Indian Women of Childbearing Age Do Not Metabolically Conserve Arginine as Do American and Jamaican Women ,

The Microbiome, Intestinal Function, and Arginine Metabolism of Healthy Indian Women Are Different from Those of American and Jamaican Women

We have reported that Indian women do not have increased Arg production during pregnancy like their American or Jamaican counterparts. There has not been a direct comparison of Arg flux, catabolism, and availability for NO synthesis in non‐pregnant American, Indian, and Jamaican women. The objective of this study was to determine whether Indian women are producing less Arg and/or catabolizing more Arg to Orn and therefore have less Arg available for anabolic pathways than their Jamaican and American counterparts. Ten healthy women of childbearing age from each country were given 6h primed, constant intravenous infusions of 15N2‐Arg, 2H2‐Cit, 15N2‐Orn, and 2H5‐Phe in both the fasted and fed states to measure Arg flux, hydrolysis, bioavailability, NO synthesis and Phe flux, an index of protein breakdown. USA India Jamaica P Value μmol/kg FFM/h μmol/kg FFM/h μmol/kg FFM/h Fasted Arg flux 56.1 ± 2.1a 54.2 ± 3.1a 66.1 ± 3.1 b 0.01 Arg hydrolysis 17.6 ± 1.5 a 23.7 ± 1.5 b 23.4 ± 1.6 b 0.01 Arg bioavailability 49.9 ± 1.3 ab 42.0 ± 2.6 a 55.5 ± 3.5 b 0.004 NO Synthesis 0.18 ± 0.01a 0.15 ± 0.01 b 0.21 ± 0.02 a 0.002 Phe flux 39.7 ± 0.9 39.0 ± 2.2 43.8 ± 2.3 0.17 Fed Arg flux 79.1 ± 3.3 a 80.3 ± 4.9 a 95.9 ± 2.9 b 0.008 Arg hydrolysis 27.3 ± 2.5 a 39.6 ± 3.7 b 37.2 ± 2.0 b 0.01 Arg bioavailability 51.8 ± 1.2 a 40.7 ± 3.5 b 57.5 ± 3.2 a <0.001 NO Synthesis 0.20 ± 0.01a 0.21 ± 0.03a 0.34 ± 0.04 b < 0.0001 Phe flux 58.8 ± 1.6 59.4 ± 3.0 63.3 ± 2.7 0.39 Means with different superscript letters are significantly different, P < 0.05 (post‐hoc Tukey's multiple comparison test).In conclusion, Indian women had increased Arg hydrolysis without a compensatory increase in Arg flux resulting in decreased bioavailability of Arg for the synthesis of proteins and other Arg‐derived biomolecules, including NO synthesis. Though American women also had slower Arg flux compared to Jamaican women, they were able to conserve Arg bioavailability because of decreased Arg hydrolysis. The results suggest that Indian women may need a higher dietary Arg intake.Supported by the Bill and Melinda Gates Foundation

Arginine (arg) supply is critical for a successful pregnancy because of its roles in protein, nitric oxide (NO) and creatine syntheses and in cell growth and differentiation. NO is especially important for vascular expansion in pregnancy and a deficiency of arg supply could underlie the high prevalence of low birth weight (LBW) neonates in Indian women and in adolescent girls. Stable isotope tracers were used to measure arg flux and NO synthesis in pregnant American, Indian and Jamaican women and teenagers. Gestation Jamaica India United States Weeks Adult N=8 Teen N=8 Norm. BMI N=10 Low BMI N=10 Adult N=6 Arg Flux (μmol/kg/h) 13 108±6 107±6 50±2 63±3 20 108±5 28 114±12 82±7 45±2 50±2 36–39 82±3 Post‐partum 73±6 Values are Mean±SEM; versus postpartum value, P<0.01 lower than Jamaican and American values, P<0.01 Except for normal BMI Indian women, NO synthesis was not different among groups at trimesters 1 and 3. Pregnant Indian women produced arg at a slower rate compared to all others. This slower arg flux was associated with slower NO synthesis in normal BMI, but not in low BMI Indian women. There were significant correlations between birth weight and arg flux at trimester 1 (r=0.54, P<0.01) and trimester 3 (r= 0.53, P<0.01), indicating a strong association between decreased arg flux and LBW. Not surprisingly, the Indian women delivered 45% LBW babies compared to 19% for Jamaicans. Grant Funding Source : USDA/ARS

