Soy-isoflavones may act as estrogenic agonists or antagonists depending on the endogenous hormone status. These clinical effects can be exerted variably in individuals by the metabolic ability to produce a more potent metabolite than precursors. The objective of this randomized, double-blind, placebo-controlled study was to investigate the skeletal effect of isoflavones according to their metabolic variability in premenopausal women. Volunteers were randomly assigned to receive either soy-extract isoflavones (n=32) or lactose (n=21) once a day for three menstrual cycles. After intervention, the urinary excretions of isoflavones and their metabolites were significantly higher in the soy group than in the placebo group and showed a large inter-individual variation. Women in the soy group were divided into subgroups according to their ability to excrete more potent metabolites. Serum osteocalcin and urine deoxypyridinoline showed a tendency to increase after a challenge in equol high-excretors. Serum osteocalcin concentration in the genistein high-excretors increased significantly after a challenge (P=0.04) but did not increase in either the placebo or genistein low-excretors. An estrogenic antagonistic effect of isoflavones on bone turnover was observed in premenopausal women who are able to produce more potent metabolites.
Adult ; Amino Acids/urine ; Bone and Bones/*drug effects/metabolism ; Double-Blind Method ; Estrogen Antagonists/*pharmacokinetics/pharmacology/urine ; Female ; Humans ; Isoflavones/*pharmacokinetics/pharmacology/urine ; Middle Aged ; Osteocalcin/blood ; *Premenopause

BACKGROUNDSericin peptide (SP) has shown a powerful anti-oxidant property in a host of studies. The present study was designed to investigate the possible protective effects of SP against alcohol-induced gastric lesions in mice and to explore the potential mechanisms.

METHODSAnimals were randomly divided into 5 groups: control, alcohol (56%, 14.2 ml/kg), SP-treated mice (0.2, 0.4, 0.8 g/kg). Mice were pretreated with SP before administering alcohol, the concentration of ethanol in serum and urine, the contents of malondialdehyde (MDA), glutathione (GSH) and the glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD) activities in the gastric mucosa were measured, subsequently, the pathological evaluation of stomach was also observed.

RESULTSOf the animals pre-treated with SP (0.4, 0.8 g/kg), the concentration of ethanol in serum was significantly decreased, while increased in urine as compared to the alcohol-administered alone animals. Alcohol administration caused severe gastric damage as indicated by markedly increased MDA levels and decreased antioxidants, such as reduced GSH, GSH-PX and SOD in the gastric tissue while the CAT activity was not altered. On SP administration there was a reversal in these values towards normal. Histopathological studies confirmed the beneficial role of SP, which was in accordance with the biochemical parameters.

CONCLUSIONSSP could protect gastric mucosa from alcohol-induced mucosal injury. These gastroprotective effects might be due to increasing 'first-pass metabolism' in the stomach and hastening ethanol elimination directly through the urine. SP might also play an important role in the protection of the structure and function of gastric mitochondria, at least partly based on their anti-oxidant effect.

Amino Acids ; analysis ; Animals ; Cytoprotection ; Ethanol ; blood ; toxicity ; urine ; Gastric Mucosa ; drug effects ; pathology ; Glutathione ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Sericins ; analysis ; pharmacology ; Superoxide Dismutase ; metabolism

OBJECTIVETo explore the effects of recombinant human growth hormone (rhGH) when applied postoperatively on the metabolism of branch chain amino acid in severely burned patients.

METHODSFifty burn patients, aged 12 - 50 years and inflicted by more than 30% TBSA with 10% or more of III degree burn and admitted from the January of 1999 to the January of 2001 were enrolled in the study. The patients were randomly divided into rhGH treating (rhGH group) and control groups. Escharectomy was performed within 3 postburn day (PBDs). rhGH (0.3 IU/kg) was injected percutaneously every evening for ten days since the 1st postoperative day (POD). The changes of the plasma levels of GH and branch chain amino acid and the urine level of 3-methyl histidine (3-MH) were observed in the morning in the patients from the two groups.

