Relationship between indices of adiposity obtained by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in pre-pubertal children

Background/Aim: The study investigated the relationship between indices of adiposity measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) in pre-pubertal children.

Subjects and methods: DXA-derived per cent body fat (%BF) was measured in 284 boys and 288 girls, aged 7–10 years. Cross-sections of the forearm (n=427) and lower leg (n=560) were obtained by pQCT to measure total cross-sectional area of the limb (Total CSA), Muscle CSA, Fat CSA, %Fat CSA (Fat CSA/Total CSA×100) and muscle density.

Results: Peripheral QCT-derived %Fat CSA in the forearm and lower leg correlated strongly with DXA-derived %BF (r=0.83–0.89, p<0.01) in both boys and girls. However, forearm and lower leg %Fat CSA were higher than whole body %BF by 5% and 10%, respectively. A better prediction of whole-body %BF was achieved by including %Fat CSA, muscle density and height into a hierarchical regression model. Using sex-specific regression equations, 87.7% of the boys and 83.7% of the girls had a predicted %BF within 3% units of the %BF obtained by DXA.

Conclusion: In pre-pubertal children, pQCT measures of adiposity are strongly associated with whole-body per cent body fat. This reproducible method could be an alternative technique to estimate body composition in this population.     

A Randomized,Double-Blind,Placebo-Controlled Study of Benfluorex in HIV-Infected Patients with Insulin Resistance or Impaired Glucose Tolerance

Abstract

Purpose: We previously reported a beneficial effect of benfluorex (BFL) on oral glucose tolerance test (OGTT) and visceral fat mass in an open-label study conducted in 60 HIV-infected patients. The objective of this study was to assess whether administration of BFL compared to placebo (PBO) improves insulin resistance (IR) in HIV+ patients with HAART- induced lipodystrophy. Method: 22 HIV-infected patients with IR or impaired glucose tolerance were double-blind randomly assigned to receive BFL 3 tablets/day or PBO for 24 weeks. Efficacy assessments included OGTT, abdominal computed tomography, and the measurement of fasting lipids. Results: Change of median insulin AUC was –53.0 μIU/mL (IQR, –126.0 to –12.7) in the BFL group vs. +33.6 μIU/mL (IQR, 7.0 to 115.6) (p = .01) in PBO group. Weight decreased significantly in the BFL group (–2 kg ± 2.6; IQR, –6.8 to 2.0) compared to the PBO group (0.8 kg ± 1.7; IQR, –2.0 to 0.5) (p = .02). No significant changes in visceral or subcutaneous fat mass and plasma lipid level were observed between the two groups. Conclusion: Added to antiretroviral therapy, a 6-month therapy with BFL improved insulin sensitivity but is not sufficient to reduce significantly visceral fat mass.     

丙戊酸对癫痫患儿骨代谢影响的Meta分析

目的采用Meta分析方法定量分析丙戊酸对癫痫患儿骨代谢的影响。方法电子检索中国维普科技期刊数据库、万方数据库、中国知网、中国生物医学文献数据库、EMCC、PubMed、OVID及Cochrance图书馆,纳入丙戊酸对癫痫患儿骨代谢影响的观察性研究,采用NOS量表评估纳入文献的质量。采用RevMan5．2软件进行Meta分析。结果14篇文献（英文10篇,中文4篇）进入Meta分析,均为病例对照研究,累计病例组507例,对照组480例。Meta分析结果显示,丙戊酸对血钙（MD=0．0l,95％CI：-0．05—0．06,P=0．13）、血磷（MD=-0．03,95％CI：-0．19—0．13,P=0．67）、碱性磷酸酶（MD=0．37,95％CI：-19．02～19．77,P=0．97）无明显影响,但丙戊酸组骨密度低于对照组,MD=-0．03,95％CI：-0．06～-0．00,P=0．03;丙戊酸组甲状旁腺激素水平显著高于对照组,MD=4．83,95％CI：1．15～8．50,P=0．01;丙戊酸组25-羟维生素D水平显著低于对照组,MD=-2．46,95％CI：-4．37～-0．55,P=0．01。结论现有证据表明,丙戊酸对癫痢患儿血钙、血磷和ALP无显著影响．但对骨密度、25-OH—VtiD和PTH有影响。     

Metabolic transitions at menopause: In post-menopausal women the increase in serum uric acid correlates with abdominal adiposity as assessed by DXA

Objectives

The present study aimed to investigate any associations between parameters of body fat mass distribution and levels of serum uric acid (sUA), a well-documented cardiovascular risk factor, among non-obese women ranging from pre- to post-menopausal status.

