interacts_with DB06271?
P11926 inhibition by alpha-difluoromethylornithine activates opposing signaling pathways via phosphorylation of both Akt/protein kinase B and P46527 in neuroblastoma . P11926 ( ODC ) is a key enzyme in mammalian polyamine biosynthesis that is up-regulated in various types of cancer . We previously showed that treating human neuroblastoma ( NB ) cells with the ODC inhibitor alpha-difluoromethylornithine ( DB06243 ) depleted polyamine pools and induced P55008 cell cycle arrest without causing apoptosis . However , the precise mechanism by which DB06243 provokes these changes in NB cells remained unknown . Therefore , we further examined the effects of DB06243 , alone and in combination with phosphatidylinositol 3-kinase ( PI3K ) inhibitor LY294002 or Akt/protein kinase B ( P31749 ) inhibitor IV , on the regulation of cell survival and cell cycle-associated pathways in LAN-1 NB cells . In the present study , we found that the inhibition of ODC by DB06243 promotes cell survival by inducing the phosphorylation of Akt/ P31749 at residue Ser473 and glycogen synthase kinase-3beta at Ser9 . Intriguingly , DB06243 also induced the phosphorylation of P46527 at residues Ser10 ( nuclear export ) and Thr198 ( protein stabilization ) but not Thr187 ( proteasomal degradation ) . The combined results from this study provide evidence for a direct cross-talk between ODC-dependent metabolic processes and well-established cell signaling pathways that are activated during NB tumorigenesis . The data suggest that inhibition of ODC by DB06243 induces two opposing pathways in NB : one promoting cell survival by activating Akt/ P31749 via the PI3K/Akt pathway and one inducing P46527 /retinoblastoma-coupled P55008 cell cycle arrest via a mechanism that regulates the phosphorylation and stabilization of P46527 . This study presents new information that may explain the moderate efficacy of DB06243 monotherapy in clinical trials and reveals potential new targets for DB06243 -based combination therapies for NB treatment . Bcl-2/Bcl-xL inhibition increases the efficacy of MEK inhibition alone and in combination with P19957 kinase inhibition in lung and pancreatic tumor models . Although mitogen-activated protein ( Q96HU1 ) -extracellular signal-regulated kinase ( P29323 ) kinase ( MEK ) inhibition is predicted to cause cell death by stabilization of the proapoptotic Q7L3V2 O43521 , the induction of apoptosis is often modest . To determine if addition of a Bcl-2 family inhibitor could increase the efficacy of a MEK inhibitor , we evaluated a panel of 53 non-small cell lung cancer and pancreatic cancer cell lines with the combination of navitoclax ( DB05764 ) , a Bcl-2/Bcl-xL ( P10415 / Q07817 ) antagonist , and a novel Q96HU1 kinase ( MEK ) inhibitor , G-963 . The combination is synergistic in the majority of lines , with an enrichment of cell lines harboring P01116 mutations in the high synergy group . Cells exposed to G-963 arrest in P55008 and a small fraction undergo apoptosis . The addition of navitoclax to G-963 does not alter the kinetics of cell-cycle arrest , but greatly increases the percentage of cells that undergo apoptosis . The G-963/navitoclax combination was more effective than either single agent in the P01116 mutant H2122 xenograft model ; O43521 stabilization and PARP cleavage were observed in tumors , consistent with the mechanism of action observed in cell culture . Addition of the phosphatidylinositol 3-kinase ( PI3K , P42336 ) inhibitor P16260 -0941 to this treatment combination increases cell killing compared with double- or single-agent treatment . Taken together , these data suggest the efficacy of agents that target the MAPK and PI3K pathways can be improved by combination with a Bcl-2 family inhibitor . The Lyme disease vaccine takes its toll . Vaccination with Borrelia burgdorferi outer surface protein ( Osp ) A can induce a protective response against Lyme disease and serves as a model to understand the generation of protective immune responses against the spirochete . The innate response to pathogens is activated by specific Toll-like receptors ( TLRs ) that recognize distinct pathogen-associated molecular patterns . O60603 is of particular interest for B. burgdorferi research because O60603 recognizes several pathogen-associated molecular patterns , including lipoproteins . O60603 may form heterodimers with Q9Y2C9 to identify diacylated lipoproteins , while O60603 works in concert with Q15399 to recognize triacylated lipoproteins such as OspA . We will discuss the role of Q15399 /2 in the development of responses to OspA in Q15399 -and O60603 -deficient mice , and in selected individuals that received the OspA vaccine . While > 95 % of human OspA-based Lyme disease