Cardiovascular Effects of Zimelidine and Tricyclic Antidepressants in Conscious Rats *

Abstract: Blood pressure, heart rate and electrocardiograms were recorded in conscious rats during intravenous injections of consecutively increasing doses of zimelidine, amitriptyline, clomipramine, desipramine and imipramine. The tricyclic antidepressants (TCA's) increased blood pressure from low doses and induced shortlasting decreases in blood pressure at higher doses. Heart rate was initially increased by amitriptyline while the other TCA's tended to decrease heart rate dose-dependently. The TCA's prolonged the QRS and QT intervals dose-dependently from low doses and the PR interval from intermediate doses. Zimelidine did not affect blood pressure or heart rate until high doses were given. The PR interval was not affected by zimelidine. Moderate to high doses of zimelidine prolonged the QT length and high doses widened the QRS complex. The results indicate a good cardiovascular tolerance for zimelidine.     

Influence of Hemodialysis on Monoamine Oxidase Kinetics in Platelets from Chronic Schizophrenic Patients

Abstract: Platelet monoamine oxidase (MAO) activity in seven chronic schizophrenic patients undergoing hemodialysis treatment was studied. The treatment was performed in a double-blind crossover design. A significant increase in MAO activity was observed after 5 h of active dialysis, whereas inactive dialysis did not significantly alter the enzyme activity. The increase in MAO activity could be explained by the observed significant decrease in apparent Km values for the amine (phenethylamine) studied. During a treatment period of 8 weeks, the MAO activity was not significantly altered with either active or sham dialysis. No relation between clinical ratings and platelet MAO activity was observed. Plasma from the seven patients was collected before and after 5 h of active or inactive dialysis and incubated with rat brain mitochondrial MAO (RBM-MAO). No difference was noted in the RBM-MAO-activity-regulating properties of the plasma sampled during either sham or active dialysis.     

The plasminogen activator activity of arteries and veins in diabetes mellitus

An abnormally low plasminogen activator activity of the vein walls is strikingly common in diabetes. We found a close correlation between the activator content of the veins and arteries in diabetics, which indicates impairment of the defence system against deposition of fibrin also in diabetic arteries. This might perhaps help to explain the high frequency of early and widespread degenerative arterial lesions in diabetes mellitus.     

Circulatory monitoring of children during anaesthesia in low field magnetic resonance imaging

Anaesthesia for patients in a Magnetic Resonance Imaging (MRI) scanner provides some problems for the design of both the anaesthetic and the monitoring equipment. This report presents a technique for continuously displaying the heart rate during anaesthesia for children in an MRI scanner. The monitoring system used light to detect differences in skin capillary circulation, and the light was transferred to and from the patient via fiberoptic cables. After amplification, the signal was displayed "on line" on a cardioscope, thus continuously presenting heart rate and, in part, a qualitative view of the skin vascular resistance.     

K cell mediated lysis of cultured colon carcinoma and urinary bladder carcinoma cells induced by monospecific antisera against carcinoembryonic antigen (CEA) and two CEA-related normal glycoproteins

Antibody dependent lymphocyte (K cell) mediated lysis of tumor cells in vitro was used to assay for cell surface associated carcinoembryonic antigen (CEA) and two CEA-related normal tissue components, “normal glycoprotein” (NGP) and biliary glyco-protein I (BGP I). Three tumor cell lines were used as target cells. These were HT-29, colon carcinoma, T-24, urinary bladder transitional cell carcinoma and Mel-1, malignant melanoma. To induce lysis we used the IgG-fraction of specific rabbit and monkey anti-CEA sera and of specific rabbit anti-NGP and anti-BGP I sera, respectively. Purified human lymphocytes were used as effector cells. HT-29 was efficiently killed by low concentrations of rabbit anti-CEA and less efficiently by monkey anti-CEA. T-24 and Mel-1 were not lysed by anti-CEA. HT-29 and T-24 were lysed by low concentrations of anti-BGP I. In contrast only HT-29 was lysed by anti-NGP. Only a fraction of the tumor cells was killed by the different antisera although kinetic studies showed that the lytic reaction was complete well before the end of the eighteen hour incubation period used in the assay. Anti-CEA and anti-BGP I gave 30–40% corrected lysis of HT-29. With anti-NGP the corresponding figure was 10–20%.     

Clinic-based cases with frontotemporal dementia show increased cerebrospinal fluid tau and high apolipoprotein E epsilon4 frequency, but no tau gene mutations

Frontotemporal dementia (FTD) belongs to a group of neurodegenerative disorders known as tauopathies, characterized by intracellular aggregation of hyperphosphorylated tau protein in the brain. Some tauopathies, like Alzheimer's disease (AD), consistently show increased levels of tau protein in cerebrospinal fluid (CSF). However, similar studies in FTD populations have shown variable results, although mutations in the tau gene are identified as causes of disease in certain FTD families. In the present study, a Swedish clinic-based FTD population was investigated with respect to CSF tau levels, apolipoprotein E (APOE) genotype distribution and occurrence of mutations in the tau gene. CSF tau levels were significantly increased among FTD patients (534 +/- 235 pg tau/ml, P < 0.001) (n = 47) compared to controls (316 +/- 137 pg tau/ml) (n = 51). Furthermore, a strong increase in the APOE epsilon4 allele frequency was found in the FTD population, as 52% were epsilon4 carriers, compared to 21% of the controls. However, no mutations in the tau gene were identified. These findings support the present notion of a common pathogenic pathway in the disease processes for several tauopathies, with both APOE epsilon4 and CSF tau being a pathological link between the different disorders. Furthermore, we conclude that mutations in the tau gene are a rare cause of FTD. .     

White matter lesions impair initiation of FAS flow

Word fluency performance is known to rely on left frontal cortical regions and has also been shown to be affected by lesions in the white matter, which may be seen as white matter hyperintensities (WMH) on magnetic resonance imaging. However, word fluency may be divided into two independent components, initial and late performance, separated in time [J Clin Exp Neuropsychol 1998;20:137-143]. The purpose of the current study was to investigate the relationship between the two components of FAS fluency performance and WMH. Patients varying in degree of memory impairment participated: Alzheimer's disease, mild cognitive impairment and subjective memory disorder. WMH were rated with the Scheltens scale in the periventricular and deep subcortical areas. Results demonstrated that WMH in this sample of patients may be summarized in two indices according to a principal factor analysis, one anterior factor mainly related to WMH in the frontal lobes and adjacent to ventricles, and a second posterior factor related to parietal and occipital WMH. The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH.     

Cerebrospinal fluid tau levels increase with age in healthy individuals

Cerebrospinal fluid (CSF) tau is a promising biochemical ante-mortem marker for Alzheimer's disease (AD). Levels are increased in AD compared to other dementias, neurological diseases and healthy controls. An age-related decrease in both soluble tau and tau bound to paired helical filaments has been shown in brains from non-demented subjects. To study tau levels in normal ageing, we investigated CSF in 29 healthy individuals aged 45-80 years. A statistically significant increase in CSF tau with increasing age was found which might be caused by neuronal loss during normal ageing and redistribution of soluble tau from the brain into CSF. We could not demonstrate any influence by the APOE genotype, though larger populations have to be investigated to confirm this result. In conclusion, we found an age-dependent increase in CSF tau in healthy individuals. We emphasise the importance of establishing an age-dependent interval of CSF tau in non-demented subjects.