JOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 3 2006
S. FADILO
ABSTRACT A detailed kinetic study on the thermal inactivation of alkaline phosphatase (ALP) added into buffer and pasteurized milk and for ALP naturally present in raw cow's milk has been performed. Kinetic parameters (rate constant, k; decimal reduction time, D; activation energy, Ea; and z value) were evaluated based on the first-order rate model at 50,80C. The temperature sensitivity of the kinetic parameters was evaluated considering the Arrhenius-type Ea model. All kinetic behaviors were well described by the first-order model (r2 > 0.91). The D values increased with increasing temperature. Higher temperatures resulted in higher rates of enzyme inactivation as indicated by lower D values and higher k values. There are significant differences (P < 0.01) among the D values for ALP in buffer and milk at treated temperatures. The rate of enzyme inactivation was much more rapid in buffer than in pasteurized milk. The evaluated Ea values for ALP added into the buffer and pasteurized milk, and for ALP naturally present in raw milk were 97.2, 149.9 and 207.8 kJ/mol, respectively. The inactivation kinetics of ALP during heat treatment was found to be dependent on the composition of the medium, and the time and temperature of the heat treatment. [source]

Platform for Highly Sensitive Alkaline Phosphatase-Based Immunosensors Using 1-Naphthyl Phosphate and an Avidin-Modified Indium Tin Oxide Electrode

ELECTROANALYSIS, Issue 19 2009
Abdul Aziz
Abstract We report a versatile platform for highly sensitive alkaline phosphatase (ALP)-based electrochemical biosensors that uses an avidin-modified indium tin oxide (ITO) electrode as a sensing electrode and 1-naphthyl phosphate (NPP) as an ALP substrate. Almost no electrocatalytic activity of NPP and good electrocatalytic activity of 1-naphthol (ALP product) on the ITO electrodes allow a high signal-to-background ratio. The effective surface covering of avidin on the ITO electrodes allows very low levels of nonspecific binding of proteins to the sensing electrodes. The platform technology is used to detect mouse IgG with a detection limit of 1.0,pg/mL. [source]

Purification and Characterization of Acid Phosphatase from the Egg of the Lady Beetle, Harmonia axyridis (Coccinellidae: Coleoptera)

ENTOMOLOGICAL RESEARCH, Issue 1 2004
Jun Hyuk LEE
ABSTRACT Acid phosphatase (AP) in the egg of the lady beetle, Harmonia axyridis, was purified and characterized. Ammonium sulfate precipitation, CM column and isoelectrofocusing (IEF) were applied to purify an estimated molecular weight of 66 kDa AP. The purity was checked by SDS PAGE, native PAGE and Western blot. AP was detected in the hemolymph of the female and the egg, but not in the male on the blotting. Km of AP for a substrate, p -nitrophenyl phosphate (p -NPP), was 1.64 x 10 -4 M. AP had the optimum enzymatic activity at pH 3.5. In inhibition tests performed with various chemicals, ammonium molybdate suppressed 99% of the enzyme activity of AP even at the concentration of 5 x 10 -4 mM. AP was stable up to 50°C. [source]

Transgenic mice expressing a dual, CRE-inducible reporter for the analysis of axon guidance and synaptogenesis,

GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 6 2007
Aurora Badaloni
Abstract Improved and modular tools are needed for the neuroanatomical dissection of CNS axonal tracts, and to study the cell-intrinsic and cell-extrinsic cues that govern their assembly and plasticity. Here we describe a general purpose transgenic tracer that can be used to visualize axonal tracts and synaptic terminals in any region of the embryonic neural tube or postnatal CNS, on any wild type or mutant genetic background. The construct permits CRE-inducible expression of a dicistronic axonal marker encoding two surface reporter proteins: a farnesylated GFP and the human Placental Alkaline Phosphatase (PLAP). Both proteins localize alongside the neuronal surface, permitting the concomitant detection of cell body, neurites, and presynaptic and postsynaptic sites in the same neuron. This provides a CRE-inducible dual system for imaging neural circuits in vivo, and to study their assembly and remodeling in cultured neurons, neural stem cells, and tissue explants derived from the reporter line. Unlike existing lines, this reporter does not encode a ubiquitously expressed, floxable LacZ gene, permitting the simultaneous analysis of beta galactosidase activity in mutant lines. genesis 45:405,412, 2007. © 2007 Wiley-Liss, Inc. [source]

Characterization of Phosphatase and Tensin Homolog expression in the mosquito Aedes aegypti: Six splice variants with developmental and tissue specificity

INSECT MOLECULAR BIOLOGY, Issue 3 2007
Michael A. Riehle
Abstract Phosphatase and tensin homologue (PTEN), an inhibitor of insulin signalling, was characterized in Aedes aegypti. Surprisingly, six splice variants were identified: three with alternative terminal exons (AaegPTEN2 : 3 : 6) and three formed by intron retention (AaegPTEN1 : 4 : 5). All variants encoded active phosphatase domains. Variants with alternative terminal exons also encoded C2 and COOH-domains, and AaegPTEN6 encoded a PDZ binding motif. These three variants also had unique expression patterns. AaegPTEN2 was expressed primarily in the ovary. AaegPTEN3 was predominant in heads and midguts, and throughout development, except early embryogenesis. AaegPTEN6 was expressed in fat body, ovaries, and throughout development. Intron retention variants were weakly expressed in most samples. These expression patterns suggest that AaegPTEN variants play unique roles in regulating insulin's pleiotropic effects. [source]

The course of some bone remodelling plasma metabolites in healthy horses and in horses offered a calcium-deficient diet