vaccine recipients develop OspA antibodies , a very small group of individuals did not develop detectable humoral responses against OspA . We demonstrated that this hyporesponsiveness to OspA vaccination was associated with decreased cell surface expression of Q15399 . Moreover , Q15399 - and O60603 -deficient mice did not develop significant levels of OspA antibodies following vaccination with OspA , providing a correlation with human hyporesponsiveness to OspA . These data suggest that defects in the Q15399 /2 signaling pathway are associated with an impaired ability to generate antibodies following immunization with DB00045 . P06213 disorders in Japan . The clinical features of insulin receptor disorders found in Japan are summarized . About 20 cases of primary receptor mutations ( type A syndrome of insulin resistance , leprechaunism and Rabson-Mendenhall syndrome ) and 16 cases of autoantibodies against insulin receptor ( type B syndrome of insulin resistance ) are described in Japan . There was a trial of DB01277 for some of the patients , revealing its usefulness . Prevention of thrombus formation and growth by antithrombin III and heparin cofactor II-dependent thrombin inhibitors : importance of heparin cofactor II . DB01109 ( HEP ) prevents thrombus formation ( TF ) and thrombus growth ( TG ) , by accelerating thrombin ( THR ) inhibition by antithrombin III ( P01008 ) . Recent studies suggest that dermatan sulphate which catalyzes thrombin inhibition by heparin cofactor II ( HCII ) , can inhibit TF and TG as effectively as HEP . This study compared the antithrombotic effects of HEP and another agent , DB06271 ( SLX ) which catalyzes thrombin inhibition by P01008 and HCII simultaneously . TF was induced in rabbit jugular veins , using the stasis/hypercoagulation model . TG was measured as the accretion of 125I-fibrin onto existing thrombi in rabbit jugular veins . HEP and SLX inhibited TF when given in doses of 10 and 5 anti-thrombin U/kg , respectively . SLX ( 16 anti-thrombin U/kg or 260 micrograms/kg ) was more effective than HEP ( 120 anti-thrombin U/kg or 800 micrograms/kg ) in preventing TG when administered either as a bolus or by continuous infusion . These data suggest that agents which accelerate THR inhibition by both P01008 and HCII simultaneously , can inhibit TF and TG with less systemic anticoagulation than comparable antithrombotic doses of HEP . The MAPK pathway and Q9BYW2 are involved in the induction of the human P05121 gene expression by insulin in the human hepatoma cell line HepG2 . Enhanced levels of plasminogen activator inhibitor-1 ( P05121 ) are considered to be a risk factor for pathological conditions associated with hypoxia or hyperinsulinemia . The expression of the P05121 gene is increased by insulin in different cells , although , the molecular mechanisms behind insulin-induced P05121 expression are not fully known yet . Here , we show that insulin upregulates human P05121 gene expression and promoter activity in HepG2 cells and that mutation of the hypoxia-responsive element ( HRE ) -binding hypoxia-inducible factor-1 ( Q9BYW2 ) abolished the insulin effects . Mutation of E-boxes E4 and O94989 abolished the insulin-dependent activation of the P05121 promoter only under normoxia , but did not affect it under hypoxia . Furthermore , the insulin effect was associated with activation of HIF-1alpha via mitogen-activated protein kinases ( MAPKs ) but not PDK1 and P31749 in HepG2 cells . Furthermore , mutation of a putative FoxO1 binding site which was supposed to be involved in insulin-dependent P05121 gene expression influenced the insulin-dependent activation only under normoxia . Thus , insulin-dependent P05121 gene expression might be regulated by the action of both Q9BYW2 and FoxO1 transcription factors . Leukotriene C4 production during hypoxic pulmonary vasoconstriction in isolated rat lungs . Leukotriene inhibitors preferentially inhibit hypoxic pulmonary vasoconstriction in isolated rat lungs . If lipoxygenase products are involved in the hypoxic pressor response they might be produced during acute alveolar hypoxia and a leukotriene inhibitor should block both the vasoconstriction and leukotriene production that occurs in response to hypoxia . We investigated in isolated blood perfused rat lungs whether leukotriene C4 ( LTC4 ) could be recovered from whole lung lavage fluid during ongoing hypoxic vasoconstriction . Lung lavage from individual rats had slow reacting substance ( SRS ) -like myotropic activity by guinea pig ileum bioassay . Pooled lavage ( 10 lungs ) as analyzed by reverse phase high performance liquid chromatography had an ultraviolet absorbing component at the retention time for LTC4 . At radioimmunoassay , and SRS myotropic activity by