Calcium-dependent intracellular signal pathways in primary cultured adipocytes and ANK3 gene variation in patients with bipolar disorder and healthy controls.

Bipolar disorder (BD) is a chronic psychiatric disorder of public health importance affecting >1% of the Swedish population. Despite progress, patients still suffer from chronic mood switches with potential severe consequences. Thus, early detection, diagnosis and initiation of correct treatment are critical. Cultured adipocytes from 35 patients with BD and 38 healthy controls were analysed using signal pathway reporter assays, that is, protein kinase C (PKC), protein kinase A (PKA), mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)), Myc, Wnt and p53. The levels of activated target transcriptional factors were measured in adipocytes before and after stimulation with lithium and escitalopram. Variations were analysed in the loci of 25 different single-nucleotide polymorphisms (SNPs). Activation of intracellular signals in several pathways analysed were significantly higher in patients than in healthy controls upon drug stimulation, especially with escitalopram stimulation of PKC, JNK and Myc, as well as lithium-stimulated PKC, whereas no meaningful difference was observed before stimulation. Univariate analyses of contingency tables for 80 categorical SNP results versus diagnoses showed a significant link with the ANK3 gene (rs10761482; likelihood ratio χ(2)=4.63; P=0.031). In a multivariate ordinal logistic fit for diagnosis, a backward stepwise procedure selected ANK3 as the remaining significant predictor. Comparison of the escitalopram-stimulated PKC activity and the ANK3 genotype showed them to add their share of the diagnostic variance, with no interaction (15% of variance explained, P<0.002). The study is cross-sectional with no longitudinal follow-up. Cohorts are relatively small with no medication-free patients, and there are no 'ill patient' controls. It takes 3 to 4 weeks of culture to expand adipocytes that may change epigenetic profiles but remove the possibility of medication effects. Abnormalities in the reactivity of intracellular signal pathways to stimulation and the ANK3 genotype may be associated with pathogenesis of BD. Algorithms using biological patterns such as pathway reactivity together with structural genetic SNP data may provide opportunities for earlier detection and effective treatment of BD.

Cryogenic pellet launcher adapted for controlling of tokamak plasma edge instabilities.

One of the main challenges posed recently on pellet launcher systems in fusion-oriented plasma physics is the control of the plasma edge region. Strong energy bursts ejected from the plasma due to edge localized modes (ELMs) can form a severe threat for in-vessel components but can be mitigated by sufficiently frequent triggering of the underlying instabilities using hydrogen isotope pellet injection. However, pellet injection systems developed mainly for the task of ELM control, keeping the unwanted pellet fueling minimized, are still missing. Here, we report on a novel system developed under the premise of its suitability for control and mitigation of plasma edge instabilities. The system is based on the blower gun principle and is capable of combining high repetition rates up to 143 Hz with low pellet velocities. Thus, the flexibility of the accessible injection geometry can be maximized and the pellet size kept low. As a result the new system allows for an enhancement in the tokamak operation as well as for more sophisticated experiments investigating the underlying physics of the plasma edge instabilities. This article reports on the design of the new system, its main operational characteristics as determined in extensive test bed runs, and also its first test at the tokamak experiment ASDEX Upgrade.

The effect of chronic alcohol treatment on the radial maze performance of rats.

The effect of chronic alcohol drinking on maze behaviour was studied in laboratory rats. Thirteen animals received 20% alcohol for 15 weeks ad libitum, and 18 were kept under identical conditions drinking tap water. Both groups were then tested twice within one day for performance in an 8 arm radial maze after 48 h fluid deprivation. Reinforcing fluid droplets were placed at the end of each arm only at the beginning of the test. Total and erroneous entries to the arms, total time spent until reaching the criterion, and strategy of arm choice was recorded for each animal. Activity of the groups did not differ significantly, nor were differences in choosing strategy found. Alcoholic rats, however, showed a significant loss of performance in the second test: they frequently entered arms already visited, and in a number of cases were unable to complete the test within time. These and earlier findings suggest no impairment of learning ability or short term memory, but rather some kind of rigidity and invariability of behaviour.

