Absorption and retention of nickel from drinking water in relation to food intake and nickel sensitivity.

Two studies were performed to examine the influence of fasting and food intake on the absorption and retention of nickel added to drinking water and to determine if nickel sensitization played any role in this regard. First, eight nonallergic male volunteers fasted overnight before being given nickel in drinking water (12 micrograms Ni/kg) and, at different time intervals, standardized 1400-kJ portions of scrambled eggs. When nickel was ingested in water 30 min or 1 h prior to the meal, peak nickel concentrations in serum occurred 1 h after the water intake, and the peak was 13-fold higher than the one seen 1 h after simultaneous intake of nickel-containing water and scrambled eggs. In the latter case, a smaller, delayed peak occurred 3 h after the meal. Median urinary nickel excretion half-times varied between 19.9 and 26.7 h. Within 3 days, the amount of nickel excreted corresponded to 2.5% of the nickel ingested when it was mixed into the scrambled eggs. Increasing amounts were excreted as the interval between the water and the meal increased, with 25.8% of the administered dose being excreted when the eggs were served 4 h prior to the nickel-containing drinking water. In the second experiment, a stable nickel isotope, 61Ni, was given in drinking water to 20 nickel-sensitized women and 20 age-matched controls, both groups having vesicular hand eczema of the pompholyx type. Nine of 20 nickel allergic eczema patients experienced aggravation of hand eczema after nickel administration, and three also developed a maculopapular exanthema. No exacerbation was seen in the control group. The course of nickel absorption and excretion in the allergic groups did not differ and was similar to the pattern seen in the first study, although the absorption in the women was less. A sex-related difference in gastric emptying rates may play a role. Thus, food intake and gastric emptying are of substantial significance for the bioavailability of nickel from aqueous solutions.

[Fulminant acne]. / Acne fulminans.

We describe a case of a 16-year old boy, who presented with sudden onset of an extreme pustular reaction in seborrhoeic areas of the skin with accompanying general malaise such as fever and arthralgia. This picture is one of fulminant acne, which is a rare disease, for which reason diagnosis may be delayed. Permanent scarring of the skin is inevitable, but scarring may be reduced if early treatment with 13 cis-retinoid is started.

Basophil histamine release induced by anti-IgE and concanavalin A. Relation to the total plasma IgE content.

The plant lectin concanavalin A (Con A) has been shown to induce basophil histamine release by an IgE-receptor-dependent process resembling that of anti-IgE-antibodies. In this study, the concentration-response for basophil histamine release from washed blood cells was analyzed in a population of blood samples from adults with a total plasma IgE content ranging from < 5 kU/l to > 18,000 kU/l (n = 108), as well as 148 cord blood samples. The concentration-response-curves for anti-IgE in all adult blood samples were similar, despite the large variation in total plasma IgE--only the cord blood samples showed a decreased sensitivity. In contrast, the optimal concentration of Con A was inversely related to plasma IgE, and this relation was most pronounced in the adult blood samples. It is proposed that IgE-receptor-mediated histamine release may be dependent not only on the number of stimulatory, dimeric cross-links formed between IgE-receptors, but also on the molecular structure of the cross-linking agent.

[Pathomimia]. / Patomimi.

Three cases of pathomimia are presented. The lesions are described and the characteristic lack of response to even prolonged treatment is illustrated. Interpretation of automanipulation as a cutaneous symptom of a psychopathological condition is discussed. The therapeutic success depends upon the psychiatric treatment which is difficult to carry out as it is frequently contrary to the patient's wishes.

Time-course studies of immediate and delayed immune reactivity in patients with atopic dermatitis treated with herbal drugs.

We followed a number of in vitro parameters in nine adult patients with atopic dermatitis for a period of 3 weeks during which the patients took herbal drugs that are claimed to improve chronic eczema. The following investigations were performed weekly: blood leucocytes, circulating eosinophils, serum IgE, mitogen responsiveness of lymphocytes, interleukin 1 release, soluble interleukin 2 receptor levels in serum, and in vitro histamine release from basophils in blood. The study demonstrated increased levels of IgE in six patients, increased levels of soluble interleukin 2 receptor in six patients, and a significant correlation between the amount of IgE in serum and the maximal release of histamine from basophils in blood. In this open study five patients experienced a clinical worsening of their disease during the intake of herbal medicine. All other parameters were within normal levels. There was no significant change in the in vitro parameters during the observation period.

Argon laser induced cutaneous sensory and pain thresholds in post-herpetic neuralgia. Quantitative modulation by topical capsaicin.

