Evaluation of the central anticholinergic activity of antidepressants. Comparison of two experimental methods

The anticholinergic effect of atropine, imipramine, clomipramine and metapramine was evaluated on oxotremorine induced trembling in the mouse as well as on contractions of the isolated guinea pig ileum induced by electrical stimulation of the mesenteric plexus. The ED 50 and IC 50 which expressed the anticholinergic activity of these substances, were found to be identifically distributed for both methods. Activity, in decreasing order was found to be: atropine much greater than imipramine greater than clomipramine greater than metapramine. There was a good correlation between results from the two methods (r = 0.97). The method using the stimulated guinea pig ileum would therefore seem suitable for characterisation of potential anticholinergic activity of a molecule.     

Differential effects of sulindac on renal hemodynamics and function in the rat

Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n=6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n=12). In the 5 mg/kg b.w. sulindac group (n=7), renal blood flow progressively and significantly increased from 7.88±0.36 to 8.98±0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n=7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n=5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P<0.025). Also, Na⁺ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n=15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n=21), it was decreased from 11.5±1.2 to 7.4±0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P<0.05; n=6). In conclusion, differential effects of sulindac on renal hemodynamics, Na⁺ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.     

Group versus individual treatment in obsessions without compulsions

The principal goal of the current study was to compare the efficacy of two treatment formats, group and individual, of an empirically proven manualized cognitive–behavioural treatment (CBT) package, for obsessions without overt compulsions. It was hypothesized that individualized treatment would be more effective both in terms of post-treatment group mean improvement and end state functioning. A secondary goal was to assess the relationship between cognitive and behavioural change during treatment and link it to symptom change. Both group and individual CBT format produced a significant clinical change, but as expected individual treatment produced the greater change in symptoms and in obsessional belief. Also, the individual format showed a clear superiority over the group format in the reduction of anxiety and depression. Severity of OCD symptoms showed little relationship with strength of obsessional beliefs at the start of treatment, but change in beliefs was strongly correlated with behavioural improvement post-treatment. The results of the study suggest that the impact of a group format may lie in the value of shared social support and motivational effect of peer feedback, but at the expense of individualized targets. Copyright © 2005 John Wiley & Sons, Ltd.     

Transplantation of embryonic noradrenergic neurons in two models of adult rat spinal cord injury: ultrastructural immunocytochemical study

The synaptic connections established by grafted noradrenergic (NA) neurons into the lesioned adult rat spinal cord were analysed using immunocytochemistry at the electron microscopic level. An embryonic cell suspension of the locus coeruleus region from E-13 rat embryos was transplanted into the spinal cord following either: (1) spinal cord transection or (2), partial selective denervation by 6-hydroxy dopamine (6-OH DA). One month after grafting, the NA-neurons established, in the two models, an innervation pattern similar to that found in the intact spinal cord. In both models, the transplanted NA-immunoreactive neurons formed extensive synaptic contacts with dendrites, spines and perikarya. The proportion of axodendritic and axospinous contacts was inverse in the two models. The first model thus reproduced more closely the normal synaptic pattern prefering dendritic targets, which could correspond to a better integration of the graft. In the second model, a partially NA-denervated spinal cord, there existed a competition between residual intrinsic and grafted neuron-derived fibres, which presumably affects synaptogenesis. In conclusion, the present study illustrate the complexity of cell interations conducting to the formation of a specific circuitry. Recognition phenomenon are likely modulated by space constraints, which ultimately shape-up the geometry of synaptic contacts.     

