Modification of tumour blood flow using the hypertensive agent, angiotensin II

The effects of different doses of angiotensin II (0.02 to 0.5 microgram kg-1 min-1 on mean arterial blood pressure, tissue blood flow and tissue vascular resistance were investigated in BD9 rats. Blood flow was measured using the uptake of 125I- or 14C-labelled iodoantipyrine (125I-IAP and 14C-IAP). Spatial heterogeneity of blood flow within tumours, before and after angiotensin II infusion, was also measured using 14C-IAP and an autoradiographic procedure. Mean arterial blood pressure rose steeply with angiotensin II dose. Blood flow to skeletal muscle, skin overlying the tumour, contralateral skin, small intestine and kidney tended to decline in a dose-dependent manner. Blood flow to the tumour was also reduced (to 80% of control values) but there was no dose response. Blood flow to the heart was slightly increased and blood flow to the brain was unaffected by angiotensin II. Vascular resistance, in all tissues, was increased by angiotensin II infusion. The increase in tumour tissue was similar to that found in skeletal muscle and small intestine and is likely to be caused by a direct vasoconstricting effect of the drug rather than autoregulation of tumour blood flow in the face of an increase in perfusion pressure. The reduction in overall blood flow at the highest perfusion pressure was due to a preferential effect of angiotensin II at the tumour periphery. These results show that some tumours, at least, can respond directly to the effects of vasoactive agents

The response of tumour vasculature to angiotensin II revealed by its systemic and local administration to 'tissue-isolated' tumours.

A tissue-isolated preparation of the P22 rat carcinosarcoma was used to investigate the tumour vascular response to angiotensin II (ATII). In particular, the relative importance of systemic and local tumour factors was assessed by comparing tumour vascular resistance during systemic administration of ATII and during administration directly into the tumour-supplying artery. The effect of hypervolaemia on tumour vascular resistance was determined as well as the effect of ATII on oxygen metabolism. Tumour vascular resistance was increased by ATII in a dose-dependent manner. The response was biphasic with an initial peak in resistance followed by a lower plateau phase. Systemic administration of ATII was more effective in increasing tumour vascular resistance than direct administration. This suggests that systemic administration is not causing any reopening of previously collapsed tumour blood vessels. Further evidence for this is that hypervolaemia caused no reduction in tumour vascular resistance and that there was no difference in oxygen extraction by tumours between groups treated with systemically and directly administered ATII. A heterogeneous distribution of ATII receptors in the P22 tumour is a more likely explanation for the known heterogeneity of blood flow response to ATII

Persistence of perennial ryegrass, tall fescue and cocksfoot following annual sowings: Influence of grass species, ryegrass cultivar and pasture age on yield, composition and density

Persistence is an important component of perennial pasture-grass productivity. Defining traits that affect persistence is essential for improving pasture longevity through plant breeding and for identifying persistence traits that should be included in cultivar ranking indices. Compared with conventional longitudinal studies, where a single sowing is monitored over time, repeated annual sowings allow the effects on persistence of sowing year and the ensuing interactions between environment and age of pasture to be identified. An experiment was commenced in 2015 under sheep grazing in Canterbury and in 2016 under cattle grazing in Waikato, where eight cultivars of perennial ryegrass representing different ploidy, flowering date, and cultivar age (release date), and one cultivar each of tall fescue and cocksfoot were sown in four randomised complete blocks in autumn each year. This paper reports interim data on spring and autumn pasture yield, composition, and density of 3-year-old, 2-year-old and 1-year-old pastures exposed to the same environmental conditions within the same, single year. There were significant effects on yield, botanical composition, basal cover and tiller density due to cultivar, pasture age, and their interaction. When the confounding effect of year-to-year variation was removed by comparing each age cohort in the same year, the underlying differences among grass species and cultivars, and ages of pasture, is starting to reveal the nature of this influence on pasture persistence

Correlation potentials and functionals in Hartree-Fock-Kohn-Sham theory

We compute molecular Hartree-Fock-Kohn-Sham correlation potentials from ab initiocoupled-cluster densities via a modified Zhao, Morrison and Parr [Phys. Rev. A, 50, (1994) 2138] scheme involving exact exchange. We examine the potential for several small systems, and observe complex structure. By fitting a functional expansion to our potentials we obtain a closed-shell functional which is an improvement over other pure correlationfunctionals in Hartree-Fock-Kohn-Sham calculations. The leading term in our functional is dependent on the number of electrons. Our results lead us to question the utility of correlation defined within the Hartree-Fock-Kohn-Sham scheme, and to consider alternative partitionings of the exchange-correlation energy

Topological analysis of the vasculature of angiopoietin-expressing tumours through scale-space tracing

This work describes the topological analysis of the vasculature of tumours. The analysis is performed with a scale-space technique, which traces the centrelines of vessels as topological ridges of the image intensities and then obtains a series of measurements, which are used to compare the vasculatures. Besides the measurements directly associated with the centrelines, the scales obtained allow the estimation of width andthusareacoveredwithvessels. Tumours of SW1222 human colorectal carcinoma xenografts were observed when growing in dorsal skin-fold window chambers in mice. Three variants of the tumours expressing either endogenous levels of angiopoietins (WT) or over-expressing either angiopoietin-1 (Ang-1) or angiopoietin-2 (Ang-2) were assessed with/without vascular targeted therapy. The scale-space technique was able to discriminate between the vasculatures of the three different tumour types prior to treatment. Results also suggested that over-expression of Ang-2 was associated with susceptibility of the tumour vasculature to the vascular disrupting agent, combretastatin A4 phosphate (CA4P). Substantiation of this finding would point to the potential of tumour Ang-2 expression as a predictive bio-marker for response to CA4P

