Accidental hypothermia: incidence, risk factors and clinical course of patients admitted to hospital

This study was initiated to identify the incidence, risk factors and outcome predictors of patients admitted to hospital in the Netherlands because of accidental hypothermia. Information about these patients was available for study through the National Health Care Data Bank. Between 1987 and 1990, 612 accidental hypothermic patients were admitted: 185 hypothermic patients also suffered from submersion (HYPSUBS), but this was not the case in the remaining 427 patients (HYPNOTSUBS). Patients in the HYPNOTSUBS group were older (average age 55.2 years versus 38.9 years; p < 0.001), remained longer in hospital (average 20.8 days versus 9.2 days; p < 0.001) and had a higher death rate than those in the HYPSUBS group (16.9% versus 5.9%; p < 0.001). In HYPNOTSUBS, increasing age correlated with increases in the length of hospital stay and death rate. This relationship was not found in HYPSUBS. Trauma was the major associated problem in both groups; these patients had the highest death rate (22.8% versus 16.7%; not significant). Death occurred within 2 days in 54% of HYPNOTSUBS non-survivors and 73% of HYPSUB non-survivors. HYPNOTSUBS admitted to university hospitals showed a lower death rate (5.9%) compared with HYPNOTSUBS admitted to non-university hospitals with less than 400 beds (13.4%) or more than 400 beds (21.7%). In contrast, the death rate in HYPSUB was higher in university hospitals (14.3%) than in non-university hospitals with less than 400 beds (5.2%) or more than 400 beds (3.6%). We observed that the incidence of accidental hypothermia is low at 1.1 per 100,000 inhabitants per year. We concluded that HYPNOTSUBS and HYPSUB are different groups of patients with respect to demographic data, risk factors and prognostic factors. Old age is an important unfavourable prognostic factor in HYPNOTSUB but not in HYPSUB. Hypothermia with trauma is an unfavourable combination in both groups. Almost half of the HYPNOTSUBS non-survivors died after more than 2 days. Because body temperature will have returned to normal by then, this must be the result of late complications. Most HYPSUB non-survivors died during the first 2 days, probably as a direct result of the submersion injury.     

Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals: association with low expression of CCR5 and high production of beta-chemokines

Escherichia coli leader peptidase, an integral membrane protein, is responsible for the cleavage of the signal sequence of many exported proteins. Recent studies suggest that it is a novel serine protease that utilizes a serine-lysine catalytic dyad. In an effort to further understand the mechanism of this enzyme, an internally quenched fluorescent peptide substrate incorporating the leader peptidase cleavage site of maltose binding protein signal peptide, Y(NO2)-F-S-A-S-A-L-A-K-I-K(Abz) (anthraniloyl), was designed and synthesized. In the intact peptide, the fluorescence of the anthraniloyl group is quenched by the 3-nitrotyrosine. This quenched fluorescence is liberated upon cleavage of the peptide by the leader peptidase, resulting in increased fluorescence that could then be monitored fluorometrically. The designed substrate can be cleaved effectively by E. coli leader peptidase as detected by both HPLC and fluorescent spectroscopy. Mass spectra of cleavage products demonstrated that the cleavage occurs at the predicted site (A-K). The cleavage of the peptide substrate has a linear dependence on the enzyme concentration (0.1 to 1.9 microM) and the kcat/K(m) was calculated to be 71.1 M-1 s-1. These data are comparable with the unmodified peptide substrate. This report represents the first direct continuous assay based on fluorescence resonance energy transfer for E. coli leader peptidase.     

Effect of oral beta-carotene supplementation on plasma human immunodeficiency virus (HIV) RNA levels and CD4+ cell counts in HIV-infected patients

We conducted a pilot, open-label study to assess the effect of short-term beta-carotene administration (180 mg/d with meals for 4 weeks) on the plasma human immunodeficiency virus (HIV) RNA levels and CD4+ lymphocyte counts in 21 HIV-infected patients. We found that plasma HIV RNA levels and CD4+ lymphocyte counts did not change following this short course of beta-carotene supplementation. Patients with lower serum concentrations of beta-carotene before supplementation were no more likely to have an increase in their CD4+ lymphocyte count or plasma HIV RNA copy number than were those with higher concentrations. No correlation was found between pre- or postsupplementation beta-carotene or vitamin A concentrations and pre- or postsupplementation CD4+ lymphocyte counts or plasma HIV RNA titers. This study provides no support for beta-carotene supplementation for HIV-infected subjects with normal baseline serum levels of beta-carotene and vitamin A.     

