Interference of chronically ingested copper in long-term potentiation (LTP) of rat hippocampus.

The objective of our study was to find the evidence of copper interaction in LTP, motivated by copper involvement in neurodegenerative illness, like Parkinson, Alzheimer and Amyotrophic Lateral Sclerosis, and we initiated the study of this element in the LTP. For this purpose we used hippocampus slices of rats chronically consuming copper dissolved in water (CuDR; n=26) and non-copper-consuming rats (CR; n=20). The CuDR rats received 8--10 mg/day during 20--25 days. Electrophysiological tests showed absence of LTP in CuDR slices, contrary to CR slices. The stimulus-response test applied before and after LTP showed significant increases of synaptic potential in the CR group. This did not occur in the CuDR group, except for the initial values, which probably seem associated to an early action of copper. The paired-pulse (PP) test, applied to CR and CuDR prior to tetanic stimulation, showed a significant reduction in PP, for the 20-, 30- and 50-ms intervals in CuDR. At the end of the experiments, copper concentration was 54.2 times higher in CuDR slices, compared to the concentration present in CR slices. Our results show that copper reduces synaptic sensibility and also the facilitation capability. These effects represent a significant disturbance in the plasticity phenomenon associated with learning and memory.

Cytoplasmic calcium buffer, calbindin-D28k, is regulated by excitatory amino acids.

Excessive intracellular calcium in neurones is thought to underlie the pathophysiology of several neurodegenerative diseases. An extensively studied animal model is the neurotoxic increases in intracellular Ca2+ induced by excitatory amino acid. We report here that the calcium-binding protein, calbindin-D28k, increases rapidly in Purkinje cells of rat cerebellar slices superfused with excitatory and excitotoxic concentrations of glutamate or its analogue, kainic acid. The increase is reversible and reproducible, is blocked by CNQX and is independent of Ca2+ influx. These results indicate that calbindin containing neurones can regulate their Ca2+ buffering capacity in response to a specific agonist and this regulation is not mediated by cytosolic calcium increases.

The immunocytochemical distribution of calbindin-D28k and parvalbumin in identified neurons of the pulvinar-lateralis posterior complex of the cat.

The calbindin-D28k and parvalbumin immunoreactivities of the neurons of the pulvinar-lateral posterior complex (Pul-LP) were studied in the cat. The neurons of the Pul-LP projecting to the cerebral cortex were identified by a retrogradely transported tracer injected in the suprasylvian gyrus. Two populations of cells were found, a calbindin-D28k-immunoreactive, large-diameter population and a parvalbumin-immunoreactive, small-diameter group. The two kinds of cells are closely intermingled. The former includes the neurons retrogradely marked, and therefore projecting to the suprasylvian gyrus. The latter includes neurons which were not retrogradely marked, and therefore presumably intrinsic elements.

Medialis dorsalis thalamic unitary response to tooth pulp stimulation and its conditioning by brainstem and limbic activation.

In nembutalized cats tooth pulp stimulation (TPS) was effective in exciting 18% of medialis dorsalis (MD) thalamic units. Facilitation of spontaneous MD unitary discharge followed high frequency stimulation of the lateral amygdala (25%), dorsal hippocampus (22%), mesencephalic reticular formation (20%) and septal nuclei (17%). Conditioning high-frequency stimulation of limbic and reticular structures, strongly facilitated the MD unitary responses to TPS. None of the thalamic neurons involved in nociception seems to project to the cerebral cortex. The conditioning effect on MD response of limbic and reticular stimulation suggests that these central structures may be involved in the modulation of the nociceptive input.

Glutamate, GABA, calbindin-D28k and parvalbumin immunoreactivity in the pulvinar-lateralis posterior complex of the cat: relation to the projection to the Clare-Bishop area.

Neurons of the pulvinar-lateralis posterior complex (Pul-LP) containing glutamate (Glu) and GABA, as presumed neurotransmitters, and calbindin- D28k (calbindin) and parvalbumin (PV), as Ca-binding proteins, were identified in the cat by using immunohistochemical methods. In vibratome sections, neurons immunoreactive (IR) to each of the four antibodies were observed throughout the Pul-LP. In semithin sections, GABA-IR neurons were also PV-IR but not calbindin-IR and some of them also co-localized Glu. The Glu-IR neurons which were negative for GABA co-localized calbindin but not PV. The neurons of the Pul-LP projecting to the Clare-Bishop area (CB) in the suprasylvian gyrus were identified with a retrogradely transported tracer and the sections were then immunostained for Glu, GABA, calbindin and PV. Only Glu- and calbindin-IR neurons were retrogradely labeled. These results show that, if calbindin and PV have a Ca-binding role, the presumably excitatory Glu-IR neurons projecting to the CB are use calbindin whereas the presumably inhibitory GABA-IR neurons are intrinsic and use PV. This relationship implies that these proteins probably have other roles specifically related to the kind of agonist to be released at the neuron.

