1.Physiological increases in lactate inhibit intracellular calcium transients, acidify myocytes and decrease force in term pregnant rat myometrium.
Hanley JA1, Weeks A2, Wray S1. J Physiol. 2015 Oct 15;593(20):4603-14. doi: 10.1113/JP270631. Epub 2015 Sep 3.
Lactate is increased in myometrial capillary blood from women in slow or non-progressive labour (dystocia), suggesting that it is detrimental to uterine contractions. There are, however, no studies of the effect of lactate on the myometrium. We therefore investigated its effects and mechanism of action on myometrial strips from term pregnant rats. The effects on spontaneous and oxytocin-induced contractility in response to sodium lactate and other weak acids (1-20 mM) were studied. In some experiments, simultaneous force and intracellular Ca(2+) or pH (pH(i)) were measured with Indo-1 or Carboxy-SNARF, respectively. Statistical differences were tested using non-parametric tests. Lactate significantly decreased spontaneous contractility with an EC50 of 3.9 mM. Propionate, butyrate and pyruvate also reduced contractions with similar potency. The effects of lactate were reduced in the presence of oxytocin but remained significant. Lactate decreased pH(i) and nulling the decrease in pH(i) abolished its effects.
2.Indomethacin-induced impairment of regional cerebrovascular reactivity: implications for respiratory control.
Hoiland RL1, Ainslie PN, Wildfong KW, Smith KJ, Bain AR, Willie CK, Foster G, Monteleone B, Day TA. J Physiol. 2015 Mar 1;593(5):1291-306. doi: 10.1113/jphysiol.2014.284521. Epub 2015 Jan 14.
Cerebrovascular reactivity impacts CO₂-[H(+)] washout at the central chemoreceptors and hence has marked influence on the control of ventilation. To date, the integration of cerebral blood flow (CBF) and ventilation has been investigated exclusively with measures of anterior CBF, which has a differential reactivity from the vertebrobasilar system and perfuses the brainstem. We hypothesized that: (1) posterior versus anterior CBF would have a stronger relationship to central chemoreflex magnitude during hypercapnia, and (2) that higher posterior reactivity would lead to a greater hypoxic ventilatory decline (HVD). End-tidal forcing was used to induce steady-state hyperoxic (300 mmHg P ET ,O₂) hypercapnia (+3, +6 and +9 mmHg P ET ,CO₂) and isocapnic hypoxia (45 mmHg P ET ,O₂) before and following pharmacological blunting (indomethacin; INDO; 1.45 ± 0.17 mg kg(-1)) of resting CBF and reactivity. In 22 young healthy volunteers, ventilation, intra-cranial arterial blood velocities and extra-cranial blood flows were measured during these challenges.
3.A novel, rapid method to quantify intraplatelet calcium dynamics by ratiometric flow cytometry.
Assinger A1, Volf I1, Schmid D1. PLoS One. 2015 Apr 7;10(4):e0122527. doi: 10.1371/journal.pone.0122527. eCollection 2015.
Cytosolic free calcium ions represent important second-messengers in platelets. Therefore, quantitative measurement of intraplatelet calcium provides a popular and very sensitive tool to evaluate platelet activation and reactivity. Current protocols for determination of intracellular calcium concentrations in platelets have a number of limitations. Cuvette-based methods do not allow measurement of calcium flux in complex systems, such as whole blood, and therefore require isolation steps that potentially interfere with platelet activation. Flow cytometry has the potential to overcome this limitation, but to date the application of calibrated, quantitative readout of calcium kinetics has only been described for Indo-1. As excitation of Indo-1 requires a laser in the ultraviolet range, such measurements cannot be performed with a standard flow cytometer. Here, we describe a novel, rapid calibration method for ratiometric calcium measurement in platelets using both Ar(+)-laser excited fluorescence dyes Fluo-4 and Fura Red.
4.Enhanced cytotoxicity of photoexcited fullerene C60 and cisplatin combination against drug-resistant leukemic cells.
Franskevych DV, Prylutska SV1, Grynyuk II1, Grebinyk DM1, Matyshevska OP1. Exp Oncol. 2015 Sep;37(3):187-91.
AIM: To evaluate the viability of leukemic cells sensitive (L1210S) and resistant (L1210R) to cisplatin, ROS production and free cytosolic Ca(2+) concentration under treatment with cisplatin or its combination with photoexcited fullerene C60.