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Biomedical subjects

S McLean

Publications and source records attributed to S McLean.

At least 37 records · Page 2Linked to original sources

Three novel monotetrahydrofuran annonaceous acetogenins from Annona montana.

Three new monotetrahydrofuran (mono-THF) acetogenins, anmontanins A-C (1-3) were isolated from the leaves of Annona montana. Anmontanin C (3) is the first stereochemically pure acetogenin reported to have a gamma-hydroxymethyl-gamma-lactone moiety. Two known mono-THF acetogenins, murisolin and annonacin, were isolated from the seeds of the plant. The structures of compounds 1-3 were elucidated by spectral methods and chemical derivatization.

Furans↗

Proctoriones A-C: 2-acylcyclohexane-1,3-dione derivatives from peperomia proctorii.

The structures of three new compounds isolated from Peperomia proctorii, named proctoriones A-C, have been established by spectroscopic and chemical methods as 2,3-dihydro-5, 8-dihydroxy-2-pentadecyl-4H-benzopyran-4-one (1) and enolic forms of 4-hydroxy-2-octadecanoylcyclohexane-1,3-dione (2) and 4-hydroxy-2-octadec-(11Z)-enoylcyclohexane-1,3-dione (3).

Cyclohexanes↗

Biotransformation of 1,8-cineole in the brushtail possum (Trichosurus vulpecula).

1. The metabolic fate of 1,8-cineole was investigated in the brushtail possum. Six possums were fed an artificial diet to which 0.5% 1,8-cineole (wet weight) was added for 2 days. Urine and faeces were collected after the second day. A sample of each was extracted into ethyl acetate and analysed for metabolites. Both free and total levels of metabolites were identified by GC-MS and LC-MS and quantified by GC-MS. 2. The pattern of metabolite excretion was very complex in the brushtail possum. Nineteen metabolites were found in total. Metabolites were categorized into four groups according to the oxidation they had undergone: hydroxycineoles (n = 3), cineolic acids (n = 2), dihydroxycineoles (n = 3) and hydroxycineolic acids (n = 11). No hydroxycineolic acid metabolites have been previously reported as metabolites of 1,8-cineole. 3. Fractional recovery of the ingested dose (2.4 +/- 0.5 g; mean +/- SD) was 0.44 +/- 0.14 (mean +/- SD) in 24 h. Sixty percent of excreted metabolites were hydroxycineolic acids, the most extensively oxidized metabolites. Conjugation with glucuronic acid was inversely related to metabolite polarity, being greatest for hydroxycineoles (41-82%) and minimal for hydroxycineolic acids. 4. Traces of most metabolites were also found in the faeces.

Animals↗

Using pressure dressings after femoral artery sheath removal.

Only one previous study has been performed to assess the efficacy of pressure dressings after removal of a femoral artery sheath. The results of a 739-patient randomised study show there is no benefit in the routine application of pressure dressings after arterial sheath removal. This practice can be abolished with no negative impact on patient safety.

Adult↗

Pharmacokinetics of intravenously administered ketamine in southern elephant seals (Mirounga leonina).

Southern elephant seals (Mirounga leonina) are large, potentially dangerous animals which must be restrained before study or treatment. However, chemical restraint is unpredictable, possibly because of differences in body composition during fasting ashore, and circulatory adaptations to enable diving. The pharmacokinetics of ketamine (1.1 mg/kg i.v.) was studied in 15 southern elephant seals which had come ashore on Macquarie Island. The animals were first sedated with pethidine (5 mg/kg i.m.) to allow intravenous access. There was great variability in the calculated pharmacokinetic parameters, possibly due to circulatory changes associated with periods of apnoea which characterise this animal's response to anaesthetics. The median values were similar to those reported for other species: distribution t1/2 = 2.5 min (range 1-11 min); elimination t1/2 = 43 min (range 17-108 min); apparent volume of distribution, 1474 ml/kg (range 830-9301 ml/kg); clearance, 33 ml/min/kg (range 12-57 ml/min/kg). This was the first investigation of drug disposition in any seal species. and the first in any free-ranging wild animal. It is important to obtain pharmacological data in animals in whom drugs are used, but pre-catheterised captive animals may provide less variable data.

Anesthetics, Dissociative↗

Induction of xenobiotic metabolising enzymes in the common brushtail possum, Trichosurus vulpecula, by Eucalyptus terpenes.

