1.
Brage, M, et al.
(författare)
Different cysteine proteinases involved in bone resorption and osteoclast formation.
2005
Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 76:6, s. 439-47
Tidskriftsartikel (refereegranskat) abstract
Cysteine proteinases, especially cathepsin K, play an important role in osteoclastic degradation of bone matrix proteins and the process can, consequently, be significantly inhibited by cysteine proteinase inhibitors. We have recently reported that cystatin C and other cysteine proteinase inhibitors also reduce osteoclast formation. However, it is not known which cysteine proteinase(s) are involved in osteoclast differentiation. In the present study, we compared the relative potencies of cystatins C and D as inhibitors of bone resorption in cultured mouse calvariae, osteoclastogenesis in mouse bone marrow cultures, and cathepsin K activity. Inhibition of cathepsin K activity was assessed by determining equilibrium constants for inhibitor complexes in fluorogenic substrate assays. The data demonstrate that whereas human cystatins C and D are equipotent as inhibitors of bone resorption, cystatin D is 10-fold less potent as an inhibitor of osteoclastogenesis and 200-fold less potent as an inhibitor of cathepsin K activity. A recombinant human cystatin C variant with Gly substitutions for residues Arg8, Leu9, Val10, and Trp106 did not inhibit bone resorption, had 1,000-fold decreased inhibitory effect on cathepsin K activity compared to wildtype cystatin C, but was equipotent with wildtype cystatin C as an inhibitor of osteoclastogenesis. It is concluded that (i) different cysteine proteinases are likely to be involved in bone resorption and osteoclast formation, (ii) cathepsin K may not be an exclusive target enzyme in any of the two systems, and (iii) the enzyme(s) involved in osteoclastogenesis might not be a typical papain-like cysteine proteinase.
2.
Jasir, Aftab, et al.
(författare)
New antimicrobial peptide active against Gram-positive pathogens
2004
Ingår i: Indian Journal of Medical Research. - 0971-5916. ; 119:Suppl., s. 74-76
Tidskriftsartikel (refereegranskat) abstract
Background & objectives: Human and animal cystatins have been shown to inhibit the replication of certain viruses and bacteria, though it is not directly demonstrated that the effects are due to protease inhibitory capacity of the cystatins. We report antibacterial properties of a novel antimicrobial peptidyl derivative, (2S)-2-(N-alpha-benzyloxycarbonyl-arginyl-leucylamido)-1-(E)-cinnamoyla mido-3-methylbutane, structurally based upon the aminoterminal segment of the inhibitory centre of the human cysteine protease inhibitor, cystatin C. Methods: Clinical isolates of group A, B, C and G streptococci were collected. The antibacterial activity of Cystapep 1 derivative was tested by agar well diffusion method. Results: Cystapep 1, displayed antibacterial activity against several clinically important Gram-positive bacteria. It displayed minimal inhibitory and bactericidal concentrations of about 16 mug/ml for both Staphylococcus aureus and Streptococcus pyogenes. In radial agar diffusion assays, groups A, B, C and G streptococci as well as staphylococci were generally susceptible to the action of Cystapep 1, whereas pneumococci and enterococci were less susceptible. No activity against Gram-negative bacteria was observed. Interpretation & conclusion: Cystapep 1 also showed high activity against methicillin-resistant Staph. aureus (MRSA) and multi-antibiotic resistant coagulase negative staphylococci (CNS), suggesting its mechanism of action to be different from most currently used antibiotics.
3.
Bengzon, Johan, et al.