Magnetic field induced lattice anomaly inside the superconducting state of CeCoIn5_5: evidence of the proposed Fulde-Ferrell-Larkin-Ovchinnikov state

We report high magnetic field linear magnetostriction experiments on CeCoIn$_5$ single crystals. Two features are remarkable: (i) a sharp discontinuity in all the crystallographic axes associated with the upper superconducting critical field $B_{c2}$ that becomes less pronounced as the temperature increases; (ii) a distinctive second order-like feature observed only along the c-axis in the high field (10 T $\lesssim B \leq B_{c2}$) low temperature ($T \lesssim$ 0.35 K) region. This second order transition is observed only when the magnetic field lies within 20$^o$ of the ab-planes and there is no signature of it above $B_{c2}$, which raises questions regarding its interpretation as a field induced magnetically ordered phase. Good agreement with previous results suggests that this anomaly is related to the transition to the Fulde-Ferrel-Larkin-Ovchinnikov superconducting state.Comment: 3 figures, 5 page

Characterisation of tumour blood flow using a 'tissue-isolated' preparation.

Tumour blood flow was characterised in a 'tissue-isolated' rat tumour model, in which the vascular supply is derived from a single artery and vein. Tumours were perfused in situ and blood flow was calculated from simultaneous measurement of (1) venous outflow from the tumour and (2) uptake into the tumour of radiolabelled iodo-antipyrine (IAP). Comparison of results from the two measurements enabled assessment of the amount of blood 'shunted' through the tumours with minimal exchange between blood and tissue. Kinetics of IAP uptake were also used to determine the apparent volume of distribution (VDapp) for the tracer and the equilibrium tissue-blood partition coefficient (lambda). lambda was also measured by in vitro techniques and checks were made for binding and metabolism of IAP using high-pressure liquid chromatography. VDapp and lambda were used to calculate the perfused fraction (alpha) of the tumours. Tumour blood flow, as measured by IAP (TBFIAP), was 94.8 +/- 4.4% of the blood flow as measured by venous outflow, indicating only a small amount of non-exchanging flow. This level of shunting is lower than some previous estimates in which the percentage tumour entrapment of microspheres was used. The unperfused fraction ranged from 0 to 20% of the tumour volume in the majority of tumours. This could be due to tumour necrosis and/or acutely ischaemic tumour regions. For practical purposes, measurement of the total venous outflow of tumours is a reasonable measure of exchangeable tumour blood flow in this system and allows for on-line measurements. Tracer methods can be used to obtain additional information on the distribution of blood flow within tumours

Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles

BACKGROUND: The production of sex steroids by follicular cells is proposed to be influenced by the maturity of the incumbent oocyte. Thus steroid levels may reflect suitability of an oocyte for IVF. We examined follicular fluids and granulosa cell production of steroid from IVF patients in order to test the relationship between steroid levels and fertilization. METHODS: Follicular fluid and granulosa cells were extracted from 206 follicles of 35 women undergoing controlled ovarian stimulation. Follicular fluid was assayed for estradiol, progesterone and testosterone. Granulosa cells were cultured from individual follicles and their culture media assayed for production of these hormones after 24 hrs in vitro. Levels of steroids were correlated with follicular diameter, oocyte recovery and subsequent fertilization. RESULTS: Follicular fluid levels of progesterone were 6100 times higher than that of estradiol, and 16,900 times higher that of testosterone. Despite the size of follicle triggered after controlled luteinization, the levels of progesterone and testosterone were maintained at relatively constant levels (median 98.1 micromoles/L for progesterone, and 5.8 nanomoles/L for testosterone). However, estradiol levels were slightly lower in the larger follicles (follicular diameter 10-15 mm, median 25.3 nanomoles/L; follicles > = 15 mm, median 15.1 nanomoles/L; linear correlation r = -0.47, p < 0.0001). With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels. Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize. Significant quantities of progesterone were produced by the granulosa cells but production was constant regardless of the size of follicle from which the cells originated. Estradiol levels were only detectable in 10 of 121 cultures examined, and testosterone in none. Interestingly, when an oocyte was present follicular estradiol levels correlated with progesterone levels. However, when absent, follicular estradiol levels correlated with testosterone levels but not with progesterone. CONCLUSIONS: The principle steroid product of luteinized pre-ovulatory granulosa is progesterone, a differentiation triggered by the gonadotropin surge. However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize

Will current rotational grazing management recommendations suit future intensive pastoral systems?

This review aimed to determine whether current grazing management practices will suit future intensive rotationally grazed pastoral systems. A review of literature on grazing management recommendations found that there was good agreement on the ‘principles’ required for optimal grazing management. While these management practices have stood the test of time, it is concluded that shifts in external pressures (e.g., climate, plant selection and breeding, system intensification) compared to the period when farm-level grazing recommendations were first developed, may necessitate a rethink of current grazing recommendations. Examples include greater pasture masses (e.g., around 4000 kg dry matter (DM)/ha vs. the recommended range of 2600 to 3200 kg DM/ha) where short-rotation (annual, biennial) and tetraploid ryegrasses are sown, provided a consistent post-grazing residual can be maintained (possibly between 40- and 70- mm height). Milder winters and the use of ryegrass cultivars with higher growth rates in late winter/early spring may necessitate either lower target pasture covers at calving or shorter rotation lengths during winter. Longer grazing rotations (well beyond the 3-leaf stage, i.e., equivalent to deferred grazing) can be recommended for select paddocks from mid-spring into summer, to increase seasonal resilience across the farm. Longer residuals (even up to 70 mm - i.e., almost double the recommended height) might improve plant survival during periods of high stress (e.g., heatwaves, droughts). Lastly, diverse species pastures may require specific management to suit dominant species other than perennial ryegrass