Cold-induced cholinergic urticaria--case report.

A 9-year-old child with cold-induced cholinergic urticaria was studied. When exposed to cold water or ambient cold air, the patient developed generalized urticaria. The lesions consisted of punctate wheals and surrounding erythema similar to that seen in cholinergic urticaria. The patient did not react to cutaneous challenge with an ice cube and a cold water immersion test was negative. Urticaria was not provoked by vigorous exercise sufficient to cause profuse sweating. The methacholine skin test was reactive. The patient was well controlled by combination therapy with hydroxyzine plus cyproheptadine.

[The role of reinnervation of the stomach in the development of recurrent ulcers]. / Znachenie reinnervatsii zheludka v vozniknovenii retsidivnykh iazv.

The interrelationship of the state of the acid- and enzyme-forming function of the stomach with the alteration of its nerve system, parietal and main cells at different time after vagotomy was studied. The following reappearance of hypersecretion and the formation of a peptic ulcer of the anastomosis in the patients appears to be a results of reinnervation of the stomach.

[Effect of the cholinergic system on EEG-detected paroxysmal activity in West syndrome]. / Vliianie kholinergicheskoi sistemy na paroksizma'lnuiu aktivnost na EEG pri sindrome Uésta.

Sixteen patients or convalescents of West syndrome (WS) were studied. The function of cholinergic neurons was investigated by means of physostigmine or atropine testing. In all the cases physostigmine had a considerable inhibitory effect and atropine++ supported the EEG paroxysmal++ activity. Cholinergic system has an important role to play in the WS pathogenesis.

Alcoholism and depressive disorders: is cholinergic sensitivity a biological marker?

There is an overlap between alcoholism and depressive disorders. However, alcoholics tend to be resistant to the effect of cholinergic agonists, whereas depressives tend to be more sensitive. A recently developed animal model of depression which is more sensitive to cholinergic agonists is also more sensitive to the acute effects of ethanol. These consistent human and animal studies suggest that cholinergic challenges may be helpful in separating alcoholics from depressives.

Hypertension following intrathecal injection of cholinergic agonists in conscious rats: role of endogenous acetylcholine.

The spinal cord is capable of initiating a significant and long-lasting pressor response following intrathecal injection of cholinergic agonists in freely moving rats. The magnitude of the pressor response to the cholinesterase inhibitor, neostigmine, was greatest when the site of injection was restricted to the thoracic level. Intrathecal (i.t.) injection of neostigmine (1-10 micrograms) elicited a dose-related increase in mean arterial pressure of up to 45 mm Hg which remained elevated for almost 2 h. Significant inhibition of acetylcholinesterase was localized to the spinal cord, with the thoracic region exhibiting the greatest degree of inhibition. Also, depletion of spinal acetylcholine levels following i.t. injection of hemicholinium-3 (HC-3) resulted in a significant reduction in the magnitude of the neostigmine-induced pressor response. Carbachol, a direct-acting cholinergic receptor agonist also increased mean arterial pressure following i.t. injection. However, the pressor response to carbachol was not reduced following HC-3. For both agonists, cardiovascular changes were accompanied by significant behavioral changes characterized by tremor, scratching, tail biting and chewing. The appearances of these behaviors following neostigmine injection were reduced in frequency and intensity in HC-3-pretreated animals. These findings demonstrate the ability of spinal cholinergic neurons to mediate a significant hypertensive response. The presence of marked behavioral changes accompanying the cardiovascular response suggests the possibility that cholinergic neurons may be part of an ascending spinal system.

Growth hormone deficiency is not associated with impaired vagal cholinergic nervous system activity in children.

Central cholinergic mechanisms mediate release of growth hormone (GH) as well as peripheral secretion of pancreatic polypeptide (PP). To determine if impaired ability to secrete GH is associated with defective PP response, we studied the PP, epinephrine, and norepinephrine responses to insulin-induced hypoglycemia in 31 children evaluated for GH deficiency by insulin-arginine stimulation (IATT) and 24-h integrated concentrations of GH (IC-GH). Eleven patients had normal GH by IATT and IC-GH (controls), 10 patients had normal GH by IATT but subnormal IC-GH, 10 patients had GH deficiency by both IATT and IC-GH. PP levels peaked at the time of glucose nadir, and remained elevated for 20 min thereafter. The peak PP and incremental PP change from baseline were not significantly different among the three groups. The log peak PP response was inversely correlated with the glucose nadir (r = -0.5, p less than 0.005). Peak PP levels were also significantly correlated with the peak epinephrine levels (r = 0.6, p less than 0.001) but not with norepinephrine. Our findings suggest that 1) GH deficiency disorders are not associated with impaired vagal cholinergic response to hypoglycemia; 2) in children the magnitude of PP response is inversely related to the degree of hypoglycemia; and 3) the peripheral hormonal manifestation of autonomic nervous system responses to hypoglycemia as measured by PP and epinephrine levels are closely correlated.