(författare)
C-reactive protein levels following standard neurosurgical procedures
2003
Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 145:8, s. 667-671
Tidskriftsartikel (refereegranskat) abstract
Background. The aim of the present study was to establish the magnitude and time-course of C-reactive protein increases following routine neurosurgical procedures in the absence of clinical and laboratory signs of infection. Method. C-reactive protein levels were studied daily following ventriculo-peritoneal shunt implantation, anterior cervical fusion, vestibular schwannoma operation, supratentorial glioma surgery, endovascular intracranial aneurysm treatment and open cerebral aneurysm surgery. Findings. The magnitude of the C-reactive protein increase depended on the extent of surgical trauma and peak-levels were recorded between postoperative day one and four after which the levels tapered off. Interpretation. Increases occur-ring after the fourth postoperative day are likely to be caused by complications of surgery, e.g. infection.
4.
Bjarnadottir, M., et al.
(författare)
The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids
2001
Ingår i: Amyloid. - 1350-6129. ; 8:1, s. 41284-41284
Tidskriftsartikel (refereegranskat) abstract
A variant of the normal extracellular cysteine protease inhibitor cystatin C (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid angiopathy (HCCAA). It has been suggested that the mutation causes cellular entrapment of L68Q-cystatin C in vivo and that the variant protein is not secreted to extracellular fluids. In order to test this hypothesis, we used matrix-assisted laser desorption ionization time-of-flight mass spectrometry in an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in plasma and cerebrospinal fluid (CSF) of HCCAA-patients. Plasma from all five investigated HCCAA-patients contained both L68Q- and wildtype cystatin C. The presence of approximately equal amounts of cystatin C dimers and monomers was demonstrated in plasma from HCCAA-patients, whereas only monomers could be found in normal plasma. L68Q-wildtype-cystatin C heterodimers seem to be present in the dimeric cystatin C population. CSF from six HCCAA-patients also contained cystatin C-dimers and monomers, bur the dimeric fraction was minute. CSF from control patients did not contain dimeric cystatin C. These results suggest that the milieu of L68Q-cystatin C is important for its stability and dimerization status and that certain milieus might hinder its further development into oligomers, amyloid fibrils and other precipiting aggregates.
5.
Blirup, Soren, et al.
(författare)
Standardization of Cystatin C: development of primary and secondary reference preparations.
2008
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68:s241, s. 67-70
Tidskriftsartikel (refereegranskat) abstract
A Primary Reference Preparation has been produced using pure, recombinant, Cystatin C in a solvent of 0.1 mol/L KCl. Dry mass determination of the Primary Reference Preparation resulted in a Cystatin C concentration of 5.20 g/L. Agarose-electrophoresis and SDS-electrophoresis, as well as N-terminal sequencing, verified the purity, homogeneity and identity of Cystatin C in the Primary Reference Preparation. For the Secondary Reference Preparation, a serum pool was collected and stabilized. A pilot batch was made to verify the selected procedure and spiking with the pure, recombinant Cystatin C. The final Secondary Reference Preparation is now produced (4468 vials) and ready for value assignment and further characterization.
6.
7.
Grubb, Anders, et al.
(författare)
Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation.
2011
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71, s. 145-149
Tidskriftsartikel (refereegranskat) abstract
Abstract Background. The plasma level of cystatin C is a better marker than plasma creatinine for successful aging. It has been assumed that the advantage of cystatin C is not only due to it being a better marker for glomerular filtration rate (GFR) than creatinine, but also because an inflammatory state of a patient induces a raised cystatin C level. However, the observations of an association between cystatin C level and inflammation stem from large cohort studies. The present work concerns the cystatin C levels and degree of inflammation in longitudinal studies of individual subjects without inflammation, who undergo elective surgery. Methods. Cystatin C, creatinine, and the inflammatory markers CRP, serum amyloid A (SAA), haptoglobin and orosomucoid were measured in plasma samples from 35 patients the day before elective surgery and subsequently during seven consecutive days. Results. Twenty patients had CRP-levels below 1 mg/L before surgery and low levels of the additional inflammatory markers. Surgery caused marked inflammation with high peak values of CRP and SAA on the second day after the operation. The cystatin C level did not change significantly during the observation period and did not correlate significantly with the level of any of the four inflammatory markers. The creatinine level was significantly reduced on the first postoperative day but reached the preoperative level towards the end of the observation period. Conclusion. The inflammatory status of a patient does not influence the role of cystatin C as a marker of successful aging, nor of GFR.
