Higher Alu methylation levels in catch-up growth in twenty-year-old offsprings.

Alu elements and long interspersed element-1 (LINE-1 or L1) are two major human intersperse repetitive sequences. Lower Alu methylation, but not LINE-1, has been observed in blood cells of people in old age, and in menopausal women having lower bone mass and osteoporosis. Nevertheless, Alu methylation levels also vary among young individuals. Here, we explored phenotypes at birth that are associated with Alu methylation levels in young people. In 2010, 249 twenty-years-old volunteers whose mothers had participated in a study association between birth weight (BW) and nutrition during pregnancy in 1990, were invited to take part in our present study. In this study, the LINE-1 and Alu methylation levels and patterns were measured in peripheral mononuclear cells and correlated with various nutritional parameters during intrauterine and postnatal period of offspring. This included the amount of maternal intake during pregnancy, the mother's weight gain during pregnancy, birth weight, birth length, and the rate of weight gain in the first year of life. Catch-up growth (CUG) was defined when weight during the first year was >0.67 of the standard score, according to WHO data. No association with LINE-1 methylation was identified. The mean level of Alu methylation in the CUG group was significantly higher than those non-CUG (39.61% and 33.66 % respectively, P < 0.0001). The positive correlation between the history of CUG in the first year and higher Alu methylation indicates the role of Alu methylation, not only in aging cells, but also in the human growth process. Moreover, here is the first study that demonstrated the association between a phenotype during the newborn period and intersperse repetitive sequences methylation during young adulthood

The comparison of percentage of Alu (above panel) methylation and the percentage of LINE-1 methylation (below panel) in participants who are absence or presence the following risk factors: catch up growth, small for gestational age, male and smoking history.

<p>The comparison of percentage of Alu (above panel) methylation and the percentage of LINE-1 methylation (below panel) in participants who are absence or presence the following risk factors: catch up growth, small for gestational age, male and smoking history.</p

The correlation analysis between the percentage of Alu and LINE-1 methylation in various nutritional factors during pregnancy and delivery.

<p>trim = trimester</p><p>The correlation analysis between the percentage of Alu and LINE-1 methylation in various nutritional factors during pregnancy and delivery.</p

The correlation analysis between the percentage of Alu and LINE-1 methylation in various current risk factors during follow up study (2010).

<p>trim = trimester</p><p>The correlation analysis between the percentage of Alu and LINE-1 methylation in various current risk factors during follow up study (2010).</p

Baseline data of participants during pregnancy and delivery period (in 1990) and during follow up period in 2010 study.

<p>Baseline data of participants during pregnancy and delivery period (in 1990) and during follow up period in 2010 study.</p

The boxplots of the total Alu methylation (%) between female and male.

<p>The boxplots of the total Alu methylation (%) between female and male.</p

The boxplots of the total Alu methylation (%) between non catch up growth group (non-CUG) and catch up growth (CUG).

<p>The boxplots of the total Alu methylation (%) between non catch up growth group (non-CUG) and catch up growth (CUG).</p

Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women.

ObjectiveTo describe darunavir (DRV) pharmacokinetics with once-and twice-daily dosing during pregnancy and postpartum in HIV-infected women.DesignWomen were enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1026s, a prospective nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included separate cohorts receiving DRV/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg twice daily.MethodsIntensive steady-state 12- or 24-hour pharmacokinetic profiles were performed during the second trimester, third trimester, and postpartum. DRV was measured using high-performance liquid chromatography (detection limit: 0.09 μg/mL).ResultsPharmacokinetic data were available for 64 women (30 once daily and 34 twice daily dosing). Median DRV area under the concentration-time curve (AUC) and maximum concentration were significantly reduced during pregnancy with both dosing regimens compared with postpartum, whereas the last measurable concentration (Clast) was also reduced during pregnancy with once daily DRV. DRV AUC with once daily dosing was reduced by 38% during the second trimester and by 39% during the third trimester. With twice daily dosing, DRV AUC was reduced by 26% in both trimesters. The median (range) ratio of cord blood/maternal delivery DRV concentration in 32 paired samples was 0.18 (range: 0-0.82).ConclusionsDRV exposure is reduced by pregnancy. To achieve DRV plasma concentrations during pregnancy equivalent to those seen in nonpregnant adults, an increased twice daily dose may be necessary. This may be especially important for treatment-experienced women who may have developed antiretroviral resistance mutations

Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women.

ObjectiveTo describe darunavir (DRV) pharmacokinetics with once-and twice-daily dosing during pregnancy and postpartum in HIV-infected women.DesignWomen were enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1026s, a prospective nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included separate cohorts receiving DRV/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg twice daily.MethodsIntensive steady-state 12- or 24-hour pharmacokinetic profiles were performed during the second trimester, third trimester, and postpartum. DRV was measured using high-performance liquid chromatography (detection limit: 0.09 μg/mL).ResultsPharmacokinetic data were available for 64 women (30 once daily and 34 twice daily dosing). Median DRV area under the concentration-time curve (AUC) and maximum concentration were significantly reduced during pregnancy with both dosing regimens compared with postpartum, whereas the last measurable concentration (Clast) was also reduced during pregnancy with once daily DRV. DRV AUC with once daily dosing was reduced by 38% during the second trimester and by 39% during the third trimester. With twice daily dosing, DRV AUC was reduced by 26% in both trimesters. The median (range) ratio of cord blood/maternal delivery DRV concentration in 32 paired samples was 0.18 (range: 0-0.82).ConclusionsDRV exposure is reduced by pregnancy. To achieve DRV plasma concentrations during pregnancy equivalent to those seen in nonpregnant adults, an increased twice daily dose may be necessary. This may be especially important for treatment-experienced women who may have developed antiretroviral resistance mutations