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2003
V. De Behr
Summary An inquiry was carried out to assess the concentrations of plasma metabolites related to bone remodelling in 21 saddle horses of Warmblood breed aged 4,26 years, five draught horses of Ardennes breed aged 4,10 years, and 10 Ardennes foals aged 9,11 months. They were fed according to normal feeding practice in Belgium. The changes in some bone remodelling plasma metabolite concentrations were studied when an unbalanced diet was offered and later corrected for four Warmblood horses. Bone formation was evaluated by bone alkaline phosphatase (BALP), total alkaline phosphatase (TALP) and osteocalcin (bone gla-protein, OC). Bone resorption was assessed by hydroxyproline (HYP). Total calcium, ionized calcium, phosphorus (P) and 25-hydroxyvitamin D3 [25-(OH)D] concentrations were more or less constant. The comparison of four bone remodelling factors between the Ardennes and Warmblood horses showed higher concentrations in the Ardennes breed. Bone marker concentrations decreased according to age. The correction of the unbalanced Ca : P diet induced inconsistent effects at plasma level. The interpretation of the different bone parameters appeared to be difficult if not associated with other parameters such as a complete anamnesis and clinical examination of the animal in addition to dietary evaluation. Zusammenfassung Verlauf verschiedener Knochenmarker bei gesunden Pferden und bei Pferden, welche mit einer in Bezug auf Kalzium unausgewogenen Ration gefüttert wurden Eine Studie zur Erfassung der Konzentrationen von Knochenmarkern wurde bei 21 Warmblütern im Alter von 4 bis 26 Jahren, fünf Ardenner Kaltblütern im Alter von 4 bis 10 Jahren und 10 Ardenner Kaltblutfohlen im Alter von 9 bis 11 Monaten durchgeführt. Die Pferde wurden gemäss der normalen Fütterungpraxis in Belgien gefüttert. Der Verlauf der Knochenmarkerkonzentrationen wurde auch bei vier Pferden gemessen, die zunächst mit einer unausgewogenen Ration in Bezug auf Kalzium und dann mit einer korrigierenden Ration gefüttert wurden. Der Knochenaufbau wurde anhand der Aktivität der knochenspezifischen alkalischen Phosphatase (BALP), der totalen alkalischen Phosphatasen (TALP) und anhand des Osteocalcin (bone gla-proteine, OC) gemessen. Der Knochenabbau wurde anhand des Hydroxyprolins (HYP) gemessen. Die Konzentrationen des totalen Kalziums, ionisierten Kalziums, Phosphors (P), und 25-Hydroxyvitamin D3 [25(OH)D] waren unverändert. Beim Vergleich der vier gemessenen Knochenmakerkonzentrationen bei den Ardenner Kaltblütern mit den Warmblutpferden konnte gezeigt werden, dass die Kaltblüter deutlich höhere Konzentrationen hatten als die Warmblüter. Die Konzentrationen der Marker nahmen mit steigendem Alter der Pferde ab. Die Korrektur der unausgewogenen Ca:P Ration ergab nicht eindeutige Veränderungen der Plasmakonzentrationen der verschiedenen Marker. Die Interpretation der verschiedenen Knochenmarker erscheint schwierig, wenn nicht andere Parameter, wie eine komplette Anamnese und eine klinische Untersuchung, sowie eine Auswertung der Ration hinzugezogen werden. [source]

Osteoblastic Tartrate-Resistant Acid Phosphatase: Its Potential Role in the Molecular Mechanism of Osteogenic Action of Fluoride,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2003
K-H William Lau
Abstract Although type 5 TRACP is recognized as a histochemical and biochemical marker of osteoclasts, there is evidence that bone forming cells, osteoblasts, and osteocytes also express a type 5 TRACP. Accordingly, an osteoblastic type 5 TRACP has been purified from human osteoblasts and from bovine cortical bone matrices. Comparison of biochemical properties of osteoblastic type 5 TRACP with those of osteoclastic type 5 TRACP suggests that osteoblastic type 5 TRACP is a different isoenzyme from osteoclastic type 5 TRACP. Two properties of osteoblastic type 5 TRACP may be relevant to its physiological functions: (1) it acts as a protein-tyrosine phosphatase (protein tyrosine phosphorylation) under physiologically relevant conditions, and (2) it is sensitive to inhibition by clinically relevant concentrations of fluoride. Because fluoride is a stimulator of osteoblastic proliferation and differentiation and a potent osteogenic agent and because protein tyrosine phosphorylation plays an important regulatory role in cell proliferation and differentiation, these unique properties and other evidence summarized in this review led to the proposal that the osteogenic action of fluoride is mediated, at least in part, by the fluoride-mediated inhibition of osteoblastic type 5 TRACP/protein tyrosine phosphorylation, which leads to a stimulation of osteoblast proliferation and differentiation, and subsequently, an increase in bone formation. [source]

Combined Pressure,temperature Inactivation of Alkaline Phosphatase in Bovine Milk: A Kinetic Study

JOURNAL OF FOOD SCIENCE, Issue 1 2000
L. Ludikhuyze
ABSTRACT: A detailed kinetic study on pressure-temperature inactivation of alkaline phosphatase has been performed in the pressure range 0.1 to 725 MPa at temperatures between 25 and 63 °C. Inactivation could be accurately described by a first order kinetic model, allowing D-values to be calculated. According to the thermal death time terminology, zr - and zp -values were calculated, expressing temperature and pressure dependence respectively. However, at high temperature, pressure dependence could not be calculated unambiguously. D-values firstly increased with increasing pressure up to 300 MPa and then decreased with further pressure increase, showing thermal inactivation to be counteracted by low pressure. Finally, a global model describing the D-value as a function of pressure and temperature has been formulated. [source]

Responses of phosphatases and arylsulfatase in soils to liming and tillage systems

