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Biomedical subjects

F T Smith

Publications and source records attributed to F T Smith.

15 recordsLinked to original sources
PubMed2005

Multi-branching flows from one mother tube to many daughters or to a network.

Multiply branching fluid flows are modelled in two contexts. The first (type I) is for one-to-many branching. Computations are described for flow through a channel, with fully developed motion upstream, which branches abruptly into a number of subchannels downstream. The differences in pressure between the upstream end of the channel and the downstream ends of the subchannels are substantial. Comparisons with recent analytical predictions show fair agreement for Reynolds numbers in the low tens and above. The second context (type II) has successive generations of bifurcation in a network. Modelling, computations and analysis include the effects of many bifurcations.

Journal Article↗
PubMed2005

Modelling the calmed region behind a spot.

A theoretical model of the laminar 'calmed region' following a three-dimensional turbulent spot within a transitioning two-dimensional boundary layer is formulated and discussed. The flow is taken to be inviscid, and the perturbation mean flow surface streamlines calculated represent disturbances to the basic slip velocity. Available experimental evidence shows a fuller, more stable, streamwise profile in a considerable region trailing the spot, with cross-flow 'inwash' towards the line of symmetry. Present results are in qualitative agreement with this evidence.

Journal Article↗
PubMed2005

Droplet impact on water layers: post-impact analysis and computations.

An inviscid model of droplet impact into a water layer is examined analytically for small times just after impact and computationally for order-one distortion times. Various layer depths are considered, as are surface-tension effects. Good correspondence is found between analysis, computation and experiments.

Journal Article↗
PubMed2003

AVM modelling by multi-branching tube flow: large flow rates and dual solutions.

Cerebral arteriovenous malformations (AVMs) present a common yet complex clinical challenge, through 'steal' phenomena, haemorrhage risks and epilepsy effects, aspects which are little understood even for individual lesions. The main difficulty lies in understanding the detailed haemodynamics of AVMs and especially the enhanced through-flow associated with steal. Mathematically, as a basic step, the paper investigates a nonlinear inviscid model for the planar incompressible flow of fluid through a branched geometry consisting of a single feeding mother tube which splits into two or more non-aligned daughter tubes. Recurrence relations between the unknown flow profiles in the daughter tubes and the incoming rotational flow profile in the mother tube are derived, analysed, and solved in detail in order to find the total flow rate. The results show greatly enhanced through-flow arising, for a fixed value of the total downstream flow area, either from non-unique solutions to the problem or more particularly from an increase in the number of daughter tubes, or from both, depending on the distribution of pressure differences applied across the branching region and the total downstream flow area. Extensions of the basic flow model are noted, along with comparisons with recent direct numerical simulations and discussion of possible repercussions in the context of treatment and clinical observations of enhanced through-flows in AVMs.

Blood Flow Velocity↗
PubMed2002

On flow through bends and branchings.

Theoretical modelling of bending and branching tube flows at medium-to-high flow rates is described for current industrial and biomedical projects. This mostly uses slender-flow modelling. Much pressure loss occurs in bends, with increased swirl, large variations in velocity components and wall shear stress, skewing of the downstream motion and reduced flow rate, but the flow regime which is established shows sensitive dependence on the imposed pressure drop and entrance conditions. A small side-branch off a mother tube produces most rapid variation in pressure and velocity near the daughter entrance, this variation now being quantifiable. A multiple branching yields large flow rates and nonunique flow patterns, depending on the form of the imposed pressure differences.

Arteries↗
PubMed1997

Activated protein C resistance, factor V Leiden and peripheral vascular disease.

Activated protein C resistance caused by factor V Leiden is an important thrombophilia disorder which predisposes to venous thromboembolism. Some studies also suggest a role in the pathogenesis of arterial thrombosis and atherosclerosis. The authors have investigated the prevalence of activated protein C resistance and factor V Leiden in a series of 45 patients with peripheral vascular disease. Twelve patients were receiving warfarin. The activated protein C resistance ratios were significantly lower in the group of 33 non-warfarinized patients with peripheral vascular disease (median 2.82 (range 1.36-3.83)) compared with 33 age- and sex-matched controls (median 2.97 range 2.24-4.11); P<0.005; Wilcoxon rank sum). Eight patients (24%) had activated protein C resistance (ratio <2.2). The prevalence of factor V Leiden in patients with peripheral vascular disease was 17.8% (8/45). This is significantly increased compared with the local population and UK published frequency of 3.5% for this genotype. The presence of factor V Leiden did not affect the late outcome of arterial reconstructive surgery in terms of graft patency (P=0.5, Fisher's Exact test).