Is nocturnal asthma caused by changes in airway cholinergic activity?

A randomised, double blind, placebo controlled crossover trial of high dose nebulised ipratropium was carried out in 10 asthmatic patients with documented nocturnal bronchoconstriction. Patients received nebulised saline or ipratropium 1 mg at 10 pm and 2 am on two nights. Absolute peak flow (PEF) rates were higher throughout the night after the patients had received ipratropium (at 2 am, for example, mean (SEM) PEF was 353 after ipratropium and 285 l/min after placebo). The fall in PEF overnight, however, was similar with ipratropium and placebo. Patients were given a further 1 mg nebulised ipratropium at 6 am on both nights. There was a significant overnight fall in PEF on the ipratropium night even when comparisons were made between the times that maximal cholinergic blockade would be expected, PEF falling between 11.30 pm and 7.30 am from 429 to 369 l/min. The percentage increase in PEF, though not the absolute values, was greater after ipratropium at 6 am than at 10 pm. These results confirm that ipratropium raises PEF throughout the night in asthmatic patients, but suggest that nocturnal bronchoconstriction is not due solely to an increase in airway cholinergic activity at night.

The effect of concussive head injury on central cholinergic neurons.

This study examined the effect of fluid percussion head injury on the activity of cholinergic neurons in specific brain areas of the rat 12 min, 4 h and 24 h following injury. Acetylcholine (ACh) turnover, used as an index of cholinergic neuronal activity, was determined using a gas chromatographic-mass spectrometric technique. The most striking changes in cholinergic activity were observed in the dorsal pontine tegmentum, where concussive head injury produced an increase in ACh turnover 12 min and 4 h following injury. This area has been previously associated with behavioral changes observed following concussive injury. ACh turnover in the thalamus, a region to which pontine cholinergic neurons project, also tended to increase 4 h following injury. On the other hand, ACh turnover tended to decrease in the amygdala 4 h following injury. Although there were no significant changes in hippocampal ACh content or turnover following injury. ACh content did tend to increase in that brain region 12 min following injury. There were no significant effects of injury on cholinergic neurons in the cingulate/frontal cortex. These changes in cholinergic neuronal activity may contribute to the neurological deficits following concussive injury. In particular, activation of cholinergic neurons in the pontine region may contribute to components of behavioral suppression associated with reversible traumatic unconsciousness. More generalized changes in cholinergic function may lead to the production of more chronic deficits.

Animal models of Alzheimer's disease: experimental cholinergic denervation.

Several animal models of AD have been developed, based upon the consistent finding of a presynaptic cholinergic deficit in AD. Significant cell loss in the NBM, the primary cortical cholinergic afferent, has been reported in AD. Lesions of the corresponding nuclei in the rodent and primate produce a persistent cholinergic deficit, but no consistent change in other neurotransmitter systems. Significant mnestic and cerebral metabolic deficits are observed acutely after lesion, which are responsive to pharmacological reversal and recover over time. Administration of AF64A produces similar mnestic and cholinergic deficits as NBM lesion, but these effects may be less responsive to pharmacological reversal. Administration of scopolamine, a muscarinic receptor antagonist, produces transient receptor blockade, mnestic deficits and deficits in cerebral metabolism, which can be reversed with a variety of pharmacological agents. The primary dissociations between these models and the deficits in AD are the lack of pharmacological response and recovery of function in AD patients and the presence of non-cholinergic neurochemical and cytoskeletal abnormalities. Future research should focus upon the systematic production and analysis of non-cholinergic neurotransmitter and cytoskeletal abnormalities to determine the contribution of these factors to the pathology seen in AD and the production of deficit in aged animals, which may more closely approximate the deficits in AD. The analysis of factors involved in recovery of function and pharmacological response in animal models may provide insight into potential treatment approaches to AD.

Cholinergic urticaria, passive transfer experiments from human to monkey.

Passive transfer experiments in cholinergic urticaria were carried out from 16 patients to a Macaca cymnologous monkey. Intravenous Evans blue dye was used to demonstrate vascular permeability. The animal was challenged after 24 h first by heating the serum-injected dorsal skin to 45 degrees C and secondly by superinjection of acetylcholine into serum-injected sites, and a control site. Local heat proved insufficient to evoke a response. Seven of 16 serum-injected sites showed positive reaction to acetylcholine, control injection of acetylcholine did not. These experiments suggest the presence of a serum factor in cholinergic urticaria which, with acetylcholine, causes increased vascular permeability.

The seminal vesicle in eight and 16 week streptozotocin-induced diabetic rats: adrenergic, cholinergic and peptidergic innervation.

