Potential bioreductively activated hypoxia probes and post-irradiation radiosensitizers related to NITP

NITP (1) is an effective marker of hypoxia in tumours for both microscopy and cell sorting studies and, additionally, the compound shows post-irradiation sensitization, probably by inhibition of repair of radiation damage to DNA. However, NITP does not have the substitution pattern which the immunochemical reagents are raised to recognize and the compound has very low solubility in water. We report the synthesis of an isomer (13) of NITP which has the desirable substitution pattern and is also soluble in very weak aqueous base. The successful synthesis of 13 uses a nitrosation and cyclization of a substituted uracil (16), but earlier approaches from 5 and 12 yielded the pyridoxanthine derivative 6. The preparative use of nitro group displacement reactions from 8-nitrocaffeine is shown to be a useful entry to a range of 8-substituted caffeines and is utilized to obtain two derivatives of NITP which carry aliphatic amine chains, i.e. 34 and 35.     

Effects of the prolonged administration of bradykinin on the rat pituitary-adrenocortical axis

The effects of a prolonged administration of bradykinin (BK) and/or D-Arg, [Hyp3, D-Phe7]-BK, a specific antagonist of BK receptors (BK-A) (daily subcutaneous injections of 4 nmol/rat for 6 days) on the function of the pituitary-adrenocortical axis were investigated. BK did not change plasma aldosterone concentration (PAC), but markedly lowered that of corticosterone (PBC) and consequently induced a compensatory hypersecretion of ACTH by the pituitary gland. BK-A did not apparently affect the function and growth of the adrenal gland, but, when administered together with BK, markedly raised both PAC and PBC, and provoked a significant atrophy of the adrenal gland, probably due to loss of parenchymal cells. Taken together, these rather puzzling findings do not appear to provide clear evidence for the involvement of BK in the physiological regulation of adrenocortical growth and steroidogenic capacity in rats.     

Communicating do-not-resuscitate orders with a computer-based system

BACKGROUND: Do-not-resuscitate (DNR) orders for critically ill patients are frequently miscommunicated between attending physicians, house staff, and nurses. A computer-based system was developed to improve the communication of a procedure-specific DNR order form. METHODS: Concordance of understanding of patients' DNR status was measured with the use of unstructured DNR orders (period 1), procedure-specific DNR order forms (period 2), and procedure-specific DNR order forms administered with a computer-based communication system (period 3). The 3 components of the DNR order assessed were (1) the clinical events to which the DNR order applied, (2) whether the DNR order withheld all elements of cardiopulmonary resuscitation, and (3) whether other treatments were to be withheld. RESULTS: For the 147 patients, the computer-based system in period 3 (n = 71) improved concordance for attending physicians and nurses or residents for all 3 of the DNR components compared with period 1 (n = 40) and some of the DNR components compared with period 2 (n = 36). Concordance was "substantial" or "almost perfect" as measured by the K statistic during period 3. The proportion of agreement for the composite of all 3 components of the DNR order increased during each period (P<.001, period 3 vs period 1). Overall agreement between all caregivers for the composite DNR order also improved from period 1 (22.2%) to period 2 (47.8%) and period 3 (61.9%; P<.001 vs period 1). Errors in order entry were detected by physicians because of the computer system and corrected in 9.9% of DNR orders in period 3. Progress note documentation of DNR status did not improve during period 3. The procedures of period 3 were considered acceptable by the physician and nursing staff. CONCLUSION: A computer-based system combined with a procedure-specific DNR order form improves communication of patients' DNR status in a critical care setting.     

Selective reduction of GluR2 protein in adult hippocampal CA3 neurons following status epilepticus but prior to cell loss

Kainic acid (KA) induces status epilepticus and delayed neurodegeneration of CA3 hippocampal neurons. Downregulation of glutamate receptor 2 (GluR2) subunit mRNA [the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) subunit that limits Ca2+ permeability] is thought to a play role in this neurodegeneration, possibly by increased formation of Ca2+ permeable AMPA receptors. The present study examined early hippocampal decreases in GluR2 mRNA and protein following kainate-induced status epilepticus and correlated expression changes with the appearance of dead or dying cells by several histological procedures. At 12 h, in situ hybridization followed by emulsion dipping showed nonuniform decreases in GluR2 mRNA hybridization grains overlying morphologically healthy-appearing CA3 neurons. GluR1 and N-methyl-D-aspartate receptor mRNAs were unchanged. At 12-16 h, when little argyrophilia or cells with some features of apoptosis were detected by silver impregnation or electron microscopy, single immunohistochemistry with GluR2 and GluR2/3 subunit-specific antibodies demonstrated a pattern of decreased GluR2 receptor protein within CA3 neurons that appeared to predict a pattern of damage, similar to the mRNA observations. Double immunolabeling showed that GluR2 immunofluorescence was depleted and that GluR1 immunofluorescence was sustained in clusters of the same CA3 neurons. Quantitation of Western blots showed increased GluR1:GluR2 ratios in CA3 but not in CA1 or dentate gyrus subfields. Findings indicate that the GluR1:GluR2 protein ratio is increased in a population of CA3 neurons prior to significant cell loss. Data are consistent with the "GluR2 hypothesis" that reduced expression of GluR2 subunits will increase formation of AMPA receptors permeable to Ca2+ and predict vulnerability to a particular subset of pyramidal neurons following status epilepticus.     

Infective endocarditis complicated with rapidly progressive glomerulonephritis: a case report

Despite a general national decline in criminal activities in the 1990s, juvenile criminal offenses continue to increase, (including violent, property, and delinquency acts). In addition increased numbers of children are being held in juvenile jails. It is all but impossible for pediatric health providers to think that "their patients" and "their practices" are immune from the epidemic of crime that affects and is caused by "just kids."     