Using SNOMED software in a large anatomic pathology laboratory.

The CAP SNOMED Microcomputer Software integrates the production of pathology reports with auto-assisted encoding of diagnostic data into a SNOMED data base. User-selected patient identifying information is stored with diagnostic and coded data and can be retrieved immediately. However, using this software in a large laboratory can present problems, the author says. Here's how his laboratory circumvented the obstacles.

The effect of X-radiation on reticulo-endothelial system and its treatment with radiodetoxified-endotoxin and trace elements in rats.

A new in vivo method has been developed for the precise observation of RES activity. Both Escherichia coli endotoxin 100 micrograms/100 g i.v. (LPS) and radiodetoxified endotoxin 100 micrograms/100 g body weight i.v. (RD-LPS, TOLERIN) both increased the granulopectic activity of RES. The RD-LPS was more effective. The preparation containing trace elements also increased the activity of RES. The treatment consisting of the use of both trace elements and RD-LPS proved to be the most effective. The activity of RES was inversely proportional to various doses of X-ray irradiation (7, 8, 9 Gy). Trace elements and RD-LPS even improved the immunity system of animals having deteriorated RES.

Effect of radiodetoxified endotoxin and trace elements on reticulo-endothelial system damaged by ethanol in rats.

For the demonstration of RES activity 99-mTc labelled nano-albumon micro-colloid solution (prepared by OSSKI, Budapest, Hungary) was injected into the prepared jugular vein of narcotized rats and the clearance rate was investigated. The effects of various materials have been observed on RES in vivo. Continuous consumption of 20% ethanol solution for 15 weeks decreased the phagocytic activity. One hundred microgram/100 g body weight (i.v.) of the radio-detoxified endotoxin preparation (RD-LPS, TOLERIN) prepared from Escherichia coli endotoxin by 60Co-gamma irradiation (150 KGy) increased the granulopectic activity of RES of intoxicated animals. The preparation containing trace elements also increased the former activity and the treatment consisting of the use of both trace elements and RD-LPD was as effective as the RD-LPD per sc.

Peculiarities of diabetes in patients with hyperthyroidism.

The authors report on 5 patients aged 25 to 63, with hyperthyroidism confirmed by high and plateau radioiodine uptake curves, protein-bound iodine of more than 7.4 micrograms/dl and low values of TSH (0.95 +/- 0.7 microU/ml). The fasting blood sugar was 157.6 mg% +/- 41 on average. Glycosuria ranged from 3.8 to 20.7 g/24 h and had a mean of 11 g 8.8 g/24 h. Determination of serum immunoreactive insulin (IRI) revealed very variable values: in one patient it was nondetectable, in 3 patients it had normal values, and in one patient it exceeded 41 microU/ml. These data confirm the authors' earlier reports on the variability of the glycoregulating mechanisms in hyperthyroidism, ranging from diabetes mellitusto hyperinsulinic reaction. However, most of the patients had normal IRI and reduced tolerance to glucose. The latter is probably due to the excess of thyroid hormones.

The role of anaerobic bacteria in the pathogenesis of urinary tract infections.

Because of the rarity of anaerobic infections of the urinary tract and the difficulty of establishing these organisms as pathogens, anaerobic culture is not included as part of routine urine bacteriological examination. Pyuria was found during examination of a 41-year-old man with a chronic renal allograft rejection reaction. Aerobic urine cultures failed to yield any pathogens. Urine cytology demonstrated intracellular organisms that proved to be Fusobacterium nucleatum on anaerobic culture. The serotypically identical organism was isolated from a needle biopsy specimen of the renal allograft. In the presence of pyuria the finding of micro-organisms in the urine sediment that fail to grow on routine aerobic cultures should lead to examination for anaerobic bacterial infection of the urinary tract.