Simultaneous determination of the lactone and carboxylate forms of irintecan (CPT-11) and its actie metabolite SN-38 by high-performance liquid chromatography: Application to plasma pharmacokinetic studies in the rat.

Irinotecan (CPT-11) and its main metabolite SN-38 are potent anticancer derivatives of camptothecin (CPT), with active lactone and inactive carboxylate forms coexisting. A simple and sensitive HPLC method using the ion-pairing reagent tetrabutylammonium hydrogen sulfate (TBAHS) was developed to simultaneously determine all four analytes in rat plasma samples. Camptothecin (CPT) was used as internal standard. The mobile phase was 0.1 M potassium dihydrogen phosphate containing 0.01 M TBAHS (pH 6.4)–acetonitrile (75:25, v/v). Separation of the compounds was carried out on a Hypersil C18 column, monitored at 540 nm (excitation wavelength at 380 nm). All four compounds gave linear response as a function of concentration over 0.01–10 μM. The limit of quantitation in rat plasma was 0.01, 0.008, 0.005 and 0.005 μM for CPT-11 lactone, CPT-11 carboxylate, SN-38 lactone and SN-38 carboxylate, respectively. The method was successfully used in the study on the effect of coadministered thalidomide on the plasma pharmacokinetics of CPT-11 and SN-38 in rats. Coadministered thalidomide (100 mg/kg body weight by intraperitoneal injection) significantly increased the AUC_0–10h values of CPT-11 lactone and CPT-11 carboxylate by 32.6% and 30.3 %, respectively, (P < 0.01), but decreased the values by 19.2% and 32.4% for SN-38 lactone and carboxylate, respectively, (P < 0.05). Accordingly, the value of total body clearance (CL) of CPT-11 lactone was significantly lower in combination group compared to the control (1.329 versus 1.837 L/h/kg, P = 0.0002). Plasma t_1/2β values for SN-38 lactone and carboxylate were significantly (P < 0.01) smaller in rats with coadministered thalidomide, as compared to rats receiving CPT-11 alone. Further studies are needed to explore the underlying mechanisms for the observed kinetic interaction between CPT-11 and thalidomide.

T-Shaped equi-channel angular pressing of Pb-Sn eutectic and its tensile properties

Equi-channel angular pressing (ECAP) of a Pb–Sn eutectic alloy up to six passes in a T-shaped die, rather than a conventional L-shaped die, was studied for grain refinement. The effect of ECAP on the hardness and tensile properties was studied. Microstructure predominately changed in the early part of the ECAP process and became equiaxed and uniformly distributed in both the longitudinal and the transverse sections after four passes. There occurred substantial softening over the first two passes—hardness of 10 Hv, yield strength of 14.2 MPa and tensile strength of 16.3 MPa in the as-cast condition decreased upon two passes to 6 Hv, 9.7 MPa and 13.0 MPa, respectively. The ductility (% elongation) increased drastically from <50% in the as-cast condition to 150% upon two passes, and further increased to 230% after four passes. Various tensile properties and concurrent microstructural evolution were used to develop a mutual relationship among them.

Acylmethyl(aryl)tellurium(IV,II) derivatives : intramolecular secondary bonding and steric rigidity

Electrophilic substitution of acylmethanes (methyl ketones), RCOCH3 (R = i-Pr, 1; Et, 2; Me, 3) with aryltellurium trichlorides, ArTeCl3 (Ar = 1-C10H7, Np, A; 2,4,6-Me3C6H2, Mes, B; 4-MeOC6H4, Anisyl, C) under mild conditions affords the corresponding acylmethyl(aryl)tellurium dichlorides (RCOCH2)ArTeCl2. Reduction of the dichlorides, gives tellurides, (i-PrCOCH2)ArTe, 1A–1C, which give the corresponding dihalides, (i-PrCOCH2)ArTeX2 (X = Cl, 1Aa–1Ca; Br, 1Ab–1Cb; I, 1Ac–1Cc) when reacted in situ with SO2Cl2, Br2 or I2. The unsymmetric tellurides are labile towards disproportionation and attempts to obtain them lead to the isolation of Ar2Te2 except in the case of (i-PrCOCH2)MesTe ( 1B), which represents an interesting example of a kinetically stable aryl(alkyl)telluride. All the dihalomesityltellurium(IV) derivatives show separate 1H and 13C NMR signals for the ortho methyls irrespective of the sizes of R and X ligands. The telluride, 1B with free rotation about Te–C(mesityl) bond shows, like the unsymmetric diorganotellurium(IV) dihalides, only one 125Te NMR signal. The 1,4-chelating behavior of the acyl ligand among diorganotellurium(IV) compounds is inferred from the X-ray diffraction data for 1Aa, 1Ac, 1Ba, 1Bb, 1Ca and 1Cc which are indicative of the presence of intramolecular TeO secondary bonding interactions (SBIs) at least in the solid state. As a consequence, steric repulsion in case of the mesityltellurium(IV) derivatives, 1Ba and 1Bb, reaches the threshold so as to cause loss of two-fold rotational symmetry of the mesityl group about the Te–C(mesityl) bond axis. Intermolecular C–HO H-bonding interactions appears to stabilize such an orientation of the aryl ligand at least in the solid state.