Phenotypic heterogeneity associated with defective apolipoprotein B-100 and occurrence of the familial hypercholesterolemia phenotype in the absence of an LDL-receptor defect within a Canadian kindred

Of 163 individuals with a diagnosis of heterozygous familial hypercholesterolemia (FH), only one subject was found to be positive for familial defective apo B-100 (FDB). The eight-member kindred ascertained through this subject who presented with both a clinical phenotype of FH and the FDB apo B-100 (Arg₃₅₀₀→-Gln) mutation was studied. Plasma lipid and lipoprotein profiles, apo E phenotypes, apo B gene markers at the 3′ hypervariable region and LDL-receptor haplotypes (ApaLI, PvuII, NcoI), were determined, together with LDL-receptor activity on freshly isolated blood lymphocytes. The FDB mutation, present in four relatives, was associated with three different phenotypes: FH and severe hypercholesterolemia, moderate hypercholesterolemia and normolipidemia. The FH phenotype occurred in the absence of any functional LDL-receptor defect. In homozygotes for the absence of the PvuII cutting site who had the apo B mutation, LDL-cholesterol levels were low in the presence of the apo E3/2 phenotype and high in the presence of the apo E4/4 phenotype. None of the major known environmental influences accounted for the wide range of variation in LDL-cholesterol among the affected members. Further observations in the spouse and offspring of the normolipidemic FDB subject confirmed the association of apo E4, the FDB mutation and the PvuH(-/-) genotype with high cholesterol levels. It is concluded that the phenotypic expression of the FDB mutation may vary widely as a function of the genetic environment within a family. The presence of phenotypic heterogeneity among individuals with the same apo B mutation may result from epistatic interaction of the apo B locus with genetic factors regulating cholesterol homeostasis, including possible involvement of the apo E and the LDL-receptor gene loci. This study also confirms that the clinical diagnosis of FH is not necessarily associated with an LDL-receptor defect.     

The relationship of drinking and birth outcome in a US national sample of expectant mothers

Alcohol consumption by pregnant women and birth outcome were studied in 9953 livebirths, 3309 fetal deaths and 5332 infant deaths from the 1988 National Maternal and Infant Health Survey. In crude analyses, race, age, mother's education, prenatal care, parity, low birthweight, gestational age, smoking and alcohol consumption during pregnancy were significantly related to the occurrence of fetal deaths and infant deaths. Among women having livebirths, race, age, mother's education, prenatal care, prematurity, gestational age, smoking and alcohol consumption during pregnancy were significantly related to having a low birthweight baby (< 2500 g). In this group, women who drank more during pregnancy also smoked more, were younger and less educated than women who drank at lower levels or not at all. The relationship of alcohol consumption during pregnancy and infant birthweight for those women having livebirths was studied using multivariable linear regression. The results indicated that race, mother's education, baby's sex, parity, mother's height, mother's body mass index and smoking, but not alcohol consumption, were significantly related to birthweight. Multivariable logistic regressions were performed for the occurrence of low birthweight, fetal death and infant death. The effect of alcohol was significant in all these analyses. These results indicate that alcohol has an important relationship with birth outcome, but that for the drinking reported in this study, the alcohol effect on mean birthweight is small relative to that of other risk factors, accounting for the non-significant result in the multiple linear regression.     

Concomitant and discriminatory validity of the Adolescents' Fear of Dental Treatment Cognitive Inventory

The revised edition of the Inventaire cognitif de la peur des traitements dentaire pour adolescent(e)s [Adolescents' Fear of Dental Treatment Cognitive Inventory] (ICPTD-A) was administered to 38 subjects chosen at random and to nine subjects chosen with an obvious dental phobia problem. Its concomitant validity was established by relating the ICPTD-A scores to those of a behavioral test. The Pearson correlation coefficients that were thus obtained were -0.66 for the general population and -0.87 for the population suffering from dental phobia. The discriminatory validity was then established with a repeated measurement variance analysis based on the scores of the dental phobics after the administration of a recognized psychological treatment program intended to reduce their phobia. The results have shown a statistically significant difference between the experimental and control groups as well as a significant difference between pre- and posttreatments. The authors have therefore concluded that the ICPTD-A is a valid tool for the assessment of dental phobia in 12-15-year-old adolescents.