Methods

In this cross-sectional population-based study we assessed body fat distribution by dual-energy-X-ray absorptiometry (DXA), and sUA levels in 101 pre- and 134 post-menopausal non-obese apparently healthy women.

Results

Multivariate stepwise regression analysis revealed that sUA was independently associated to the indicators of overall fatness, i.e. body mass index (β = 0.339, p < 0.001) and DXA-assessed total and percentage body fat (β = 0.366, p < 0.001 and β = 0.412, p < 0.001, respectively), only among post-menopausal women. Within this sample subset, trunk (i.e. central) fat mass emerged as a strong predictor of sUA (β = 0.408, p < 0.001), after taking the potential confounders (including body mass index) into account.

Conclusion

Central fat accumulation was found to be independently associated with higher sUA levels among non-obese women in post- but not among those in pre-menopause.     

Fabrication and statistical optimization of surface engineered PLGA nanoparticles for naso-brain delivery of ropinirole hydrochloride: in-vitro–ex-vivo studies

Ropinirole hydrochloride (RPN), a nonergot dopamine D₂-agonist used in the management of Parkinson’s disease, has poor oral bioavailability (52%) due to extensive hepatic metabolism. The intent of present research work was aimed at design and statistical optimization of RPN-loaded poly (lactic-co-glycolic acid) (PLGA)-based biodegradable nanoparticles (NPs) surface modified using natural emulsifier, vitamin E (d-α-tocopheryl polyethylene glycol 1000 succinate [TPGS]) for direct nose-to-brain delivery in order to avoid hepatic first-pass metabolism, and improve therapeutic efficacy with sustained drug release. RPN-NPs were prepared by modified nanoprecipitation technique and optimized using 2³ factorial design of experiment. The effect of polymer and emulsifier concentration was evaluated on particle size and entrapment efficiency (EE%). Formulation PL₆ was considered as desirable with highest EE% (72.3?±?6.1%), PS (279.4?±?1.8?nm), zeta potential (?29.4?±?2.6?mV), and cumulative drug diffusion of 96.43?±?3.1% in 24?h. The ANOVA results for the dependent variables demonstrated that the model was significant (p value?<?0.05) for response variables. Histopathological study of optimized batch (PL₆) demonstrated good retention of NPs with no severe signs of damage on the integrity of nasal mucosa. Differential scanning calorimetry revealed the absence of any chemical interaction between RPN, PLGA, and TPGS while SEM study confirmed spherical shape of optimized NPs. Accelerated stability studies of freeze-dried optimized batch demonstrated negligible change in the average PS and EE% after storage at 25?±?2?°C/60?±?5% (relative humidity (RH) for the period of three months. The promising results of optimized batch suggested practicability of investigated system for enhancement of bioavailability and brain targeting of CNS acting drugs like RPN.     

Differential Association of Adiposity Measures with Heart Rate Variability Measures in Koreans

Purpose

Although obesity has been associated with imbalances in cardiac autonomic nervous system, it is unclear whether there are differential relationships between adiposity measures and heart rate variability (HRV) measures. We aimed to examine differences in the relationship between adiposity measures and HRV indices in a healthy Korean population.

Materials and Methods

In all, 1409 non-smokers (811 males, 598 females) without known histories of cardiovascular (CV), endocrine, or neurological diseases underwent adiposity measurements [(body mass index (BMI), percentage of body fat mass (PBF), and waist-to-hip ratio (WHR)], the HRV assessment (SDNN, RMSSD, LF, HF, LF/HF, and pNN50), and examination for CV risk factors (fasting glucose, LDL-cholesterol, HDL-cholesterol, triglycerides, hs-CRP, and blood pressure).