RESULTSThe plasma GH level before operation decreased obviously in two groups of patients when comparing with normal value (P < 0.05). The plasma GH level in rhGH group was evidently higher than that in control group since the 3rd POD (P < 0.05). There was significant increase of the output amount of urine 3-MH in all patients, but which was obviously higher in control group than that in rhGH group (P < 0.05). The plasma levels of branch chain amino acid in burn patients before and one day after operation were lower than normal levels. The plasma levels of valine, isoleucine and leucine increased to peak values at POD 3 in rhGH group and at POD 7 in control group and decreased thereafter. The plasma branch chain amino acid level in rhGH group was evidently lower than that in control group since POD 7 (P < 0.05). The plasma GH level in rhGH group was negatively and significantly correlated with the urine output amount of 3-MH (P < 0.01).

CONCLUSIONPostoperative application of rhGH in major burn patients might be beneficial to the protein synthesis from amino acids by skeletal muscles and to the decrease of muscle protein degrading rate.

Adolescent ; Adult ; Amino Acids ; metabolism ; urine ; Burns ; blood ; metabolism ; urine ; Child ; Female ; Human Growth Hormone ; blood ; pharmacology ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; drug effects ; metabolism ; Recombinant Proteins ; blood ; pharmacology

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) act by irreversibly binding to the H+-K+-ATPase of the proton pump in parietal cells and may possibly affect the vacuolar H+-ATPase in osteoclasts. METHODS: We investigated the effect of 8 weeks of PPI treatment on the parameters of bone turnover and compared PPI with revaprazan, which acts by reversibly binding to H+-K+-ATPase in proton pumps. This study was a parallel randomized controlled trial. For 8 weeks, either a PPI or revaprazan was randomly assigned to patients with gastric ulcers. The parameters of bone turnover were measured at the beginning of and after the 8-week treatment period. RESULTS: Twenty-six patients (PPI, n=13; revaprazan, n=13) completed the intention-to-treat analysis. After the 8-week treatment period, serum calcium and urine deoxypyridinoline (DPD) were increased in the PPI group (serum calcium, p=0.046; urine DPD, p=0.046) but not in the revaprazan group. According to multivariate linear regression analysis, age > or =60 years was an independent predictor for the changes in serum calcium and urine DPD. CONCLUSIONS: In elderly patients, administering a PPI for 8 weeks altered bone parameters. Our study suggested that PPIs might directly alter bone metabolism via the vacuolar H+-ATPase in osteoclasts.
Aged ; Amino Acids/drug effects/urine ; Bone Remodeling/*drug effects ; Bone and Bones/*metabolism ; Calcium/blood ; Female ; Humans ; Intention to Treat Analysis ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Osteoclasts/*metabolism ; Prospective Studies ; Proton Pump Inhibitors/*pharmacology ; Pyrimidinones/*pharmacology ; Tetrahydroisoquinolines/*pharmacology

OBJECTIVETo investigate the regulatory effect of Jiangu Granule (JGG) on osteoblast and its effect on bone absorption on the molecular level and from aspect of bone metabolism.

METHODSOsteoporosis model SD rats established by ovariectomy were interfered by drug. Levels of urinary deoxypyridinoline (D-Pyr) and osseous integrin beta1 (Itgbeta1) mRNA expression were detected by ELISA and in situ hybridization, respectively.

RESULTSLevel of urinary D-Pyr increased (P < 0.01) and osseous Itgbeta1 mRNA expression decreased significantly in the model rats. After treatment with JGG for 12 weeks, the D-Pyr levels in them decreased significantly (P < 0.05), while the quantity of osteoblasts and the expression of Itgbeta1 mRNA in bone tissue increased obviously. Conclusion JGG can not only decrease the catabolism of collagen fiber type I in bone matrix, but also promote the osteogenic activity of osteoblast. So, it can improve or reverse the pathological tendency of osteogenesis shortage caused by E2 reduction to play its action in strengthening bone.