Associations between self-reported sleep duration and cardiometabolic risk factors in young African-origin adults from the five-country modeling the epidemiologic transition study (METS)

This study assessed abdominal organ motion induced by gastroduodenal motilities in volunteers during fasting and postprandial states, using cine magnetic resonance imaging (cine-MRI). Thirty-five volunteers underwent cine-MRI while holding their breath in the fasting and postprandial states. Gastric motility was quantified by the amplitude and velocity of antral peristaltic waves. Duodenal motility was evaluated as the change of duodenal diameter. Abdominal organ motion was measured in the liver, pancreas and kidneys. Motion was quantified by calculating maximal organ displacement in the left–right, antero–posterior and caudal–cranial directions. Median antral amplitude and velocity in the fasting and postprandial states were 7.7 and 15.1 mm (P < 0.01), and 1.3 and 2.5 mm/s (P < 0.01), respectively. Duodenal motility did not change. Median displacement for all organs ranged from 0.9 to 2.9 mm in the fasting state and from 1.0 to 2.9 mm in the postprandial state. Significant increases in abdominal organ displacement in the postprandial state were observed in the right lobe of the liver, pancreatic head and both kidneys. Differences in the median displacement of these organs between the two states were all <1 mm. Although the motion of several abdominal organs increased in the postprandial state, the difference between the two states was quite small. Thus, our study suggests that treatment planning and irradiation need not include strict management of gastric conditions, nor the addition of excess margins to compensate for differences in the intra-fractional abdominal organ motion under different gastric motilities in the fasting and postprandial states.

To study the effect of dipeptidyl peptidase-4 (DPP-4) inhibition with saxagliptin on β-cell function as reflected by the stimulated insulin secretion rate after an enteral glucose load in patients with type 2 diabetes. Patients in this randomized, parallel-group, double-blind, placebo-controlled study were drug-naïve, aged 43-69 years, with baseline haemoglobin A1c (HbA1c) 5.9-8.1%. Twenty patients received saxagliptin 5 mg once daily; 16 received placebo. Patients were assessed at baseline and week 12 by intravenous hyperglycaemic clamp (0-180 min, fasting state), and intravenous-oral hyperglycaemic clamp (180-480 min, postprandial state) following oral ingestion of 75 g glucose. Primary and secondary endpoints were percent changes from baseline in insulin secretion during postprandial and fasting states, respectively. Insulin secretion was calculated by C-peptide deconvolution. After 12 weeks, saxagliptin significantly increased insulin secretion percent change from baseline during the postprandial state by an 18.5% adjusted difference versus placebo (p = 0.04), an improvement associated with increased peak plasma concentrations of intact glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. In the fasting state, saxagliptin significantly increased insulin secretion by a 27.9% adjusted difference versus placebo (p = 0.02). Saxagliptin also improved glucagon area under the curve in the postprandial state (adjusted difference -21.8% vs. placebo, p = 0.03). DPP-4 inhibition with saxagliptin improves pancreatic β-cell function in postprandial and fasting states, and decreases postprandial glucagon concentration. Given the magnitude of enhancement of the insulin response in the fasting state, further study into the effect of DPP-4 inhibition on the β-cell is warranted.