The autonomic innervation of the seminal vesicle from 8 and 16 week streptozotocin-induced diabetic rats and age-matched controls was studied by pharmacological, histochemical and immunohistochemical methods. Contractions in response to electrical field stimulation, which were abolished using prazosin (2 microM) or tetrodotoxin (one to 1.6 microM), and to noradrenaline were significantly increased in both eight and 16 week diabetic animals. The contractile response to acetylcholine was significantly increased in the 16 week diabetic rats only, when compared with controls. Although these responses were significantly increased, no difference was found in ED50 and EF50 values between control and diabetic rats. Vasoactive intestinal polypeptide (0.3 microM) had no effect on resting tension or nerve-mediated responses. In seminal vesicles from control animals, both vasoactive intestinal polypeptide-immunoreactive and acetylcholinesterase-containing nerves were localised around the folds of the columnar epithelium of secretory cells, in contrast to neuropeptide Y-immunoreactive and catecholamine-containing nerves which were found in the smooth muscle layers. In seminal vesicles from both eight and 16 week diabetic animals no difference was seen in distribution or density of acetylcholinesterase-containing nerves; there was an increase in density and fluorescence intensity of vasoactive intestinal polypeptide- and neuropeptide Y-immunoreactive nerves and a decrease in catecholamine-containing nerves compared with controls. The results are discussed in relation to autonomic neuropathy in diabetes.

Novel approaches to the pathophysiology of heatstroke: the energy depletion model.

De-emphasis of the role of anhydrosis as the primary cause of heatstroke has resulted in increased usage and acceptance of animal models for heatstroke research. When the total amount of work achieved by the running rat prior to exhaustion was plotted against the rate of heat storage, a heretofore unrecognized relationship emerged. These new data suggest that physical exhaustion and heat exhaustion represent opposite ends of a continuum related to the rate of heat storage. Changes in thermoregulatory and/or physical performance can be estimated by a two-dimensional shift in the work-output/thermal storage ratio. Potassium depletion reduces thermoregulatory/physical performance; a combination of atropine plus diazepam appears to improve it. The role of the cholinergic nervous system in eliciting alterations in thermoregulatory and physical ability is reviewed; endurance training, shivering, acclimatization, set-point theory, the anticholinergic syndrome, lithium intoxication, and choline deficiency are discussed.

Rats with nucleus basalis magnocellularis lesions mimic mnemonic symptomatology observed in patients with dementia of the Alzheimer's type.

College students, healthy elderly subjects, patients diagnosed with mild or moderate dementia of the Alzheimer's type, as well as rats with small or large lesions of nucleus basalis magnocellularis (NBM) were tested on an order memory task for a 6- or 8-item list of varying spatial locations. Similar patterns of order memory deficits as a function of serial order position were observed in rats with small or large NBM lesions and patients with mild or moderate dementia of the Alzheimer's type. The results provide support for the possibility that rats with NBM lesions might mimic the mnemonic symptomatology of Alzheimer's disease.

Chorea.

A variety of neurotransmitters have been implicated in the pathophysiology of chorea as exemplified by Huntington's chorea. These include dopamine, serotonin, acetylcholine, GABA and a variety of neuropeptides including substance P and somatostatin. Despite biochemical data that suggests that alterations in other neurotransmitters may be of greater significance, pharmacologic data still supports a major role of dopamine in the actual clinical manifestation of chorea.

Cholinergic-dependent cognitive deficits in Parkinson's disease.

In a double-blind cross-over study, the effects of a subthreshold dose of scopolamine (0.25 mg) on memory were compared in 32 control subjects and 32 parkinsonian patients who were without any sign of intellectual and mnemic impairment. Although the scores of the controls in the memory test battery showed no deterioration after the administration of scopolamine, the same dose resulted in significantly reduced memory performance in parkinsonian patients in two tests which involved the recognition of meaningless drawings. The selective vulnerability of parkinsonian subjects without cognitive impairment to a subthreshold dose of scopolamine suggests the existence of an underlying alteration of central cholinergic transmission. The neuropsychological findings in our study agree with postmortem biochemical data, which showed decreased cortical choline acetyltransferase activity in all parkinsonian patients, suggesting the existence of neuronal compensation in parkinsonian patients who are without cognitive impairment.

Wechsler Intelligence Scale profiles, the cholinergic system, and Alzheimer's disease.

Forty-one patients with putative Alzheimer's Disease (AD) were evaluated to determine the diagnostic utility of a profile of Wechsler Adult Intelligence Scale (WAIS) subtests which has been proposed by Fuld (1984) to identify cholinergic dysfunction. Only nine (21.9%) of these patients had positive Wechsler profiles. Half (n = 21) of the AD patients had been given the WAIS, and the other half (n = 20) the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Positive profiles occurred more often in the AD subgroup given the WAIS-R, but this difference was not statistically significant. Specificity of the formula was evaluated using Wechsler results of 42 older normals and 30 patients who were being evaluated for dementia but who did not have AD. One of the 42 normals (2.4%) and five of the patient controls (16.7%) showed a positive Wechsler profile. Because of the Fuld formula's low sensitivity, a negative Wechsler profile cannot be used to help rule out AD. Although specificity of the formula is high, the diagnostic value of a positive Wechsler profile is modest even under the most favorable AD baserate conditions.