Effect of CYP2D1 inhibition on the behavioural effects of d-amphetamine

In rats, amphetamine (AMP) conversion to 4-OH-AMP is metabolized by CYP2D1, the rat equivalent of the human enzyme CYP2D6. To determine the impact of impaired AMP metabolism on its behavioural effects, AMP-induced hyperactivity, AMP discrimination and AMP self-administration were examined in male Wistar rats with or without pretreatment with the CYP2D1 inhibitors quinine and budipine. In vivo, quinine (20 mg/kg) and budipine (10 mg/kg) increased the plasma area under the curve of AMP 4-fold and 3.6-fold respectively, and decreased the plasma levels of 4-OH-AMP, 3-fold and 8.6-fold, confirming that the doses used suppressed CYP2D1 activity. Both inhibitors prolonged AMP-induced hyperactivity (0.3 mg/kg) and prolonged the duration of AMP-appropriate responding for periods of up to 90 min post-AMP administration in a drug discrimination procedure. In rats given a preload dose of AMP (0.8 mg/kg) 3 h prior to the self-administration test session, CYP2D1 inhibition resulted in fewer AMP infusions being taken compared with rats receiving the AMP preload dose alone. These studies indicate that AMP is responsible for the behavioural effects seen in rats and that a rat phenocopy model of the human CYP2D6 deficiency state can be produced by CYP2D1 inhibitors.     

Systemic release of soluble TNF receptors after high-dose TNF in isolated limb perfusion

Isolated limb perfusion (ILP) with high dose tumour necrosis factor (TNF), interferon gamma and melphalan (TIM) is an efficient treatment for patients with regionally advanced melanoma and sarcoma. In 44 patients, we determined the kinetics of soluble TNF receptors (sTNF-RI and RII) plasma concentrations, and correlated them with systemic TNF and interleukin 6 (IL-6) levels and shock. Seven patients treated conventionally by ILP without cytokine served as controls. Elevated levels of both sTNF-Rs were observed within 30 min after beginning of the TIM-ILP. A first peak of sTNF-Rs levels was observed 3 h after ILP and was followed by a rapid decrease reaching a nadir at 12-14 h post ILP. This first peak was followed by a second, long-lasting elevation of both sTNF-Rs levels persisting for 4 to 5 days after TIM-ILP. Patients treated by ILP without TNF/interferon gamma (IFN-gamma) had no detectable increase in either sTNF-Rs or in circulating TNF, demonstrating that the release of TNF-Rs was dependent upon the administration of TNF/IFN-gamma. High plasma levels of TNF and IL-6 were observed in patients that had more than 5% leakage during the TIM-ILP, but no significant correlation between TNF levels and the peak values of both sTNF-Rs was observed. The levels of TNF and IL-6 were, however, significantly related to each other. TNF systemic levels, but not sTNF-Rs concentrations, correlated significantly with the severity of the shock observed after TIM-ILP. Patients in which sTNF-RII concentration was in excess over circulating TNF, had no shock or grade I shock only, suggesting that sTNF-RII may play a protective, although limited, role in inhibiting activity of circulating TNF.     

The role of the blood-brain barrier transporter PTS-1 in regulating concentrations of methionine enkephalin in blood and brain

The entrainment of the circadian rhythm of locomotor activity was studied in the field mouse Mus booduga in order to examine the relationship between the free-running period (tau) and minimum tolerable light pulse interval of the skeleton photoperiods. The animals were entrained under three different light/dark (LD) schedules, each out of phase with the other. They were then subjected to various skeleton photoperiods created by two repeated light pulses (LPs) interrupting darkness. Animals that selected the shorter interval between the LPs as their "subjective night" had significantly shorter tau (23.13 +/- 0.38 h) as compared to those that selected the longer dark interval as subjective night (tau = 23.87 +/- 0.18 h). When the longer dark interval was 12 h, animals selecting that interval as their subjective night included both long-tau and short-tau individuals. When both intervals of darkness were of equal duration, no difference in the selection of subjective night was seen between short and long-tau animals. When the "dusk" LP for the animals that selected the longer dark interval as subjective night was advanced by 2 h to create a new skeleton photoperiod, the number of transient cycles appearing before steady-state entrainment was found to depend on the duration of the photoperiods. When the night defined by the two LPs was reduced below 6h, a dramatic "phase jump" in the activity rhythm was observed, and the initial phase relationship was restored after a relaxation in the night duration. We observed considerable interindividual variation in the "minimum tolerable light pulse interval of skeleton photoperiods," which we suggest may be due to the observed variation in tau among individuals.     

Polypropylene/date stone flour composites: Effects of filler contents and EBAGMA compatibilizer on morphology,thermal, and mechanical properties

This work aims to study the effects of date stone flour (DSF) on morphology, thermal, and mechanical properties of polypropylene (PP) composites in the absence and presence of ethylene‐butyl acrylate‐glycidyl methacrylate (EBAGMA) used as the compatibilizer. DSF was added to the PP matrix at loading rates of 10, 20, 30, and 40 wt %, while the amount of compatibilizer was fixed to the half of the filler content. The study showed through scanning electron microscopy analysis that EBAGMA compatibilizer improved the dispersion and the wettability of DSF in the PP matrix. Thermogravimetric analysis (TGA) indicated a slight decrease in the decomposition temperature at onset (T_onset) for all composite materials compared to PP matrix, whereas the thermal degradation rate was slower. Differential scanning calorimetry (DSC) data revealed that the melting temperature of PP in the composite materials remained almost unchanged. The nucleating effect of DSF was however reduced by the compatibilizer. Furthermore, the incorporation of DSF resulted in the increase of stiffness of the PP composites accompanied by a significant decrease in both the stress and strain at break. The addition of EBAGMA to PP/DSF composites improved significantly the ductility due to the elastomeric effect of EBAGMA. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013