It is known that insulin resistance plays role in diabetic dyslipidemia especially hypertriacylglycerolemia (HTAG). However, in good metabolic controlled type2 diabetes mellitus who have normal fasting triacylglycerol level, the HTAG can observed only in postprandial state. In this research, the influence of insulin resistance on lipoprotein profiling and apoprotein of triacylglycerol-rich lipoprotein especially very low-density liprotein (VLDL) were studied. Eleven type2 diabetic subjects with moderated metabolic control (HbA1c &lt;8%), were classified as lower insulin resistance, LIR (HOMA-IR&lt;2.5), n=5 and higher insulin resistance, HIR (HOMA-IR 2.5-5.0), n=6 comparable to 10 nondiabetic controls. After at least 12 hours of fasting, subjects consumed a fat-rich meal. Before and the 4 hours after the meal, blood samples were taken for determination of glucose, insulin, lipids and lipoproteins in Experiment I. The increasing of postprandial triacylglycerol was found in chylomicron VLDL and HDL fractions especially in HIR group. For Experiment II, VLDL was isolated using sequential ultracentrifugation, delipidated and separated with 2D-PAGE and identified using ESI-IT, LC-MS/MS and MALDI-TOF MS. In total 26 protein spots representing 14 proteins including novel protein, transthyretin (TTR) with their isoforms were identified in VLDL. The comparisons of 14 proteins were analyzed in 6 pooled VLDL between fasting state and postprandial state within the same group as well as among different groups. The significant alterations compared between fasting and postprandial state of VLDL proteins (p&lt;0.05) in all groups were observed among apoC-II, apoC-III, apoE, apoA-I, except for TTR which was found only in HIR one. In fasting state, the significant changes of apoA-I, apoA-IV, and apoC-II were observed in LIR and HIR, whereas of apoC-III, apoE and TTR were observed in HIR in comparison to controls. In addition, significant modifications were found in apoA-I, apoC-II, apoC-III, apoE, and TTR of postprandial state compared to controls. These findings illustrate that insulin resistance is not only associated with increased VLDL triacylglycerol levels but also with alterations in VLDL protein composition which possibly affect the lipoprotein metabolism in diabetic patients.

BackgroundElevated level of low-density lipoprotein cholesterol (LDL-C) is concerned as one of the main risk factors for cardiovascular disease, in both the fasting and postprandial states. This study aimed to compare the measured LDL-C with LDL-C calculated by the Friedewald, Martin–Hopkins, Vujovic, and Sampson formulas, and establish which formula could provide the most reliable LDL-C results for Chinese subjects, especially at the postprandial state.MethodsTwenty-six subjects were enrolled in this study. The blood samples were collected from all the subjects before and after taking a daily breakfast. The calculated LDL-C results were compared with LDL-C measured by the vertical auto profile method, at both the fasting and postprandial states. The percentage difference between calculated and measured LDL-C (total error) and the number of results exceeding the total error goal of 12% were established.ResultsThe calculated LDL-CF levels showed no significant difference from LDL-CVAP levels at the fasting state. The calculated LDL-CS were significantly higher than LDL-CVAP at the fasting state (P < 0.05), while the calculated LDL-Cs were very close to LDL-CVAP levels after a daily meal. At the fasting state, the median total error of calculated LDL-CF was 0 (quartile: −3.8 to 6.0), followed by LDL-CS, LDL-CMH, and LDL-CV. At the postprandial states, the median total errors of LDL-CS were the smallest, 1.0 (−7.5, 8.5) and −0.3 (−10.1, 10.9) at 2 and 4 h, respectively. The calculated LDL-CF levels showed the highest correlation to LDL-CVAP and accuracy in evaluating fasting LDL-C levels, while the Sampson formula showed the highest accuracy at the postprandial state.ConclusionThe Friedewald formula was recommended to calculate fasting LDL-C, while the Sampson formula seemed to be a better choice to calculate postprandial LDL-C levels in Chinese subjects.

We conducted a phase I bioequivalence trial in healthy Chinese subjects in the fasting and postprandial states. The goal of this trial was to compare the pharmacokinetics and safety of the test preparation Cefaclor granule (Disha Pharmaceutical Group Co., Ltd.) and the reference preparation Cefaclor suspension (Ceclor®, Eli Lilly and Company). In this trial, 24 subjects were selected in the fasting and postprandial states, respectively. Enrolled subjects randomly accepted a single dose of 0.125 g Cefaclor granule or Cefaclor suspension. The washout period was set as 2 days. Blood samples were collected within 8 h after administration in the fasting state and within 10 h after administration in the postprandial state. Plasma concentrations were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters (AUC, Cmax) were used to evaluate bioequivalence of the two drugs. In the fasting trial, the geometric mean ratios (90% confidence intervals CIs) for Cmax, AUC0-t, and AUC0-∞ were 93.01% (85.96%–100.63%), 97.92% (96.49%–99.38%) and 97.95% (96.52%–99.41%), respectively. The GMR (90% CIs) for Cmax, AUC0-t, and AUC0-∞ in postprandial state were 89.27% (81.97%–97.22%), 97.31% (95.98%–98.65%) and 97.31% (95.93%–98.71%), respectively. The 90% CIs of AUC and Cmax in the fasting and postprandial states were within the 80–125% bioequivalence range. Therefore, Cefaclor granule and Cefaclor suspension were bioequivalent and displayed similar safety profiles. Furthermore, food intake affected the pharmacokinetic parameters of both drugs.

