Assay method for the perfluorooctyl bromide (perflubron) in rat blood by gas chromatography-mass spectrometry

This paper describes a GC-MS method (SIM mode) for the analysis of perfluorooctyl bromide (perflubron, I) in rat blood. The chromatographic separation was performed by injection in the split mode using a CP-select 624 CB capillary column. Following destruction of the emulsion by addition of ethanol, the analytical procedure involves a liquid-liquid extraction with 1,1,2-trichlorotrifluoroethane. The bis(F-butyl)ethene (II) was used as internal standard. Observed retention times were 3.22 min for I and 2.32 min for II. Two calibration curves were used; linear detection responses were obtained for concentrations ranging from 0.009 to 0.9 mg/ml and from 0.9 to 13.5 mg/ml. The extraction efficiency averaged 50% for I and 93% for II. Precision ranged from 0.7 to 14%, and accuracy was between 91 and 109%. The limit of quantification was 9 microg/ml. The method validation results indicate that the performance characteristics of the method fulfilled the requirements for assay method for use in pharmacokinetic studies.     

Association between variation in the vesicular monoamine transporter 1 gene on chromosome 8p and anxiety-related personality traits

Vesicular monoamine transporters are involved in the presynaptic packaging of norepinephrine, dopamine and serotonin into storage vesicles. The vesicles release their content upon arrival of an action potential into the synaptic cleft. Dysregulation of monoaminergic neurotransmission has been long postulated to play a relevant role in the etiology of neuropsychiatric disorders. The gene encoding the vesicular monoamine transporter 1 (VMAT1/SLC18A1) maps to chromosome 8p21, a region where several linkage peaks overlap between schizophrenia, bipolar disorder and anxiety-related personality traits. In this study, we tested the hypothesis that the missence variation Thr136Ile in the VMAT1/SLC18A1 gene is associated with anxiety-related personality traits. We tested a total of 337 unrelated subjects of German descent (167 male, 170 female). All participants were carefully screened for psychiatric disorders. The self-report State–Trait Anxiety Inventory (STAI) was completed by all subjects. Genotypes were obtained for the Thr136Ile (rs1390938) variation in the VMAT1 gene for all subjects. Genotype effects on personality variables were computed with MANOVA including age as a co-variant and gender as independent factor (MANCOVA). Results show that STAI scores were significantly affected by genotype (F = 3.108; d.f. = 4,331; p = 0.015) and age (F = 7.233; d.f. = 2,331; p = 0.001) but not by gender. A gender-by-genotype effect was observed for both the STAI state (p = 0.052) and trait score (p = 0.035). Dissection of the group by gender and subsequent contrast analysis of the genotype effects performed within the female group showed significant results (STAI state: Thr/Ile vs. Ile/Ile: T = 4.408, p = 0.0004; STAI trait: Thr/Ile vs. Ile/Ile: T = 3.074, p = 0.009) but not in the male group. Our findings support the hypothesis that anxiety-related personality traits are associated with variation in the VMAT1/SLC18A1 gene.     

Effect of sensory stimulus on striatal dopamine release in humans and cats: a [(11)C]raclopride PET study

BACKGROUND: Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain. OBJECTIVES: To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [(11)C]raclopride. Experiments in humans were paralleled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [(11)C]raclopride binding (BP(raclo)), a radioligand probing DA D2-receptors. RESULTS: In humans no significant difference of BP(raclo) in caudate (with sensory stimulation: 2.0 +/- 0.3 versus without sensory stimulation: 2.2 +/- 0.3; P = 0.3) or putamen (2.6 +/- 0.3 versus 2.6 +/- 0.2; P = 0.9) ipsilateral to the stimulus was disclosed as a result of sensory stimulation. Similarly, no change of BP(raclo) was observed contralaterally to the stimulation in the caudate nucleus (with sensory stimulation: 2.0 +/- 0.4 versus without sensory stimulation: 2.1 +/- 0.2; P = 0.5) and the putamen (2.5 +/- 0.4 versus 2.6 +/- 0.2; P = 0.4). In cats the same results were obtained in the ipsilateral to stimulation striatum (with sensory stimulation: 2.5 +/- 0.03 versus without sensory stimulation: 2.4 +/- 0.05; P = 0.7). No change was also observed contralaterally to the stimulation (2.4 +/- 0.04 versus 2.5 +/- 0.06; P = 0.6). The [(11)C]raclopride binding remained unchanged by sensory stimuli in both humans and cats. CONCLUSION: This suggests that the DA release induced by sensory stimulus is mostly extrasynaptic whereas the synaptic DA release is probably small, which fits well with the absence of [(11)C]raclopride displacement. The mechanism of this extrasynaptic DA release could be related to a local action of glutamate on dopaminergic terminals via a thalamo-cortico-striatal loop. Present results also underline homology between cat and human responses to sensory stimuli and validate the use of cat brain to find physiological concepts in humans.     

Genetic and biochemical characterization of Malassezia pachydermatis with particular attention to pigment-producing subgroups.

