Effects of malaoxon on phosphatidylinositol signaling in convulsing and non-convulsing non-pregnant and pregnant female rats and their offspring.

Phosphatidylinositol (PI) signaling during organophosphate (OP) induced convulsions and tissue Ca2+ changes in 10 weeks old male, and 14 weeks old non-pregnant and pregnant female rats, and the offspring of the latter were explored. Brain inositol and inositol-1-phosphate (Ins1P) served as indices of alterations in brain PI signaling, and brain tissue Ca2+ as an index of early neuronal injury. A dose of malaoxon OP, which produced convulsions in about 60% of the exposed rats in different rat groups, was 39.2 for male, and 8.2 mg/kg for pregnant female rats, respectively. Malaoxon (8.2 mg/kg) did not produce convulsions in non-pregnant female rats. All the rats were followed for 1 or 4 hr subsequent to malaoxon. Malaoxon decreased cerebral inositol in both male and female rats, and the decrease was similar in spite of the dose difference. The decrease was larger in the convulsing than in the non-convulsing rats. A tendency towards a decrease of brain inositol also occurred in the offspring. Ins1P levels were markedly increased in male, and also in non-pregnant female rats, but not in the brains of pregnant female rats. Ins1P was not markedly changed in the brains of the offspring. Malaoxon elevated brain tissue Ca2+ in male but not in female rats or their offspring. Cholinergic systems and PI signaling in the brain seem to be associated with OP-induced convulsions both in male and female rats; females seem to be more sensitive than males. Malaoxon may also have slightly modified PI signaling in the offspring brain. Hormonal factors are likely to modify OP CNS toxicity and cholinergic stimulation of brain PI signaling.     

Assessment of class-specific antibodies against denatured DNA in patients with systemic lupus erythematosus

In this retrospective study 103 serum samples from 16 females with systemic lupus erythematosus (SLE), obtained during a mean follow-up time of 2 years, were investigated for the presence of anti-denatured [single-stranded (ss)] DNA antibodies of the IgG, IgM, and IgA classes. The anti-ssDNA antibodies were determined by an enzyme-linked immunosorbent assay (ELISA), and the results were expressed in three ways: as units derived from a single serum dilution and as two parameters,E andA, calculated from the dose-response curve,E being an estimate of the effective amount of antibodies andA a function of the reaction constant between the antigen and the antibody. The simultaneous occurrence of anti-ssDNA antibodies of all three immunoglobulin classes was seen most often in the patients with the shortest duration of the disease. Clinically active disease was found to correlate with high reaction constants of the IgA anti-ssDNA antibodies. There was also an association between the IgA anti-ssDNA antibody levels and the presence of nephritis. Great fluctuations in the amounts of effective antibodies of the IgG class were seen in seven patients, in six of whom changes in the disease activity also were seen. Changes in the disease activity were unaccompanied by fluctuations in the IgG anti-ssDNA levels in four patients; two of these patients were positive for antibodies against extractable nuclear antigens. We conclude that it is of value to express the results of the anti-ssDNA ELISA as a function of the dose-response curve when monitoring patients with SLE and that immunoglobulin class-specific determinations of anti-ssDNA antibodies may provide information about the disease activity in many patients with SLE.     

Comparison of electrical thresholds of intradental nerves and jaw-opening reflex in the cat

In experimental animals the jaw-opening reflex in response to stimulation of pulp nerves has been used as a nociceptive reflex. However, there seems to be only scanty information about the amount and types of pulp nerve fibres that mediate the reflex. In the present work on 8 anesthetized cats electrical thresholds of single functional pulp nerve units were compared to the thresholds of jaw-opening reflex. Monopolar cathodal current pulses were applied to each canine tooth. Reflex responses of the digastric muscle were recorded. The inferior alveolar nerve of the left side in 3 cats was exposed for nerve dissection and responses of pulp nerve units coming from the lower left canine tooth were recorded. The mean threshold of the jaw-opening reflex with 10 ms pulses was 5.9 +/- 3.0 (SD) microA. Below or at the level only part of the fast conducting pulp nerve units could be activated. Thresholds of A- (n = 32) and C- (n = 24) fibres were 9.9 +/- 5.7 and 37.4 +/- 14.5 (SD) microA respectively. Nerves of the periodontal tissues (20 units recorded) were not activated with current pulses of up to 200 microA applied to the tooth. Consequently, at threshold level the jaw-opening reflex in response to the present type of stimulation is mediated by the fast conducting intradental nerve units.     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Summary Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4° C or +23° C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG∶NA and 5-HIAA∶5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

Catecholamines in pericardial fluid of normotensive, spontaneously hypertensive and reserpine-treated rats

In this study our aims were to investigate the presence and source of catecholamines in pericardial fluid of normotensive, reserpine-treated and spontaneously hypertensive rats. We found that noradrenaline is the only detectable catecholamine present in rat pericardial fluid. The effect of reserpine 6, 12, and 214 h after pre-treatment with 5 mg kg(-1) (8.2 micromol kg(-1)) i.p. shows that the concentration of noradrenaline in pericardial fluid reflects the amount of noradrenaline released within the heart rather than the amount of noradrenaline in plasma. Using spontaneously hypertensive rats (SHR) as a model for primary hypertension we could show that the level of pericardial noradrenaline is approximately threefold in the pericardial fluid of the SHRs when compared to respective values of age-matched normotensive Wistar-Kyoto rats (WKY), suggesting that there was an increased noradrenaline overflow in the hearts of the SHRs. In conclusion, determination of the noradrenaline concentration in the pericardial fluid might provide a new method for estimating the release of noradrenaline in the heart.     

Polymorphisms of xenobiotic-metabolizing enzymes and susceptibility to cancer

The variation in individual responses to exogenous agents is exceptionally wide. It is because of this large diversity of responsiveness that risk factors to environmentally induced diseases have been difficult to pinpoint, particularly at low exposure levels. Opportunities now exist for studies of host factors in cancer or other diseases in which an environmental component can be presumed. Many of the studies have shown an elevated disease proneness for individuals carrying the potential at-risk alleles of metabolic genes, but a number of controversial results have also been reported. This article is an overview of the data published to date on metabolic genotypes related to individual susceptibility to cancer.     

Cast treatment and intramedullary locking nailing for simple and spiral wedge tibial shaft fractures--a cost benefit analysis

BACKGROUND AND AIMS: The aim of this retrospective study was to compare the relative costs of treating simple and spiral wedge (requiring closed reduction under anaesthesia) tibial shaft fractures in a plaster cast or with intramedullary locking nail. MATERIAL AND METHODS: The material consisted of 26 fractures treated in a plaster cast and 51 fractures treated with an intramedullary locking nail. The costs caused by the direct costs (treatment, hospitalisation, and outpatient appointments) as well as indirect costs (lost productivity) were taken into account. Costs caused by complications were also included in the analysis. RESULTS: Mean direct costs per patient were FIM 22920 and FIM 26952 and mean overall costs per patient were FIM 120486 and FIM 82224 in plaster cast and intramedullary locking nailing groups, respectively (FIM 1 = USD 0.19). The higher mean overall costs of the plaster cast group were attributable to the longer sick leave periods in this group (218 days in plaster cast group and 124 in intramedullary nailing group). CONCLUSION: Plaster cast treatment of simple and spiral wedge tibial shaft fractures requiring closed reduction under anaesthesia is more expensive to society than operative treatment with intramedullary locking nail.