We tested the hypothesis that a mental task attenuates the meal-induced vasodilation in the splanchnic vasculature. Ten subjects performed a 5-min colour-word conflict test (CWT) under fasting and postprandial conditions. Subjects in the postprandial condition had ingested solid food with an energy content of 300 kcal (1,255 kJ) before either performing the CWT (mental task trial) or resting (resting control trial). The mean blood velocities (MBV) in the coeliac artery (CA) and superior mesenteric artery (SMA), and the mean arterial pressure (MAP) were measured. The MBV in the CA and SMA were divided by the MAP to assess the vascular conductance (VC). The MBV in the CA and SMA were significantly increased by the CWT under fasting conditions. In the postprandial condition, the MBV in the CA and SMA significantly increased immediately after the meal in both the mental task and resting control trials. The VC in the SMA, but not in the CA, was significantly decreased by the CWT under fasting conditions. In the postprandial conditions, there was no significant difference in the VC in both arteries between mental task and resting control trials. These results suggest that a mental task exerts different effects on the CA and SMA under fasting but not postprandial condition. The vasoconstrictive effect of a mental task on the SMA does not counter the vasodilatory effect of meal ingestion.

The high incidence and prevalence of coronary heart disease in diabetes mellitus is clearly established. The usual lipid pattern found in type II diabetic patients is a moderate increase in fasting triglyceride levels associated with low HDL cholesterol levels. These abnormalities are further amplified in the postprandial state. To study the effect of these alterations on reverse cholesterol transport, we isolated lipoprotein containing apoA-I but not apoA-II (LpA-I) particles by immunoaffinity chromatography from the plasma of well-controlled type II diabetic patients and nondiabetic matched control subjects. Different parameters involved in this antiatherogenic pathway were measured in both fasting and postprandial states. Diabetic patients had reduced levels of LpA-I particles that were protein enriched and phospholipid depleted. Gradient gel electrophoresis showed that control LpA-I particles had five distinct populations, whereas diabetic particles lacked the largest one. LpA-I isolated from diabetic plasma exhibited a decreased capacity to induce cholesterol efflux from Ob 1771 adipose cells both in fasting (15.1 +/- 10.0% versus 7.5 +/- 2.7%, P < .05) and postprandial (17.7 +/- 11.2% versus 7.7 +/- 3.9%, P < .05) states, whereas only control particles showed significantly higher ability to promote cholesterol efflux after the test meal (P = .02). Lecithin:cholesterol acyltransferase activity measured with an exogenous substrate showed a 54% increase and an 18% decrease postprandially for control subjects and patients, respectively. Thus, the different abnormalities found in the fasting state were further amplified in the postprandial situation. This resulted in LpA-I particles with aberrant size and composition and decreased ability to accomplish their antiatherogenic role in type II diabetic patients.

Effect of maternal vitamin A supplementation on retinol concentration in colostrum

Effect of maternal vitamin A supplementation on retinol concentration in colostrum

Urbanicity, Income, and Mammography-Use Disparities Among American Indian Women

BackgroundCloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine.ObjectiveThe purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers.MethodsA single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUC0–72h), under the plasma concentration-time curve from zero to infinity (AUC0–∞) and the maximal plasma concentration (Cmax). The equivalence standard range (80.0–125.0%) was used to evaluate the BE of the two preparations. The safety parameter as secondary endpoint was mainly evaluated by the occurrence of adverse events (AEs).ResultsA total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the Cmax, AUC0–72h and AUC0–∞ were 102.1%, 103.8% and 104.0% in the fasting condition, respectively. In the postprandial condition, the GMR of the T/R for the Cmax, AUC0–72h and AUC0–∞ were 94.2%, 98.8% and 99.0%, respectively. All the values fell within the range (80.0–125.0%). The Cmax and AUC0–72h values of the T and R preparations in fasting and postprandial conditions were not statistically significant (P > 0.05). Furthermore, no serious adverse events (SAEs) occurred during the whole trial.ConclusionsThe T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40268-022-00406-2.