Results

Compared with BMI and PBF, WHR was more strongly correlated with each HRV index and more likely to predict decreased HRV (<15 percentile vs. ≥15 percentile of each HRV index) in ROC curves analysis. In linear regression analysis, all adiposity measures were inversely associated with each HRV measure before adjusting for age, gender, and CV risk factors (p<0.05). After adjusting for the covariates, WHR was inversely related to RMSSD, LF, and pNN50; PBF with RMSSD, HF, and pNN50; BMI with RMSSD (p<0.05). The inversed association between HRV indices and the gender-specific WHR tertile was significant for subjects with BMI ≥25 kg/m², but not for those with BMI <25 kg/m².

Conclusion

WHR and PBF appear to be better indicators for low HRV than BMI, and the association between abdominal adiposity and HRV may be stronger in overweight subjects.     

Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies

In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self‐administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy–cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy–cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy–cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy–cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.     

Serial measurement of hepatic lipids during chemotherapy in patients with colorectal cancer: a 1H MRS study

Hepatic steatosis is a hallmark of chemotherapy‐induced liver injury. We made serial ¹H MRS measurements of hepatic lipids in patients over the time course of a 24‐week chemotherapeutic regimen to determine whether ¹H MRS could be used to monitor the progression of chemotherapy‐induced steatosis. Thirty‐four patients with stage III or IV colorectal cancer receiving 5‐fluorouracil, folinic acid and oxaliplatin (n = 21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n = 13) were studied prospectively. ¹H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A ¹H MR spectrum was acquired from the liver during a breath hold and the ratio of fat to fat + water (FFW) was calculated to give a measure of hepatic triglycerides (HTGCs). The methodology was histologically validated in 18 patients and the reproducibility was assessed in 16 normal volunteers. Twenty‐seven patients completed baseline, 6‐week and 24‐week ¹H MRS examinations and one was censored. Thirteen of 26 patients (50%) showed an increase in FFW after completion of treatment. Six patients (23%) developed hepatic steatosis and two patients converted from steatosis to nonsteatotic liver. Patients whose 6‐week hepatic lipid levels had increased significantly relative to baseline also had a high probability of lipid elevation relative to baseline at the completion of treatment. Serial ¹H MRS is effective for the monitoring of HTGC changes during chemotherapy and for the detection of chemotherapy‐associated steatosis. Six of 26 patients developed steatosis during chemotherapy. Lipid changes were observable at 6 weeks. Copyright © 2012 John Wiley & Sons, Ltd.     

In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1‐13C] and [2‐13C]pyruvate

Hyperpolarized ¹³C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl‐coenzyme A (acetyl‐CoA). [1‐¹³C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in ¹³C‐bicarbonate production after dichloroacetate (DCA) administration. With [1‐¹³C]pyruvate, the ¹³C label is released as ¹³CO₂/¹³C‐bicarbonate, and, hence, does not allow us to follow the fate of acetyl‐CoA. Pyruvate labeled in the C₂ position has been used to track the ¹³C label into the TCA (tricarboxylic acid) cycle and measure [5‐¹³C]glutamate as well as study changes in [1‐¹³C]acetylcarnitine with DCA and dobutamine. This work investigates changes in the metabolic fate of acetyl‐CoA in response to metabolic interventions of DCA‐induced increased PDC flux in the fed and fasted state, and increased cardiac workload with dobutamine in vivo in rat heart at two different pyruvate doses. DCA led to a modest increase in the ¹³C labeling of [5‐¹³C]glutamate, and a considerable increase in [1‐¹³C]acetylcarnitine and [1,3‐¹³C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2‐¹³C]lactate, [2‐¹³C]alanine and [5‐¹³C]glutamate. The change in glutamate with dobutamine was observed using a high pyruvate dose but not with a low dose. The relative changes in the different metabolic products provide information about the relationship between PDC‐mediated oxidation of pyruvate and its subsequent incorporation into the TCA cycle compared with other metabolic pathways. Using a high dose of pyruvate may provide an improved ability to observe changes in glutamate. Copyright © 2013 John Wiley & Sons, Ltd.