Intracellular Acidification in a Rat C6 Glioma Model following Cariporide Injection Investigated by CEST-MRI.

Acidification of cancerous tissue induced pharmacologically may slow tumor growth and can be detected using magnetic resonance imaging. Numerous studies have shown that pharmacologically inhibiting specific transporters, such as the Na+/H+ exchanger 1 (NHE1), can alter glycolitic metabolism and affect tumor acidosis. The sodium proton exchanger inhibitor Cariporide can acidify U87MG gliomas in mice. This study aimed to determine whether Cariporide could acidify C6 glioma tumors in rats with an intact immune system. C6 glioma cells were implanted in the right brain hemisphere of ten rats. Chemical exchange saturation transfer (CEST) MRI (9.4T) was acquired on days 7-8 and 14-15 after implantation to measure in vivo tissue intracellular pH (pHi) within the tumors and on the contralateral side. pHi was basic relative to contralateral tissue at both time points assessed using the amine and amide concentration-independent detection (AACID) value. On day 14-15, measurements were made before and up to 160 min after Cariporide injection (N = 6). Twenty minutes after drug injection, the average AACID value in the tumor significantly increased by ∼6.4% compared to pre-injection, corresponding to 0.31 ± 0.20 lower pHi, while in contralateral tissue, AACID value increased significantly by ∼4.3% compared to pre-injection, corresponding to 0.22 ± 0.19 lower pHi. Control rats without tumors showed no changes following injection of Cariporide dissolved in 10% or 1% DMSO and diluted in PBS. This study demonstrates the sensitivity of CEST-based pH-weighted imaging for monitoring the response of tumors to pharmacologically induced acidification.

Daytime Napping and Nighttime Sleep During Pregnancy and Preterm Birth in Iran.

OBJECTIVES: This study investigated the relationship between sleep quality during pregnancy and preterm birth. METHODS: This longitudinal study was conducted between August 2018 and May 2019. The participants were 150 pregnant women who had been referred to 7 healthcare centers in the city of Qazvin, Iran and met the inclusion criteria. The Petersburg Sleep Quality Index, the Epworth Sleepiness Scale, and 2 questions about daytime sleep status and a demographic questionnaire were administered at 14-18 weeks and 28-32 weeks of gestation. Data were analyzed using the Mann-Whitney test, the Fisher exact test, and univariate and multivariable logistic regression. RESULTS: In the present study, poor sleep quality affected 84.7% of the participants at 14-18 weeks and 93.3% at 28-32 weeks of gestation. The final model for preterm birth prediction incorporated age and the Petersburg Sleep Quality Index score in the second and third trimesters. Preterm birth increased by 14% with each unit increase in age. With each unit increase in the Petersburg Sleep Quality Index score in the second and third trimesters, preterm birth increased by 42% and 28%, respectively, but the p-values of these factors were not significant. CONCLUSIONS: Although a significant percentage of pregnant women had poor sleep quality, no significant relationship was found between sleep quality during pregnancy and preterm birth.

Dynamic light scattering study of inhibition of nucleation and growth of hydroxyapatite crystals by osteopontin.

We study the effect of isoforms of osteopontin (OPN) on the nucleation and growth of crystals from a supersaturated solution of calcium and phosphate ions. Dynamic light scattering is used to monitor the size of the precipitating particles and to provide information about their concentration. At the ion concentrations studied, immediate precipitation was observed in control experiments with no osteopontin in the solution, and the size of the precipitating particles increased steadily with time. The precipitate was identified as hydroxyapatite by X-ray diffraction. Addition of native osteopontin (nOPN) extracted from rat bone caused a delay in the onset of precipitation and reduced the number of particles that formed, but the few particles that did form grew to a larger size than in the absence of the protein. Recombinant osteopontin (rOPN), which lacks phosphorylation, caused no delay in initial calcium phosphate precipitation but severely slowed crystal growth, suggesting that rOPN inhibits growth but not nucleation. rOPN treated with protein kinase CK2 to phosphorylate the molecule (p-rOPN) produced an effect similar to that of nOPN, but at higher protein concentrations and to a lesser extent. These results suggest that phosphorylations are critical to OPN's ability to inhibit nucleation, whereas the growth of the hydroxyapatite crystals is effectively controlled by the highly acidic OPN polypeptide. This work also demonstrates that dynamic light scattering can be a powerful tool for delineating the mechanism of protein modulation of mineral formation.