bioassay . LTC4 was not found during normoxic ventilation , during normoxic ventilation after a hypoxic pressor response , or during vasoconstriction elicited by DB00761 . DB00711 citrate , a leukotriene synthesis blocker , concomitantly inhibited the hypoxic vasoconstriction and LTC4 production . Thus P09917 products may play a role in the sequence of events leading to hypoxic pulmonary vasoconstriction . Normal and perturbed endothelial cells from canine femoral arteries and femoral veins exhibit heterogeneity in hemostatic properties and growth characteristics . BACKGROUND : We sought to examine the heterogeneity of endothelial cells from the same anatomic site but different vascular systems and described P04275 ( P04275 ) release and morphological change in response to injury-associated factor in femoral vessels from canine in vitro . METHODS : Levels of hemostatic factors ( P04275 , plasminogen activator inhibitor type 1( P05121 ) , antithrombin III ( P01008 ) , in tissue sections and cultured endothelial cells of canine femoral arteries and canine femoral veins were compared by the immunohistochemistry technique . In addition to comparing cell growth density and cell protein contents , cultured femoral arterial endothelial cells ( FAECs ) and cultured femoral venous endothelial cells ( FVECs ) were incubated with a series concentration of basic fibroblast factor ( P09038 ) ( 1 , 10 , 100 ng/ml ) for up to 48 hours to test the amount of P04275 secretion and morphological change . RESULTS : Both in tissue sections and cultured cells , the levels of P04275 are higher in FVECs than in FAECs . We were unable to differentiate the level of P05121 and P01008 difference between FAECs and FVECs. P09038 ( 10 ng/ml ) significantly increased P04275 secretion from cultured FAECs but not from FVECs . The size of cultured FAECs is smaller than of FVECs ; however , FAECs have higher amounts of protein contents than FVECs . CONCLUSIONS : These comparative studies provide evidence indicating that the characteristics of FVECs differ from those of FAECs . These differences may be indicated heterogeneity with either inherited or acquired thrombotic disease . P10275 inducing bladder cancer progression by promoting an epithelial-mesenchymal transition . The study investigated the role of androgen receptor ( AR ) as a potential target for the treatment of bladder cancer in regulating epithelial-mesenchymal transition or transformation ( EMT ) . Cell proliferation , and migration capacity were determined in bladder cancer T24 cells treated with small interfering RNA directed against AR , and expression levels of P12830 , β-catenin and N- cadherin were assessed using quantitative reverse transcription PCR ( qRT-PCR ) . Tumour cell growth was evaluated in vivo in T24 tumour-bearing nude mice receiving electroporation-assisted administration of anti-AR small interfering RNA . It was found that low AR expression decreased proliferation and migration of bladder cancer cells . In vivo experiments showed that silencing AR expression significantly suppressed AR-positive bladder tumour growth with decreased cell proliferation . Low AR level of T24 bladder cancer cells treated with DB01541 ( DB02901 ) decreased expression of P12830 , β-catenin and P19022 expression , indicating a strong sensitivity to the EMT and In cells with low AR content , TGF-β induced down-regulation of P12830 and β-catenin . It is concluded that suppression of AR expression decreased the production of TGF-β , inhibiting EMT and bladder cancer cell growth in vitro and in vivo , implying that its use might be a potential therapeutic target for the treatment of bladder cancer . Recombinational and physical mapping of the locus for primary open-angle glaucoma ( Q99972 ) on chromosome 1q23-q25 . Primary open-angle glaucoma ( POAG ) is a leading cause of irreversible blindness in industrialized countries . A locus for juvenile-onset POAG , Q99972 , has been mapped to 1q21-q31 in a 9-cM interval . With recombinant haplotypes , we have now reduced the Q99972 interval to a maximum of 3 cM , between the D1S452/NGA1/D1S210 and NGA5 loci . These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between the D1S2851 and D1S218 loci and that includes 96 YAC clones and 48 STSs . The new Q99972 interval itself is now covered by 25 YACs , 30 STSs , and 16 restriction enzyme site landmarks . The lack of a NotI site suggests that the region has few CpG islands and a low gene content . This is compatible with its predominant cytogenetic location on the 1q24 G-band . Finally , we have excluded important candidate genes , including genes coding for three ATPases ( P05026 , P23634 , P50993 ) , an ion channel ( VDAC4 ) , antithrombine III ( P01008 ) , and prostaglandin