Effect of magnesium valproate on amygdala-kindled seizures in the rat: comparison with sodium valproate.

The anticonvulsant activity of a salt of valproic acid (VA), magnesium valproate (MgV), was assessed against amygdala-kindled seizures in rats. The anti-epileptic power of MgV was compared with that of sodium valproate (NaV). Kindling was obtained by delivering daily to one of the amygdala a 2 s train of monophasic square-wave pulses (1 ms, 60 c.p.s., 100-130 microA) via chronically implanted electrodes. Magnesium valproate and NaV were tested once kindling was stabilized and the post-kindling threshold for generalized convulsions was determined. The drugs were administered intraperitoneally in doses ranging from 25 to 200 mg/kg. The injection/test interval was 30 min. Each animal received a single dose every 24 h. Magnesium valproate exhibited an anticonvulsant activity qualitatively and quantitatively similar to that of NaV. Statistically significant differences were not found between the two drugs with respect to the reduction of seizure severity and afterdischarge (AD) duration. The calculated ED50's were 94.58 and 97.41 mg/kg for the suppression of generalized seizures, 176.96 and 129.26 mg/kg for the suppression of partial seizures, 275.96 and 224.13 mg/kg for the suppression of the local AD in the MgV and NaV treated groups, respectively.

[Urinary excretion of arylsulfatases A and B in patients with renal transplants]. / L'escrezione urinaria di arilsolfatasi A e B nei pazienti sottoposti a trapianto renale.

Arylsulfatase A and B activities have been determined in urine samples from four patients who received a Kidney allograft from living donors as a treatment for terminal uraemia. The values have been compared with those obtained in the urine of the respective donors. Two patients, with optimal renal functionality, the enzymatic activities were in the order of that observed in the urine of the donor in one case and lower than that of the donor in the other case. A patient showing kidney rejection episodes, reversed by the specific therapy, had the enzymatic activities higher than those shown by the donor. Another patient who suffered for two rejections, the last one irreversible, showed a constant higher value of the two enzymatic activities compared with those of the donor and a further increase during the rejection period. In the light of these preliminary results it seems that the determination of the arylsulfatase activities in the urine of transplanted subjects could contribute to establishing the functional activity of the transplanted kidney and also in establishing the tendency of the kidney to undergo rejection.

[Esterification of cholesterol in patients with renal transplants. Determination of lecithin:cholesterol-acyl-transferase (LCAT) activity]. / Esterificazione del colesterolo in portatori di trapianto renale. Determinazione dell'attività lecitin: colesterol-acil-transferasica (LCAT).

In man, cholesterol esterification is controlled by lecithin:cholesterol-acyl-transferase (LCAT), which is a key-role enzyme of lipid metabolism. Though LCAT is synthesized by the hepatocytes, its activity seems to be linked to the kidney: in fact, LCAT activity is lowered in uremic and anephric subjects, and probably also in long-term haemodialysis patients. On the contrary, in successfull renal allografts we found fully restored LCAT activity. But physiopathological mechanisms underlying relationships between LCAT and kidney are still unclarified.

Donor and recipient postoperative complications in living related kidney transplantation. A multicentric study.

BACKGROUND: Living related kidney transplantation is considered a gold standard of renal transplantation in order to overcome end-stage renal disease within the same family members. Living donation, albeit decreasing cadaveric donor shortage, exposes donors to the risk of surgical complications. METHODS: In order to assess the postoperative complication rate in donors and recipients, we reviewed retrospectively 90 consecutive living related kidney transplants in a multicentric study. All nephrectomies were performed extraperitoneally through a left flank incision. RESULTS: Major perioperative complications (first 3 weeks after surgery) occurred in 12 subjects: these included bleeding (2.2%), symptomatic pneumothorax (1.1%), iliac thrombophlebitis (3.3%), iliac artery dissection (1.1%), laparotomic dehiscence (2.2%), perirenal hematoma (1.1%), renal artery stenosis (1.1%), urinary fistula (1.1%). Minor perioperative complications took place in 8 cases. One recipient died. Donor postoperative major complications occurred in 2 subjects. CONCLUSIONS: On the basis of these results we conclude that living related kidney transplantation is an important treatment of end stage renal disease, due to the associated low major complication rate and the high feasibility of this methodology.

The integrative sensorimotor function of the LP-pulvinar complex.

