Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to assess a possible role of the natural glutathione defense system in the pathogenesis of rheumatoid arthritis (RA), serum reduced glutathione levels (GSH), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and alkaline phosphatase (ALP) activities, lipid peroxidation (MDA content) and indexes of inflammation were evaluated in 58 rheumatic patients. Rheumatoid athritis was associated with significant depletion (ca. 50%) in GSH levels compared with normal control subjects. Serum levels of the detoxifying enzymes GSR and GSH-Px decreased by ca. 50% and 45%, respectively, whereas a threefold increase in the activity of GST was observed. A 1.2-fold increase in ALP was observed in patients with RA. These effects were accompanied by a 3.1-fold increase in serum MDA content. The MDA content was higher in RA patients who were seropositive for rheumatoid factor as well as positive for C-reactive proteins. The erythrocyte sedimentation rate for all patients with RA was approximately 13.8-fold higher than for the control group, and was higher among RA patients who were positive for C-reactive proteins and exhibited seropositivity for rheumatoid factor. Patients with RA receiving gold therapy exhibited significantly lower MDA levels whereas all other factors that were measured were not effected. The results support a hypothesis that defense mechanisms against reactive oxygen species are impaired in RA.
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PMID:The glutathione defense system in the pathogenesis of rheumatoid arthritis. 1118 Feb 82

This article describes the prefabrication of a vascularized bone graft composed of autologous particulate cancellous bone and marrow (PCBM), a vessel bundle, and a biodegradable membrane. The PCBM was placed around the saphenous vessel bundle of rats and rolled with a biodegradable membrane of L-lactide-epsilon-caprolactone copolymer to prepare the prefabricated vascularized bone graft (group A). As controls, combinations of PCBM and membrane (group B), vessel bundle and membrane (group C), and PCBM and vessel bundle (group D) were prepared. A radiographic study revealed radio-opacity in the implantation site of group A 1 week later, in contrast to the other groups. Newly formed bone in the membrane roll was histologically confirmed, and neomicrovasculature circulating from the vessel bundle through the newly formed bone tissue was observed. The increase in alkaline phosphatase activity and osteocalcin content was significant for the group A preparation compared with the other groups. We concluded that the combination of autologous PCBM, a vessel bundle, and a biodegradable membrane was promising in the prefabrication of vascularized bone with good blood circulation.
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PMID:Prefabrication of vascularized bone graft using guided bone regeneration. 1536 55

A 1-year prospective, open, randomized, controlled trial was conducted as a pilot study to examine the effect of intermittent administration of 200 IU intranasal salmon calcitonin and 1alpha(OH) vitamin D3 [1alpha(OH)D3] on bone mineral density (BMD) of the lumbar spine and hip as well as on the markers of bone metabolism in women with postmenopausal osteoporosis. A total of 102 randomly recruited women received either 200 IU intranasal salmon calcitonin (Miacalcic nasal 200, Novartis, Basel, Switzerland) daily, 1 month on-1 month off, 0.25 mug 1alpha(OH)D3, and 500 mg elemental calcium continuously (n=57 women) or only 0.25 mug 1alpha(OH)D3 and 500 mg calcium (n=45 women) for a period of 1 year. BMD of the lumbar spine and hip plus biochemical markers reflecting calcium (Ca) metabolism and bone turnover [serum Ca, serum phosphorus, intact parathormone (iPTH), total and bone-specific alkaline phosphatase, osteocalcin levels, 24-h urinary Ca, morning fasting urinary Ca/creatinine, and Pyrilinks-D/creatinine ratio] were measured at the beginning of the study before treatment and after 6 and 12 months of treatment. Baseline characteristics of participants, including age, body mass index, lumbar and hip BMD, and biochemical markers were similar between the two groups. A total of 91 patients completed the study (50 in the salmon calcitonin nasal spray group and 41 in the other group). Lumbar BMD increased significantly in the salmon calcitonin group from baseline (3.0%, p=0.005) and in comparison to the non-calcitonin-treated group (p=0.009). The salmon calcitonin group also had a significant increase in femoral neck BMD compared with baseline values (3.1%, p=0.0005) and in comparison to the non-calcitonin-treated group (p=0.0005) in Ward's triangle BMD (2.9% from baseline values, p=0.009) and in comparison to the non-calcitonin-treated group (p=0.005) in trochanteric BMD (3.4% from baseline values, p=0.007) and in comparison to the non-calcitonin-treated group (P=0.01). Urinary Ca/creatinine and Pyrilinks-D/creatinine levels were significantly decreased from baseline in the salmon calcitonin-treated group (-6.1 and -6.3%, respectively, p=0.001). Bone-specific alkaline phosphatase levels were also significantly decreased from baseline in the salmon calcitonin-treated group (-3.6%, p=0.003). In the same group, a significant decrease in iPTH serum levels compared to baseline values (-2.5%, p=0.005) and in comparison to the non-calcitonin-treated group (p=0.005) was noted. In conclusion, in this pilot study, 1-year intermittent treatment with 200 IU intranasal salmon calcitonin and low doses of 1alpha(OH)D3 produced a significant effect on bone turnover and BMD in postmenopausal women with osteoporosis.
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PMID:Effect of intermittent administration of 200 IU intranasal salmon calcitonin and low doses of 1alpha(OH) vitamin D3 on bone mineral density of the lumbar spine and hip region and biochemical bone markers in women with postmenopausal osteoporosis: a pilot study. 1564 69