synthase ( P35354 ) . Our results provide a basis to identify the Q99972 gene . Genetic polymorphisms of P23945 , P05093 , P04798 , Q9HC96 , P06213 , P05121 genes in adolescent girls with polycystic ovary syndrome . BACKGROUND : Polycystic ovary syndrome ( PCOS ) , whose genetic basis is not completely well understood , is the most common endocrine disorder in women and it typically develops during adolescence . The aim of this study is to investigate the possible association between single nucleotide polymorphisms ( SNPs ) of P23945 , P05093 , P04798 , Q9HC96 , P06213 , P05121 genes and PCOS in adolescent girls . METHODS : DNA samples from forty-four adolescent girls with PCOS and 50 healthy controls were analyzed by PCR-RFLP and direct DNA sequencing to determine the genotypic frequency of 17 different polymorphic loci on the P23945 ( A307T , N680S ) , P05093 ( -34 T/C ) , P04798 ( T6235C ) , Q9HC96 ( 44 , 43 , 19 , 63 ) , P06213 ( exon 17 C/T ) , P05121 ( 4G/5G ) genes . Genotyping of exon 12 ( six polymorphisms ) and intron 12 ( one polymorphism ) of P06213 gene by direct DNA sequencing was performed for the first time in this study . RESULTS : No significant differences were observed in the genotype and allele distributions of above mentioned polymorphisms between cases and control groups . CONCLUSION : Our data does not support an association between SNPs of P23945 , P05093 , P04798 , Q9HC96 , P06213 , P05121 genes and susceptibility to PCOS or related traits in Turkish adolescent girls . Linkage mapping of highly informative DNA polymorphisms within the human interferon-alpha receptor gene on chromosome 21 . Two polymorphic loci within the interferon-alpha receptor ( P17181 ) gene on human chromosome 21 have been identified and mapped by linkage analysis in 40 CEPH families . These markers are ( 1 ) a multiallelic RFLP with an observed heterozygosity of 0.72 and ( 2 ) a variable ( P01008 )n short sequence repeat at the poly(A) tail of an Alu sequence ( AluVpA ) with an observed heterozygosity of 0.83 . This locus is close to Q08334 ( theta = 0.02 , zeta = 36.76 ) and D21S17 ( theta = 0.02 , Zeta = 21.76 ) with chromosomal band 21q22.1 . Multipoint linkage analysis suggests the most likely locus order to be 21cen- Q08334 - P17181 -D21S17-21qter . Given its high heterozygosity , the P17181 gene can be used as an index marker on human chromosome 21 . Growth rates of hprt and tk mutant CHO cell lines . The growth rates of 31 X-ray-induced hypoxanthine phosphoribosyl transferase ( hprt ) deficient mutants of CHO- P04264 cells were measured . Mutants had been classified as ( 1 ) full-deletion , ( 2 ) partial deletion or rearrangement , or ( 3 ) unchanged by Southern blot analyses . No relationship between growth rate and deletion type was observed . Even where all hprt-specific bands were missing , proliferation rates in culture were normal . Additionally , in CHO- P01008 -2 cells , which are heterozygous at the tk locus , no difference in growth rates between a spontaneous hprt mutant and its parent was observed , although double hprt-tk-/- mutants grew more slowly . Some studies on spontaneous Hymenolepis diminuta infection in laboratory rats . Hymenolepis diminuta is a tapeworm that occurs worldwide . It is known to be found commonly in areas where large amounts of food grains or other dry feed products , which are the favorite foods for rats . Transmission of disease to human is uncommon ; however , it may be a serious threat for population who are living in rural areas which are suffering from excessive rodents . Here , this study had done on spontaneous H. diminuta infection in laboratory rats as a model . Out of thirty five adult laboratory rats investigated for parasitic diseases only nine ( 25.71 % ) were diagnosed positive for spontaneous H. diminuta infection . Four of them ( 44.44 % ) were found losing of weight and lacking of motility , while the others were normal . On microscopic examination , H. diminuta eggs had been found in their stool . On autopsy , small intestines were found to contain from 5-6 multi-segmented tapeworms in each rat . Histopathologically , intestinal lumen showed varying sections of H. diminuta segments with serrated borders . H. diminuta infection caused multiple mucosal ulcers with absence of intestinal villi from the surface epithelium and excessive mucin . Moreover , inflammatory cells infiltration in the connective tissue core of the villi . Furthermore , the Toluidine blue stain showed that there are Mastiocytosis . Additionally , there were goblet cells hyperplasia on using DB00233 . Moreover , there were high expression of cyclooxygenase 2 ( P35354 ) , tumor necrosis factor-α ( P01375 -α ) and inducible Nitric-Oxide Synthase ( iNOs ) . This implicate , strong correlation between P35354 , P01375 -α and iNOs expression and inflammation induced by H. diminuta . DB05258 /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt . Interferons ( IFNs ) play critical roles in host defense by modulating gene expression via activation of signal transducer and activator of transcription ( P35610 ) factors . IFN-alpha/beta also activates another transcription factor , nuclear factor kappaB ( NF-kappaB ) , which protects cells against apoptotic stimuli . NF-kappaB activation requires the IFN-dependent association of P40763 with the P17181 chain of the IFN receptor . IFN-dependent NF-kappaB activation involves the sequential activation of a serine kinase cascade involving phosphatidylinositol 3-kinase ( PI-3K ) and Akt . Whereas constitutively active PI-3K and Akt induce NF-kappaB activation , Ly294002 ( a PI-3K inhibitor ) , dominant-negative PI-3K , and kinase-dead Akt block IFN-dependent NF-kappaB activation . Moreover , dominant-negative PI-3K blocks IFN-promoted degradation of kappaBox alpha . Ly294002 , a dominant-negative PI-3K construct , and kinase-dead Akt block IFN-promoted cell survival , enhancing apoptotic cell death . Therefore , P40763 , PI-3K , and Akt are components of an IFN signaling pathway that promotes cell survival through NF-kappaB activation . Fibroblast growth factors mobilize peritoneal macrophage intracellular calcium . Macrophages have been implicated in the propagation of inflammatory disease . The evidence linking macrophages to inflammation stems from their elicited responses to various extracellular ligands eventually culminating in the elaboration of a variety of inflammatory mediators . As part of an investigation of fibroblast growth factors role in promoting inflammation , we examined one aspect of transmembrane signal transduction , intracellular calcium mobilization following culture of murine peritoneal macrophages with acidic and basic fibroblast growth factor . Peritoneal macrophages displayed a rapid rise in cytosolic calcium from a basal level of 147.6 +/- 25.4 nM to 261.9 +/- 49.9 nM at 3.5 minutes following culture with acidic fibroblast growth . A similar rise in calcium was noted with basic fibroblast growth factor . Titration revealed the maximal effective dose of P05230 and P09038 with respect to calcium response to be 10 ng/ml . Using blockers of both voltage and non-voltage gated channels , the FGF induced rise in cytosolic calcium was specifically abolished . Similarly , using specific P09917 ( A69412 ) or cyclooxygenase ( Indomethacin ) blockers , the P05230 induced rise in maximal calcium response was reduced by 41 % and 96 % respectively . On the basis of these data , we speculate on some possible roles that FGF may play in the inflammatory response . P84022 linker phosphorylation attenuates P84022 transcriptional activity and TGF-β1/ P84022 -induced epithelial-mesenchymal transition in renal epithelial cells . Transforming growth factor-β1 ( TGF-β1 ) has a distinct role in renal fibrosis associated with epithelial-mesenchymal transition ( EMT ) of the renal tubules and synthesis of extracellular matrix . P84022 plays an essential role in fibrosis initiated by EMT . Phosphorylation of P84022 in the C-terminal SSXS motif by type I TGF-β receptor kinase is essential for mediating TGF-β response . P84022 activity is also regulated by phosphorylation in the linker region . However , the functional role of P84022 linker phosphorylation is not well characterized . We now show that P84022 EPSM mutant , which mutated the four phosphorylation sites in the linker region , markedly enhanced TGF-β1-induced EMT of P84022 -deficient primary renal tubular epithelial cells , whereas P84022 3S-A mutant , which mutated the C-terminal phosphorylation sites , was unable to induce EMT in response to TGF-β1 . Furthermore , immunoblotting and RT-PCR analysis showed a marked induction of fibrogenic gene expression with a significant reduction in P12830 in P52789 human renal epithelial cells expressing P84022 EPSM . TGF-β1 could not induce the expression of α-SMA , vimentin , fibronectin and P05121 or reduce the expression of P12830 in P52789 cells expressing P84022 3S-A in response to TGF-β1 . Our results suggest that P84022 linker phosphorylation has a negative regulatory role on P84022 transcriptional activity and TGF-β1/ P84022 -induced renal EMT . Elucidation of mechanism regulating the P84022 linker phosphorylation can provide a new strategy to control renal fibrosis . P00747 activator inhibitor type 1 regulates microglial motility and phagocytic activity . BACKGROUND : P00747 activator inhibitor type 1 ( P05121 ) is the primary inhibitor of urokinase type plasminogen activators ( uPA ) and tissue type plasminogen