Accidental Hypothermia in a Swiss Alpine Trauma Centre-Not an Alpine Problem.

BACKGROUND: Research in accidental hypothermia focuses on trauma patients, patients exposed to cold environments or patients after drowning but rarely on hypothermia in combination with intoxications or on medical or neurological issues. The aim of this retrospective single-centre cohort study was to define the aetiologies, severity and relative incidences of accidental hypothermia, methods of measuring temperature and in-hospital mortality. METHODS: The study included patients ≥18 years with a documented body temperature ≤35 °C who were admitted to the emergency department (ED) of the University Hospital in Bern between 2000 and 2019. RESULTS: 439 cases were included, corresponding to 0.32 per 1000 ED visits. Median age was 55 years (IQR 39-70). A total of 167 patients (38.0%) were female. Furthermore, 63.3% of the patients suffered from mild, 24.8% from moderate and 11.9% from severe hypothermia. Exposure as a single cause for accidental hypothermia accounted for 12 cases. The majority were combinations of hypothermia with trauma (32.6%), medical conditions (34.2%), neurological conditions (5.2%), intoxications (20.3%) or drowning (12.0%). Overall mortality was 22.3% and depended on the underlying causes, severity of hypothermia, age and sex.

Comparative analysis between cyclic GMP and cyclic AMP signalling in human sperm.

The principal involvement of cyclic nucleotides in regulating sperm functions is well established, but the factors controlling their generation and actions have not yet been entirely resolved. In particular, specific roles for cyclic (c)GMP in mammalian sperm are poorly understood. In this study, we have characterized comparatively the cAMP and cGMP signalling systems in ejaculated human sperm. Mean concentrations of cGMP (0.1 micromol/l) were found to be 100-fold lower than those of cAMP in non-stimulated cells, and adenylyl cyclase (AC) activities predominate by far guanylyl cyclase (GC) activities in both particulate and soluble protein fractions. By different experimental approaches (photoaffinity labelling, cyclase assays, immunoblotting), we provide evidence for the presence (guanylyl cyclase-A, soluble guanylyl cyclase, regulatory and catalytic subunits of cAMP-dependent protein kinase) or absence (guanylyl cyclase-B, natriuretic peptide clearance receptor, neuronal nitric oxide synthase, cGMP-dependent protein kinase I) of different factors involved in either cAMP or cGMP pathways. Functional studies showed that cGMP, at high concentrations, can enhance sperm protein tyrosine phosphorylation but not serine phosphorylation of glycogen synthase kinase. This study reveals that human sperm are characterized by an exceptional predominance of cAMP signalling and indicates potential roles for cGMP.

Characterization of VIP and PACAP receptors in cultured rat penis corpus cavernosum smooth muscle cells and their interaction with guanylate cyclase-B receptors.

Penile corpus cavernosum smooth muscle relaxation can be induced by both cyclic AMP and cyclic GMP-elevating agents, but possible interactions between these two signalling pathways are still poorly understood. Using in vitro cultured rat penile corpus cavernosum smooth muscle (CCSM) cells, we have characterized the local expression and functional activities of receptors for the cAMP-elevating peptides, PACAP and VIP, and for the cGMP-elevating peptides, CNP and ANP. Stimulation of the cells with various concentrations of PACAP(-27/-38) or VIP resulted in rapid and dose-dependent increases in cyclic AMP levels. RT-PCR analyses revealed gene expression of PAC(1) and VPAC(2) but not of VPAC(1) receptors in the cells. The natriuretic peptide, CNP, and the nitric oxide donor, sodium nitroprusside, were capable of enhancing cyclic GMP formation, indicating the presence of membrane-associated in addition to soluble guanylate cyclase (sGC) activities in these cells. Findings that cyclic GMP formation was preferentially activated by CNP but not by the related peptide, ANP, were consistent with RT-PCR analyses, demonstrating gene expression of the CNP receptor, GC-B, but not of the ANP receptor, GC-A, in these cells. Prior exposure of the cells to 10(-8) M PACAP resulted in a marked down-regulation of GC-B activity, whereas sGC was not affected. These findings provide functional and molecular evidence for the presence of three receptors, PAC(1), VPAC(2) and GC-B, involved in cyclic nucleotide signalling in penile CCSM cells. The observed cross-talk of the PACAP/VIP receptors with GC-B but not with sGC may have implications for the therapy of erectile dysfunction.