Aged↗
PubMed1994

Inhibition of membrane fusion by lysophosphatidylcholine.

The ability of lysophosphatidylcholine to inhibit membrane fusion at subsolubilizing concentrations (between 1 and 9 mol % with respect to the membrane lipids) was examined. Fusion between N-methyldioleoylphosphatidylethanolamine (DOPE) large unilamellar vesicles (LUV) and fusion between Sendai virus and N-methyl-DOPE LUV were measured. A contents mixing fusion assay was used for LUV fusion (ANTS/DPX), and a lipid mixing assay (octadecylrhodamine B) was used for the virus fusion experiments. Lysophosphatidylcholine was effective at inhibiting both LUV fusion and Sendai virus/LUV fusion. Lysophosphatidylcholine also inhibited leakage from N-methyl-DOPE LUV, 31P nuclear magnetic resonance data were obtained of N-methyl-DOPE in the presence of lysophosphatidylcholine. Lysophosphatidylcholine stabilized the lamellar phase and reduced the incidence of nonlamellar structures at all temperatures. The destabilization of nonlamellar structures with a negative radius of curvature may be a mechanism for inhibition of fusion by lysophosphatidylcholine in these systems.

Hydrogen-Ion Concentration↗
PubMed1994

Effects of [(N-alkyl-1,3-dihydro-1-oxoisoindolin-5-yl)oxy]alkanoic acids on chloride transport in primary astroglial cultures.

It has been demonstrated that agents which inhibit chloride influx and, therefore, lower intracellular chloride levels in the astrocyte, a major cell type in the cerebral gray matter, inhibit astrocytic swelling in vitro and in vivo. Herein, we report additional examples of a series of [(N-alkyl-1,3-dihydro-1-oxoisoindolin-5-yl)oxy]alkanoic acids and their effects upon ion transport in primary rat astrocyte cultures. The 4-chloro-substituted 1-oxoisoindolines demonstrated superior astrocytic chloride influx inhibitory activity as compared to the 6-chloro and non-chlorinated analogs. The four-carbon acid side chain derivatives were more active than the three- and two-carbon analogs. The pharmacological profile of these compounds was examined with respect to inhibition of the Cl(-)-Cl-/Cl(-)-HCO3- anion exchanger and Na(+)-K(+)-2Cl- cotransport mechanisms in glia, and the compounds were found to exhibit a similar profile to that of furosemide by inhibiting both transporters.

Animals↗
PubMed1994

Conformational analysis, molecular modeling, and quantitative structure-activity relationship studies of agents for the inhibition of astrocytic chloride transport.

Molecular modeling studies were carried out on a series of 1-oxoisoindolines which are pharmacologically active as inhibitors of astrocytic chloride transport. Conformational analysis revealed that the halogen substituent exerted a pronounced steric directing effect on the acid side chain. The 4-substituted analogs apparently provided for the best spatial arrangement of pharamacophoric elements of the molecules. Conventional quantitative structure-activity relationship (QSAR) studies using lipophilic and dipole moment characteristics of the molecules as physical descriptor variables in the regression equation yielded a statistically significant model. Comparative molecular field analysis (CoMFA) was utilized as a three-dimensional QSAR technique to explore changes in the steric and electrostatic fields of the molecules that can account for differences in biological activity values. A highly predictive model was attained which supported the results from the qualitative and conventional quantitative structure-activity relationship analyses. These modeling techniques represent the evolutionary process by which structure-activity methods were employed to aid in the development of novel more potent inhibitors of astrocytic chloride transport.

Astrocytes↗
PubMed1993

The antiviral peptide carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine changes the average conformation of phospholipids in membranes.