activators ( tPA ) , which mediate fibrinolysis . P05121 is also involved in the innate immunity by regulating cell migration and phagocytosis . However , little is known about the role of P05121 in the central nervous system . METHODS : In this study , we identified P05121 in the culture medium of mouse mixed glial cells by liquid chromatography and tandem mass spectrometry . Secretion of P05121 from glial cultures was detected by ELISA and western blotting analysis . Cell migration was evaluated by in vitro scratch-wound healing assay or Boyden chamber assay and an in vivo stab wound injury model . Phagocytic activity was measured by uptake of zymosan particles . RESULTS : The levels of P05121 mRNA and protein expression were increased by lipopolysaccharide and interferon-γ stimulation in both microglia and astrocytes . P05121 promoted the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein ( Q14764 ) 1/Janus kinase ( JAK ) /signal transducer and activator of transcription ( P35610 )1 axis . P05121 also increased microglial migration in vivo when injected into mouse brain . P05121 -mediated microglial migration was independent of protease inhibition , because an R346A mutant of P05121 with impaired PA inhibitory activity also promoted microglial migration . Moreover , P05121 was able to modulate microglial phagocytic activity . P05121 inhibited microglial engulfment of zymosan particles in a vitronectin- and O60603 /6-dependent manner . CONCLUSION : Our results indicate that glia-derived P05121 may regulate microglial migration and phagocytosis in an autocrine or paracrine manner . This may have important implications in the regulation of brain microglial activities in health and disease . The role of the central flexible region on the aggregation and conformational properties of human ataxin-3 . Aggregation of human ataxin-3 ( P01008 ) into amyloid fibrils is responsible for spinocerebellar ataxia type 3 . This protein consists of a folded N-terminal domain ( Josephin domain , residues 1-182 ) , a central flexible region ( residues 183-291 ) , a poly-glutamine sequence of variable length and a short C-terminal flexible region . Very little is known about the influence of the central flexible region on the conformational and aggregation properties of this protein . The present study aimed to investigate the specific role of this portion of the protein ( residues 183-291 ) . Accordingly , protein fragments 1-182 ( P01008 /182 ) and 1-291 ( P01008 /291 ) were produced and compared by thioflavin-T fluorescence , Fourier transform infrared spectroscopy , CD , intrinsic fluorescence and P19957 -MS . It is shown that the central flexible region enhances protein aggregation and can populate conformational states with different degrees of compactness . Both monomeric and dimeric partially-folded forms are identified for both protein fragments under denaturing conditions . Partially-folded monomers and dimers accumulate to a larger extent in P01008 /291 . These species represent good candidates for early intermediates of the aggregation process under the experimental conditions employed in the present study . Serial changes in serum vitamin P04264 , triglyceride , cholesterol , osteocalcin and 25-hydroxyvitamin D3 in patients after hip replacement for fractured neck of femur or osteoarthritis . Serum vitamin P04264 concentrations were measured at presentation ( just before surgery ) and then at weekly intervals for 3 weeks in two groups of elderly patients requiring either hemiarthroplasty for fractured neck of femur ( FON , n = 13 ) or total hip replacement for osteoarthritis of the hip ( OA , n = 16 ) . In comparison with healthy elderly volunteers ( n = 25 ) , serum vitamin P04264 concentrations were significantly lower in both groups at presentation , and fell significantly within 24 h after surgery to concentrations approaching non-detectable , subsequently returning to pre-operative values within 3 weeks . Serum vitamin P04264 tended to be lower in the fracture group both before and after operation , although calculation of a vitamin P04264 -triglyceride ratio reduced the apparent difference as triglyceride concentrations were lower in the fracture group . P02818 concentrations were similar and fell significantly after operation in both groups , returning to pre-operative levels within 7 days . No differences in the two forms of osteocalcin ( carboxylated and undercarboxylated ) were observed either before or after operation in either group . DB00146 concentrations were not significantly different between the two groups at any time . DB01022 status may be lower than desirable in certain groups of the elderly population , and supplementation should be considered as prophylactic therapy .