Preparation of bioactive porous Ti-Sn-Nb alloy for biomedical applications

A porous Ti-16Sn-4Nb alloy with an average pore size of 300 µm and porosity of 60 % was prepared by powder metallurgy, and a bone-like apatite coating was obtained by soaking the samples in a concentrated simulated body fluid (lOx SBF). The changes of the microstructure and composition on the surface with soaking time were investigated by using X-ray diffractometry (XRD), and scanning electron microscopy equipped with energy dispersive spectroscopy (SEM-EDS), The bone-like apatite granules started to deposit throughout the porous Ti alloy foam aner 1 h soaking, and the number of granules increased with the increase of the soaking time. A uniform bone-like apatite layer covered the entire surface of the sample after soaking in Ihe lOx SBF for 6h. The Ti-16Sn-4Nb foam showed a good bioactivity after a thermochemical process and soaking into a 1Ox SBF.

Effects of process control agent on the microstructure and mechanical properties of Ti-Sn-Nb alloy prepared by mechanical alloying

In the present study, the influence of process control agent (PCA) on the characteristics of powder and bulk sintered Ti-16Sn-4Nb (wt. %) alloy prepared by mechanical alloying has been investigated. The elemental Ti, Sn and Nb powders were mechanically alloyed in a planetary ball mill for a short period of time using two types of PCA, namely stearic acid (SA) and ethylene bis-stearamide (EBS). The powder morphology, microstructural evolution of the bulk sintered alloy, phase formation and hardness of the alloy have been studied as a function of PCA. Results indicated that the addition of PCA leads to a delay in aIloy formation and introduces contaminations (mainly carbon and oxygen) into the material. The microstructural observation of the bulk alloy revealed a homogeneous distribution of fine Nb-rich colonies (ß-phase) within the a-Ti matrix for small amount of PCA. The hardness values of samples exhibited a significant increase with increasing amount of PCA, reaching a value of ~ 600 BV.

Integration and coordination of care

The health care systems in Australia are under pressure from workforce shortages, increasing costs and an ageing population with a high prevalence of chronic disease. There is a well-established description of inequity in health outcomes among rural and remote populations. Most of the inequity appears to be due to poorer access to services than higher levels of health risk factors, such as cholesterol, blood pressure or obesity. Over the last 15 years, the science of improvement has led to quality improvement techniques, such as collaboratives, managed clinical networks and collaborative care, all of which have been tried successfully in Australia. Each of these offers ways to reduce the inequity in health outcomes attributed to rurality or remoteness.

Energetics of interlimb coordination

While the traditional dependent variables of motor skill learning are accuracy and consistency of movement outcome, there has been increasing interest in aspects of motor performance that are described as reflecting the ‘energetics’ of motor behaviour. One defining characteristic of skilled motor performance is the ability to complete the task with minimum energy expenditure (Sparrow & Newell, 1998). A further consideration is that movements also have costs in terms of cognitive ‘effort’ or ‘energy’. The present project extends previous work on energy expenditure and motor skill learning within a coordination dynamics framework. From the dynamic pattern perspective, a coordination pattern lowest on the 11KB model potential curve (Haken, Kelso & Bunz, 1985) is more stable and least energy is required to maintain pattern stability (Temprado, Zanone, Monno & Laurent, 1999). Two experiments investigated the learning of stable and unstable coordination patterns with high metabolic energy demand. An experimental task was devised by positioning two cycle ergometers side-by-side, placing one foot on each, with the pedals free to move independently at any metronome-paced relative phase, Experiment 1 investigated practice-related changes to oxygen consumption, heart rate, relative phase, reaction time and muscle activation (EMG) as participants practiced anti-phase, in-phase and 90°-phase cycling. Across six practice trials metabolic energy cost reduced and AE and VE of relative phase declined. The trend in the metabolic and reaction time data and percent co-contraction of muscles was for the in-phase cycling to demonstrate the highest values, anti-phase the lowest and 90°-phase cycling in-between. It was found that anti- and in-phase cycling were both kinematically stable but anti-phase coordination revealed significantly lower metabolic energy cost. It was, therefore, postulated that of two equally stable coordination patterns, that associated with lower metabolic energy expenditure would constitute a stronger attractor. Experiment 2 was designed to determine whether a lower or higher energy-demanding coordination pattern was a stronger attractor by scanning the attractor layout at thirty-degree intervals from 0° to 330°. The initial attractor layout revealed that in-phase was most stable and accurate, but the remaining coordination patterns were attracted to the low energy cost anti-phase cycling. In Experiment 2 only 90°- phase cycling was practiced with a post-test attractor layout scan revealing that 90°-phase and its symmetrical partner 270°-phase had become attractors of other coordination patterns. Consistent with Experiment 1, practicing 90°-phase cycling revealed a decline in AE and VE and a reduction in metabolic and cognitive cost. Practicing 90°-phase cycling did not, however, destabilise the in-phase or anti-phase coordination patterns either kinematically or energetically. In summary, the findings suggest that metabolic and mental energy can be considered different representations of a ‘global’ energy expenditure or ‘energetic’ phenomenon underlying human coordination. The hypothesis that preferred coordination patterns emerge as stable, low-energy solutions to the problem of inter-and intra-limb coordination is supported here in showing that the low-energy minimum of coordination dynamics is also an energetic minimum.

