Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.     

Causal relationship between a tumour growth and the changes in histamine metabolism in tissues of sarcoma-bearing rat

The relationship between malignancy and histamine metabolism in the liver and the small intestine has been examined in sarcoma-bearing Wistar rats two weeks after subcutaneous implantation of a transplantable methylcholanthrene sarcoma Sa1828 and on the 3, 7 and 14th days after tumour extirpation. Two weeks after tumour implantation, the histamine level was increased by 100% and 50% in the liver and the small intestine, respectively. On the 3rd day after extirpation of the tumour the level of histamine had returned to the control values and remained unchanged during the next 10 days. Neither of the histamine catabolizing enzymes, diamine oxidase with a putrescine as a substrate or histamine methyltransferase were influenced by the existing tumour or by its extirpation except on the 14th day where a high increase in diamine oxidase activity was found. Some changes in the distribution of histamine metabolites suggest an involvement of an oxidative pathway of histamine catabolism as well as the aldehyde catabolizing enzymes in tumour development.     

Separation of temperature sensitive and temperature insensitive components of the postsynaptic potentials in the frog motoneurons

Intracellular measurements were made in the in situ spinal cord of the frog at temperatures below 5 degrees C. Responses to volleys in the sciatic nerve, in the descending fibres and in the motor axons were studied. About 30% of the motoneurons responded to sciatic volleys with 1-3 ms segmental latency, which was short enough to assume electrotonic mediation of these responses. Another group of motoneurons responded with 6-8 ms latency, i.e. with the expected delay at chemical synapses at low temperature. Latency distribution of the sciatic-evoked postsynaptic potentials was clearly bimodal in contrast with that found at higher temperatures. Postsynaptic discharges occurred with rather long latency and they were attributed to chemically-mediated excitation. Some of the postsynaptic potentials to descending volleys also occurred with quite short latency, indicating possible electrotonic transmission from supraspinal centres to motoneurons. Latency distribution of the action potentials evoked from the motor axons was bimodal, corresponding to the different, i.e. antidromic and recurrent facilitatory, mechanism of these spikes. Calculated Q10 ratios for the sciatic-evoked reflex discharges and the afferent fibre volleys were about 2.3 and 1.8, respectively. We concluded that cooling helps to separate postsynaptic potentials according to their electrotonic and chemical mediation and that electrotonic excitation does not seem to have a primary role in the generation of postsynaptic discharges initiated by dorsal root volleys in the frog.     

Dopamine, serotonin and noradrenaline changes in the striatum of C57BL mice following myelin oligodendrocyte glycoprotein (MOG) 35-55 and complete Freund adjuvant (CFA) administration.

Many data suggest involvement of inflammation in neurodegeneration. However, the exact mechanisms of this cooperation are poorly understood. We have previously shown that induction of inflammatory reaction, both before and after injury of the striatum, affects regeneration of dopaminergic neurons. In the present research we studied the role of inflammatory reaction in non-injured striatum. We used myelin oligodendrocyte glycoprotein (MOG) 35-55 in complete Freund's adjuvant (CFA) to elicit experimental autoimmune encephalomyelitis (EAE) mice model. As determined by HPLC, striatal dopamine (DA) and serotonin levels in mice treated with either MOG 35-55 in CFA or CFA alone were significantly higher compared to vehicle-treated controls on 13th day after induction. The ratio of homovanilic acid/dopamine (HVA/DA) and 3, 4 dihydroxyphenylacetic acid/dopamine (DOPAC/DA) were significantly lower in the MOG and CFA groups on 13th day, indicating decreased DA metabolism. Noradrenaline (NA) concentration did not differ between groups. Moreover, the striatal mRNA IL-1beta and TNF-alpha levels were elevated during induction phase of EAE in both groups, as determined by RT-PCR. Our data indicate regulatory connection between dopaminergic and immune systems.     

The role of histamine in wound healing. II. The effect of antagonists and agonists of histamine receptors (H1 and H2) on collagen levels in granulation tissue

The effects of mepyramine (H₁-receptor antagonist), cimetidine (H₂-receptor antagonist), IEM-813 (H₁-receptor agonist) and 4-Met-Hi (H₂-receptor agonist) on collagenogenesis processes in subcutaneous implanted sponges of rats were studied. Administration into sponges of cimetidine 30 min before histamine injection blocked both the stimulatory effect of low histamine doses and the inhibitory effect of high histamine doses on collagen formation. Low doses of 4-Met-Hi increased collagen levels but reduced the levels at high doses. Mepyramine and IEM-813 did not influence collagen biosynthesis.     