The ability to generate new bone for reconstructive surgery use is a major clinical need. Tissue engineering with osteoprogenitor cells isolated from the patient's periosteum and seeded into bioresorbable scaffolds offers a promising approach to the generation of skeletal tissue. To our knowledge, there is no description about the expression of Ets2 in tissue engineered "bone neotissue." The aim of our study was to manufacture cell-seeded three-dimensional bone constructs with human periosteal cells on poly (lactic-co-glycolic acid) polymer fleeces to describe the expression pattern of Ets2 and its target genes osteocalcin and osteopontin; expression analysis of type I collagen, core-binding factor-1, alkaline phosphatase, and osteonectin; the ability of matrix mineralization and ALP enzymatic activity showed the osteogenic character of the constructs. A significant correlation between the expression of Ets2 and osteopontin mRNA (r = -0.70; p < 0.05) could be shown. A 1.35-fold increase of Ets2 expression from days 1 to 9 was detected, followed by a slight decrease from days 11 to 15. Until the end of the culture period, the expression of Ets2 reached a comparable high level as detected on day 9. In contrast, the expression level of osteopontin mRNA reached a maximum at day 7, followed by a progressive 3.04-fold decrease until day 21. This study shows for the first time that Ets2 gene and its transcriptional target genes are expressed in tissue-engineered bone constructs. These findings have the potential to provide much-needed information about the role and function of Ets2 in human osteogenesis processes and creation of "bone neotissue."
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PMID:Expression pattern of the chromosome 21 transcription factor Ets2 in cell-seeded three-dimensional bone constructs. 1590 Jun 11

We conducted the first nationwide survey to clarify the clinical features, treatment methods, and prognoses for polycythemia vera (PV) and essential thrombocythemia (ET). A 1-page questionnaire was mailed to members of the Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG). Surveys on 647 patients (PV, 266 patients; ET, 381 patients) were returned and analyzed. Thrombotic events at diagnosis and during follow-up occurred at rates of 15.4% and 8.5%, respectively, in PV cases and 17.6% and 8.7% in ET cases. Splenomegaly was observed in only 28.8% of PV patients and 10.8% of ET patients. The leukocyte alkaline phosphatase score was elevated in only 46.2% of PV patients. The incidences of abnormal karyotypes were less than 10% in both PV and ET cases. The rates of transformation to myelofibrosis were 2.6% in both PV and ET cases, and acute leukemia was noted in 1.1% of PV patients and 2.9% of ET patients. Prognostic factors were thrombotic history for PV and thrombotic history and age (>or=60 years) for ET. The present study clearly demonstrated clinical differences between Japanese and Western patients for PV and ET. Concerning the treatment of PV and ET, the study revealed considerable variation among Japanese hematologists. These results suggest the necessity of developing treatment guidelines according to risk stratification that are suitable for Japanese PV and ET patients.
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PMID:Clinical features of polycythemia vera and essential thrombocythemia in Japan: retrospective analysis of a nationwide survey by the Japanese Elderly Leukemia and Lymphoma Study Group. 1678 77

Information on the effect of garlic on the liver and optimal dose of garlic to avoid liver damage is not known. This study was planned to determine the safe dose of garlic. Male wistar rats (110-170g) were fed fresh garlic homogenate (FSH) orally in three different doses (1.0, 2.5 and 5.0 g/kg body weight/day) daily for 28 days. Liver histology, serum transaminases, bilirubin and alkaline phosphatase were estimated at 0, 14, 21 and 28 days in control and experimental animals. 1.0, 2.5 and 5.0 g/kg body weight/day of garlic showed significant (P<0.001) deterioration in liver function tests (LFT's) after 21, 14 and 7 days respectively. A 1.0 g/kg body weight/day dose of garlic was associated with marked histological damage in liver after 21 days. Therefore, three lower doses of garlic (0.1, 0.25 and 0.5 g/kg body weight/day) were given orally to another group of similar rats to determine the safe dose of garlic. LFT's were serially measured and animals were sacrificed on the 29th day of experiment. All three lower doses showed significant deterioration in the LFT's values of animals after 28 days of feeding the freshly prepared garlic homogenate. Both doses of garlic i.e. 0.1 and 0.25 g/kg body weight/day were associated with normal histology of liver, but 0.5 g/kg body weight/day dose of garlic showed morphological changes in the liver of one animal. Therefore, the present study suggests that garlic with high dose has the potential ability to induce liver damage and low doses (0.1 or 0.25 g / kg body weight/day) are safe doses of garlic.
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PMID:Garlic hepatotoxicity: safe dose of garlic. 1691 57

