Tacrine restores cholinergic nicotinic receptors and glucose metabolism in alzheimer patients as visualized by positron emission tomography

Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [¹⁸F]-fluoro-deoxy-glucose (¹⁸F-FDG) (tracer for glucose metabolism); ¹¹C-butanol (cerebral blood flow) and (S)(−)- and (R)(+)-[N-¹¹C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of ¹¹C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(−)- and (R)(+)¹¹C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(−)¹¹C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement.     

Autoantibodies to C-reactive protein is a common finding in SLE,but not in primary Sjögren's syndrome,rheumatoid arthritis or inflammatory bowel disease

The occurrence of antibodies to human C-reactive protein (CRP) was analysed by enzyme-linked immunosorbent assay (ELISA) in 56 patient sera known to contain antibodies to double-stranded DNA (dsDNA) and in 16 sera from patients with primary Sj?gren's syndrome (SS), 15 rheumatoid arthritis, 31 Crohn's disease, and 37 ulcerative colitis. Eighty-seven per cent of the patients with anti-dsDNA antibodies had systemic lupus erythematosus (SLE) and the remaining had autoimmune hepatitis. The cut-off for positive anti-CRP test was set at the 95th percentile of 100 healthy blood donors. Twenty of 56 anti-dsDNA sera (36%) and two of 16 SS sera (13%) had antibodies reactive with human CRP, whereas all other samples were negative. Thirteen of 27 SLE patients (48%) were positive on at least one occasion. The sera containing anti-CRP antibodies only reacted with surface-bound antigen, but not with native CRP in solution. In conclusion, we found that autoantibodies to CRP are common in sera from patients with anti-dsDNA antibodies. It is not likely that this explains the relative failure of CRP response in patients with active SLE. However, it cannot be excluded that anti-CRP autoantibodies have other biological potentials of pathophysiological interest in SLE, for instance by binding to CRP deposited on cell and tissue surfaces.     

Effect of a new synthetic serum replacement on insulin and somatostatin secretion from isolated rat pancreatic islets in long-term culture

Summary Serum contains insulin degrading components. We have evaluated the insulin and somatostatin secretion from isolated rat pancreatic islets during a 2-wk culture period using three different serum-containing media, and one serum-free medium with a synthetic serum replacement. Islets incubated in serum-free medium elicited significantly higher daily insulin and somatostatin secretions than islets incubated in the serum-containing media. After a 2-wk culture period, islets from the serum-free medium secreted significantly more insulin and somatostatin than islets cultured in other media when stimulated with 25 mmol/liter glucose together with 15 mmol/liter theophylline. We conclude that the serum-free medium is superior for long-term culture of rat pancreatic islets.     

Blood Lymphocyte Proliferation Response to Pollen Extract as a Monitor of Immunotherapy

In a study of immunotherapy 41 children with seasonal rhinoconjunctivitis due to deciduous tree pollen allergy were monitored by means of symptom scoring, patient self-evaluation, conjunctival provocation tests and lymphocyte proliferation in vitro to the allergen. The lymphocyte responsiveness to birch pollen decreased significantly during the first year of immunotherapy. However, neither the lymphocyte responsiveness before treatment nor changes in lymphocyte reactivity during the immunotherapy correlated with the clinical efficacy of the therapy as evaluated by changes in symptom scores, self-evaluation or conjunctival provocation test changes in the individual patients. The results indicate the lymphocyte responsiveness to an allergen cannot be used to select patients for immunotherapy, i.e. to predict whether a patient would benefit from immunotherapy or not, or to evaluate the effects of immunotherapy after beginning the treatment. However, lymphocyte proliferation response to an allergen indicates clinical sensitivity.     

Tardive dyskinesia on Hungarian psychiatric wards

The authors found tardive dyskinesia (TD) in 23.5% of 200 hospitalized schizophrenic patients, most of whom had received neuroleptic treatment for at least two years. The frequency and severity of TD increased with age, and the more advanced the age at which the patient started taking neuroleptics, the more likely it was that TD would develop. Severe TD was more common in men than in women. Prolonged treatment with neuroleptics or the use of antiparkinsonism drugs increased the risk of TD.     