An important number of studies have paid attention to the sensorial function of the LP-pulvinar complex and its probable polisensorial integrative role. In the present review, on the basis of some experimental results, we have tried to emphasize the importance of the LP-pulvinar complex in the motor function. In this sense, this thalamic complex appears as a probable sensorimotor integrative structure. Considering the behavior elicited by electrical as well as chemical stimulation of the LP-pulvinar complex, it would seem that this structure is related to the type of behavior that researches and examines the environment, mainly, by internal motivation. Furthermore, the possible role of the LP-pulvinar complex in the sleep and wakefulness mechanism and in the epileptic phenomena, is mentioned.

Effects of subcortical electrolytic lesions on the head-eye turning response induced by electrical stimulation of the cat's pulvinar-lateralis posterior nucleus complex.

The relations between three subcortical structures and P-LP, all of them capable of inducing contralateral head-eye turning responses when electrically stimulated, were studied in three groups of cats. In all the experiments stainless steel electrodes were chronically implanted in P-LP and in each group of five cats. Electrodes were also placed respectively in the caudate nucleus, superior colliculus and nucleus centralis lateralis. Series of current intensity threshold values for evoking head-eye turning responses were determined in each group, before and after electrolytic lesion of these three subcortical structures. The total observation period was approximately 30 days. Only the destruction of the superior colliculus produced the loss of the ability of the ipsilateral P-LP to evoke turning response. According to these results it is postulated that the efferent pathway that carries the information for turning response from P-LP runs through the ipsilateral superior colliculus.

Copper interaction on the long-term potentiation.

The role of copper on the CA1 piramidal neurons and their sinaptic connections to the Schaffer's collateral was investigated using the field excitatory post-sinaptic potential (fEPSP). The same fEPSP was used to study copper effects on Long-term potentiation (LTP). We have found that copper 10 microM has an inhibitory action on the fEPSP. Similar effects were demonstrated with 10 microM of GABA. Moreover, copper showed a strong inhibitory action on the consolidated LTP. However, copper washout left a significant and persistent excitatory response. In our opinion, copper shows a dual sinaptic effect depending on the sinaptic experience.

Copper sensitivity in dorsal hippocampus slices.

The action of copper on the pyramidal neurons in CA1 of the hippocampus is little understood. Our main aim was to study the possible interaction of copper on the synaptic network in CA1 pyramidal neurons. We used Wistar rats hippocampus slices in a recording chamber. The population response ("population of spikes") collected by an extracellular micropipette under baseline conditions served as control. Copper, GABA, bicuculline and picrotoxin were delivered in different experimental conditions to the slice. One, 10 and 100 microM of copper concentration decreased significantly the amplitude and duration of the population spikes in relation to the control response. This effect did not show concentration dependency. Copper in bicuculline medium decreased significantly the duration response in relation to the control response and in relation to copper effect in a free bicuculline medium. This phenomenon emphasizes the copper action on the GABA (B) and (C) receptors. Copper in a picrotoxin medium increased significantly the excitability of the response. This new effect suggests that copper acts on non-GABA receptors, an effect that could be detected when the GABA receptors were inactivated. As a result of these findings it appears that, under our experimental conditions, copper generated transient sensitivity changes in pyramidal neurons of CA1 dorsal hippocampus.

Neuronal changes induced by chronic toluene exposure in the cat.

Chronic toluene inhalation provokes significant deleterious neurological effects in young glue sniffers and exposed workers. We have developed a chronic toluene inhalation model in the cat to address this issue. Neuronal changes using Loyez and acid fuchsinegallocianine stainings were studied at prefrontal cortex, cerebellun and hippocampus. All this structures showed varying degrees of neuronal degeneration to necrosis. Even if injury signs were widespread, the neuronal layers weren't equally affected and there were clear differences in injury severity. In the prefrontal cortex, injured neurons were observed in layers II, III and V/VI extending over several gyri. Lesions were time related, as was more clearly observed in Purkinje cells. In dorsal hippocampus alterations were particulary severe in CA1 and CA3. In ventral hippocampus damaged neurons were scarce and located mainly in CA2. The possible relation of this findings with behavioral changes observed during chronic toluene inhalation are noted.

Effects of cortical ablations on the turning response evoked by stimulation of the pulvinar-lateralis posterior nucleus complex in the cat.

The role played by the cerebral cortex on turning responses elicited by electrical stimulation of P-LP was studied in 9 chronic cats. In three animals the sensorimotor cortex was bilaterally ablated and the threshold values for inducing a turning response were determined. None of the cats showed abnormal threshold values. In six cats the cerebral cortical area known to have reciprocal anatomical connections with P-LP was unilaterally removed. Seven days after surgery, 50% of the electrodes gave no responses; 25% evoked responses with high thresholds and 25% with normal thresholds. One month after surgery the percentages were: 14, 18 and 68 respectively. Histological findings show important fiber and neuronal degeneration in P-LP. It is postulated that this area of the cerebral cortex plays, a facilitatory role on the P-LP ability to induce turning response and that the recovery of this ability can be explained by the development of P-LP denervation supersensitivity.