Shear stress is an important biomechanical parameter in regulating human mesenchymal stem cell (hMSC) construct development. In this study, the biomechanical characteristics of hMSCs within highly porous 3-D poly (ethylene terephthalate) (PET) matrices in a perfusion bioreactor system were analyzed for two flow rates of 0.1 and 1.5 mL/min, respectively over a 20-day culture period. A 1.4 times higher proliferation rate, higher CFU-F formation, and more fibronectin and HSP-47 secretion at day 20 were observed at the flow rate of 0.1 mL/min compared to those at the flow rate of 1.5 mL/min. The higher flow rate of 1.5 mL/min upregulated osteogenic differentiation potential at day 20 as measured by the expression of alkaline phosphatase activity and calcium deposition in the matrix after 14 days osteogenic induction, consistent with those reported in literatures. Mathematical modeling indicated that shear stress existed in the range of 1 x 10(-5) to 1 x 10(-4) Pa in the constructs up to a depth of 70 microm due to flow penetration in the porous constructs. Analysis of oxygen transport in the constructs for the two flow rates yielded oxygen levels significantly higher than those at which cell growth and metabolism are affected (Jiang et al., 1996). This indicates that differences in convective transport have no significant influence on cell growth and metabolism for the range of flow rates studied. These results demonstrate that shear stress is an important microenvironment parameter that regulates hMSC construct development at a range significantly lower than those reported previously in the perfusion system.
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PMID:Effects of shear stress on 3-D human mesenchymal stem cell construct development in a perfusion bioreactor system: Experiments and hydrodynamic modeling. 1694 69

A 1-year cycle of observations was performed in four Sicilian transitional water systems (Oliveri-Tindari, Cape Peloro, Vendicari and Marsala) to characterise their ecological status. A panel of variables among which trophic and microbial (enzyme activities, abundance of hetetrophic bacteria and of bacterial pollution indicators) parameters, were selected. Particulate organic carbon (POC) and nitrogen (PON) and chlorophyll-a (Chl-a) contents defined the trophic state, while microbial hydrolysis rates and abundance gave insights on microbial community efficiency in organic matter transformation and on allochthonous inputs. To classify the trophic state of examined waters, the synthetic trophic state index (TRIX) was calculated. Microbial hydrolysis rates correlated positively with POC and Chl-a, which increased along the eutrophication gradient. The significant relationships among TRIX, trophic and microbial parameters suggested the use of leucine aminopeptidase, alkaline phosphatase and POC as suitable parameters to implement the Water Framework Directive when assessing the ecological status of transitional water systems.
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PMID:Assessment of the ecological status of transitional waters in Sicily (Italy): first characterisation and classification according to a multiparametric approach. 2065 71

The selective cathepsin K inhibitor odanacatib (ODN) progressively increased bone mineral density (BMD) and decreased bone-resorption markers during 2 years of treatment in postmenopausal women with low BMD. A 1-year extension study further assessed ODN efficacy and safety and the effects of discontinuing therapy. In the base study, postmenopausal women with BMD T-scores between -2.0 and -3.5 at the lumbar spine or femur received placebo or ODN 3, 10, 25, or 50 mg weekly. After 2 years, patients (n = 189) were rerandomized to ODN 50 mg weekly or placebo for an additional year. Endpoints included BMD at the lumbar spine (primary), total hip, and hip subregions; levels of bone turnover markers; and safety assessments. Continued treatment with 50 mg of ODN for 3 years produced significant increases from baseline and from year 2 in BMD at the spine (7.9% and 2.3%) and total hip (5.8% and 2.4%). Urine cross-linked N-telopeptide of type I collagen (NTx) remained suppressed at year 3 (-50.5%), but bone-specific alkaline phosphatase (BSAP) was relatively unchanged from baseline. Treatment discontinuation resulted in bone loss at all sites, but BMD remained at or above baseline. After ODN discontinuation at month 24, bone turnover markers increased transiently above baseline, but this increase largely resolved by month 36. There were similar overall adverse-event rates in both treatment groups. It is concluded that 3 years of ODN treatment resulted in progressive increases in BMD and was generally well tolerated. Bone-resorption markers remained suppressed, whereas bone-formation markers returned to near baseline. ODN effects were reversible: bone resorption increased transiently and BMD decreased following treatment discontinuation.
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PMID:Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. 2125 31

Elevated serum alkaline phosphatase (ALP) is a screening marker for the diagnosis of vitamin D deficiency, which may fail to be diagnosed if serum ALP is not elevated. Here, we describe a case of vitamin D deficiency without elevation of serum ALP. A 1-year-old Japanese girl was referred to our hospital for the evaluation of genu varum. Her serum intact PTH level was elevated, while her serum ALP level was normal. Furthermore, her serum 25-hydroxyvitamin D level was reduced, and her urine phosphoethanolamine (PEA) level was mildly elevated. ALPL gene analysis revealed she was a heterozygous carrier of hypophosphatasia (c.1559delT). Serum intact PTH and urine PEA evaluations were helpful for diagnosing vitamin D deficiency and hypophosphatasia carrier status, respectively. Therefore, the possibility of vitamin D deficiency without elevation of serum ALP should be considered.
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PMID:A Case of Vitamin D Deficiency without Elevation of Serum Alkaline Phosphatase in a Carrier of Hypophosphatasia. 2417 Sep 64


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