Phytoplankton Productivity and Standing Crop in the Vicinity of the Lake Huron-Saginaw Bay Front

Continuous underway sampling was used in four research cruises near the mouth of Saginaw Bay in order to locate the bay-lake front, where eutrophic bay water mixes with oligotrophic Lake Huron water. Although mixing between these water masses normally occurs in outer Saginaw Bay, the distribution was variable, depending on wind force and direction as well as water temperature. Large algal crops in inner Saginaw Bay had reduced soluble nutrients, particularly silicate and nitrate-nitrogen, in the outer bay to levels lower than the adjacent lake water. Nonetheless, outer bay water supported high algal biomass (up to 14 μg/L chlorophyll a) and ¹⁴C uptake (up to 73 μg /L/h). The phytoplankton community at the nutrient front between bay and lake waters was characterized by high chlorophyll a biomass ($\overline{x}$ = 4.47 μg/L), low ¹⁴C uptake ($\overline{x}$ = 7.12 μg/L/h), and high bacterial activity (V_max$\overline{x}$ = 1.33) indicating the presence of a senescent assemblage. Decomposition and settling of phytoplankton in the vicinity of the front apparently served to remove much of the bay plankton from the water column before mixing into the open lake. But, during mid-summer, occasional large inputs of nutrients and/or phytoplankton from the bay into the open lake were observed.     

Thermal conductivity measurements and molecular association in a series of alcohol vapors: Methanol,ethanol, isopropanol,and t-butanol

Thermal conductivity measurements on the vapors of methanol, ethanol, isopropanol, and t-butanol are reported as a function of temperature (330–420 K) and pressure (11–240 kPa). The thermal conductivity versus pressure isotherms for all four alcohols exhibit upward curvatures at the lower temperatures and nearly linear increases at higher temperatures. This behavior is indicative of a dimeric species and one or more polymeric clusters in the vapor in addition to the monomer. Quantum mechanical calculations have indicated that tetramers are the most likely polymeric species. Detailed analyses of the data provide thermodynamic data (H,S) for the dimerization and tetramerization reactions and show interesting correlations with the size of the monomer unit.     

Refinement of wavelength calibrations of hyperspectral imaging data using a spectrum-matching technique

The concept of imaging spectrometry, or hyperspectral imaging, is becoming increasingly popular in scientific communities in recent years. Hyperspectral imaging data covering the spectral region between 0.4 and 2.5 μm and collected from aircraft and satellite platforms have been used in the study of the earth's atmosphere, land surface, and ocean color properties, as well as on planetary missions. In order to make such quantitative studies, accurate radiometric and spectral calibrations of hyperspectral imaging data are necessary. Calibration coefficients for all detectors in an imaging spectrometer obtained in a laboratory may need to be adjusted when applied to data obtained from an aircraft or a satellite platform. Shifts in channel center wavelengths and changes in spectral resolution may occur when an instrument is airborne or spaceborne due to vibrations, and to changes in instrument temperature and pressure. In this paper, we describe an algorithm for refining spectral calibrations of imaging spectrometer data using observed features in the data itself. The algorithm is based on spectrum-matching of atmospheric water vapor, oxygen, and carbon dioxide bands, and solar Fraunhofer lines. It has been applied to real data sets acquired with airborne and spaceborne imaging spectrometers.     

Fused ring and linking groups effect on overcharge protection for lithium-ion batteries

The derivatives of 1,3-benzodioxan (DBBD1) and 1,4-benzodioxan (DBBD2) bearing two tert-butyl groups have been synthesized as new redox shuttle additives for overcharge protection of lithium-ion batteries. Both compounds exhibit a reversible redox wave over 4 V vs Li/Li⁺ with better solubility in a commercial electrolyte (1.2 M LiPF₆ dissolved in ethylene carbonate/ethyl methyl carbonate (EC/EMC 3/7) than the di-tert-butyl-substituted 1,4-dimethoxybenzene (DDB). The electrochemical stability of DBBD1 and DBBD2 was tested under charge/discharge cycles with 100% overcharge at each cycle in MCMB/LiFePO₄ and Li₄Ti₅O₁₂/LiFePO₄ cells. DBBD2 shows significantly better performance than DBBD1 for both cell chemistries. The structural difference and reaction energies for decomposition have been studied by density functional calculations.     

Protein kinase C regulates a vesicular class of calcium channels in the bag cell neurons of aplysia

Protein kinase C (PKC) acutely increases calcium currents in Aplysia bag cell neurons by recruiting calcium channels different from those constitutively active in the plasma membrane. To study the mechanism of PKC regulation we previously identified two calcium channel alpha1-subunits expressed in bag cell neurons. One of these, BC-alpha1A, is localized to vesicles concentrated primarily in somata and growth cones. We used antibodies to BC-alpha1A to analyze its expression in the bag cell neurons of juvenile Aplysia at a developmental stage at which PKC-sensitive calcium currents have previously been shown to be low. We find that vesicular BC-alpha1A staining is generally reduced in juvenile bag cell neurons but that its expression level can vary among juvenile animals. In 17 bag cell clusters examined, the percentage of neurons that displayed punctate alphaBC-alpha1A staining ranged from 0 to 85%. Sampling of calcium currents from cells of the same clusters by whole cell patch-clamp techniques revealed that the PKC-sensitive calcium current density is significantly correlated with the degree of vesicular staining. In contrast, no correlation of basal calcium current levels with aBC-alpha1A staining was found. These results strongly suggest that BC-alpha1A, a member of the ABE-subfamily of calcium channels, carries the PKC-sensitive calcium current in bag cell neurons. They are consistent with a model in which PKC recruits channels from the vesicular pool to the plasma membrane.