Phosphopyridoxal complexes with histamine and histidine (5) the kinetics of cyclic compound formation between histamine and pyridoxal-5′-phosphate in the presence of pig kidney diamine oxidase and rat intestinal histaminase

Pig kidney diamine oxidase (DAO) and rat intestinal histaminase (Hi-are) activities are inhibited in vitro by high concentrations of both a substrate (histamine) and a coenzyme (pyridoxal-5-phosphate). This inhibition may be at least partially associated with the formation of a cyclic compound between histamine (Hi) and pyridoxal-5-phosphate (PLP).The dynamics of this cyclic compound formation in the presence of both enzymes has been examined. In an incubation mixture containing partially purified pig kidney DAO, the rate of cyclization decreased slightly as compared with a buffer. On the contrary, in the presence of crude rat intestinal histaminase, the rate of cyclization was inhibited significantly; this inhibition was proportional to the amount of enzyme preparation present in the incubation mixture. The possible mechanism of the influence of enzyme protein on the rate of cyclic compound formation, and its possible biological significance, are discussed.     

A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems

Intradermal inoculation of rats at the tail base with Mycobacterium butyricum led to the gradual development of an arthritic swelling of the limbs which peaked at 3 weeks and subsided thereafter. Arthritic rats displayed a loss of body weight, hypophagia, and hypodipsia in addition to a disruption of the diurnal rhythms of ingestive behavior and of core temperature. The activity of adenohypophyseal beta-endorphin-(beta-EP) secreting corticotrophs, in contrast to prolactin-(PRL) secreting lactotrophs, was increased in arthritic rats. Indeed, hypertrophy of the adrenal glands was seen. Arthritic rats also showed an elevation in spinal cord levels of immunoreactive dynorphin (DYN), an endogenous ligand of the kappa-opioid receptor. The paws and tail of arthritic rats showed lower thresholds in response to noxious pressure (hyperalgesia), higher thresholds in response to noxious heat (hypoalgesia), and no change in their response to noxious electrical stimulation. Neither naloxone nor ICI-154, 129 (a preferential delta-receptor antagonist) modified the responses of the paw or tail to pressure. However, MR 2266 (an antagonist with higher activity at kappa-receptors) decreased thresholds to pressure in arthritic, but not control, rats; that is, it potentiated the hyperalgesia. This action was stereospecific. None of the antagonists modified the response to heat. MR 2266 did not affect the response to pressure in rats with acute inflammation produced by yeast. Thus, the potentiation of pressure hyperalgesia by MR 2266 in chronic arthritic rats is highly selective. Arthritic rats showed a reduced response to the analgesic effect of a kappa-agonist (U-50,488H), whereas the response to a mu-agonist (morphine) was enhanced. These effects were specific to nociception in that their influence upon endocrine secretion (PRL and beta-EP) was otherwise changed. The secretion of beta-EP and PRL was stimulated by both morphine and U-50,488H, and the influence of U-50,488H upon the release of beta-EP (from the adenohypophysis) was enhanced in arthritic rats. It is suggested that polyarthritis is a complex condition entailing many changes, both behavioral and endocrinological. Further, arthritic rats cannot simply be described as "hyperalgesic": of critical importance is the nature of the nociceptive stimulus applied. The parallel alterations in spinal cord pools of DYN and kappa-receptors (see also Millan et al., 1986) and the changes in the influence on nociception of kappa-agonists and kappa-antagonists suggest an increased activity of spinal DYN. Thus, spinal kappa-receptors may play a role in the modulation of nociception under chronic pain.(ABSTRACT TRUNCATED AT 400 WORDS)     

Electrophysiological characteristics and morphological properties of dentate granule--and CA3 pyramidal cells in slices cut from neonatally irradiated rats

Neonatal irradiation reduces the dentate granule cells by 60-80%, and consequently the mossy fiber projection toward the CA3 and hilar areas decreases. The number of hilar cells diminishes. Thorny excrescences on the dendrites of the CA3 pyramidal cells get smaller both in number (from 20-30 per neuron in normal to 1-6 per neuron after irradiation) and in size. In spite of these morphological changes functional efficacy of the mossy-fiber projection to CA3 pyramidal cells remains sufficient to generate monosynaptic action potentials when stimulated electrically. Inhibitory circuits activated by mossy fiber volleys seem to be unaffected by irradiation. Main biophysical properties of CA3 pyramidal and surviving granule cells remain within the normal range. Further work should determine if efficacy of the mossy fiber projection increases to compensate for the substantial decrease of presynaptic input, or the power of transmission far exceeds the level needed to fire postsynaptic cells in normal rats.