Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women

Homocysteine (Hcy) is thought to play an important role in the development of osteoporosis and fracture. Methionine synthase reductase (MTRR) is an enzyme involved in the conversion of Hcy to methionine. We hypothesized that certain genetic polymorphisms of MTRR leading to reduced enzyme activity may cause hyperhomocysteinemia and affect bone metabolism. We therefore examined the associations of the A66G and C524T polymorphisms of the MTRR gene with bone mineral density (BMD) and serum osteocalcin levels in postmenopausal women. Although we did not detect any significant associations between MTRR polymorphisms and BMD or serum osteocalcin levels, we found that the 66G/524C haplotype, which has reduced enzyme activity, was significantly associated with serum osteocalcin levels in a gene-dose dependent manner (P = 0.002). That is, the highest osteocalcin levels (34.5 +/- 16.8 ng/ml) were observed in subjects bearing two copies, intermediate osteocalcin levels (32.6 +/- 14.4 ng/ml) were observed in subjects bearing one copy, and the lowest levels of osteocalcin (28.8 +/- 10.9 ng/ml) were observed in subjects bearing no copies. These results suggest that the 66G/524C haplotype of the MTRR gene affect bone turn over rate.     

Clinical evaluation of osteocalcin in sera of the patients with neoplasms of bone

The clinical significance of osteocalcin in sera of bone tumors were measured in sera of various kinds of bone tumors. The levels of osteocalcin were higher in bone tumors than those in normal subjects. Serum osteocalcin levels in hypercalcemic groups of bone metastasis and myeloma showed a remarkable increase in a parallelism with serum ALP and LDH levels. These results suggested to be directly or indirectly activated on osteoblast by bone tumors and to be synthesized osteocalcin in osteoblast.     

Pharmacological evaluation of LiuWei Zhuanggu Granules in rats

Many commonly consumed foods, herbs and spices contain a complex array of naturally occurring bioactive molecules called phytochemicals, which may confer health benefits. In this study, the impact of LiuWei Zhuanggu Granules (LWZGG) on mineral metabolism in osteopenia development was evaluated. Results showed that serum estrogen, bone gla protein (BGP), and calcitonin (CT) levels, bone Ca, Zn and Cu levels, femur, lumbar vertebrae and trabecular bone density, tibia maximum stress and maximum bending strength were increased, and serum parathyroid hormone (PTH), serum and urine Ca, Zn and Cu levels were decreased in rat bone. It can be concluded that LWZGG is useful to improve bone quality in ovariectomized (OVX) rats.     

Markers of bone pain in hemodialysis patients with renal insufficiency

The patients receiving maintenance hemodialysis were divided into two groups in the absence and the presence of bone pain and investigated the markers of bone pain in these patients. These results suggested that the duration of receiving hemodialysis, serum concentrations of alkaline phosphatase, osteocalcin and parathyroid hormone became to be the markers of bone pain.     

Simultaneous determination of blood glucose and isoleucine levels in rats after chronic alcohol exposure by microwave-assisted derivatization and isotope dilution gas chromatography/mass spectrometry

Blood glucose and isoleucine are two biomarkers of chronic alcohol exposure. Simultaneous determination of blood glucose and isoleucine levels helps to illuminate the influence of alcohol on the metabolism of glucose and amino acids. The most accurate method for the detection of serum glucose is isotope dilution gas chromatography/mass spectrometry (ID GC/MS). In this study, a rapid, simple and sensitive technique was developed for the quantitative analysis of glucose and isoleucine in rats after chronic alcohol exposure by microwave-assisted derivatization (MAD) and ID GC/MS. Serum glucose and isoleucine were rapidly derivatized by N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) with microwave irradiation, and the trimethylsilyl derivatives were analyzed by GC/MS. This technique was used to demonstrate that pyrroloquinoline quinone (PQQ), a non-covalently bound prosthetic group in some quinoproteins involved in the metabolism of some sugar or alcohol, could reverse alcohol exposure induced glucose elevation. On the other hand, it did not affect the metabolism of isoleucine whose level was elevated along with serum glucose. The combination of MAD and ID GC/MS has been shown to be an accurate, rapid, simple and sensitive method for the quantification of glucose and isoleucine in serum samples.     

Influences of serum magnesium on measurements of serum parathyroid hormone

The amino sequence recognizable parathyroid hormones (PTH) in lower and non-lower magnesemic groups in randomized samples were measured by using various kinds of the well established PTH kits. The levels of carboxy terminal, mid-region and intact PTH in lower magnesemic group were more decreased than these in non-lower magnesemic group. It is likely that the shortage of magnesium in serum makes a suppression of PTH secretion.     

