Diabetic ketoacidosis and rhabdomyolysis following excessive intake of a weight reducing diet

We describe two unusual cases in sheep of subclinical mastitis caused by Streptococcus parasanguinis. This bacterium has been associated with the development of experimental endocarditis; its presence at relatively high concentrations in apparently healthy sheep milk may pose a health risk in persons with predisposing heart lesions.     

The Australian brushtail possum (Trichosurus vulpecula) gonadotrophin alpha-subunit: analysis of cDNA sequence and pattern of expression

Substantial evidence has accumulated to suggest that in the near future implementation of the veto-cell-suppressor concept in the treatment of kidney allograft recipients might lead to the establishment of life-long specific allograft tolerance in the absence of further immunosuppressive therapy. Veto suppression prevents the generation of antigen-specific T-helper and cytotoxic T lymphocytes in vitro provided that the T-lymphocyte precursors specifically recognize antigenic peptides associated with the major histocompatibility complex molecules class II and class I, respectively, expressed on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft tolerizing effect of pretransplant donor blood transfusions in kidney graft recipients. A prerequisite for a veto-active environment in vivo is the establishment of lymphoid microchimerism, in which veto-active donor and recipient cells mutually downregulate potential alloaggression.     

In vivo labelling of the mouse brain 5-hydroxytryptamine1A receptor with the novel selective antagonist 3H-NAD-299

The in vivo labelling of 5-hydroxytryptamine (5-HT)1A receptors in the mouse brain was studied with the novel selective 5-HT1A receptor antagonist, NAD-299 ((R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran- 5-carboxamide hydrogen (2R,3R)-tartrate monohydrate). 3H-NAD-299 was injected in a tail vein and the radioactivity in various brain regions was determined. More than 90% of the radioactivity in hippocampus, 15 min after the injection, was intact NAD-299. At this time the amount of 3H-NAD-299 was highest in hippocampus followed by frontal cortex, mesencephalon, hypothalamus, striatum and cerebellum. The specific accumulation of radioactivity (after subtracting cerebellum values) in frontal cortex and hippocampus was maximal 10 to 30 min after the injection and had almost disappeared after 2 h. Saturation kinetics derived Bmax (pmol/g wet weight tissue) values of 19.6+/-2.0 in frontal cortex and 38.0+/-3.5 in hippocampus. The apparent Kd values expressed in nmol/kg 3H-NAD-299 injected, were 12.3+/-2.2 in frontal cortex and 20.3+/-3.1 in hippocampus. The 5-HT1A receptor antagonist, WAY-100,635 competitively inhibited the specific accumulation of 3H-NAD-299 and was about equipotent with unlabelled NAD-299 with ED50 values of 20-30 nmol/kg s.c. These compounds were about 10 times more potent than the 5-HT1A receptor antagonists, p-MPPI and NDL-249 and 100 times more potent than (S)-UH-301. 5-HT1A receptor agonists, e.g. 8-OH-DPAT and flesinoxan and partial agonists, e.g. pindolol, buspirone and ipsapirone had low potency in this in vivo assay. Spiperone and methiothepin inhibited the 3H-NAD-299 accumulation at 10 micromol/kg s.c. The alpha1-adrenoceptor antagonist, prazosin at 2 micromol/kg s.c. increased significantly the specific accumulation of 3H-NAD-299. Pretreatment of the mice with the non-selective, irreversible receptor antagonist, EEDQ produced a dose related long-lasting decrease in the accumulation of 3H-NAD-299. It is concluded that NAD-299 is a very suitable ligand for studies of 5-HT1A receptors in the brain in vivo.     

Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease

Using autoradiographic binding methodology with monoiodinated peptide YY together with the agonists neuropeptide Y (NPY) and NPY (13-36), as well as in situ hybridization with oligonucleotide probes complementary to the NPY Y2 receptor (Y2-R) mRNA, we have studied whether or not intracerebral prion inoculation affects Y2-Rs in male CD-1 mice. Monoiodinated peptide YY binding, mainly representing Y2-Rs, was down-regulated by 85% in the CA1 strata oriens and radiatum and by 50-65% in the CA3 stratum oriens 110-140 days postinoculation. In the CA3 stratum radiatum, where the mossy fibers from the dentate granule cells project, there was a significant decrease in PYY binding at 110-120 days. Y2-R mRNA, moderately expressed both in the CA1 and CA3 pyramidal cell layers and the granule cell layer in the dentate gyrus, showed a slight, but not significant, decrease in CA3 neurons 130 days postinoculation. The results indicate that the accumulation of the scrapie prion protein in the CA1-3 region strongly inhibits NPY binding at the Y2-Rs, which, however, is only marginally due to reduced Y2-R mRNA expression. The loss of the ability of NPY to bind to inhibitory Y2-Rs may cause dysfunction of hippocampal circuits and may contribute to the clinical symptoms in mouse scrapie.     

Non-invasive assessment of magnitude and dispersion of atrial cycle length during chronic atrial fibrillation in man

AIMS: Atrial fibrillation cycle lengths can be assessed from right precordial ECG leads and the unipolar oesophageal ECG using a non-invasive method called Frequency Analysis of Fibrillatory ECG. The purpose of this report is to present the results from application of this method in a large group of patients with long-term atrial fibrillation and to examine the differences between patients with 'coarse' and 'fine' atrial fibrillation. METHODS AND RESULTS: Simultaneous 15 min recordings from V1, V2 and an oesophageal lead at a position behind the posterior atrium were obtained in 28 patients, aged 41 to 78 years, with long-term (> 1 month) atrial fibrillation. In each lead, using the time averaging technique, the QRST complexes were suppressed. Thereafter, the frequency distribution of the residual ECG was estimated by means of Fast Fourier Transform. In the 3-12 Hz range of each lead, the dominant atrial cycle length, the power maximum and the spectral width were calculated. In 26 patients (93%), frequency spectra in the 3-12 Hz range could be obtained. The dominant atrial cycle length ranged from 120 to 175 ms, mean 150+/-16 (SD) ms in V1, and from 120 to 190 ms, mean 150+/-16 in an oesophageal lead (ns). The absolute difference in the dominant atrial cycle length between V1 and the oesophageal lead was 10.4+/-7.7 ms. There was no significant difference in the dominant atrial cycle length in V1 between patients with coarse and fine atrial fibrillation. The power maximum in V1 was significantly greater in patients with coarse compared to fine atrial fibrillation (P=0.01). The spectral widths ranged from 10 to 55 ms and demonstrated significantly higher mean values in lead V2 compared to V1 (P=0.001). Compared to V1, the mean values tended to be smaller in the oesophageal lead (P=0.05). CONCLUSIONS: Using the Frequency Analysis of Fibrillatory ECG method, the dominant atrial cycle length, power maximum and spectral width can be estimated from the frequency spectra in the majority of patients with atrial fibrillation. Spatial dispersion of the dominant atrial cycle length occurs in some patients and may be an important proarrhythmic marker. The distinction between coarse and fine atrial fibrillation cannot be used as a marker of the atrial cycle length.