Sensory and pain thresholds to cutaneous argon laser stimulation were determined in patients with post-herpetic neuralgia before and during treatment with topical capsaicin. Before treatment both thresholds were significantly elevated on the affected side compared to the contralateral normal area. After one week of capsaicin treatment both thresholds were significantly increased compared to the pre-treatment values, and the subjective pain relief, measured on a visual analogue scale (VAS) was 24%. More than 10% decrease in VAS pain score was obtained by 62.5% of the patients. Laser stimulations at levels at which the sensory and pain thresholds are reached were initially described as burning or stinging with pain projecting outside the stimulated area. This allodynia to laser stimulations changed during capsaicin treatment towards normal sensory and pain perception qualities. Both sensory and pain thresholds and the subjective pain score evaluated on a visual analogue scale were attenuated during the capsaicin treatment, suggesting a significant role of the cutaneous sensory and pain receptors in postherpetic neuralgia.

Histamine release from skin mast cells and basophils in patients with urticaria pigmentosa.

Histamine release from dispersed skin mast cells may be used for functional studies on the mast cell. However, technical difficulties have hampered such studies. In the present study a new fiberglass-based histamine assay was applied to previously described dispersion techniques, using excision biopsies from 7 patients with urticaria pigmentosa, 3 with psoriasis as well as 4 with urticaria. However, sufficient mast cell numbers for performing histamine release could only be obtained from patients with urticaria pigmentosa. The average mast cell yield was 935 +/- 470 cells (mean +/- SD) per mg wet weight of tissue. The skin mast cells from these patients responded with dose-dependent histamine release to anti-IgE, calcium ionophore A23187, and N-formyl-methionyl-leucyl-phenylalanine challenge without previous passive sensitization. The pattern of histamine release of mast cells and corresponding blood basophils did not indicate substantial differences between the two cell types.

Prenatal methylazoxymethanol treatment potentiates d-amphetamine- and methylphenidate-induced motor activity in male and female rats.

The effects of the stimulant drugs, d-amphetamine and methylphenidate, upon the motor activity of male and female off-spring of pregnant rats, treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg) were studied in four experiments. Cortical and striatal hypoplasia induced by prenatal administration of MAM resulted in increased concentrations of catecholamines in those regions. Administration of d-amphetamine and methylphenidate caused significant increases in motor activity; this effect was markedly potentiated in the MAM-treated rats, both the male and female off-spring. Thus, the locomotion and total activity parameters showed similar, but not identical, drastic increases in behaviour induced by the stimulant drugs as a result of the prenatal MAM treatment whereas for the rearing parameter a lesser potentiation by the MAM treatment was observed. This potentiation of the excitatory effects of the stimulant compounds upon the behavioural parameters is interpreted in terms of a relative increase in the density of catecholaminergic terminals in the forebrain regions of the central nervous system. The present results are discussed with regard to the utility of prenatal MAM treatment as a possible animal model for certain neurological disorders.

Selective attention and place navigation in rats treated prenatally with methylazoxymethanol.

Prenatal treatment of rats on gestation day 15 with methylazoxymethanol (MAM) caused forebrain microencephaly. The behavioral analyses included measures of spontaneous motor activity and tests for cognitive deficits, and were performed when the rats had reached adult age. Female MAM-treated rats failed to demonstrate contextual control of latent inhibition, which confirms earlier findings with male rats. Male MAM-treated rats demonstrated a notable impairment of place navigation in a swim-maze, but showed as strong sensory preconditioning as the control animals. Biochemical analyses indicated considerable increases in catecholamine levels in the cerebral cortex, hippocampus and striatum. The cognitive deficits, characterised by the various conditioning (taste-aversion) and instrumental learning (swim-maze) tasks, suggested that the MAM rats are deficient in their capacity to attend selectively to the relevant stimulus in complex arrangements of the stimulus situation.

Impaired selective attention in methylazoxymethanol-induced microencephalic rats.

Prenatal treatment of rats on gestation day 15 with methylazoxymethanol (MAM) caused forebrain microencephaly. Several behavioral tests were performed when the rats had reached an adult age. MAM treated rats were hyperactive, and were severely impaired in the acquisition of successive position reversal in a T-maze. The microencephalic rats failed also to demonstrate contextual control of latent inhibition (the stimulus preexposure effect) in taste-aversion conditioning. These results indicate that MAM treatment disrupts attentional processes and that this may account for the learning impairment.

Central noradrenaline depletion antagonizes aspects of d-amphetamine-induced hyperactivity in the rat.