The mixed function oxidase (MFO) activity and content was studied in the liver of common brushtail possums fed for 10 days on a diet containing a mixture of terpenes found in Eucalyptus leaves on which possums commonly browse. The MFOs were compared to the MFOs in possums fed a control diet of fruits and cereals only. The terpenes chosen were 1,8-cineole, p-cymene, alpha-pinene and limonene. The selected terpenes caused induction of P450 enzymes, as shown by a 53% higher cytochrome P450 content and a 45% increase in aminopyrine demethylase activity in the test animals. Aniline hydroxylase activity was significantly increased, with levels of 2.95 and 1.43 nmol min(-1) mg(-1) microsomal protein in the test and control animals, respectively. There was also a significant increase in androstenedione 16alpha-hydroxylase activity in the test group, 0.85 as compared to 0.50 nmol mg(-1) min(-1) in the control group. Western blot studies using human CYP2E1 and rat CYP2C11 and CYP2C6 antibodies gave CYP2E, CYP2C11 and CYP2C6 immunoreactive bands of greater intensity in the test animals as compared to the control group. This study has shown experimentally that dietary terpenes cause enzyme induction in folivorous marsupials. It also confirms the importance of knowledge of diet when studying xenobiotic metabolising enzymes, particularly in wild animals such as the brushtail possum.

Animals↗

Alvaradoins A-D. Anthracenone C arabinosides from alvaradoa jamaicensis

The aerial parts of Alvaradoa jamaicensis have yielded four new compounds. These are both C-10 epimers of 10-C-[4'-O-acetyl-3'-O-(3-methylbut-2-enoyl)]-beta-D-arabinopyranosyl -1,8-dihydroxy-6-methoxy-3-methyl-anthracen-9(10H)-one (3 and 4) and of 10-C-[4'-O-acetyl-3'-O-(3-methylbut-2-enoyl)]-beta-D-arabinopyranosyl -1,8,10-trihydroxy-6-methoxy-3-methyl-anthracen-9-one (5 and 6). The anthraquinones chrysophanol (1) and physcion (2) were also isolated.

Journal Article↗

Limonoids from Swietenia macrophylla and S. aubrevilleana.

An investigation of the seeds of Swietenia macrophylla and S. aubrevilleana (Meliaceae) is reported. Three new compounds, augustineolide (1) and 3beta,6-dihydroxydihydrocarapin (2) from S. macrophylla and 6-acetoxyhumilinolide C (3) from S. aubrevilleana were isolated and characterized along with fifteen known compounds. Four of the compounds were subjected to an antifeedant bioassay on the final instar larvae of Spodoptera frugiperda. The antifeedant activity was comparable to that of bicyclononanolides previously tested.

Animals↗

Respiratory syncytial virus upregulates expression of the substance P receptor in rat lungs.

Respiratory syncytial virus (RSV) is a major respiratory pathogen in infants. The first goal of this study was to determine whether the infection following endotracheal inoculation of RSV in Fischer 344 rats results in increased inflammatory responses to substance P (SP) either released by capsaicin from sensory nerves or injected into the circulation. Five days after inoculation, the extravasation of Evans blue-labeled albumin after capsaicin or SP was significantly greater in RSV-infected airways than in pathogen-free controls. The peptide-degrading activity of the regulatory enzyme neutral endopeptidase was unaffected by RSV. However, SP(NK(1)) receptor mRNA levels increased fivefold in RSV-infected lungs, and the density of SP binding sites in the bronchial mucosa increased threefold. These data suggest that RSV makes the airways abnormally susceptible to the proinflammatory effects of SP by upregulating SP(NK(1)) receptor gene expression, thereby increasing the density of these receptors on target cells. This effect may contribute to the inflammatory reaction to the virus and could be a target for the therapy of RSV disease and its sequelae.

Animals↗

Chronic non-peptide neurokinin receptor antagonist treatment alters striatal tachykinin peptide and receptor gene expression in the rat.

The neurokinin-1 receptor (NK-1R) and the tachykinin peptide substance P (SP) are found throughout the central nervous system (CNS) and are involved in the regulation of sensory, cardiovascular, and inflammatory function. Selective antagonists for the NK-1R such as CP-122,721 block NK-1R-mediated responses both in vitro and in vivo. This study investigated the effects of long-term daily CP-122,721 treatment on gene expression of SP and the NK-1R in the striatum and hindbrain of the rat. The striatum and hindbrain of rats receiving CP122,721 (5, 30, or 150 mg/kg) once-daily for 30 days were assayed for SP- and NK-1R-encoding mRNAs using solution hybridization-nuclease protection assays. Results show that treatment with CP-122,721 significantly increased SP-encoding mRNA and NK-1R mRNA levels in the striatum, but not in the hindbrain. The ability of CP-122,721 to alter SP and NK-1R gene expression may provide a use for non-peptide neurokinin receptor antagonists in the modulation of systems regulated by NK-1R function.

Animals↗

Influence of triple-lumen central venous catheters coated with chlorhexidine and silver sulfadiazine on the incidence of catheter-related bacteremia.

