Increased incidence of gap junctional coupling between spinal motoneurones following transient blockade of NMDA receptors in neonatal rats

Neonatal rat motoneurones are electrically coupled via gap junctions and the incidence of this coupling declines during postnatal development. The mechanisms involved in this developmental regulation of gap junctional communication are largely unknown. Here we have studied the role of NMDA receptor-mediated glutamatergic synaptic activity in the regulation of motoneurone coupling. Gap junctional coupling was demonstrated by the presence of graded, short latency depolarising potentials following ventral root stimulation, and by the transfer of the low molecular weight tracer Neurobiotin to neighbouring motoneurones. Sites of close apposition between the somata and/or dendrites of the dye-coupled motoneurones were identified as potential sites of gap junctional coupling. Early postnatal blockade of the NMDA subtype of glutamate receptors using the non-competitive antagonist dizocilpine maleate (MK801) arrested the developmental decrease in electrotonic and dye coupling during the first postnatal week. These results suggest that the postnatal increase in glutamatergic synaptic activity associated with the onset of locomotion promote the loss of gap junctional connections between developing motoneurones.     

Symptomatic reversible duodenal compression due to iatrogenic retroperitoneal hematoma

Selective serotonin reuptake inhibitors are frequently employed to treat depression. However, although rarely, coagulation abnormalities have been described following the use of these compounds, and these effects appear to be enhanced by simultaneous use of nonsteroidal anti-inflammatory drugs. We describe a case of reversible symptomatic duodenal compression caused by a retroperitoneal hematoma after ingestion of sertraline and nimesulide.     

Sleep complaints and their relation with drug treatment in patients suffering from Parkinson's disease.

The aim of this research was to quantify sleep problems in patients suffering from Parkinson's disease by means of the new Parkinson's Disease Sleep Scale (PDSS) and to correlate such problems with the possible influence of current drug treatment. A total of 70 patients (36 men and 34 women) with a diagnosis of Parkinson's disease were enrolled. Their mean age was 69.7 +/- 8.2 years, and duration of disease was 7.4 +/- 4.8 years. All patients completed the PDSS and the Unified Parkinson's Disease Rating Scale (UPDRS Parts I-IV). Drug consumption and doses were registered. The mean score on the PDSS scale was 109.23 +/- 19.75 and on the UPDRS III scale was 25.24 +/- 11.35. The lowest scores were obtained in Item 3 (sleep fragmentation): 5.53 (2.46); and in Item 8 (nocturia): 5.75 (2.91). There was a weak correlation between the PDSS and UPDRS III (cc = -0.355, P = 0.003), PDSS and UPDRS I (cc = -0.272, P = 0.02), and PDSS and UPDRS IV (cc = -0.416, P < 0.001). Motor conditions, mental state, and drug complications influence sleep quality. Although this effect was significant, it was not of a great magnitude. Dopaminergic drugs did not increase daytime sleepiness. As a whole, sleep quality in patients who took dopaminergic agonists did not differ from that of patients who took levodopa in monotherapy.     

Age-related changes in the turnover rates of D1-dopamine receptors in the retina and in distinct areas of the rat brain

The steady-state density and the turnover rates of D₁-dopamine receptors were investigated in the striatum, nucleus accumbens, substantia nigra, and retina of adult (3-month-old) and aged (23-month-old) rats. The turnover rates were measured by monitoring the repopulation kinetics of D₁-dopamine receptors labeled with [³H]-SCH 23390 after the irreversible inactivation induced by a single dose of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 mg/kg, s.c.). In all the neural tissues examined, the repopulation of D₁ dopamine receptors could be adequately described by a theoretical model that assumes a constant rate of receptor production (i.e. zero order) and a rate of degradation that is dependent on the receptor density at any time (i.e. first order). The results obtained indicate that the reduction in the density of D₁-dopamine receptors in the striatum, nucleus accumbens and substantia nigra of aged rats is the result of a larger decrease in the receptor production rate (−44 to −60%) than in the receptor degradation rate (−21 to −46%). By contrast, the production rate of D₁-dopamine receptors in the retina of aged rats remains unchanged, whilst the degradation rate is reduced by 25%. This results in an age-related increase in the density of D₁-dopamine receptors in the rat retina.     

Early Postnatal Changes in the Somatodendritic Morphology of Ankle Flexor Motoneurons in the Rat

The development of locomotor function in the rat spans the first 3 postnatal weeks. We have studied morphological features of the soma and dendrites of motoneurons innervating the physiological flexor muscles of the ankle, tibialis anterior and extensor digitorum longus, by intracellular injection in vitro between the first and ninth postnatal days. We obtained serial optical sections of 96 adequately filled motoneurons in whole-mounted hemisected spinal cords by confocal microscopy, projected them onto a single plane and analysed them morphometrically. On the day after birth, the somatodendritic surfaces of most such motoneurons were covered in growth-associated spiny, thorny or hair-like appendages. These had disappeared from the soma by the fourth postnatal day and from most proximal dendrites by day 7, but were still common distally on day 9. During this period there was little or no net growth of either the soma (which was still much smaller than in the adult) or the dendritic tree. A dorsal dendritic bias was present and 'sprays' of long, loosely bundled dorsal dendrites were often seen. The mean number of primary dendrites remained constant at about eight, and their combined diameter was already significantly correlated with mean soma diameter, as in the adult cat. Thus, the critical neonatal period during which these ankle flexor motoneurons are known to change their electrophysiological properties and to be particularly sensitive to interference with neuromuscular interaction is characterized by major changes in the neuronal surface, presumably linked to synaptogenesis.     

The late growth hormone rise induced by oral glucose is enhanced by cholinergic stimulation with pyridostigmine in normal subjects

OBJECTIVE: We have investigated the late GH rise occurring 3-5 hours after oral glucose administration. We have assessed the effect of endogenous cholinergic enhancement with pyridostigmine on the delayed GH rise following oral glucose loading in normal subjects. DESIGN: Placebo or 75 g oral glucose was given to the normal subjects 3 hours before 120 mg oral pyridostigmine or placebo. Four tests were carried out at random. (0 min) + placebo (180 min); test 2: glucose (0 min) + placebo (180 min); test 3: placebo (0 min) + pyridostigmine (180 min); test 4: glucose (0 min) + pyridostigmine (180 min). SUBJECTS: We studied eight normal subjects (four male and four female), ages 19-29 years, body mass indices 18-22 kg/m2. MEASUREMENTS: Plasma glucose and serum GH concentrations were measured for 6 hours after oral glucose or placebo administration. RESULTS: Pyridostigmine treatment significantly enhanced the GH releasing effect of prior (3 h) oral glucose. Late GH peak obtained by oral glucose loading rose from (mean +/- SEM) 17.4 +/- 4.6 to 37.2 +/- 9.0 mU/l (P < 0.05) after pyridostigmine, while GH peak following placebo plus pyridostigmine was 12.4 +/- 2.0 mU/l (P < 0.05 vs glucose plus pyridostigmine). The analysis of GH area under curves (AUCs) in the second phase of the tests (180-360 min) confirmed that glucose plus pyridostigmine released a greater amount of GH (4128 +/- 764 mU/l/3h) than glucose (1694 +/- 494 mU/l/3h, P < 0.001) or pyridostigmine alone (1292 +/- 150 mU/I/3h, P < 0.001). CONCLUSIONS: Pyridostigmine, an indirect cholinergic drug likely to inhibit somatostatin secretion from the hypothalamus, enhanced the late GH releasing activity of oral glucose. There is evidence that glucose suppresses plasma GH initially by increasing hypothalamic somatostatin release. This would result in an increase in the pituitary stores of GH. We propose that the delayed GH rise after oral glucose occurs when there is a fall in hypothalamic somatostatinergic tone; this is further reduced by the administration of pyridostigmine. At this time the pituitary stores of GH are released as a consequence of resumption of hypothalamic GHRH activity. This leads to the late GH rise.