Upregulation of Calbindin-D-28k immunoreactivity by excitatory amino acids.

Excessive or prolonged exposure to excitatory amino acids (EAA) are thought to be neurotoxic by altering calcium homeostasis. A protective role of Calbindin-D-28 k (Calbindin) has been postulated due to its capacity to buffer calcium. Calbindin is highly expressed in the Purkinje cells (PCs), of the cerebellar cortex. Changes of the Calbindin immunoreactivity (IR) by the EAA has been here investigated in cerebellar slices maintained in vitro. It was found that at low temperature, PCs are very slightly immunoreactive and therefore the experiments were done at 22 degrees C. The results show that Calbindin-IR increases in PCs exposed to the neurotoxic agonists, Kainic acid (KA) and AMPA as well as to glutamate (Glu), the endogenous EAA. The increase is very rapid and slowly reversible; is induced by excitatory and excitotoxic concentrations of the agonists; is independent of the calcium influx. While KA- and AMPA-induced Calbindin-IR is blocked by CNQX, the KA/AMPA receptor antagonist, Glu-induced Calbindin-IR is only slightly decreased by CNQX and AP5, the NMDA receptor antagonist. It is concluded that Calbindin-containing neurons can increase their calcium buffering capacity in response to EAA binding to specific receptors, the response being independent of, but concomitant to calcium influx.

Electrophysiological projections of pulvinar-lateralis posterior complex (P-LP) upon superior colliculus units in the cat.

The effect of Pulvinar-Lateral Posterior (P-LP) electrical stimulation on superior colliculus unitary responses and eye movements is analyzed in 17 encéphale isolé cats. Twelve of them were curarized. Out of a total of 190 recorded units, 117 were localized in the superior colliculus and 73 units in the Mesencephalic Reticular Formation (MRF) below the superior colliculus. Thirty eight per cent (n = 45) of the collicular units modified their discharge frequency when the ipsilateral P-LP was electrically stimulated. The current intensity thresholds of transynaptic activation had a range between 0.5 and 2.0 mA. Most of the orthodromic responses were produced by ipsilateral P-LP stimulation and were localized in the intermediate and deep layers of the superior colliculus. Three types of responses were obtained: short latency responses between 2 and 10 ms (57%); intermediate latency responses between 15 and 40 ms (29%), and long latency responses between 50 and 200 ms (14%). Thirty one per cent (n = 18) of the units recorded in the MRF responded to P-LP stimulation with 10 ms pulse-trains duration. In the MRF 3 types of responses were observed: 1) a decrease or blockade in the resting discharge during 20 to 100 ms after stimulation (20%); simple responses with a latency between 25 and 150 ms (40%), and complex responses with an early response and a latency between 15-40 ms, and a late response with a latency between 150 and 200 ms (40%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Atypical retinitis pigmentosa in Laurence-Moon-Biedl-Bardet syndrome. Report of a case of chronic renal insufficiency under periodic hemodialysis treatment]. / La retinite pigmentosa atipica nel quadro della sindrome di Laurence-Moon-Biedl-Bardet. Osservazione di un caso in trattamento emodialitico periodico per insufficienza renale cronica.

A case of Laurence-Moon-Biedl-Bardet syndrome in a patient undergoing hemodialysis is reported. The principal characteristics of this congenital syndrome are described. A possible pathogenetic mechanism of the atypical form of retinitis pigmentosa (sine pigmento) is discussed.

[The parenteral administration of essential amino acids in patients on periodic hemodialysis treatment. A pilot study]. / Somministrazione parenterale di aminoacidi essenziali (AAE) nei pazienti in trattamento emodialitico periodico. Studio pilota.

In an attempt to improve the nutritional status of seven hemodialysed patients, 500 ml of a 5.5% nephrological essential amino acid solution (EAA) were administered during each dialysis session for 2 months. At the end of this treatment, a significant increase in albuminemia was found (p < 0.05). These results are an encouragement to continue this therapy, especially if it is kept in mind that the half-life of albumin is much shorter than the period of EAA administration.

[Surveillance by skeletal radiography of patients under hemodialysis. Radiographic examination of the vertebral column]. / La sorveglianza radiologica scheletrica nei pazienti emodializzati. L'esame radiografico della colonna vertebrale.

The authors describe damage to the spine observed by x-ray in patients on maintenance hemodialysis. They stress the importance of including x-ray examination of the spine among the routine checks performed in these patients.