The aim of the study was the characterization of Malassezia pachydermatis and its pigment-producing subgroup using biochemical tests and RAPD. It was of interest to determine whether particular RAPD patterns could be used to indicate pigment production, as well as a close genetic relatedness to Malassezia furfur. Therefore, 210 strains of M. pachydermatis were examined for morphology, catalase and ss-glucosidase activity, lipid and carbohydrate assimilation and the tryptophan-dependent synthesis of pigments. Of these, 114 strains were subjected to RAPD analyses. A multivariate logistic regression model was applied to classify M. pachydermatis isolates regarding their pigment production by using genetic and biological parameters. Biological and RAPD findings showed a high biological and genetic diversity within the species M. pachydermatis and within pigment producers. RAPD analysis revealed 28 genotypes within 114 strains tested. Pigment producing strains could not be assigned to a common RAPD profile, but a genetic relatedness of pigment-producing M. pachydermatis with M. furfur can be assumed. A particular RAPD pattern allowed statistically significant probability of pigment production (P<0.001) and might be used as a tool to rapidly detect pigment producing M. pachydermatis, e.g. in Malassezia-associated pityriasis versicolor. The reported method is useful for identification of pigment producing M. pachydermatis isolates and has advantages over established tests.     

Characterization of tissue amyloid by immunofluorescence microscopy

Immunohistochemical classification of amyloid type was possible in 44 of 50 (88%) patients as judged by the concordance of immunofluorescence, clinical, serum, and urine immunoelectrophoresis, and bone marrow data. In frozen tissue sections incubated with a panel of antisera monospecific for immunoglobulin heavy chains, kappa and lambda light chains, and amyloid-A-related protein, the amyloid was classified as AL in 20 and AA in 24. In 6 patients the amyloid could not be classified because of the absence of reactivity in 2 and overlap staining in 4. The findings indicate that routine immunofluorescence examination of diagnostic biopsies is an important adjunct in the classification of amyloid.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Using the demand–control model of job strain to predict caregiver burden and caregiver satisfaction in the informal caregivers of heart failure patients

Objectives The demand–control (D–C) model of job strain has generated a considerable body of empirical support in predicting psychological health outcomes in the context of work. This study aimed to extend previous work using the D–C model of job strain to predict caregiver burden and satisfaction in the informal caregivers of patients with heart failure. Design and method Data were gathered from 60 caregiver/patient dyads in a cross‐sectional design. Patients with chronic stable heart failure were recruited from out‐patient clinics. The dependent variables were caregiver burden and satisfaction. Demand and control were measured using both patient‐ and caregiver‐derived measures. Results The D–C model accounted for 15 and 19% of the variance in caregiver burden, after controlling for age, gender and relationship to the patient. Lower control was associated with higher burden. The D–C model did not predict caregiver satisfaction. Conclusion The D–C model was associated with caregiver burden, but not satisfaction in caregivers, with control being the dominant predictor. Research linking the theory and findings from job strain and informal caregiving studies may elucidate both fields of research. Using the demand–control model of job strain to predict caregiver burden and caregiver satisfaction in the informal caregivers of heart failure patients.     

Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia

Eicosanoids generated via cyclooxygenase-2 (COX-2) and nitric oxide produced from inducible nitric oxide synthase (NOSII) have been implicated in endotoxin-induced tissue injury. In the present studies, we characterized COX-2 and NOSII activity in rat hepatic macrophages and their interaction during acute endotoxemia. Kupffer cells from control animals were found to constitutively express COX-2 and NOSII mRNA and protein. Whereas treatment of the cells with lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma) had no major effect on COX-2, NOSII expression increased. Induction of acute endotoxemia resulted in a rapid and transient increase in constitutive COX-2 expression and prostaglandin E2 (PGE2) production by liver macrophages as well as NOSII expression and nitric oxide release. Cells from endotoxin-treated rats were also sensitized to generate more nitric oxide and express increased NOSII in response to LPS and IFN-gamma. Inhibition of NOSII with aminoguanidine reduced COX-2 mRNA and protein expression as well as PGE2 production by activated macrophages from endotoxemic, but not control animals. In contrast, SC236, a specific COX-2 inhibitor, had no effect on NOSII mRNA or protein levels or on nitric oxide production by hepatic macrophages, even after endotoxin administration. These data suggest that activation of COX-2 may be important in the pathophysiological response of hepatic macrophages to endotoxin. Moreover, nitric oxide is involved in regulating COX-2 in activated liver macrophages during acute endotoxemia.     

The effect of 1-phenylalanine mustard on anti-globulin antibodies in multiple myeloma

An immunochemical and serological study of a patient with rheumatoid arthritis who developed multiple myeloma and was treated with 1-phenylalanine mustard showed a striking difference in the effect of this drug on the rapidly dividing cells, as opposed to the resting plasma cells. The titres of anti-globulin antibodies such as the IgG serum agglutinators and the IgM rheumatoid factors were little altered although the IgG myeloma spike has disappeared following therapy. Fractionation of two different serum samples from 1966 and 1970 showed the IgG paraprotein to be serologically inactive for anti-globulin activity. This paraprotein was also characterized by producing only a single IgG precipitin line with horse anti-human whole serum antibody while the normal IgG globulins always showed a double line.     

A Survey of Laboratory Computers in Psyehophysiology

Since the mid 196O's there has hcen a growing interest in and use of computers in psychophysiology laboratories. There are even a growing number of accepted physiological measures which are fully dependent on computer technology for their derivation. Although minicomputers have been in use for over a decade, recent developments in microcomputer and microprocessor technology have led to rapid acceptance of microcomputers for laboratory work. These rapid advances have produced a need to survey the current state of laboratory computer applications and development. A comprehensive survey was mailed to 301 psychophysiology laboratory groups during the spring and summer of 1979 and completed surveys were received from 61% of the mailing. Sun'ey results are reported on computer hardware and configuration, dependent measures and user satisfaction, and use and cost of engineering and programming support. Developments in computer hardware and user services are also discussed.