Bioavailability,disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes

The pharmacokinetics of isoflavones in 10 healthy women were determined from serum appearance/disappearance concentration profiles and urinary excretions after single-bolus ingestion of 10, 20 or 40 g of soy nuts delivering increasing amounts of the conjugated forms of daidzein (6.6, 13.2 and 26.4 mg) and genistein (9.8, 19.6 and 39.2 mg). Peak serum daidzein and genistein concentrations were attained after 4-8 h, and elimination half-lives were 8.0 and 10.1 h, respectively. There were no differences in the pharmacokinetics of daidzein and genistein between pre- and postmenopausal women, indicating absorption and disposition of isoflavones to be independent of age or menopausal status. A curvilinear relationship was observed between the bioavailability of daidzein and genistein, apparent from the area under the curve to infinity (AUC(inf)) of the serum concentration-time profiles and the amount of isoflavones ingested. The mean fraction of the isoflavones excreted in urine decreased with increasing intake when expressed as a percentage of the administered dose (63.2 +/- 8.0, 54.4 +/- 8.1 and 44.0 +/- 4.3%, respectively, for daidzein, and correspondingly, 25.2 +/- 5.3, 13.4 +/- 2.1 and 15.8 +/- 2.7% for genistein), underscoring the trend toward nonlinear pharmacokinetics. Equol was identified as a metabolite in 30% of women; it was present consistently in urine and blood from the same subjects. Its delayed appearance was consistent with colonic synthesis. On the basis of the pharmacokinetics, optimum steady-state serum isoflavone concentrations would be expected from modest intakes of soy foods consumed regularly throughout the day rather than from a single highly enriched product.     

Fetal gastrointestinal malformations

In an audit to evaluate fetal gastrointestinal (GIT) malformations, case sheets of all mothers who gave birth to newborns with GIT malformations were analysed regarding the maternal history, prenatal ultrasound and the postnatal structural malformations and perinatal management. In 1999, eleven babies were born with gastrointestinal malformations, one was a still birth. Nine had associated malformations of other systems, two had trisomy 21. Eight babies were operated in the immediate newborn period, 5 survived. Ultrasound was not very accurate in the diagnosis of GIT anomaly in this series. In view of associated chromosomal and structural anomaly a fetal ECHO and genetic amniocentesis is warranted. Most of these babies require immediate surgery after birth, so they need to be delivered in a centre which is equipped with good neonatal and pediatric surgery care.     

Diagnostic accuracy of contrast echocardiography during adenosine stress for detection of abnormal myocardial perfusion: a prospective comparison with technetium-99 m sestamibi single-photon emission computed tomography

Myocardial contrast echocardiography (MCE) utilizes compressible microbubbles behaving similarly to red blood cells. Destruction of microbubbles and observation of the gradual refill into the myocardium are key to evaluating perfusion using real-time MCE. We aimed to assess the feasibility and diagnostic accuracy of qualitative MCE utilizing a 17-segment model for localization of myocardial perfusion abnormalities compared with simultaneous technetium-99 m sestamibi single-photon emission computed tomography (SPECT). From July 2005 through August 2007, 97 patients with known or suspected coronary artery disease underwent simultaneous SPECT and realtime MCE during adenosine stress. Qualitative MCE and tracer uptake were analyzed visually using a 17-segment model in a blinded manner. Diagnostic accuracy and 95% confidence interval (CI) were determined. Myocardial contrast echocardiography was completed in 91 patients (age, mean [SD], 69.3 [10.9] years; body mass index, 30.0 [6.3]; 59 males [65%]). Myocardial contrast echocardiography analysis was feasible in 88 (97%) patients (261 of 264 [99%] territories; 1299 of 1497 [87%] segments). At patient level, MCE sensitivity was 88% (95% CI, 79%–94%); specificity was 85% (77%–90%). For disease detection in individual coronary territories, sensitivity and specificity were 84% (71%–92%) and 79% (72%–84%) for the left anterior descending artery; 62% (38%–80%) and 88% (83%–91%) for the left circumflex artery; and 73% (57%–82%) and 94% (89%–97%) for the right coronary artery. For MCE combined with wall-motion analysis, concordance with SPECT improved from 80% to 86%. Myocardial contrast echocardiography interobserver concordance was 81% (κ [SE], 0.611 [0.78]). Myocardial contrast echocardiography accuracy was comparable in patients classified in accordance with presence of diabetes mellitus, myocardial infarction, hypertension, or percutaneous coronary intervention. Improved MCE specificity in detecting perfusion defects was seen in patients with no history of coronary bypass graft surgery (P = 0.005). Real-time MCE with a 17-segment model for analysis has good feasibility and accuracy in evaluation of myocardial perfusion during adenosine stress.     