The influence of the antiviral peptide, carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine (ZfFG), on the average conformation of phosphatidylcholine in hydrated bilayers was investigated with multinuclear solid state magnetic resonance (NMR). Phosphatidylcholine was specifically deuterated (separately) in the choline N-methyls, the alpha and beta positions of the choline, the C2 carbon of the acyl chains, and at all the carbons of the acyl chains of the phosphatidylcholine. Phosphatidylcholine was also synthesized with the carbonyl carbons of the ester bonds between the glycerol and the hydrocarbon chains enriched in 13C. 2H NMR of the phosphatidylcholine perdeuterated in the acyl chains showed a loss of intensity from the deuteriums with the largest quadrupole splitting in the presence of ZfFG, while the remainder of the powder pattern was largely unaffected. The phosphatidylcholine specifically deuterated at the C2 carbon (representative of the C-D bonds giving rise to the largest quadrupole splittings) showed the same loss of intensity suggesting changes in the phospholipid conformation and conformational dynamics near the glycerol. Analysis of the powder patterns in the 13C NMR spectrum of phosphatidylcholine labeled with 13C in the carbonyl carbons revealed a significant change in the average orientation of the sn-1 carbonyl due to the presence of the ZfFG and no change in the sn-2 carbonyl orientation. Changes in the headgroup conformation, as detected by 2H NMR of the deuteriums in the alpha and beta methylenes of the choline headgroup and 31P NMR of the phosphate segment, reflected the electrostatic nature of the interaction of the carboxyl of ZfFG with phosphatidylcholine bilayers.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Liquid chromatographic studies on the aqueous solution conformation of substituted benzamides related to remoxipride.

A series of disubstituted benzamides related to the sterically hindered 2,6-dimethoxybenzamide drugs, such as remoxipride, are prepared. The structure-retention relationships for these compounds are studied on hydrocarbon stationary phases in various hydroorganic mobile phases. The 2,6-dimethoxybenzamide displays a very low capacity factor under these reversed-phase conditions, suggesting that steric crowding prevents the formation of an amide-methoxy N-H...O intramolecular hydrogen bond. The corresponding 2-hydroxy-6-methoxybenzamide shows a dramatic increase in affinity for the hydrocarbon stationary phase, which is characteristic of strong intramolecular hydrogen bonding in these compounds. These results suggest that the aromatic ring--carbonyl aqueous solution conformation is almost 90 degrees in amides like remoxipride and changes to coplanarity upon demethylation of one methoxy group.

Antipsychotic Agents↗
PubMed1987

Effects of [(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]alkanoic acids, [(N-alkyl-1-oxo-1H,3H-isoindolin-5-yl)oxy]butanoic acids, and related derivatives on chloride influx in primary astroglial cultures.

It has been shown that agents that inhibit chloride influx and therefore lower intracellular chloride levels in a major cell type in cerebral gray matter, the astrocyte, inhibit astrocytic swelling in vitro and in vivo. In our laboratories, 4-[(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]alkanoic acids and related derivatives have been synthesized and tested for ability to lower intracellular astrocytic chloride levels in an established in vitro cultured rat astrocyte model. In general, derivatives with nitrogen substituents such as relatively small alkyl groups are active at 0.1 mM and/or 0.5 mM levels whereas larger substituents such as cyclopentyl and cyclohexyl are less active. Halogen substitution on the aromatic ring did not enhance activity. Derivatives with acid side chains of four carbons demonstrated superior activity to those of two carbons.

Animals↗
PubMed1987

Antitumor agents. 89. Psychorubrin, a new cytotoxic naphthoquinone from Psychotria rubra and its structure-activity relationships.

A new naphthoquinone, isolated from the alcoholic extract of Psychotria rubra, exhibited significant cytotoxicity in the KB cell assay (ED50 = 3.0 micrograms/mL). Spectral data was used to assign the structure of psychorubrin as 2. Naphthoquinone derivatives 6, 8, 13, and 14 were prepared and exhibited superior cytotoxic activity to that of psychorubrin. All were potential Michael acceptors whose conjugation had been extended. However, when a hydrophilic hydroxy group was present in such compounds, reduced in vitro activity was observed.

Antineoplastic Agents, Phytogenic↗