JOURNAL OF PLANT NUTRITION AND SOIL SCIENCE, Issue 3 2003
Mine Ekenler
Abstract This study was carried out to investigate the long-term influence of lime application and tillage systems (no-till, ridge-till, and chisel plow) on the activities of phosphatases and arylsulfatase in soils at four research sites in Iowa, USA. The activities of the following enzymes were studied: acid and alkaline phosphatases, phosphodiesterase, and arylsulfatase at their optimal pH values. With the exception of acid phosphatase, which was significantly (P < 0.001) but negatively correlated with soil pH (r ranged from ,0.65** to ,0.98***), the activities of other enzymes were significantly (P < 0.001) and positively correlated with soil pH, with r values ranging from 0.65** to 0.99*** for alkaline phosphatase, from 0.79*** to 0.97*** for phosphodiesterase, and from 0.66*** to 0.97*** for arylsulfatase. The , activity/, pH values were calculated to determine the sensitivity of each enzyme to changes in soil pH. Acid phosphatase was the most sensitive and arylsulfatase the least sensitive to changes in soil pH. Activities of the enzymes were greater in the 0 , 5,cm depth samples than those in 0 , 15,cm samples under no-till treatment. With the exception of acid phosphatase, enzyme activities were mostly significantly (P < 0.001) and positively correlated with microbial biomass C (Cmic), with r values ranging from 0.28 (not significant) to 0.83*** and with microbial biomass N (Nmic), with r values ranging from 0.31 (not significant) to 0.94***. Liming and tillage systems significantly affected the activities of some enzymes but not others, as was evident from the specific activity values (g of p -nitrophenol released kg,1 Corg h,1). Reaktionen von Phosphatasen und Arylsulfatasen in Böden auf Kalkung und differenzierte Bodenbearbeitung In vier langjährigen Feldversuchen in Iowa, USA, wurde der Einfluss von Kalkung und differenzierter Bodenbearbeitung (Direktsaatverfahren, reduzierte Bearbeitung und Grubberverfahren) auf die Aktivitäten von Phosphatasen und Arylsulfatase in Böden untersucht. Die Aktivitäten von saurer und alkalischer Phosphatase, Phosphodiesterase und Arylsulfatase wurden unter dem optimalen pH-Wert für das jeweilige Enzym bestimmt. Mit Ausnahme der sauren Phosphataseaktivität, welche signifikant negativ (P < 0.001) mit dem pH-Wert des Bodens korreliert war (r = ,0.65** bis ,0.98***), waren die Aktivitäten der anderen Enzyme signifikant (P < 0.001) positiv mit dem Boden-pH korreliert. Dabei variierten die Korrelationskoeffizienten zwischen r = 0.65** und 0.99*** für die alkalische Phosphatase, zwischen r = 0.79*** und 0.97*** für die Phosphodiesterase und zwischen r = 0.66*** und 0.97*** für die Arylsulfatase. Die Verhältnisse von , Aktivität / , pH-Wert wurden berechnet, um die Empfindlichkeit der untersuchten Enzyme gegenüber pH-Wertveränderungen im Boden festzustellen. Dabei erwies sich die saure Phosphatase als das emfindlichste und die Arylsulfatase als das am wenigsten emfindlichste Enzym. In der Direktsaatvariante waren die Enzymaktivitäten in 0 , 5,cm Bodentiefe höher als in 0 , 15,cm Tiefe. Mit Ausnahme der sauren Phosphatase waren die Enzymaktivitäten signifikant positiv mit dem mikrobiell gebundenen C (Cmik) und N (Nmik) korreliert. Die Korrelationskoeffizienten variierten dabei zwischen r = 0.28 (nicht signifikant) und 0.83*** für Cmik und zwischen r = 0.31 (nicht signifikant) und 0.94*** für Nmik. Die spezifischen Enzymaktivitäten (g p -Nitrophenol kg,1 Corg h,1) zeigten, dass die Aktivitäten von einigen Enzymen signifikant von Kalkung und Bodenbearbeitungssystem abhängig waren. [source]

Effect of cropping systems on phosphatases in soils

JOURNAL OF PLANT NUTRITION AND SOIL SCIENCE, Issue 1 2003
Daniel E. Dodor
Abstract Phosphatases are widely distributed in nature and play a major role in phosphorus nutrition of plants. The effects of crop rotations and nitrogen fertilization on the activities of phosphatases (acid phosphatase, alkaline phosphatase, and phosphodiesterase) were studied in soils from two long-term cropping systems at the Northeast Research Center (NERC) in Nashua and the Clarion Webster Research Center (CWRC) in Kanawha, Iowa, USA. Surface soils (0,15 cm) were taken in 1996 and 1997 from replicated field plots in corn, soybeans, oats, or meadow (alfalfa) that received 0 or 180 kg N ha,1 before corn. Because of differences in organic C contents among soils of the two sites, the soils from the CWRC sites contained greater enzyme activity values than those from the NERC site. Plots under oats or meadow showed the greatest activity values, whereas those under continuous corn at the CWRC site and soybean at the NERC site showed the least activities. Analysis of variance indicated that the activities of the phosphatases were significantly affected by crop rotation (P < 0.001) in both years at the NERC site but not at the CWRC site. Nitrogen fertilization affected the activity of acid phosphatase in soils from the CWRC site in both years and alkaline phosphatase only in 1997; but it did not affect the activities of the phosphatases in the soils from the NERC site. With the exception of alkaline phosphatase (CWRC) and phosphodiesterase (NERC) in soils sampled in 1997, activities of alkaline phosphatase and phosphodiesterase were significantly correlated with microbial biomass C (C mic) in soils from both sites and years, with r values ranging from 0.366* to 0.599***. Cropping systems and N fertilization affected the specific activities of phosphomonoesterases, especially acid phosphatase, but not of phosphodiesterase. Regression analysis showed that activities of phosphatases were significantly correlated with organic C contents of soils from the NERC site but not from the CWRC site. Einfluss von Managementsystemen auf Phosphatasen in Böden Phosphatasen sind weit verbreitet in der Natur und spielen eine entscheidende Rolle in der Phosphorversorgung von Pflanzen. Die Auswirkungen von Managementsystemen und Stickstoffdüngung auf Phosphataseaktivitäten in Böden (saure und alkalische Phosphatase, Phosphodiesterase) wurden in zwei langjährigen Feldversuchen am Northeast-Research Center (NERC) in Nashua und am Clarion-Webster Research Center (CWRC) in Kanawha, Iowa, USA untersucht. In den Jahren 1996 und 1997 wurden Oberbodenproben (0,15cm) von Parzellen unter Mais, Sojabohne, Hafer und Luzerne entnommen, welche in jeweils drei Wiederholungen angelegt waren. Die Parzellen erhielten zusätzlich Düngergaben von 0 bzw. 180 kg N ha,1 , die vor Mais appliziert wurden. Infolge der unterschiedlichen Gehalte der Böden an organischem Kohlenstoff waren die Enzymaktivitäten auf den CWRC-Flächen höher als auf den NERC-Flächen. Die Parzellen unter Hafer und Luzerne wiesen die höchsten, Parzellen unter Monokulturen von Mais (CWRC) bzw. Soja (NERC) die geringsten Aktivitäten auf. Die Ergebnisse der Varianzanalyse zeigten, dass die Phosphataseaktivitäten auf den NERC-Flächen in beiden Jahren signifikant durch das Managementsystem beeinflusst wurden (P < 0, 001). Die Stickstoffdüngung hatte auf den CWRC-Flächen in beiden Jahren einen signifikanten Einfluss auf die saure Phosphataseaktivität und auf die alkalische Phosphataseaktivität im Jahr 1997. Auf den NERC-Flächen war hingegen kein Düngungseinfluss nachzuweisen. Die alkalische Phosphatase und Phosphodiesterase waren, mit Ausnahme der alkalischen Phosphatase auf den CWRC-Flächen und der Phosphodiesterase auf den NERC-Flächen, signifikant mit dem Gehalt der Böden an mikrobieller Biomasse (C mic) korreliert (r = 0, 366* bis 0, 599***). Die Management- und N-Düngungssysteme beeinflussten die spezifischen Aktivitäten von Phosphomonoesterasen, v.a. von saurer Phosphatase, jedoch nicht die spezifischen Phosphodiesteraseaktivitäten. Regressionsanalysen ergaben einen signifikanten Zusammenhang zwischen den Phosphataseaktivitäten und dem Gehalt der Böden an organischem C für die NERC-Flächen, jedoch nicht für die CWRC-Flächen. [source]

