somatosensory potentials were evoked in the cerebral cortex by stimulation of the skin of the whiskery part of the face. Flupirtine injected i.p. dose-dependently prolonged the latency and reduced the amplitude of SEP with ID50-values of 5.4 mg/kg (2.6-9.3 mg/kg) and 7.9 mg/kg (3.9-13.8 mg/kg), respectively. This effect of flupirtine (10 mg/kg, i.p.) on the latency and the amplitude of SEP, did not change when naloxone (1 mg/kg, i.p.) was given before flupirtine. The results indicate that the analgesic flupirtine decreases the primary somatosensory evoked potential by diminishing the excitability of cortical neurons. Opioid mechanisms are not involved.     

Effect of dipyridamole on glomerular mesangial cell ecto-5′-nucleotidase expression

Although dipyridamole has been extensively studied as an anti-aggregating agent, its mechanism of action has not been elucidated. Cultured mesangial cells were treated with dipyridamole 1–100 M from 6–72 h. Ecto-5-nucleotidase activity approximately doubled (from 115±11 to 226±14 nmol/min/mg) after treatment with 100 M dipyridamole for 72 h. This effect was concentration- and time-dependent. Cycloheximide, an inhibitor of protein synthesis, did not alter basal 5-nucleotidase activity. However, it prevented stimulation by 5 M dipyridamole. Adenosine availability at the receptor sites was increased by dipyridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI), which inhibit adenosine uptake into the cell. Addition of dipyridamole or NBTI to the adenosine-treated mesagial cells produced an additive increase in ecto-5-nucleotidase activity. Dipyridamole, through its effect on extracellular adenosine and ecto-5-nucleotidase, may have an influence upon regulation of the glomerular microcirculation.     

Filamentous bodies in human glomerulonephritis

Filamentous bodies have been identified in the glomerular cells of human kidney biopsies. These structures have a close morphological resemblance to ciliary rootlets, although the cells of the glomerular tuft only occasionally bear cilia. Their significance could be, as for cilia, of a cellular disdifferentiation of a pathological cellular proliferation.     

Effects of S-adenosylmethionine and S-adenosylhomocysteine on in vivo synthesis of noradrenaline and serotonin in different parts of the rat brain]

S-adenosylmethionine (0,1 mg/kg/ip) decreases in vivo, norepinephrine (NE) synthesis and does not affect 5-hydroxytryptamine (5 HT) synthesis in the Rat brain. S-adenosylhomocysteine (7 mg/kg/ip) increases NE synthesis and decreases 5 HT synthesis. Neither nucleoside affects dopamine synthesis.     

The COMT inhibitor tolcapone potentiates the anticataleptic effect of Madopar in MPP+-lesioned mice

Orally administered Madopar (levodopa/benserazide 41) dose-dependently antagonized haloperidol-induced (1 mg/kg s.c.) catalepsy in MPP⁺-lesioned mice. Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy. The ability of tolcapone to increase the Madopar effect was significantly attenuated by high doses of 3-O-methyldopa (3-OMD) (800 mg/kg i.p.). This might suggest a competitive blockade of the active transport of levodopa through the blood-brain barrier. In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD.