Interactions between essential fatty acid,prostanoid, polyol pathway and nitric oxide mechanisms in the neurovascular deficit of diabetic rats

Summary Impaired -6 essential fatty acid metabolism and exaggerated polyol pathway flux contribute to the neurovascular abnormalities in streptozotocin-diabetic rats. The potential interactions between these mechanisms were examined by comparing the effects of threshold doses of aldose reductase inhibitors and evening primrose oil, alone and in combination, on neurovascular deficits. In addition, highdose aldose reductase inhibitor and evening primrose oil treatment effects were challenged by co-treatment with the cyclo-oxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, N^G-nitro-l-arginine. Eight weeks of diabetes caused an 18.9% reduction in sciatic motor conduction velocity (p<0.001). This was only modestly ameliorated by a 0.1% dietary supplement of evening primrose oil or the aldose reductase inhibitors ZD5522 (0.25 mg · kg^–1 · day^–1) and WAY121509 (0.2 mg · kg^–1· day^–1) for the final 2 weeks. However, joint treatment with primrose oil and ZD5522 or WAY121509 caused marked 71.5 and 82.4% corrections, respectively, of the conduction deficit. Sciatic nutritive blood flow was 43.1% reduced by diabetes (p<0.001) and this was corrected by 67.8% with joint ZD5522 and primrose oil treatment (p<0.001). High-dose WAY121509 (10 mg · kg^–1 · day^–1) and primrose oil (10% dietary supplement) prevented sciatic conduction velocity and nutritive blood flow deficits in 1-month diabetic rats (p<0.001). However, these effects were abolished by flurbiprofen (5 mg · kg^–1 · day^–1) and N^G-nitro-l-arginine (10 mg · kg^–1 · day^–1) co-treatment (p<0.001). Thus, the data provide evidence for synergistic interactions between polyol pathway/nitric oxide and essential fatty acid/cyclo-oxygenase systems in the control of neurovascular function in diabetic rats, from which a potential therapeutic advantage could be derived.Abbreviations ARI Aldose reductase inhibitor - EPO evening primrose oil - NCV nerve conduction velocity - NO nitric oxide - NOLA N^G-nitro-l-arginine     

NMDA receptor-independent mechanisms responsible for the rate of rise of cumulative depolarization evoked by trains of dorsal root stimuli on rat spinal motoneurones

The mechanisms responsible for the rate of rise (RR) of cumulative depolarization induced by dorsal root stimulus trains were investigated with intracellular recordings from motoneurones of the rat isolated spinal cord. The NMDA receptor antagonists CPP or APV depressed the cumulative depolarization but not its RR which could still be fast enough to elicit action potential wind-up. RR size was correlated with a slow synaptic potential (detected in CPP or APV solution) with which it shared similar voltage dependence. The NK1 antagonist SR 140333 depressed cumulative depolarization, RR and slow synaptic potentials. It appears that the RR (and the ability to express wind-up) was determined by summation of slow synaptic potentials partly mediated via activation of NK1 receptors.     

Spinal accessory nerve palsy due to neurovascular compression. Report of a case diagnosed by magnetic resonance imaging and magnetic resonance angiography

The case of a young patient with left accessory nerve paralysis is reported. He had slight tilting of the head to the right side, developed over a period of about 6 months. On neurological examination hypotrophy of the left sternocleidomastoid and trapezius muscles was observed. MRI and MR-angiography imaged the presence of a neurovascular compression between the medulla oblungata, at the level of the nerve entry zone, and a vessel loop of an elongated left vertebral artery. In spite of the absence of a surgical demonstration it is our opinion that the neurovascular conflict is the cause of the accessory nerve palsy.     

Continuous infusion of rocuronium in a paediatric intensive care unit

Purpose  

To evaluate prospectively the efficacy and dose requirements of rocuronium administered by continuous infusion for neuromuscular blockade in a paediatric ICU population.     

Bilateral traumatic abducens nerve paralysis with cervical spine flexion injury

Bilateral traumatic abducens nerve palsy is a rare condition. We report a case associated with cervical spine flexion injury. This may be the first such case report, as no similar case was found in our review of the literature. The mechanisms of injury in this case are relevant to theories that explain hyperextension injuries.     

Lymphocyte stimulation by acetylcholine receptor in polymyositis

Summary Lymphocytes of twenty-seven patients with polymyositis were incubated in vitro with cholinergic receptor rich membranes obtained from the electric organs of Torpedo Marmorata.Lymphocytes of polymyositic patients were slightly stimulated; positive responses were present mainly in patients affected from more than a year. Sensitization against the nicotinic cholinergic receptor may explain the occurrence of the myasthenic syndrome with polymyositis.Fellow of the A. Villa Rusconi foundation     

Denervation supersensitivity of the urethra to α-adrenergics in the chronic neurogenic bladder

Summary The response of the urethral pressure profile to the administration of various autonomic drugs was compared between a group of eight patients with chronic neurogenic bladder as evidenced by denervation supersensitivity to besacholine^R and a group of 10 control subjects. A supersensitive response to the administration of an -stimulant with a rise of maximum urethral pressure of 10 mmHg or more above the control urethral pressure was uniformly observed in the urethra of patients with chronically denervated bladders. Mechanisms of supersensitivity are postulated and the significance of -adrenergic innervation of the urethra are stressed. These results appear to add pharmacological evidence of -adrenergic predominance in the urethra which is now believed to be dually innervated.     