Amino Acids ; urine ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Nerve Tissue Proteins ; metabolism ; Osteoblasts ; metabolism ; Osteogenesis ; drug effects ; Osteoporosis ; metabolism ; prevention & control ; Ovariectomy ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley

Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. Therefore, it is not clear which effect of genipin on kidneys occurs, when it is used in the treatment of diabetes. In the present study, we performed nuclear magnetic resonance (NMR)-based metabolomics analysis of urine and kidney tissue samples obtained from diabetic rats to explore the change of endogenous metabolites associated with diabetes and concomitant kidney disease. Nine significant differential metabolites that were closely related to renal function were screened. They were mainly related to three metabolic pathways: synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, and butanoate metabolism, which are involved in methylamine metabolism, energy metabolism and amino acid metabolism. In addition, after the intervention of genipin, the metabolic levels of all the metabolites tended to be normal, indicating a protective effect of genipin on kidneys. Our results may be helpful for understanding the antidiabetic effect of genipin.
Amino Acids ; metabolism ; Animals ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; metabolism ; urine ; Energy Metabolism ; drug effects ; Hypoglycemic Agents ; pharmacology ; Iridoids ; pharmacology ; Kidney ; drug effects ; metabolism ; Male ; Metabolic Networks and Pathways ; drug effects ; Metabolome ; drug effects ; Metabolomics ; Methylamines ; metabolism ; Proton Magnetic Resonance Spectroscopy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo assess bone health in epileptic children who have been treated with carbamazepine (CBZ) or valproate (VPA) by using quantitative ultrasound (QUS) and determining the biochemical indices of bone metabolism, and to provide a proposal to improve quality of life of epileptic children.

METHODSNinety-two epileptic children who had been treated with CBZ or VPA for more than two years were evaluated for bone mineral density (BMD) at the mid-shaft tibia and the distal third of the radius. Biochemical indices of bone metabolism including urine deoxypyridinoline (DPD) and serum osteocalcin (OC), and daily calcium intake were also evaluated. Thirty-five age-matched healthy children were used as controls. Reduced BMD was defined as speed of sound (SOS) Z scores of the mid-shaft tibia and (or) the distal third of the radius less than -0.7.

RESULTSBMD was reduced in epileptic children significantly when compared to the controls (P < 0.05). In addition, a negative correlation was found between the duration of anti-epileptic drugs (AEDs) use and BMD (r(s) = -0.21 - -0.31, P < 0.05), the lowest BMD was observed in those who had been treated for the longest time. The serum values of OC in epileptic children were significantly reduced relative to the controls (P < 0.01), children who took VPA had the lowest value of OC. However, the urine values of DPD showed no significant difference between epileptic and healthy children (P > 0.05); children who took CBZ had the highest value of DPD. Thirty-two epileptic children (35%) and five (14%) sex- and age-matched healthy children had reduced BMD, significant difference was found between them (P < 0.05). Moreover, epileptic children with reduced BMD seemed to have higher body mass index (BMI) (P < 0.05), take less daily calcium intake (P < 0.01), and had longer duration of AEDs (P < 0.01). The two risk factors of having reduced BMD in epileptic children were those who had been treated with AEDs for more than five years and higher BMI, while the protective factor was daily calcium intake.

CONCLUSIONSLong-term use of CBZ or VPA is associated with bone metabolism abnormalities, which include reduced BMD and decreased bone turnover (mainly decreased bone formation). Long-term anti-epileptic therapy is an important factor for impaired bone health in epileptic children, and that low calcium intake and high BMI could be two aggravating factors. QUS is a useful method to evaluate BMD of epileptic children who are on long-term anti-epileptic therapy, and to recognize the status of bone health, in helping to promote bone health and improve quality of life in epileptic children by the use of calcium and vitamin D supplementation.

Amino Acids ; urine ; Anticonvulsants ; adverse effects ; therapeutic use ; Bone Density ; drug effects ; Bone and Bones ; diagnostic imaging ; drug effects ; metabolism ; Calcium, Dietary ; analysis ; Carbamazepine ; adverse effects ; therapeutic use ; Child ; Epilepsy ; drug therapy ; Female ; Humans ; Male ; Osteocalcin ; blood ; Radius ; diagnostic imaging ; Tibia ; diagnostic imaging ; Ultrasonography ; Valproic Acid ; adverse effects ; therapeutic use