Studies of hypervalent organotin complexes and organotin clusters

(119)Sn, (31)P and (13)C variable temperature NMR spectroscopies have been used to examine the effective coordination spheres in solution of a series of hypervalent organotin(IV) dithiolate compounds RnSnXm(S-S)4-n-m where R = Ph, Me, nBu, tBu; X = Cl, Br; (S-S) = S2CNR'2, S2COR', S2P(OR')2 (R' = Me, Et, iPr) and n = 1, 2, 3; m = 0,1,2. Stereochemical nonrigidity is a common phenomenon found for these hypervalent compounds. On the basis of heteronuclear NMR data and X-ray crystallographic data, dynamic behaviors of these hypervalent compounds have been established. The system of hypervalent organotin(IV) fluoride complexes has also been investigated by variable temperature heteronuclear NMR techniques. A series of monomeric pentacoordinate complexes [RnSnC1mF5-n-m]-(R = Ph, Me, nBu, tBu; n = 2, 3; m - 0, 1, 2, 3) and dimeric complexes [(Me3SnX)F(Me3SnX')]- (X = F, Cl; X' = F, Cl) and hexacoordinate complexes [RnSnClmF6-n.m]2- (R = Ph, Me, nBu; n = 1, 2; m = (X 1, 2, 3,4) are identified in solution. The fluoride is of higer affinite to tin than the chloride. The stereochemistry and dynamic behavior of these complexes in solution has been studied. Fluoride ion may induce phenyl group disproportionation of phenyhin(IV) compounds. It is also found that in pentacoordinate diorganotin complexes, such as [Ph2SnCl2F]- and [Ph2SnClF2]- fluorine can be less apicophilic than chlorine. Studies of stereochemistry and dynamic behavior of bi-functional Lewis acid bis(haloorganosiannes) have also been carried out. The bis(haloorganostannes) exhibit strong chelate ability towards halide, with high selectivity on fluoride, forming heterocyclic chelating rings, the stability of which depend on the ring size. In further exploration of the Lewis acidity of organotin(IV) halides, complexation of organotin(IV) halides with bis(tertiary phosphinc) ligands has been studied by 119Sn and 31P NMR spectroscopy and X-ray crystallography. The phenyl group disproportionation is often observed in the complexation reaction. Furthermore, organotin(IV) clusters such as [(RSn)12O14(OH)6]Cl2-2H2O (R = iPr, nBu) have been successfully prepared by base hydrolysis of RSnCl3. These clusters contain 12 tin atoms in one molecule and the cores of the clusters are dications. Other organotin clusters such as [nBuSn(O)O2CCH3]6 and [(nBuSn(OH)O2PPh2)3][O2PPh2) are readily formed by reaction of the 12-tin-atom cluster with an appropriate acid. The reactivity of and interconversion between organotin(FV) clusters have also been studied.

Assessment of movement participation for children with developmental coordination disorders

The Caregiver Assessment of Movement Participation was developed to identify children of 5-10 years old for movement participation difficulties in home contexts. Its psychometric properties were investigated including its usefulness as a screening instrument using both classical test theory methods and Rasch analysis. Results confirmed its validity and reliability.

Improving the coordination of care for low back pain patients by creating better links between acute and community services

This paper reports on the development of a care-pathway to improve service linkages between the acute setting and community health services in the treatment of low back pain. The pathway was informed by two processes: (1) a literature review based on best-practice guidelines in the assessment, treatment and continuity of care for low back pain patients; and (2) consultation with staff and key stakeholders. Stakeholders from both the acute and community sectors comprised the Working Group, who identified central areas of concern to be addressed in the care-pathway, with the goal of preventing chronicity of low back pain and reducing emergency department presentations. The main outcomes achieved include: the development of a new care-coordinator role, which would support a greater focus on integration between acute and community sectors for low back pain patients; identifying the need to screen at-risk patients; implementation of the SCTT (Service Coordination Tool Templates) tool as a system of referral across the acute and community settings; and agreement on the need to develop an evidence-based self-management program to be offered to low back pain patients. The benefits and challenges of implementing this care pathway are discussed.