Effects of Nigella orientalis and N. segetalis fixed oils on blood biochemistry in rats

PHYTOTHERAPY RESEARCH, Issue 1 2006
G. Kökdil
Abstract Nigella orientalis and N. segetalis fixed oils were administered orally (1 mL/kg/day) to Wistar Kyoto rats for 4 weeks. The effects of the oils on biochemical parameters were compared with a control group that received distilled water under identical conditions. LDL-cholesterol level was decreased significantly in both oil groups while serum total cholesterol and VLDL-cholesterol were decreased significantly following administration of only N. orientalis fixed oil when compared with the control group. The HDL-cholesterol levels were increased significantly in both oil groups. N. orientalis fixed oil significantly reduced Aspartateaminotransferase (AST), Alkaline Phosphatase (ALP), bilirubin and urea levels in rats. There was an increase in the albumin, uric acid and mean corpuscular volume (MCV) concentrations, while the mean corpuscular hemoglobin concentration (MCHC) and RDW (red cell distribution width) levels decreased significantly. In N. segetalis fixed oil treated rats, the levels of ALP, Blood Urea Nitrogen (BUN), MCHC, RDW were decreased significantly, whereas a significant increase was found in albumin, fibrinogen, Hematocrit (HCT) and MCV levels. The effects of 4 weeks oral intake of N. orientalis and N. segetalis fixed oils on blood malondialdehyde (MDA) and total antioxidant status (TOS) were also investigated in rats. The study showed that the oils had no significant effect on MDA production. N. orientalis and N. segetalis fixed oils caused a significant increase in the total antioxidant status in rats. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cells,

THE PROSTATE, Issue 10 2006
Z. Wu
Abstract BACKGROUND Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is lost as a function of prostate tumor androgen dependence. While the transcriptional activity of the androgen receptor (AR) is inhibited by PTEN in androgen sensitive prostate cancer (CaP), the role of PTEN in androgen disease is unclear. METHODS We developed a system where PTEN can be conditionally re-expressed at physiologic levels into a PTEN null metastatic human CaP cell line, C4-2, and androgen responsiveness examined. RESULTS PTEN induction reduces cell growth and blocks the growth effect of synthetic androgen R1881. The anti-androgen Casodex enhances the growth-inhibitory action of PTEN and this effect is independent of Akt phosphorylation. Combined PTEN induction and Casodex, result in a further decrease in prostate specific antigen promoter activity compared to PTEN but not Casodex alone. CONCLUSIONS PTEN induction confers androgen independent CaP cells enhanced responsiveness to the anti-proliferative effects of anti-androgens and this action may involve non-AR mediated effects. Prostate 66: 1114-1123, 2006. © 2006 Wiley-Liss, Inc. [source]

Identification of Thiazolidinones Spiro-Fused to Indolin-2-ones as Potent and Selective Inhibitors of the Mycobacterium tuberculosis Protein Tyrosine Phosphatase,B,

ANGEWANDTE CHEMIE, Issue 34 2010
Viktor
Das beste aus 40,000: Detaillierte Untersuchungen zur Struktur-Aktivitäts-Beziehung enthüllten Schlüsselstrukturelemente von Indolin-2-on-3-spirothiazolidinonen (siehe Beispiel) und deren für eine starke Inhibierung des pathophysiologisch wichtigen Titelproteins geeignete Konfiguration. [source]

A Secreted Enzyme Reporter System for MRI,

ANGEWANDTE CHEMIE, Issue 23 2010

Mal sehen, was rauskommt: Ein extrazelluläres enzymatisches Genreporter-System für die Kernspintomographie (MRI) reagiert mit deutlichen und reversiblen Kontraständerungen auf die Exprimierung von sezernierter alkalischer Phosphatase (SEAP; siehe Bild), wie mit einem Sensor auf Eisenoxidbasis belegt wurde. Das Kontrastmittel wird nicht vom Enzym verbraucht, muss nicht durch die Zelle aufgenommen werden, und multimodale Detektion ist möglich. [source]

Purification and Concentration of Alkaline Phosphatase by Selective Permeabilization of Escherichia coli Using Reverse Micellar Solutions

BIOTECHNOLOGY PROGRESS, Issue 6 2003
Ritu Bansal-Mutalik
Recovery of alkaline phosphatase (AP) from the periplasm of Escherichia coli using reverse micellar solutions (RMSs) of sodium dioctyl sulfosuccinate (AOT) in aliphatic hydrocarbons has been attempted. A variety of surface-active agents, solvents, and reverse micellar conditions were screened, and an excellent recovery of the enzyme in a concentrated form, with a high purification factor, was obtained in a single-step process. The permeabilization process strongly depended on the water content of the RMS as well as on the amount of water coating the microbial cell surface. The product was almost free from nucleic acids. In addition, because of the low affinity of AOT and the organic solvent for the aqueous phase, contamination by the permeabilizing agents would also be negligible. [source]

Halenaquinone and Xestoquinone Derivatives, Inhibitors of Cdc25B Phosphatase from a Xestospongia sp.