Effects of age, sex and genes on sister chromatid exchange

Sister chromatid exchange (SCE) was studied in cultured lymphocytes from a limited series of 21 like-sexed twin pairs; 11 monozygotic (MZ) and 10 dizygotic (DZ) pairs. The 18 subjects, who were between 57 and 61 years old, had an SCE mean value () of 8.0 whereas the 24 subjects between 33 and 39 years of age had a mean of 6.8. The difference was statistically significant ( P <0.001). The effect of age appeared to be present in both sexes. No significant difference was found between females (%7.3) and males (%7.5), nor between smokers (%7.3) and non-smokers (%7.4). Drug users had a slightly higher mean (%7.9) than non-users (= 7.0) ( P < 0.05). This trend was found in each age group. The within-pair variance was slightly higher in DZ than in MZ pairs. The difference was not significant. We conclude that genetic factors are probably not a major source of subject variation in SCE mean value.     

Comparison of two urinary antigen tests for establishment of pneumococcal etiology of adult community-acquired pneumonia

The Binax NOW immunochromatographic test (ICT) detecting the pneumococcal C polysaccharide and a serotype-specific latex agglutination (LA) test detecting 23 pneumococcal capsular antigens were evaluated for establishing pneumococcal etiology in community-acquired pneumonia (CAP) by use of nonconcentrated urine. ICT was considered to be strongly positive for result lines at least as intense as the control line and weakly positive for less intense result lines. When 215 adult CAP patients were tested, strong ICT, weak ICT, and LA positivity were found in 28, 24, and 16 patients, respectively; of these patients, 13 (46%), 6 (25%), and 13 (81%), respectively, had pneumococcal bacteremia and 27 (96%), 17 (71%), and 15 (94%), respectively, had Streptococcus pneumoniae isolated from blood, sputum, and/or nasopharynx. Among 108 controls tested, 2 (1.9%) were weakly ICT positive. When weak positivity was considered negative, the sensitivity of ICT decreased from 79% (19 of 24) to 54% (13 of 24), while the specificity increased from 83% (158 of 191) to 92% (176 of 191); no controls were false positive. The sensitivity and specificity of LA were 54% (13 of 24) and 98% (188 of 191), respectively. Eight of nine LA serotypes corresponded to culture serotypes. In conclusion, using nonconcentrated urine and dividing ICT-positive results into strongly and weakly positive results is a suitable way of performing ICT. While weak ICT positivity should be interpreted with caution, strong ICT positivity and LA positivity should be considered supportive of pneumococcal etiology in adult CAP. As such, these assays might have implications for antibiotic use in CAP. LA has promising potential for pneumococcal serotyping, although further evaluation is required.     

Serum lipids and lipoproteins in relation to endogenous and exogenous female sex steroids and age. The Women's Health in the Lund Area (WHILA) study

BACKGROUND: Different studies have presented conflicting results concerning the effect of menopause on lipid levels. AIMS: To describe the serum lipid profile and the prevalence of hyperlipidemia in women aged 50-60 and the perceived relation to endogenous and exogenous hormones and age. METHODS: Out of a total population of 10,766 women aged 50-59 years, 6908 (64%) participated in a health assessment program, including a lipid profile evaluation. The women were grouped according to hormonal status into pre-menopausal (PM), post-menopausal without hormone replacement therapy (PM0) (HRT) and post-menopausal with hormone replacement therapy (PMT). Age groups used were 50-54, 55-59 and >60 years. RESULTS: Serum cholesterol and triglycerides increased significantly by age in PM0 (P < 0.0001) and triglycerides also in PMT (P < 0.0001). Serum high-density lipoprotein cholesterol (HDL) levels decreased significantly by age in PMT (P = 0.002) and low-density lipoprotein cholesterol (LDL) increased in PM0 (P < 0.0001) and PMT (P = 0.007). The co-prevalence of levels of cholesterol >7 and triglycerides >2 mmol/l decreased by age in PM, but increased by age in PM0 and PMT. The prevalence of high-risk lipid levels and the prevalence of coexisting additional two metabolic risk factors were higher in the PM0 compared to the PMT group. The prevalence of serum triglycerides >1.5 and serum cholesterol >5 mmol/l were increasing by age in each of the hormonal groups. CONCLUSIONS: These data suggest that loss of endogenous sex steroids contribute substantially to an increased atherogenic lipid profile. Hormone replacement therapy may partly reverse these differences.