8.
Kristensen, Karl, et al.
(författare)
Increased plasma levels of ss(2)-microglobulin, cystatin C and ss-trace protein in term pregnancy are not due to utero-placental production.
2008
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 649-653
Tidskriftsartikel (refereegranskat) abstract
Objective . To study concentration gradients of the low molecular mass proteins, ss(2)-microglobulin, cystatin C and ss-trace protein, between the uterine and ante-cubital veins, the umbilical artery and vein and in the amniotic fluid compartment. Material and methods. The study comprised 27 healthy women with uncomplicated pregnancies undergoing caesarean section at term. Samples were collected simultaneously and paired t-tests were used to compare mean plasma concentrations. Results . There was no significant concentration gradient in the plasma levels of ss(2)-microglobulin, cystatin C or ss-trace protein between the uterine and antecubital veins. There were no correlations between the protein levels in the compartments. Conclusion . The utero-placental unit does not contribute significantly to the maternal levels of ss(2)-microglobulin, cystatin C and ss-trace protein in normal pregnancy, and the proteins are not likely to be transferred across the placental barrier.
9.
Kristensen, Karl, et al.
(författare)
Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia.
2009
Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 67:4, s. 275-280
Tidskriftsartikel (refereegranskat) abstract
Aims: To study plasma levels of serum amyloid A protein and C-reactive protein in pregnant women with and without preeclampsia and non-pregnant women. Plasma levels of haptoglobin, orosomucoid and ceruloplasmin were also analyzed. Methods: The study included 295 women with uncomplicated pregnancies, 57 women diagnosed with preeclampsia, and 58 healthy non-pregnant women. Plasma concentrations of acute phase proteins were analyzed by particle-enhanced immunoassays. Non-parametric Kruskal-Wallis and Mann-Whitney U tests were used to test differences between the groups. Results: Plasma levels of C-reactive protein and ceruloplasmin were increased in pregnant women with and without preeclampsia compared to non-pregnant women. Plasma levels of serum amyloid A protein and C-reactive protein were not elevated in women with preeclampsia compared to women with normal pregnancy. Conclusion: The description of preeclampsia as a systemic inflammatory state was not reflected in the plasma levels of serum amyloid A protein and C-reactive protein.
10.
Kristensen, Karl, et al.
(författare)
Temporal changes of the plasma levels of cystatin C, beta-trace protein, beta(2)-microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process
2007
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 67:6, s. 612-618
Tidskriftsartikel (refereegranskat) abstract
Objective. To determine the plasma levels of the renal functional markers creatinine, urate, cystatin C, beta(2)-microglobulin and beta-trace protein in samples from the first, second, early third and late third trimesters of 398 healthy women with uncomplicated singleton pregnancies. Material and methods. Plasma samples from 58 healthy non-pregnant women served as controls. The creatinine levels were significantly lower at all time-points in pregnancy, whereas the urate levels were lower during the first and second trimesters but increased in the late third trimester. The cystatin C, beta(2)-microglobulin and beta-trace protein levels displayed similar changes with increased levels in the third trimester but unaltered levels during the first and second trimesters. Results. The results indicate an increased filtration of low-molecular weight molecules during pregnancy, particularly during the first and second trimesters, whereas filtration of 10-30 kDa molecules is decreased in the third but unaltered in the first and second trimesters. The levels of albumin and alpha(2)-macroglobulin were measured in the same samples. Conclusions. The albumin levels decreased in the second and third trimesters, whereas the levels of alpha(2)-macroglobulin were unchanged, which is compatible with a virtually unaltered transfer of alpha(2)-macroglobulin between the intra-and extravascular space during pregnancy and a significantly increased extravascular fraction of albumin.
