Effects of sleeping in a chemical protective mask on sleep quality and cognitive performance

PURPOSE: We wanted to determine whether sleep is disrupted when soldiers sleep in a new chemical protective mask, the M40. Sleep quantity and quality, extent of protection provided by the mask during sleep, and next day performance were assessed. METHOD: After several days of training, 9 male soldiers slept with and without the M40 mask on four occasions. RESULTS: Soldiers were able to tolerate the mask for most or all of the night. However, sleep, as assessed by wrist-worn activity monitors, was significantly disturbed. Minutes (mean +/- SEM) of waking significantly increased, from 25 +/- 2.1 to 86 +/- 8.5 per night (p < 0.001), and number of awakenings rose from 8 +/- 0.6 to 20 +/- 0.9 (p < 0.0001). Soldiers reported that it took longer and was more difficult to fall asleep when wearing the mask. Errors on a choice reaction time task increased significantly and subjects reported greater fatigue and sleepiness the day after sleeping in the mask. Protection provided by the masks varied substantially among subjects and declined over the course of the study. Some soldiers were protected throughout the night but others were only protected intermittently. CONCLUSION: We conclude that sleeping in the chemical protective mask should only be done when necessary, given the adverse effects on sleep and daytime function, as well as the variability of protection, of the mask.     

Determination of glycyrrhizin and glycyrrhetinic acid in traditional Chinese medicinal preparations by capillary electrophoresis

A simple, rapid, accurate and reproducible capillary electrophoretic method was developed for the assay of glycyrrhizin and glycyrrhetinic acid in traditional Chinese medicinal preparations. The buffer solution used in this method was acetonitrile and 0.02 M sodium dihydrogen-phosphate solution adjusted to pH 7.5 with 0.05 M sodium hydroxide. The linear calibration range was 0.04-2.00 mg/ml (r = 0.9988) for glycyrrhizin and 0.007-0.35 mg/ml (r = 0.9985) for glycyrrhetinic acid and recoveries were 98.1-101.3% for glycyrrhizin and 98.5-101.4% for glycyrrhetinic acid. The relative standard deviations were 1.02% (n = 6) for glycyrrhizin and 0.91% (n = 6) for glycyrrhetinic acid. The content of these two acids in Glycyrrhizae Radix and Glycyrrhizae Radix-containing Chinese medicinal preparations was successfully determined within 10 min.     

N-acetyl-cysteine causes a late re-specification of the anteroposterior axis in the Xenopus embryo

N-acetyl cysteine is an agent which has been shown to interrupt signal transduction processes linking a wide range of stimuli to the activation of NF-kappa B in mammalian cells. We have investigated its effect on the early development of Xenopus embryos by injecting it into blastulae, using concentrations comparable to those effective on cultured cells. High concentrations at the late blastula or early gastrula stage suppress posterior and enhance anterior development, yielding embryos with enlarged cement glands and otherwise consisting of little except head in extreme cases. Reducing the amount of N-acetyl cysteine injected leads to progressively more posterior structures developing. Injection into one- or two-cell embryos gives similar phenotypes, but of reduced severity and the cement gland is not so enlarged. Explants of animal cap cells taken several hours after injection develop to give large amounts of cement gland material. We have examined the expression of a number of genes in the anteriorised embryos. Posterior markers and Xsna are reduced. Noggin and Goosecoid mRNA are up-regulated through the gastrula and persist at these levels until at least the late neurula stage, whereas in controls Noggin is much lower and Goosecoid is absent at these stages. The most anteriorised phenotype may be a consequence of this changed expression.     

The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study

1. We have studied the effects of muscarinic cholinoceptor agonists and subtype-preferring antagonists on the isometric contraction of smooth muscle strips from dog prostate. 2. Acetylcholine and carbachol induced contraction of prostate strips from the peripheral zone, ('the capsule'). Bethanechol contracted the tissue but not at lower doses. McN-A-343 and oxotremorine-M showed the same effects. 3. Blocking alpha- and beta-adrenoceptors with phentolamine and propranolol, respectively, did not modify carbachol-induced contractions. 4. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M) did not affect the contractile response evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic receptor antagonist, atropine (10(-11)-10(-9) M), inhibited it in a competitive manner. 5. The muscarinic M1 (pirenzepine), M2 [AF-DX 116, himbacine (M2/M4) and methoctramine], M3 (HHSID and f-F-HHSID), and putative M4 (tropicamide) antagonists reduced significantly the carbachol-induced contractions. The pIC50 values were: atropine (10.01) > himbacine (8.3) > methoctramine (7.85) > AF-DX 116 (7.60) > HHSID (7.21) > p-F-HHSID (7.10) > pirenzepine (7.30) > tropicamide (7.00). 6. The antagonist profile indicates that an predominant M2 receptor subtype could mediate the muscarinic contraction in the canine prostate.     