Responses of long descending propriospinal neurons to natural and electrical types of stimuli in cat

Long descending propriospinal (LDP) neurons (antidromically identified) having cell bodies of origin in the cervical enlargement and projecting axons at least as far as the L2 segment were studied. Extracellular recording of responses to natural and electrical stimuli was done in high-spinal cats.

(1) A receptive field for natural stimuli was found for 123 LDP neurons. An additional 108 LDP cells were not activated by the natural stimuli used, but some of these fired spike potentials in response to electrical stimulation of peripheral nerves of the forelimb. There was no distinction between neurons activated and those not activated by natural stimuli on the basis of location or conduction velocity.

(2) The most effective natural stimuli were mechanical manipulation of the skin (both low and high threshold), movement of joints of the paw, and pressure to the deep tissues, especially to the extensor side of the arm. These modalities of stimuli were most often excitatory, but could be inhibitory as well.

(3) On the basis of modality, 4 subgroups of LDP cells were identified: those which were responsive only to mechanical-cutaneous, joint-movement, or deep-pressure stimuli, and those which responded to several of these modalities of stimuli, the multimodal group. These subgroups could not be distinguished on the basis of conduction velocity.

(4) The receptive fields varied in size from small (one digit) to large (all of a forelimb). For single LDP cells they included ones with single and/or multimodal input from one or both forelimbs and various combinations of excitation and/or inhibition. However, those in the dorsal horn had only ipsilateral receptive fields, mainly of the mechanical-cutaneous type. Cells with bilateral receptive fields were mainly located medially in the ventral gray in laminae VII and VIII.

(5) A comparison of the location of the subtypes of LDP cells revealed that neurons activated by mechanical-cutaneous stimuli were in laminae I and IV–VIII; whereas deep-pressure and multimodal activated neurons were almost exclusively in laminae VII and VIII.

(6) LDP cells receiving input from deep-pressure receptors in the extensor muscles of the arm, joint-movement, or deep-pressure receptors of the paw probably relay position or weight-bearing information about the forelimbs to the lumbosacral spinal cord. This arrangement suggests that LDP neurons function in interlimb coordination and would be active during locomotion. They probably participate also in other reflexes elicited by cutaneous and deep stimuli.

Methyldopa produces central inhibition of parasympathetic activity in the cat

Summary -Methyldopa (10–100 mg/kg i.v.) produced a dose-dependent pupillary dilation in anaesthetized cats which was antagonized by subsequent administration of yohimbine hydrochloride (0.5 mg/kg i.v.). The peak effects were observed approximately 2–3h after injection. This -methyldopa-induced mydriasis was present only when the parasympathetic innervation to the iris was intact. Prior treatment with yohimbine (0.5 mg/kg i.v.) 30 min before -methyldopa also antagonized the mydriatic effect, whereas pretreatment with phenoxybenzamine (2.5 mg/kg i.v.) did not. In contrast, phenoxybenzamine, but not yohimbine, effectively antagonized the pupillary dilation produced by adrenaline (0.3–10.0 g/kg i.v.). These results suggest that -methyldopa produces mydriasis in the cat by means of CNS inhibition of tonic outflow from the oculomotor nucleus and that an -adrenergic inhibitory mechanism may be involved. This conclusion is supported further by experiments in which direct measurements of ciliary nerve activity were made.     

Oxolinic acid and diazepam: Their reciprocal antagonism in rodents

The stimulant effects of oxolinic acid were investigated in rats and mice. This drug, given orally, consistantly induced, in doses ranging from 16 to 256 mg·kg^-1, locomotor stimulation and stereotyped behavior.These effects were antagonized by pimozide (1 mg·kg^-1), -methyltyrosine (64 mg·kg^-1) or reserpine (4 mg·kg^-1, 24 h before testing) pretreatment, suggesting a facilitatory role of oxolinic acid on catecholaminergic processes.Diazepam (4–16 mg·kg^-1) reduced the stimulant effects induced by oxolinic acid but not those induced by amphetamine; oxolinic acid (8 mg·kg^-1) markedly reduced the antipunishment effect elicited in rats by diazepam (2 mg·kg^-1). Since benzodiazepines have been reported to enhance GABA functioning, these data suggest that oxolinic acid may impair GABA transmission. However, neither muscimol (0.5–1 mg·kg^-1) or -acetylenic-GABA (16–64 mg·kg^-1) selectively reduced the stimulant effects elicited by oxolinic acid. Therefore, the possible facilitation exerted by this drug on catecholaminergic systems may not derive from the release of an inhibitory GABAergic control.