The effects of noradrenaline (NA) depletion upon amphetamine-induced hyperactivity were examined in five experiments. Central NA depletion via either systemic DSP4 or neonatal 6-OHDA antagonised the amphetamine-induced (2 mg/kg SC) increase in rearing behaviour, whereas lesions of the dorsal noradrenergic bundle using 6-hydroxydopamine antagonised the increase in locomotor activity. Peripheral NA depletion following systemic 6-hydroxydopamine to adult rats did not cause any changes in motor activity after acute amphetamine administration. Desipramine, the selective NA uptake inhibitor, blocked the effects of DSP4 upon amphetamine-induced rearing. NA depletion antagonised hyperactivity produced by the 2 mg/kg dose of amphetamine, but not the hyperactivity (rearing or locomotion) effects of amphetamine at 1, 4 or 8 mg/kg.

Increased total activity in the rat after L-tryptophan plus the monoamine oxidase-A inhibitor amiflamine but not after L-tryptophan plus clorgyline.

The effect of pretreatment with either saline or the monoamine oxidase-A inhibitors clorgyline and amiflamine upon the total activity, locomotion and rearing behaviour of the rat induced by various doses of the monoamine precursor L-tryptophan was studied by use of automated activity boxes. Amiflamine (2.5 and 5.0 mg kg-1, i.p.) increased in a dose-dependent manner total activity and to a lesser extent, locomotion when given 60 min before L-tryptophan (100 mg kg-1, i.p.). The increased activity was seen after amiflamine plus either 25 or 75 mg kg-1 L-tryptophan. Rearing behaviour was not affected. Analysis of 5-hydroxytryptamine (5-HT) and its deaminated metabolite 5-hydroxyindoleacetic acid (5-HIAA) by high performance liquid chromatography with electrochemical detection indicated that in both frontal cortex and hypothalamus, amiflamine (at both doses) increased 5-HT and reduced 5-HIAA concentrations. Combination of amiflamine with L-tryptophan (100 mg kg-1, i.p.) resulted in a higher 5-HT concentration being found than after amiflamine alone. L-Tryptophan treatment alone did not change 5-HT concentrations but increased 5-HIAA concentrations. Clorgyline, at a dose of either 1 or 5 mg kg-1 i.p. plus L-tryptophan (25 or 100 mg kg-1, i.p.) did not increase total activity, locomotion or behaviour. A number of possible explanations for the differences in the behavioural effects of clorgyline and amiflamine when given with L-tryptophan are discussed. It is concluded that in addition to monoamine oxidase-A inhibition, other pharmacological effects of the drugs, such as 5-HT release (amiflamine) and inhibition of tryptophan hydroxylation (clorgyline) may be of importance in determining the magnitude of the increase in activity when the compounds are given together with L-tryptophan.

Role of olfactory bulbectomy and DSP4 treatment in avoidance learning in the rat.

Olfactory bulbectomized rats and DSP4-treated rats were studied on a two-way active avoidance task as well as on step-down passive avoidance and fear conditioning and retention tasks in three experiments. The DSP4-treated, but not olfactory bulbectomized, rats were impaired in acquiring two-way avoidance; bulbectomized, but not DSP4-treated, rats were found to show notable passive avoidance and fear retention deficits. Bulbectomized rats treated with DSP4 did not show passive avoidance and fear retention deficits, nor did these animals evidence the two-way avoidance impairment of the DSP4-treated rats. No alteration of dopamine-beta-hydroxylase activity in the frontal cortex and hippocampus as a result of the bulbectomy operation was indicated. The double dissociation between bulbectomized and DSP4-treated rats is discussed in terms of opponent behavioral processes, influenced by olfactory bulbectomy and DSP4, which may permit insights into experimental investigations of stress, anxiety, and depression.

T-maze learning, spontaneous activity and food intake recovery following systemic administration of the noradrenaline neurotoxin, DSP4.

Following systemic administration of the noradrenaline (NA) neurotoxin, DSP4 (50 mg/kg), rats were found to be retarded in the rate at which they acquired the "right-turn" running response in a modified T-maze choice situation, as measured by the total number of errors per session and median latency to reach the goal box. Desipramine (DMI, 20 mg/kg), injected 30 min before DSP4 blocked the acquisition retardation. DSP4 was found to have a short-lasting effect upon spontaneous motor activity, while food and water intake recovery was complete within 7 days of the injection. Both the NA-accumulation data and endogenous NA concentrations indicated profound NA, but not 5-hydroxytryptamine (5-HT) and dopamine (DA), depletions in the cortex, hippocampus and cerebellum. These data seem to confirm the role of the locus coeruleus-noradrenaline (LC-NA) system in an instrumental learning situation.

The relationship between marginal bone loss and serum zinc levels.

Serum was analyzed for zinc in 51 patients of varying age and with varying degrees of alveolar bone loss as recorded on roentgenograms. There was a reversed correlation between marginal alveolar bone loss and serum zinc levels. The observations are discussed in relation to the physiological functions of zinc.