The measurement of serum human parathyroid hormone (h-PTH53-84) and effect of exercise on calcium metabolism

This study was focussed our attention on the measurement within the upper physiological level of human serum parathyroid hormone (PTH), using kits of human PTH 53-84. This assay kit was able to detect serum PTH in sera with subtle changes of serum calcium concentrations before and after short term exercise. These serum PTH levels before and after exercise seemed to be changed within the upper physiological levels of PTH. Thus, this study suggested that the assay kit was likely to become a useful tool of the measurement of the physiological level of serum PTH in humans.     

再障头发、血清和骨髓组织钴、锂元素含量的变化

采用原子吸收光谱技术测定再障４３例患者头发、血清和骨髓组织的钴、锂元素含量，并与急性白血病２０例、缺铁性贫血１０例和正常人４４例作对照比较，再障头发、骨髓钴、锂和血清钴含量均低于正常人，Ｐ＜０．０５，而与急性白血病和缺铁性贫血之间，以及各种类型再障之间则无差异性．再障头发锂含量与血红蛋白、红细胞数呈负相关，Ｐ＜０．０５，说明再障确实存在着钴、锂元素代谢异常．     

Inorganic arsenic: A dangerous enigma for mankind

Human being have been using inorganic arsenic for a long time. Many reports on arsenic poisoning have been published: eg case reports, examination reports, post mortem reports, and epidemiological studies. Several aspects and features of arsenic poisoning are discussed in this report. Methods of inferring arsenic-related disease, disease classification according to acute or chronic criteria, exposure route, interaction, confounding factors, and the oxidation state of arsenic are all discussed. The effects of arsenic are classified into skin, respiratory system, gastrointestinal tract, liver, cardiovascular system, nervous system, and bone marrow effects. Carcinogenicity is an important chronic effect of arsenic poisoning, so special attention is paid to it in this review. In Japan, there have been many incidents of arsenic poisoning. In this review, we often use data from these cases, such as the Morinaga powdered-milk poisoning case, the Ube soy-sauce poisoning case, the Toroku mine incident, and the Nakajo well-water poisoning case. We emphasize here the necessity of planning follow-up studies and total health care for patients exposed to arsenic.     

Historical cohort studies in three arsenic poisoning areas in japan

The results of historical cohort studies of three arsenic poisoning incidents in Japan are presented. The first episode was in a small mountainous community near an arsenic mine and refinery, at Toroku, where patients with chronic arsenism were certified by application of the Pollution Health Damage Compensation Law. The second area was in a small town, Namiki-cho, near Nakajo-machi, where wells were poisoned by arsenic produced in an arsenic(III) sulfide factory. As to the third cohort, eight residents of Nishikawa-machi who ingested well-water suffered arsenic poisoning about 35 years ago. The standardized mortality ratios were used in analyzing these data. Excesses of cancer mortality, especially lung cancer, were observed among the subjects in these areas. In Japan, there are many arsenic poisoning episodes, involving for example soy-sauce poisoning, powdered-milk poisoning and other incidents associated with arsenic mines. Thus it is necessary to clarify the chronic effects of arsenic in these areas.     

The correlation of serum parathyroid hormones among patients with dementia of vascular type, hemodialysis, and bone-joint disorders

PTH levels were analysed in sera of patients receiving maintenance hemodialysis, with the vascular type of dementia and orthopedic patients with bone-joint disorders, using PTH assay kits. There were significant interrelationship among all kinds of PTH levels in the hemodialysis patients, but not in patients with the vascular type of dementia and the bone-joint disorders. Renal functions might be responsible for fragmentation of PTH in blood stream. These results suggested that the measurement of PTH levels is needed to examine various kinds of amino-sequence of PTH levels in keeping normal function of kidney.     

The measurement of parathyroid hormone in sera of hemodialysis patients with renal insufficiency by employing the various kinds of parathyroid hormone kits

This study focussed on elucidating difference of blood PTH levels, by employing the various kinds of PTH kits. We carried out the measurements of PTH levels in sera of the hemodialysis patients with renal insufficiency presumably inactivated PTH degradative regulation in kidney. Our results showed the remarkable significant relationships among blood PTH levels of carboxyl and mid-region PTH and intact PTH in hemodialysis patients and was deduced that the difference of PTH levels by using various kinds of PTH kits was responsible of PTH cleavage effect in the kidney.     

Accumulation velocity of 99mTc-HMDP in hip joint diseases

The accumulation rate and velocity of 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) in hip joints were determined within four minutes after a bolus of injection of 99mTc-HMDP in the patients with hip joint disorders. There exist a significant relationship between accumulation velocity of 99mTc-HMDP in the affected joint and serum osteocalcin in the patients with eight cases of degenerative osteoarthropathy and six cases of femoral necrosis. This result indicates that the accumulation velocity of 99mTc-HMDP in the affected joint is likely to become a marker of bone turnover in hip joint disorder.     