Temporal neurotransmitter conditioning restores the functional activity of adult spinal cord neurons in long-term culture

The ability to culture functional adult mammalian spinal cord neurons represents an important step in the understanding and treatment of a spectrum of neurological disorders including spinal cord injury. Previously, the limited functional recovery of these cells, as characterized by a diminished ability to initiate action potentials and to exhibit repetitive firing patterns, has arisen as a major impediment to their physiological relevance. In this report, we demonstrate that single temporal doses of the neurotransmitters serotonin, glutamate (N-acetyl-DL-glutamic acid) and acetylcholine-chloride lead to the full electrophysiological functional recovery of adult mammalian spinal cord neurons, when they are cultured under defined serum-free conditions. Approximately 60% of the neurons treated regained their electrophysiological signature, often firing single, double and, most importantly, multiple action potentials.     

The ongoing quest for biomarkers in Ankylosing Spondylitis

Ankylosing Spondylitis poses significant challenges in terms of early diagnosis, assessment of disease activity, predicting response to the treatment and monitoring radiographic progression. With better understanding of underlying immunopathogenesis, effective targeted therapies are available which improve symptoms, quality of life and possibly slow the radiographic progression. There has been a growing interest in the discovery of biomarkers for defining various aspects of disease assessment and management in Ankylosing Spondylitis. The C‐reactive protein and HLA‐B27 are most commonly used biomarkers. This review describes many other newer biomarkers which have potential clinical applications in this chronic inflammatory disease.     

Homocysteine Metabolism in Children with Idiopathic Nephrotic Syndrome

Background

Homocysteine metabolism is altered in children with idiopathic nephrotic syndrome. Hyperhomocysteinemia is a risk factor of early atherosclerosis and glomerulosclerosis and may occur at time of first occurrence of idiopathic nephrotic syndrome.

Methods

Thirty children with first episode of idiopathic nephrotic syndrome (FENS) aged 1–16 years along with 30 age‐ and sex‐matched healthy controls were enrolled in this study. Homocysteine and cysteine were measured with HPLC; vitamin B₁₂ and folic acid were measured with electro‐chemilumiscence immunoassay. Primary outcome measure was plasma homocysteine level in children with FENS and in controls. Secondary outcome measures were (1) plasma and urine homocysteine and cysteine levels in children with FENS at 12 weeks and 1 year (remission) and (2) plasma and urine levels of vitamin B₁₂ and folic acid in children with FENS, at 12 weeks and 1 year (remission).

Results

Plasma homocysteine and cysteine levels were comparable to controls in children with FENS, at 12 weeks and 1‐year remission. Plasma levels of vitamin B12 and folic acid were significantly decreased compared to controls in FENS due to increased urinary excretion, which normalize during remission at 12 weeks and 1 year. Urinary homocysteine and cysteine levels were significantly raised in FENS compared to controls and continued to be raised even at 12‐week and 1‐year remission.

Conclusion

Homocysteine metabolism is deranged in children with FENS. Renal effects of long‐term raised urinary homocysteine levels need to be studied.