The syntaxin Tlg1p mediates trafficking of chitin synthase III to polarized growth sites in yeast

Tlg1p and Tlg2p, members of the syntaxin family of SNAREs in yeast, have been implicated in both endocytosis and the retention of late Golgi markers. We have investigated the functions of these and the other endocytic syntaxins Pep12p and Vam3p. Remarkably, growth is possible in the absence of all four proteins. In the absence of the others, Pep12p and Tlg1p can each create endosomes accessible to the endocytic tracer dye FM4-64. However, although Pep12p is required for the ligand-induced internalization of the alpha factor receptor and its passage via Pep12p-containing membranes to the vacuole, Tlg1p is not. In contrast, Tlg1p is required for the efficient localization of the catalytic subunit of chitin synthase III (Chs3p) to the bud neck, a process that involves endocytosis and polarized delivery of Chs3p. In wild-type cells, internalized Chs3p cofractionates with Tlg1p and Tlg2p, and in a strain lacking the other endocytic syntaxins, either Tlg1p or Tlg2p is sufficient for correct localization of the enzyme. Pep12p is neither necessary nor sufficient for this process. We conclude that there are two endocytic routes in yeast that can operate independently and that Tlg1p is located at the junction of one of these with the polarized exocytic pathway.     

Dose-related effects of Ampligen (poly(I).poly(C12U)), a mismatched double-stranded RNA, in a bleomycin-mouse model of pulmonary fibrosis

The antifibrotic effect of the mismatched double-stranded RNA, Ampligen (poly(I).poly(C12U)), was evaluated in a bleomycin-mouse model of pulmonary fibrosis. Mice received a single intratracheal dose of bleomycin (0.125 U/mouse) or saline (50 microL) at the beginning of the experiment, followed by 5 or 6 intraperitoneal injections of Ampligen (1.0, 5.0, 10.0, 15.0, or 25.0 mg/kg) or saline at regular intervals for 2 weeks. Ampligen did not produce increased mortality or weight loss by itself. However, it produced varying degrees of mortality in combination with bleomycin. Five injections of 10 mg/kg Ampligen or three injections of 25 mg/kg Ampligen plus three injections of 10 mg/kg Ampligen in combination with bleomycin .produced significant reductions in lung collagen accumulation as indicated by lung hydroxyproline content compared to the bleomycin control group. Animals receiving bleomycin plus Ampligen at all dosages had significantly reduced prolyl hydroxylase activity compared to the bleomycin control group. Lipid peroxidation and bronchoalveolar lavage fluid (BALF)-supernatant protein content for the groups receiving bleomycin plus Ampligen were not reduced compared to the bleomycin control group. In the BALF-supernatant, the activity of acid phosphatase, a lysosomal enzyme produced by neutrophils, monocytes, and macrophages, was significantly decreased in the group receiving bleomycin plus 10 mg/kg Ampligen. Also, selected BALF differential immune cell counts were reduced in some of the groups receiving bleomycin plus Ampligen, but not in a consistent or dose-dependent manner. The results of this study indicate that Ampligen can significantly reduce the bleomycin-induced increased collagen accumulation and may be therapeutically useful in the management of lung fibrosis in humans.     

In vivo roles of receptor tyrosine kinases and cytokine receptors in early thymocyte development

The early phases of T-cell development require both cell-cell interactions and soluble factors provided by stromal cells within the thymic microenvironment. Still, the precise nature of the signals delivered in vivo by cytokines (resulting in survival, proliferation or differentiation) remains unclear. Recent studies using mice deficient in cytokines or in their receptors have helped to identify essential signaling pathways required for the development of intrathymic precursors to mature alpha beta and gamma delta T cells. In addition, cytokine requirements for the development of natural killer cells were revealed in such mutants. The results obtained demonstrate that the development of all classes of lymphocytes (natural killer, gamma delta T cells and alpha beta T cells) is cytokine dependent, but the specific requirements differ for each lineage.     

Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis

We evaluated 48 archival cases of acute erythroleukemia and divided them into 3 groups: M6a, corresponding to the traditional French-American-British M6 category; M6b, which is pure erythroleukemia; and M6c, in which myeloblasts and pronormoblasts each account for more than 30% of cells by the French-American-British exclusion criteria. No significant differences were noted among the subtypes for ratio of males to females; age; or exposure to toxins, alcohol, or both. However, compared with the patients in the M6a group, patients in the M6b and M6c groups demonstrated a statistically significant increase in cytogenetic aberrations, proliferation markers (proliferating cell nuclear antigen and Ki67), and ringed (type III) sideroblasts. Marked survival differences were noted between the M6a (30.1 +/- 29.5 months) and M6b (3.15 +/- 4.2 months) groups, with patients in the M6c group demonstrating an intermediate prognosis (10.5 +/- 12.7 months). Chemotherapeutic regimens induced remission in all treated patients in the M6a and M6c groups but did not appear to affect the M6b group. However, the patients in the M6c group remained in remission for a significantly shorter period of time than did patients in the M6a group. Overall, survival appeared to depend on the ratio of pronormoblasts to myeloblasts at diagnosis and demonstrated a rapid decline with increasing pronormoblast and decreasing myeloblast counts. We must, therefore, devise chemotherapeutic regimens that target both blastic components of this disease.     

Highly active antiretroviral therapy results in a decrease in CD8+ T cell activation and preferential reconstitution of the peripheral CD4+ T cell population with memory rather than naive cells

Criteria for detection of chromosome aberrations by Comparative Genomic Hybridization (CGH) are not standardized and improvement of this part of the analysis is of paramount importance to the applicability of the technique. The aim of this work was to suggest CGH detection criteria that increase the specificity and sensitivity and at the same time include chromosome regions previously excluded from CGH analysis. We analyzed 33 hybridizations with normal DNA and modified our CGH software in order to use a selection of these normal analyses as a model for interpretation of analyses of unknown samples. This approach was successfully tested on 14 samples with known aberrations.