A Device to Provide Respiratory-Mechanical Unloading

A commercially available and widely used servo-controlled ventilator has been modified to provide controlled inspiratory resistive unloading of the human respiratory system. This is achieved by establishing a positive mouth pressure throughout inspiration in a constant proportion to instantaneous flow, i.e., the ratio of mouth pressure to flow, which defines the "assistance," remaining constant. The performance of this device has been evaluated in four healthy subjects during steady-state, constant-load cycling (20-120 W). It is demonstrated that i) the device can successfully implement controlled degrees of inspiratory assistance on a breath-to-breath basis; ii) the assistance can be sustained over a substantial range of ventilatory drive (i.e., for ventilations up to some 30 1/min) and to an extent which approaches a 100 percent reduction of the normal respiratory resistance. This device should prove useful in experimental and clinical investigations of the respiratory responses to resistive unloading of the respiratory system.     

Determination of limonene oxidation products using SPME and GC-MS

Limonene is a common component found in consumer goods ranging from beverages to cleaning compounds. Limonene oxidation products, however, have a less desirable flavor and fragrance. Early detection of limonene oxide formation would aid quality control. A method is developed to determine the concentration of limonene oxide in essential oils and beverages using solid-phase microextraction (SPME). A headspace sampling technique is used to reduce or eliminate the presence of less volatile components. Several different SPME fibers are tested, varying in polymer thickness, polymer cross-linking and bonding, and polarity of the polymer. For each fiber tested, the sampling time is optimized for reproducible results. The 7-microm-thick bonded poly(dimethylsiloxane) fiber provides the best results. External standards are used for quantitation.     

Natural abundance 13C - 13C coupling constants observed via double quantum coherence. Structural elucidation by the one- and the two-dimensional NMR experiements of velloziolone,a new seco-diterpene.

With the help of Natural Abundance ¹³C - ¹³C Coupling Constants, observed via double quantum coherence, the structural determination of VELLOZIOLONE (1), a new diterpene, has been carried out.     

Metabonomics: the use of electrospray mass spectrometry coupled to reversed-phase liquid chromatography shows potential for the screening of rat urine in drug development

The application of liquid chromatography/mass spectrometry (LC/MS) followed by principal components analysis (PCA) has been successfully applied to the screening of rat urine following the administration of three candidate pharmaceuticals. With this methodology it was possible to differentiate the control samples from the dosed samples and to identify the components of the mass spectrum responsible for the separation. These data clearly show that LC/MS is a viable alternative, or complementary, technique to proton NMR for metabonomics applications in drug discovery and development.     

The Role of Oxygen in the Antiviral Activity of Hypericin and Hypocrellin

The light-induced antiviral activity of hypericin and hypocrellin in the presence and absence of oxygen was examined under experimental conditions where the effect of oxygen depletion could be quantified. There was a significant reduction of light-induced antiviral activity of hypericin and hypocrellin under hypoxic conditions. Interestingly, antiviral activity of hypocrellin was not observed at low oxygen levels at which hypericin retained measurable virucidal activity. This suggests that additional pathways, such as the generation of protons from excited states of hypericin, may enhance the biological activity of activated oxygen species.     

Synthesis and characterisation of a series of alkylmagnesium amide and related oxygen-contaminated "alkoxy" compounds

Synthesised either by an unusual tert-butyl metathesis between tert-butyllithium and a n,s-butylmagnesium amide or by reaction of an alkyl Grignard reagent and a sodium amide, five tert-butylmagnesium amides, Bu(t)MgDBA (5)(DBA=dibenzylamide), Bu(t)MgDA (6)(DA=diisopropylamide), Bu(t)MgHMDS (7)(HMDS=1,1,1,3,3,3-hexamethyldisilazide), Bu(t)MgTMP (8)(TMP=2,2,6,6-tetramethylpiperidide) and Bu(t)MgNCy2 (9)(cy=cyclohexyl) have been isolated as crystalline solids. All five amides have been characterised by X-ray crystallography and solution NMR spectroscopic studies. The former studies reveal a common dimeric molecular structure with amido bridges in a planar (MgN)2 ring and terminal Bu(t) ligands on the Mg atoms. Also described is the dodecameric primary amide [Bu(n)MgN(H)Dipp]12 (10a) and its monomeric solvate Bu(n)MgN(H)Dipp.TMEDA (10b)(Dipp=2,6-diisopropylphenyl; TMEDA=N,N,N',N'-tetramethylethylenediamine). The crystal structures of the oxo-insertion products Bu(t)MgOBu(t).THF (11), Bu(t)Mg(mu-OBu(t))(mu-TMP)MgTMP (12) and Mg(OBu(n))HMDS.solv [solv=THF (13a) or Et2O (13b)], made fortuitously during the course of this work, are also presented.     

Interactions in water-alcohol mixtures studied by NMR and infrared spectroscopy

By using low temperatures and largely deuterated solvents, the rate of OH proton exchange for aqueous solutions of alcohols is reduced sufficiently to give separate NMR signals from water and alcohol OH protons. The limiting shifts for dilute alcohols in water are down-field of both the water resonance and those of the pure alcohols. This contrasts with the limiting shift for water in the alcohols, which is to high field of the bulk water resonance. The resonance shifts initially to low fields as [ROH] increases, the rate of shift being greatest for t-butyl alcohol. For dilute aqueous solutions, all the alcohols reduce the total concentration of free OH groups, as judged by the overtone infrared spectra. Some of these results are interpreted in terms of a scavenging of free OH groups by the excess lone-pairs of the alcohol molecules. An extra, temperature dependent, down-field shift in the water proton resonance induced by t-butyl alcohol is assigned to a clathrate cage effect.