再障患者锗元素检测和粒单祖细胞培养的临床意义探讨

采用原子吸收光谱技术测定再障患者４３例头发，血清和骨髓组织的锗元素含量，并与急性白血病２０例，缺铁性贫血１０例和正常人４４例作对照比较，再障，急性白血病和缺铁性贫血组头发，血清锗含量均低低于正常人，Ｐ〈０．０５；再障骨髓锗含量同时也低于正常人，Ｐ〈０．０５；再障骨髓锗含量同时也低于正常人，Ｐ〈０．０５；原发生再障发锗含量低于继发性再障，Ｐ〈０．０５。再障骨髓ＧＭ－ＣＦＵ的数量则显著低于正常人，Ｐ〉     

A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption—Alcoholic Cardiomyopathy

Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson’s trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM.     

Serum metabolomics using ultra-high performance liquid chromatography–Q-Exactive tandem mass spectrometry reveals the mechanism of action of exercise training on chronic obstructive pulmonary disease rats

Exercise training is the cornerstone component of pulmonary rehabilitation, which results in symptom-reducing, psychosocial, and health economic benefits for chronic obstructive pulmonary disease (COPD) patients. However, the potential mechanisms of its action are poorly understood. This study conducted serum metabolomics using ultra-high performance liquid chromatography–Q-Exactive tandem mass spectrometry to determine the metabolic changes in COPD rats, and the effects of exercise training on improvement in COPD were further investigated. Twelve differential metabolites—which are primarily related to tryptophan metabolism, sphingolipid metabolism, glycerophospholipid metabolism, riboflavin metabolism, pantothenate and CoA biosynthesis, and lysine degradation—were identified in relation to COPD. After the intervention of exercise training, the levels of most metabolites were restored, and the changes in five metabolites were statistically significant, which suggested that exercise training provided effective protection against COPD and might play its role by rebalancing disordered metabolism pathways. This work enhanced our comprehension of the protective mechanism of exercise training on COPD.     

Analysis of Serum Metabolomics in Rats with Osteoarthritis by Mass Spectrometry

Osteoarthritis is a common multifactorial chronic disease that occurs in articular cartilage, subchondral bone, and periarticular tissue. The pathogenesis of OA is still unclear. To investigate the differences in serum metabolites between OA and the control group, liquid chromatography/mass spectrometry (LC/MS)-based metabolomics was used. To reveal the pathogenesis of OA, 12 SD male rats were randomly divided into control and OA groups using collagenase to induce OA for modeling, and serum was collected 7 days after modeling for testing. The OA group was distinguished from the control group by principal component analysis and orthogonal partial least squares-discriminant analysis, and six biomarkers were finally identified. These biomarkers were metabolized through tryptophan metabolism, glutamate metabolism, nitrogen metabolism, spermidine metabolism, and fatty acid metabolism pathways. The study identified metabolites that may be altered in OA, suggesting a role in OA through relevant metabolic pathways. Metabolomics, as an important tool for studying disease mechanisms, provides useful information for studying the metabolic mechanisms of OA.     

The measurements of parathyroid hormones in sera of elderly osteoporotic patients with serum high alkaline phosphatase activity

This study was carried out to investigate effects of drugs treated in the elderly osteoporotic patients on measurements of carboxy terminal, mid-region and intact PTH, by using the various kinds of PTH kits. The drugs such as 1 alpha(OH)D3, calcitonin and so on, in the treatment of osteoporotic patients, was brought about no significant inter-relationships among carboxy terminal, mid-region and intact PTH in sera of the elderly osteoporotic patients with serum high alkaline phosphatase activity.     

Anti-Osteoporotic activity of metal complexes of amine carboxyboranes

Metal complexes of trimethylamine carboxyborane successfully suppressed calcium flux from both paired pup calvaria bones and rat UMR-106 osteosarcoma cultured cells over a 48 h period. These agents increased uptake of calcium into the cell cultures and accelerated [³H]proline incorporation into collagen. Copper and iron complexes of the trimethylamine carboxyborane were more potent compared with the cobalt and chromium complexes. The agents effectively reduced Iysosomal enzyme activity and also proteolytic enzyme activities of macrophages. Since macrophages invade the bone surface and assist in the demineralization and digestion of collagen, those agents may be potentially useful to retard diseases involving bone reconstruction. Influx of white blood cells and macrophages to sites of degradation most probably would be inhibited by the agents, based on sponge test observations in mice. Osteoporosis induced by ovariectomy was minimized by injections of tetrakis[u-(trimethylamine-boranecarboxylato)-bis(trimethylamine-carboxyborane)dicopper(II)] into rats at 3.5 mg kg^?1 day^?1 for 14 days. Bone volume, density, weight and calcium content returned to normal baseline control values. In addition, the copper complex returned serum calcium, serum parathyroid hormone (PTH) and vitamin D₃ values to normal levels. One possible mode of action of these derivatives is the regulation of the production and release of chemical mediators initiating bone loss, e.g. tumor necrosis factor, TNF α and interleukins 11 or 11-2.