OBJECTIVE: To evaluate the efficacy of triple-lumen central venous catheters coated with a combination product of chlorhexidine and silver sulfadiazine (CSS) in reducing the incidence of local catheter infection and catheter-related bacteremia. DESIGN: Randomized, controlled trial. SETTING: The surgical intensive care units in a university hospital. PATIENTS: All patients who needed central venous catheterization were randomized to receive either an uncoated triple-lumen catheter (n = 157) or a catheter coated with CSS (n = 151). MAIN OUTCOME MEASURE: Catheters were removed when no longer needed or suspected as a cause of infection. The tip and a 5-cm segment of the intradermal portion of the catheter were cultured semiquantitatively. Blood cultures were obtained when clinically indicated. The remaining segment of catheters coated with CSS were cut and incubated on an agar plate with strains of Staphylococcus aureus and Enterococcus. Zone of inhibition was determined 24 hours later. Data were analyzed by survival and logistic multivariate regression methods. RESULTS: Catheters coated with CSS were effective in reducing the rate of significant bacterial growth on either the tip or intradermal segment (40%) compared with control catheters (52%; P = .04). However, there was no difference in the incidence of catheter-related bacteremia (3.8% [uncoated] vs 3.3% [coated]; P = .81). In vitro activity of catheters with CSS against S aureus was evident up to 25 days but activity against Enterococcus dissipated more quickly over time and was absent by day 4. The most common colonizing organisms were coagulase-negative staphylococcus and enterococcus. Variables that were associated with a significant amount of growth on the tip or intradermal segment were a duration of catheterization of longer than 7 days, jugular insertion site, and the absence of a CSS coating. The use of a guidewire when the catheter was removed was associated with a lower risk of significant bacterial growth. CONCLUSIONS: The use of CSS reduces the incidence of significant bacterial growth on either the tip or intradermal segments of coated triple-lumen catheters but has no effect on the incidence of catheter-related bacteremia. In this patient population, catheters coated with CSS provide no additional benefit over uncoated catheters.

Anti-Infective Agents, Local↗

Capillary electrophoretic determination of trace metals in hair samples and its comparison with high performance liquid chromatography and atomic absorption spectrometry techniques.

Capillary electrophoresis (CE) is compared with high performance liquid chromatography (HPLC) and atomic absorption spectrometry (AA) for the determination of trace concentrations of selected metals in human hair. CE and HPLC methods are based upon the chelation of the metals with 2-(5'-bromo-2'-pyridylazo)-5-diethylamino phenol (5-Br-PADAP) followed by ultraviolet-visible (UV-Vis) detection. Large volume sample stacking (LVSS)-CE using injection times of up to 300 s is applied to the simultaneous determination of Co and Zn providing lower limits of detection (LODs) of 4.2 x 10(-8) mol dm(-3) and 6.0 x 10(-8) mol dm(-3), respectively, than can be achieved by conventional CE. The LVSS procedure could not be applied to hair samples due to a higher run current existing when the sample is introduced into the capillary. Conventional CE with cetyltrimethylammonium bromide (CTAB) present in the run buffer to retain the ligand in solution is used for the determination of metal concentrations in hair samples. Only Zn could be determined in this way as it exists at relatively high levels in hair. Co, Ni and Hg could be detected when spiked hair samples were analysed with estimated LODs of 5.0 x 10(-7) mol dm(-3), 1.0 x 10(-6) mol dm(-3) and 3.0 x 10(-5) mol dm(-3), respectively. HPLC was successfully used to determine Co and Cu in hair samples, with levels of 57.6 ppb and 17.31 ppm being found, respectively, and corresponded closely to results produced by AA. Fe also gave a signal together with unidentified coeluting species. In a separate HPLC study the determination of Ni and Hg as their complexes with hydrogen peroxide and 5-Br-PADAP was also investigated and LODs of 2.0 x 10(-6) mol dm(-3) and 5.0 x 10(-6) mol dm(-3), respectively, were achieved. AA was used as a reference method to determine levels of Co, Cu, Fe, Pb and Zn in hair and the results produced were in order of magnitude agreement with accepted literature values.

Azo Compounds↗

Minor cassane diterpenoids of caesalpinia bonduc

Seven cassane diterpenes, including the known caesaldekarin A, were isolated from the roots of Caesalpinia bonduc, collected in Barbados. The 1H and 13C NMR spectra of all seven compounds were completely assigned by using a combination of 2D NMR experiments, which included 1H-1H COSY, HSQC, HMQC, and HMBC sequences.

Journal Article↗

A "reader's theater" intervention to managing grief: posttherapy reflections by a family and clinical team.

The sudden and accidental death of a child can be one of the most devastating events in the life of a family. This paper describes one couple's reflections of their grief and mourning following the death of their adolescent son as well as the clinical team's reflections of therapy. The uniqueness of this paper is that it offers a "reader's theater" intervention that enabled further change to occur. The clinical team used a belief model, emphasizing that altering constraining beliefs is at the heart of healing from such tragedies as sudden death (Wright, Watson, & Bell, 1996). This approach is operationalized through therapeutic conversations between family members, clinician, and clinical team. Interventions such as reflecting teams, therapeutic letters, and "homework tasks" were used to modify or challenge constraining beliefs of both the family members and the clinical team members. However, the intent to co-author a paper with this couple provided the serendipity intervention of a "reader's theater" that further served to identify, affirm, and solidify facilitating beliefs.

Adolescent↗