CHEMINFORM, Issue 26 2005
Shugeng Cao
Abstract For Abstract see ChemInform Abstract in Full Text. [source]

Structure-Based Optimization of Benzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B and Low Molecular Weight Protein Tyrosine Phosphatase

CHEMMEDCHEM, Issue 6 2009
Rosanna Maccari Dr.
Abstract We have optimized previously discovered benzoic acids 1, which are active as inhibitors of PTP1B and LMW-PTP, two protein tyrosine phosphatases that have emerged as attractive targets for the development of novel therapeutic agents for the treatment of diabetes, obesity, and cancer. Our efforts led to the identification of new and more potent analogues with appreciable selectivity toward human PTP1B and the IF1 isoform of human LMW-PTP. [source]

A New 4.0-Generation Dendrimer Phosphorescence Labeling Reagent and Its Application to Determination of Trace Alkaline Phosphatase by Affinity Adsorption Solid Substrate-room Temperature Phosphorimetry

CHINESE JOURNAL OF CHEMISTRY, Issue 10 2007
Zhi-Ming LI
Abstract A Triton X-100-4.0G-D (4.0G-D refers to a 4.0-generation dendrimer) was brought forward as a new phosphorescence labeling reagent. Two types of specific affinity adsorption (AA) reactions (direct method and sandwich method) were carried out between the labeling product of Triton X-100-4.0G-D-Wheat germ agglutinin (WGA) and alkaline phosphatase (ALP), the product of AA reaction preserved the good characteristics of room temperature phosphorescence (RTP) of 4.0G-D and ,IP of the product was proportional to the content of ALP. According to the fact stated above, a new method for the determination of trace ALP by affinity adsorption solid substrate-room temperature phosphorimetry (AA-SS-RTP) was established on the basis of WGA labeled with the Triton X-100-4.0G-D. The detection limits were 0.20 ag·spot,1 (corresponding concentration: 5.0×10,16 g·mL,1, namely 5.0×10,18 mol·L,1) for a direct method and 0.14 ag·spot,1 (corresponding concentration: 3.5×10,16 g·mL,1, namely 3.5×10,18 mol·L,1) for a sandwich method, respectively. For their high sensitivity, good repeatability and high accuracy, the direct method and sandwich method have been successfully applied to determine the content of ALP in human serum, and the results were coincided with the clinical detection results of the enzyme-linked immunosorbent assay method by the Zhangzhou Hospital of Traditional Chinese Medicine. Meanwhile, the mechanism for the determination of trace ALP by AA-SS-RTP was discussed. [source]

Tissue response to titanium implantation in the rat maxilla, with special reference to the effects of surface conditions on bone formation

CLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2003
Masaki Shirakura
Abstract: Tissue responses to titanium implantation with two different surface conditions in our established implantation model in rat maxillae were investigated by light and transmission electron microscopy and by histochemistry for tartrate-resistant acid phosphatase (TRAPase) activity. Here we used two types of implants with different surface qualities: titanium implants sandblasted with Al2O3 (SA-group) and implants coated with hydroxyapatite (HA-group). In both groups, bone formation had begun by 5 days postimplantation when the inflammatory reaction had almost disappeared in the prepared bone cavity. In the SA-group, however, the bone formation process in the bone cavity was almost identical to that shown in our previous report using smooth surfaced implants (Futami et al. 2000): new bone formation, which occurred from the pre-existing bone toward the implant, was preceded by active bone resorption in the lateral area with a narrow gap, but not so in the base area with a wide gap. In the HA-group, direct bone formation from the implant toward the pre-existing bone was recognizable in both lateral and base areas. Many TRAPase-reactive cells were found near the implant surface. On the pre-existing bone, new bone formation occurred with bone resorption by typical osteoclasts. Osseointegration around the implants was achieved by postoperative day 28 in both SA- and HA-groups except for the lateral area, where the implant had been installed close to the cavity margin. These findings indicate that ossification around the titanium implants progresses in different patterns, probably dependent on surface properties and quality. Résumé Les réponses tissulaires à l'implantation du titane avec deux conditions de surfaces différentes dans le maxillaire du rat ont étéétudiées par microscopie optique et électronique à transmission et par histochimie pour l'activité de l'acide phosphatase résistant au tartrate (TRAPase). Deux types d'implants avec différentes qualité de surface ont été utilisés : des implants en titane sablés par du AL2O3 (groupe SA) et des implants couverts par de l'hydroxyapatite (groupe HA). Dans les deux groupes la formation osseuse avait démarré cinq jours après l'implantation, lorsque la réaction inflammatoire avait presque disparue de la cavité osseuse préparée. Cependant, dans le groupe SA le processus de formation osseuse de la cavité osseuse était quasi identique à celle montrée dans un rapport précédent utilisant des implants à surface lisse (Futami et al., 2000) : la néoformation osseuse qui démarre de l'os préexistant vers l'implant, était précédée par une résorption osseuse active dans l'aire latérale avec une brèche étroite, mais pas dans l'aire de base avec un espace large. Dans le groupe HA, une formation osseuse directe de l'implant vers l'os préexistant était reconnaissable tant dans les aires latérales qu'au niveau de la base. Beaucoup de cellules réactives au TRAPase ont été trouvées près de la surface de l'implant. Sur l'os préexistant une néoformation osseuse est apparue avec une résorption osseuse par des ostéoclastes typiques. L'ostéoïntégration autour des implants a été achevée au jour 28 après l'opération tant dans le groupe SA que HA excepté pour l'aire latérale où l'implant avait été inséré près du rebord de la cavité. Ces découvertes indiquent que l'ossification autour des implants en titane progresse de manière différente dépendant probablement de la qualité et des propriétés de surface. Zusammenfassung Die Gewebsantwort auf implantiertes Titan in einem Rattenoberkiefer. Spezielles Augenmerk auf die Einflüsse der Oberflächenbeschaffenheit auf die Knochenbildung. An unserem etablierten Implantationsmodell am Rattenoberkiefer wurde die Gewebsantwort nach der Titanimplantation von zwei Prüfkörpern mit verschiedener Oberfläche mit Hilfe der Licht- und Transmissionselektronenmikroskopie, sowie mittels Histochemie zum Aktivitätsnachweis der tartratresitenten sauren Phosphatase (TRAPase) untersucht. Wir benutzten hier zwei Implantattypen mit verschiedenen Oberflächen: Mit Al2O3 sandgestrahlte Titanimplantate (SA-Gruppe) und mit Hydroxylapatit beschichtete Implantate (HA-Gruppe). Bei beiden Gruppen begann die Knochenbildung 5 Tage nach der Implantation, sobald die Entzündungsreaktion im präparierten Knochenbett am verschwinden war. In der SA-Gruppe aber, zeigte sich im präparierten Implantatbett ein beinahe gleicher Knochenbildungsvorgang, wie in unseren früheren Berichten für glatte Implantatoberflächen beschrieben (Futami et al., 2000): Die vom bereits vorhandenen Knochen ausgehende Knochenneubildung gegen das Implantat hin erfolgte erst nach einer aktiven Knochenresorption im lateralen Bereich. Es entstand eine minime Spalte zwischen Knochen und Implantat, währenddem im apicalen Bereich eine breitere Spalte entstand. In der HA-Gruppe konnte man sowohl im lateralen, wie auch im apicalen Bereich eine direkt vom Implantat ausgehende Knochenbildung in Richtung des vorhandenen Knochens feststellen. In der Nähe der Implantatoberfläche fand man viele TRAPase-reaktive Zellen. Beim vorhandenen Knochen erfolgte die Knochenneubildung gleichzeitig mit der Knochenresorption durch typische Osteoklasten. Die Osseointegration rund um die Implantate herum erreichte man, ausser im lateralen Bereich gegen den Rand des Implantatbettes hin, in der SA-und der HA-Gruppe am 28igsten postoperativen Tag. Diese Ergebnisse zeigen, dass die Ossifikation um Titanimplantate in verschiedenen Mustern abläuft, wahrscheindlich in Abhängigkeit von der Oberflächeneigenschaft und -qualität. Resumen Se investigó las respuestas tisulares a la implantación con titanio con dos condiciones diferentes de superficie en nuestro modelo establecido de implantación en el maxilar de la rata por medio de microscopía óptica y electrónica de transmisión y por medio de histoquímica para la actividad de fosfatasa alcalina tartrato resistente (TRAPase). Hemos usado aquí dos tipos de implantes con diferentes calidades de superficies: Implantes de titanio pulverizados con Al2O3 (grupo-SA), e implantes cubiertos con hidroxiapatita (grupo-HA). En ambos grupos la formación de hueso comenzó a los 5 días de la implantación cuando la reacción inflamatoria hubo casi desaparecido en la cavidad ósea preparada. De todos modos, en el grupo SA, el proceso de formación de hueso en la cavidad ósea fue casi idéntico a aquel mostrado en nuestro informe previo usando implantes de superficies lisas (Futami et al., 2000): neoformación de hueso, que tuvo lugar desde el hueso preexistente hacia el implante, siendo precedida por reabsorción ósea activa en el área lateral con un espacio estrecho, pero no así en el área basal con espacio ancho. Se encontraron muchas células TRAPase reactivas cerca de la superficie del implante. En el hueso preexistente, la neoformación ósea tuvo lugar con reabsorción ósea con osteoclastos típicos. La osteointegración alrededor de los implantes se logró al día 28 tras la operación en ambos grupos SA y HA excepto para el área lateral, donde el implante se instaló cerca del margen de la cavidad. Estos hallazgos indican que la osificación alrededor de los implantes de titanio progresa con patrones diferentes, probablemente dependiendo de las propiedades y las calidades de la superficie. [source]

Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome

ACTA PAEDIATRICA, Issue 2 2000
R Lala
McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/ kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome. [source]

The regulation of muscle glycogen: the granule and its proteins

ACTA PHYSIOLOGICA, Issue 4 2010
T. E. Graham
Abstract Despite decades of studying muscle glycogen in many metabolic situations, surprisingly little is known regarding its regulation. Glycogen is a dynamic and vital metabolic fuel that has very limited energetic capacity. Thus its regulation is highly complex and multifaceted. The stores in muscle are not homogeneous and there appear to be various metabolic pools. Each granule is capable of independent regulation and fundamental aspects of the regulation appear to be associated with a complex set of proteins (some are enzymes and others serve scaffolding roles) that associate both with the granule and with each other in a dynamic fashion. The regulation includes altered phosphorylation status and often translocation as well. The understanding of the roles and the regulation of glycogenin, protein phosphatase 1, glycogen targeting proteins, laforin and malin are in their infancy. These various processes appear to be the mechanisms that give the glycogen granule precise, yet dynamic regulation. [source]

Optimization of a flow cytometry-based protocol for detection and phenotypic characterization of multipotent mesenchymal stromal cells from human bone marrow

CYTOMETRY, Issue 6 2006
Elena A. Jones
Abstract Background: To study the biology of rare bone marrow (BM) multipotent mesenchymal stromal cells (MSCs), recognized protocols are needed. Colony-forming unit-fibroblast (CFU-F) assays have historically been used for the enumeration of MSCs. However, the need to isolate and further analyze MSCs requires new strategies based on cell surface markers. The purpose of this work was to verify the phenotype of BM MSCs in vivo and to develop flow cytometry-based methods for their evaluation. Methods: Pre-enrichment with D7-FIB-conjugated microbeads, cell sorting for CD45lowD7-FIB+LNGFR+ cells, and CFU-F assay were used to confirm the phenotype of BM MSCs in vivo. Further phenotypic characterization of MSCs was performed using three-color flow cytometry following pre-enrichment or by direct four-color flow cytometry. The sensitivity of direct flow cytometry/rare event analysis for the accurate enumeration of MSCs was validated using 85 samples from patients with neoplastic BM diseases. Results: In normal BM, a significant correlation was found between the frequencies of CFU-Fs and CD45lowD7-FIB+LNGFR+ cells (n = 19, R = 0.719, P = 0.001). Following cell sorting, ,15% of these cells were clonogenic. The same cells were enriched using LNGFR-based positive selection, CD45/Glycophorin A-based depletion, or plastic adherence. CD45lowD7-FIB+LNGFR+ cells expressed classic makers of cultured MSCs CD73/SH3 and CD105/SH2 and markers of stromal reticular cells CD106/VCAM and alkaline phosphatase. Novel markers were identified including leukemia inhibitory factor receptor and gp130. CD45lowD7-FIB+LNGFR+ cells were increased fourfold in the floating fat fraction of normal BM aspirates. Their frequency was decreased in chronic lymphocytic leukemia (threefold, n = 13, P = 0.049) and chronic myelogenous leukemia (ninefold, n = 11, P = 0.001) compared with that in age-matched controls (n = 26 and n = 31, respectively). Conclusions: This study demonstrates the usefulness of flow cytometry-based methods for the detection, enumeration and further phenotypic analysis of BM MSCs. These findings have broad applications for the future evaluation of BM MSCs in health and disease. © 2006 International Society for Analytical Cytology [source]

