School of Science, Engineering and Technology
http://hdl.handle.net/10373/3
Tue, 09 Feb 2016 07:45:22 GMT2016-02-09T07:45:22ZA spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels
http://hdl.handle.net/10373/2236
A spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels
Fernandes, Gonçalo; Dasai, Navin; Kozlova, Natalia; Mojadadi, Albaraa; Gall, Mandy; Drew, Ellen; Barratt, Evelyn; Madamidola, Oladipo A.; Brown, Sean G.; Milne, Alison M.; Martins da Silva, Sarah J.; Whalley, Katherine M.; Barratt, Christopher L. R.; Jovanović, Aleksandar
STUDY QUESTION: Could drugs targeting ATP-sensitive K+ (KATP) channels prevent any spontaneous increase in intracellular Ca2+ that may occur in human metaphase II (MII) oocytes under in vitro conditions?
SUMMARY ANSWER: Pinacidil, a KATP channel opener, and glibenclamide, a KATP channel blocker, prevent a spontaneous increase in intracellular Ca2+ in human MII oocytes.
WHAT IS KNOWN ALREADY: The quality of the oocyte and maintenance of this quality during in vitro processing in the assisted reproductive technology (ART) laboratory is of critical importance to successful embryo development and a healthy live birth. Maintenance of Ca2+ homeostasis is crucial for cell wellbeing and increased intracellular Ca2+ levels is a well-established indicator of cell stress.
STUDY DESIGN, SIZE, DURATION: Supernumerary human oocytes (n = 102) collected during IVF/ICSI treatment that failed to fertilize were used from October 2013 to July 2015. All experiments were performed on mature (MII) oocytes. Dynamics of intracellular Ca2+ levels were monitored in oocytes in the following experimental groups: (i) Control, (ii) Dimethyl sulfoxide (DMSO; used to dissolve pinacidil, glibenclamide and 2,4-Dinitrophenol (DNP)), (iii) Pinacidil, (iv) Glibenclamide, (v) DNP: an inhibitor of oxidative phosphorylation, (vi) Pinacidil and DNP and (vii) Glibenclamide and DNP.
PARTICIPANTS/MATERIALS/SETTINGS/METHODS: Oocytes were collected under sedation as part of routine treatment at an assisted conception unit from healthy women (mean ± SD) age 34.1 ± 0.6 years, n = 41. Those surplus to clinical use were donated for research. Oocytes were loaded with Fluo-3 Ca2+-sensitive dye, and monitored by laser confocal microscopy for 2 h at 10 min intervals. Time between oocyte collection and start of Ca2+ monitoring was 80.4 ± 2.1 h.
MAIN RESULTS AND THE ROLE OF CHANCE: Intracellular levels of Ca2+ increased under in vitro conditions with no deliberate challenge, as shown by Fluo-3 fluorescence increasing from 61.0 ± 11.8 AU (AU = arbitrary units; n = 23) to 91.8 ± 14.0 AU (n = 19; P < 0.001) after 2 h of monitoring. Pinacidil (100 µM) inhibited this increase in Ca2+ (85.3 ± 12.3 AU at the beginning of the experiment, 81.7 ± 11.0 AU at the end of the experiment; n = 13; P = 0.616). Glibenclamide (100 µM) also inhibited the increase in Ca2+ (74.7 ± 10.6 AU at the beginning and 71.8 ± 10.9 AU at the end of the experiment; n = 13; P = 0.851. DNP (100 mM) induced an increase in intracellular Ca2+ that was inhibited by glibenclamide (100 µM; n = 9) but not by pinacidil (100 µM; n = 5).
LIMITATIONS, REASONS FOR CAUTION: Owing to clinical and ethical considerations, it was not possible to monitor Ca2+ in MII oocytes immediately after retrieval. MII oocytes were available for our experimentation only after unsuccessful IVF or ICSI, which was, on average, 80.4 ± 2.1 h (n = 102 oocytes) after the moment of retrieval. As the MII oocytes used here were those that were not successfully fertilized, it is possible that they may have been abnormal with impaired Ca2+ homeostasis and, furthermore, the altered Ca2+ homeostasis might have been associated solely with the protracted incubation.
WIDER IMPLICATIONS OF THE FINDINGS: These results show that maintenance of oocytes under in vitro conditions is associated with intracellular increase in Ca2+, which can be counteracted by drugs targeting KATP channels. As Ca2+ homeostasis is crucial for contributing to a successful outcome of ART, these results suggest that KATP channel openers and blockers should be tested as drugs for improving success rates of ART.
Fri, 18 Dec 2015 00:00:00 GMThttp://hdl.handle.net/10373/22362015-12-18T00:00:00ZThe asymptotics of a generalised Beta function
http://hdl.handle.net/10373/2235
The asymptotics of a generalised Beta function
Paris, Richard B.
We consider the generalised Beta function introduced by Chaudhry et al. [J. Comp. Appl. Math. 78 (1997) 19–32] defined by B(x, y; p) = ʃ 1 0 tx−1(1 − t)y−1 exp [−p / 4t(1 − t)] dt, where ℜ(p) > 0 and the parameters x and y are arbitrary complex numbers. The asymptotic behaviour of B(x, y; p) is obtained when (i) p large, with x and y fixed, (ii) x and p large, (iii) x, y and p large and (iv) either x or y large, with p finite. Numerical results are given to illustrate the accuracy of the formulas obtained.
Thu, 01 Jan 2015 00:00:00 GMThttp://hdl.handle.net/10373/22352015-01-01T00:00:00ZThe expansion of a finite number of terms of the Gauss hypergeometric function of unit argument and the Landau constants
http://hdl.handle.net/10373/2234
The expansion of a finite number of terms of the Gauss hypergeometric function of unit argument and the Landau constants
Paris, Richard B.
We obtain convergent inverse factorial expansions for the sum Sn(a, b; c) of the first n ≥ 1 terms of the Gauss hypergeometric function 2F1(a, b; c; 1) of unit argument. The form of these expansions depends on the location of the parametric excess s := c−a−b in the complex s-plane. The leading behaviour as n → ∞ agrees with previous results in the literature. The case a = b = 1/2 , c = 1 corresponds to the Landau contants for which an expansion is obtained.
Thu, 01 Jan 2015 00:00:00 GMThttp://hdl.handle.net/10373/22342015-01-01T00:00:00ZA note on an integral associated with the Kelvin ship-wave pattern
http://hdl.handle.net/10373/2233
A note on an integral associated with the Kelvin ship-wave pattern
Paris, Richard B.
The velocity potential in the Kelvin ship-wave source can be partly expressed in terms of space derivatives of the single integral F(x, ρ, α) = ʃ ∞ −∞ exp [−1/2ρ cosh(2u − iα)] cos(x cosh u) du, where (x, ρ, α) are cylindrical polar coordinates with origin based at the source and −1/2π ≤ α ≤ 1/2π. An asymptotic expansion of F(x, ρ, α) when x and ρ are small, but such that M ≡ x2/(4ρ) is large, was given using a non-rigorous approach by Bessho in 1964 as a sum involving products of Bessel functions. This expansion, together with an additional integral term, was subsequently proved by Ursell in 1988. Our aim here is to present an alternative asymptotic procedure for the case of large M. The resulting expansion consists of three distinct parts: a convergent sum involving the Struve functions, an asymptotic series and an exponentially small saddle-point contribution. Numerical computations are carried out to verify the accuracy of our expansion.
Thu, 01 Jan 2015 00:00:00 GMThttp://hdl.handle.net/10373/22332015-01-01T00:00:00Z