Intracellular sodium modulates the state of protein kinase C phosphorylation of rat proximal tubule Na+,K+ -ATPase

ACTA PHYSIOLOGICA, Issue 2 2002
F. R. IBARRA
ABSTRACT The natriuretic hormone dopamine and the antinatriuretic hormone noradrenaline, acting on , -adrenergic receptors, have been shown to bidirectionally modulate the activity of renal tubular Na+,K+ -adenosine triphosphate (ATPase). Here we have examined whether intracellular sodium concentration influences the effects of these bidirectional forces on the state of phosphorylation of Na+,K+ -ATPase. Proximal tubules dissected from rat kidney were incubated with dopamine or the , -adrenergic agonist, oxymetazoline, and transiently permeabilized in a medium where sodium concentration ranged between 5 and 70 mM. The variations of sodium concentration in the medium had a proportional effect on intracellular sodium. Dopamine and protein kinase C (PKC) phosphorylate the catalytic subunit of rat Na+,K+ -ATPase on the Ser23 residue. The level of PKC induced Na+,K+ -ATPase phosphorylation was determined using an antibody that only recognizes Na+,K+ -ATPase, which is not phosphorylated on its PKC site. Under basal conditions Na+,K+ -ATPase was predominantly in its phosphorylated state. When intracellular sodium was increased, Na+,K+ -ATPase was predominantly in its dephosphorylated state. Phosphorylation of Na+,K+ -ATPase by dopamine was most pronounced when intracellular sodium was high, and dephosphorylation by oxymetazoline was most pronounced when intracellular sodium was low. The oxymetazoline effect was mimicked by the calcium ionophore A23187. An inhibitor of the calcium-dependent protein phosphatase, calcineurin, increased the state of Na+,K+ -ATPase phosphorylation. The results imply that phosphorylation of renal Na+,K+ -ATPase activity is modulated by the level of intracellular sodium and that this effect involves PKC and calcium signalling pathways. The findings may have implication for the regulation of salt excretion and sodium homeostasis. [source]

Myosin16b: The COOH-tail region directs localization to the nucleus and overexpression delays S-phase progression

CYTOSKELETON, Issue 1 2007
Richard S. Cameron
Abstract Rat Myo16a and Myo16b comprise the founding members of class XVI myosin and are characterized by an N-terminal ankyrin repeat domain thought to mediate an association with protein phosphatase 1 catalytic subunits 1, and 1,. Myo16b is the principal isoform and reveals predominant expression in developing neural tissue. Here, we use COS-7 cells as a model system to develop an understanding of Myo16b function. We find that Myo16b displays predominant localization in the nucleus of cells transitioning through interphase, but is not associated with processes of mitosis. Using a panel of EGFP-Myo16b-expression plasmids in transient transfection studies, we identified the COOH-terminal residues 1616,1912 as necessary and solely sufficient to target Myo16b to the nucleus. We show that the Myo16b-tail region directs localization to a nuclear compartment containing profilin and polymerized actin, which appears to form a three-dimensional meshwork through the depth of the nucleus. Further, we demonstrate that this compartment localizes within euchromatic regions of the genome and contains proliferating cell nuclear antigen (PCNA) and cyclin A, both markers of S-phase of the cell cycle. Cells transiently expressing Myo16b or Myo16b-tail region show limited incorporation of BrdU, delayed progression through S-phase of the cell cycle, and curtailed cellular proliferation. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source]

Causal mapping as a tool to mechanistically interpret phenomena in cell motility: Application to cortical oscillations in spreading cells

CYTOSKELETON, Issue 9 2006
Gabriel E. Weinreb
Abstract Biological processes that occur at the cellular level and consist of large numbers of interacting elements are highly nonlinear and generally involve multiple time and spatial scales. The quantitative description of these complex systems is of great importance but presents large challenges. We outline a new systems biology approach, causal mapping (CMAP), which is a coarse-grained biological network tool that permits description of causal interactions between the elements of the network and overall system dynamics. On one hand, the CMAP is an intermediate between experiments and physical modeling, describing major requisite elements, their interactions and paths of causality propagation. On the other hand, the CMAP is an independent tool to explore the hierarchical organization of cell and the role of uncertainties in the system. It appears to be a promising easy-to-use technique for cell biologists to systematically probe verbally formulated qualitative hypotheses. We apply the CMAP to study the phenomenon of contractility oscillations in spreading cells in which microtubules have been depolymerized. The precise mechanism by which these oscillations are governed by a complex mechano-chemical system is not known but the data observed in experiments can be described by a CMAP. The CMAP suggests that the source of the oscillations results from the opposing effects of Rho activation leading to a decreased level of myosin light chain phosphatase and a cyclic calcium influx caused by increased membrane tension and leading to a periodically enhanced activation of myosin light chain kinase. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source]

Protein phosphatase 1, is required for murine lung growth and morphogenesis

DEVELOPMENTAL DYNAMICS, Issue 4 2004
Kadija-Kathy Hormi-Carver
Abstract Protein phosphatase 1 (PP1) plays important roles in cell cycle control and apoptosis, two processes that impinge on morphogenesis and differentiation. Following the precedent set by other molecules regulating the cell cycle and apoptosis, we hypothesized that PP1 may have context-specific roles in development. Therefore, we have studied the spatial and temporal expression of PP1, during murine lung development and determined the consequences of loss of PP1, function on branching morphogenesis. By using an immunohistochemical approach, we show here that PP1, was expressed throughout the epithelium and mesenchyme upon the emergence of the lung primordium on embryonic day 10, with immunostaining exclusively extranuclear. During the late pseudoglandular stage, PP1, was predominantly expressed in the distal lung epithelium, whereas the mesenchyme contained very little or no PP1, protein. Peri- and postnatally, PP1, immunostaining was mostly nuclear in apparently differentiated cells, as judged by colocalization with well-known markers for lung differentiation. Exposure of fetal lung explants to antisense oligodeoxynucleotides against PP1,, resulted in decreased overall size of the cultured lung, a defect in forming new airways, lack of expression of surfactant protein C, and histologic signs of poor differentiation. These data suggest that PP1, is required for branching morphogenesis and differentiation. Developmental Dynamics 229:791,801, 2004. © 2004 Wiley-Liss, Inc. [source]

Posttranslational regulation of BCL2 levels in cerebellar granule cells: A mechanism of neuronal survival

DEVELOPMENTAL NEUROBIOLOGY, Issue 13 2009
Laura Lossi
Abstract Apoptosis can be modulated by K+ and Ca2+ inside the cell and/or in the extracellular milieu. In murine organotypic cultures, membrane potential-regulated Ca2+ signaling through calcineurin phosphatase has a pivotal role in development and maturation of cerebellar granule cells (CGCs). P8 cultures were used to analyze the levels of expression of B cell lymphoma 2 (BCL2) protein, and, after particle-mediated gene transfer in CGCs, to study the posttranslational modifications of BCL2 fused to a fluorescent tag in response to a perturbation of K+/Ca2+ homeostasis. There are no changes in Bcl2 mRNA after real time PCR, whereas the levels of the fusion protein (monitored by calculating the density of transfected CGCs under the fluorescence microscope) and of BCL2 (inWestern blotting) are increased. After using a series of agonists/antagonists for ion channels at the cell membrane or the endoplasmic reticulum (ER), and drugs affecting protein synthesis/degradation, accumulation of BCL2 was related to a reduction in posttranslational cleavage by macroautophagy. The ER functionally links the [K+]e and [Ca2+]i to the BCL2 content in CGCs along two different pathways. The first, triggered by elevated [K+]e under conditions of immaturity, is independent of extracellular Ca2+ and operates via IP3 channels. The second leads to influx of extracellular Ca2+ following activation of ryanodine channels in the presence of physiological [K+]e, when CGCs are maintained in mature status. This study identifies novel mechanisms of neuroprotection in immature and mature CGCs involving the posttranslational regulation of BCL2. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source]

Genetic and perinatal factors as risk for childhood type 1 diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2004
Karin Larsson
Abstract The mechanisms by which gestational infections, blood incompatibility, birth weight, mother's age and other prenatal or neonatal events increase the risk for type 1 diabetes are not understood. Studies so far have been retrospective, and there is a lack of population-based prospective studies. The possibility of identifying children at type 1 diabetes risk among first-degree relatives has resulted in prospective studies aimed at identifying postnatal events associated with the appearance of autoantibody markers for type 1 diabetes and a possible later onset of diabetes. However, the majority (85%) of new onset type 1 diabetes children do not have a first-degree relative with the disease. Population-based studies are therefore designed to prospectively analyse pregnant mothers and their offspring. One such study is DiPiS (Diabetes Prediction in Skåne), which is examining a total of about 10 000 pregnancies expected every year in the Skåne (Scania) region of Sweden that has 1.1 million inhabitants. Blood samples from all mothers in this region are obtained during pregnancy and at the time of delivery. Cord blood is analysed for HLA high-risk alleles and for autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GADA), the protein tyrosine phosphatase,related IA-2 antigen (IA-2A) and insulin (IAA) as a measure of prenatal autoimmune exposure. Identifying high-risk children by genetic, autoimmune and gestational risk factors followed by prospective analyses will make it possible to test the hypothesis that gestational events may trigger beta cell autoimmunity as a prerequisite for childhood type 1 diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Urinary excretion of inositol phosphoglycan P-type in gestational diabetes mellitus

DIABETIC MEDICINE, Issue 11 2007
M. Scioscia
Abstract Objective The mechanisms underlying insulin resistance during normal pregnancy, and its further exacerbation in pregnancies complicated by gestational diabetes mellitus (GDM), are generally unknown. Inositolphosphoglycan P-type (P-IPG), a putative second messenger of insulin, correlates with the degree of insulin resistance in diabetic subjects. An increase during normal pregnancy, in maternal and fetal compartments, has recently been reported. Methods A cross-sectional study was carried out in 48 women with GDM and 23 healthy pregnant women. Urinary levels of P-IPG were assessed spectrophotometrically by the activation of pyruvate dehydrogenase phosphatase in urinary specimens and correlated with clinical parameters. Results Urinary excretion of P-IPG was higher in GDM than in control women (312.1 ± 151.0 vs. 210.6 ± 82.7 nmol NADH/min/mg creatinine, P < 0.01) with values increasing throughout pregnancy in control subjects (r2 = 0.34, P < 0.01). P-IPG correlated with blood glucose levels (r2 = 0.39, P < 0.01 for postprandial glycaemia and r2 = 0.18 P < 0.01 for mean glycaemia) and birthweight in the diabetic group (r2 = 0.14, P < 0.01). Conclusions Increased P-IPG urinary excretion occurs in GDM and positively correlates with blood glucose levels. P-IPG may play a role in maternal glycaemic control and, possibly, fetal growth in GDM. [source]

HMG-CoA reductase inhibitors prevent bone loss in patients with Type 2 diabetes mellitus

DIABETIC MEDICINE, Issue 9 2004
A. Nakashima
Abstract Aims It has been reported that 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors increase bone mineral density (BMD) in vivo. We investigated the effect of HMG-CoA reductase inhibitors on BMD in patients with Type 2 diabetes mellitus. Patients and methods We selected 122 patients with Type 2 diabetes, who were not taking active vitamin D preparations. Their mean age was 67.3 ± 9.2 years. They were divided into a control group (n = 63) without HMG-CoA reductase inhibitor therapy and an HMG-CoA group (n = 59) who were treated with these drugs. The BMD of the distal one-third of the radius was measured by dual-energy X-ray adsorptiometry at baseline and after 2 years. Results There were no significant differences between the control and HMG-CoA groups at baseline with respect to age, gender, body mass index, duration of diabetes, haemoglobin A1c, fasting plasma glucose, adjusted calcium, serum phosphorus, alkaline phosphatase, albumin excretion rate and radial BMD. However, there was a significantly smaller annual decrease of the radial BMD in the HMG-CoA group. Multiple regression analysis with a forward elimination procedure revealed a positive correlation of the radial BMD Z-score with body mass index, while there was a negative correlation with alkaline phosphatase and albumin excretion rate. In addition, the annual rate of change of the radial BMD showed a positive correlation with HMG-CoA reductase inhibitor therapy. Conclusions These findings suggest that HMG-CoA reductase inhibitors may prevent bone loss in patients with Type 2 diabetes. [source]