Publications by authors named "Anna Szydlo"

7 Publications

  • Page 1 of 1

The challenges of hypervolemic therapy in patients after subarachnoid haemorrhage.

Neurol Neurochir Pol 2014 13;48(5):328-36. Epub 2014 Oct 13.

Department of Neurosurgery, Medical University of Gdansk, Gdansk, Poland.

Purpose: The triple-H therapy is widely used for cerebral vasospasm (CV) prevention and treatment in patients after subarachnoid haemorrhage (SAH). However, this practice is based on low level evidence. Aim of this study was to evaluate errors in fluid administration, fluid balance monitoring and bedside charts completeness during a trial of triple-H therapy.

Materials And Methods: An audit of the SAH patient charts was performed. A total of 508 fluid measurements were performed in 41 patients (6 with delayed cerebral ischaemia; DCI) during 14 days of observation.

Results: Underestimating for intravenous drugs was the most frequent error (80.6%; 112), resulting in a false positive fluid balance in 2.4% of estimations. In 38.6% of the negative fluid balance cases, the physicians did not order additional fluids for the next 24h. In spite of that, the fluid intake was significantly increased after DCI diagnosis. The mean and median intake values were 3.5 and 3.8l/24h respectively, although 40% of the fluid balances were negative. The positive to negative fluid balance ratio was decreasing in the course of the 14 day observation.

Conclusions: This study revealed inconsistencies in the fluid orders as well as mistakes in the fluid monitoring, which illustrates the difficulties of fluid therapy and reinforces the need for strong evidence-based guidelines for hypervolemic therapy in SAH.
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http://dx.doi.org/10.1016/j.pjnns.2014.09.001DOI Listing
January 2015

Optimization of genetic engineering and homologous recombination of collagen type I genes in rat bone marrow mesenchymal stem cells (MSC).

Cell Reprogram 2010 Jun;12(3):275-82

Department of General and Molecular Biology and Genetics, Medical University of Silesia, Katowice, Poland.

Mutations in COL1A1 or COL1A2 genes lead to osteogenesis Imperfecta (OI) in humans. There are three possiblities to successfully treat OI including (1) gene therapy, (2) mesenchymal stem cell (MSC) therapy, or (3) a combination of both. The aim of this study was to develop a model for combined gene/cell OI therapy by targeting Col1a1 and Col1a2 genes with isogenic sequences from corresponding human genes in rat bone marrow (BM)-derived MSCs. The recombination efficacy was tested for five different rat-human-rat hybrid DNAs with rat fragments that were 1 to 4 kb long. For selection of transfected clones a neomycine resistance gene was cotransfected, and clones resistant to G418 (G418(+)) were recovered and screened for integration of specific gene loci in the rat genome. Over 90% of G418(+) clones correctly integrated the rat-human-rat hybrid DNAs, and both OI loci in the rat genome were targeted to a similar degree. Longer homologous sequences integrated into rat collagen genes approximately 10 times more efficiently. Based on our data the nonviral gene targeting technology could be potentially employed to repair collagen genes in OI patients.
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http://dx.doi.org/10.1089/cell.2009.0084DOI Listing
June 2010

Anticancer effects of CAMEL peptide.

Lab Invest 2010 Jun 8;90(6):940-52. Epub 2010 Mar 8.

Department of Molecular Biology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.

This study analyzed whether therapy with CAMEL, an antimicrobial peptide (KWKLFKKIGAVLKVL), possess anticancer benefits. Although the peptide was cytotoxic for all the cell lines tested, it did not cause hemolysis, which suggests that CAMEL does not damage cell membranes. After cellular internalization, CAMEL localized to mitochondria and lowered the mitochondrial potential, resulting in the organelles' swelling, a decrease in cellular ATP level and, finally, cellular breakdown. High mobility group box 1 (HMGB1) protein, a necrotic death marker, was shown to be released from cells treated with CAMEL. Growth of B16-F10 melanoma tumors was clearly restrained after injections with CAMEL and could be kept in check throughout the period of peptide administration. However, if therapy was stopped, tumors started to grow again 3-4 days later. To reduce tumor volume and block tumor relapse, a combined therapy was required involving CAMEL and plasmid DNA carrying the interleukin-12 (IL-12) gene. The two therapeutic agents used in combination (a series of CAMEL injections first, followed by daily administration of plasmid DNA) delayed tumor growth and extended survival of treated animals in a statistically significant manner. Complete tumor regression was found in 60% of cases.
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http://dx.doi.org/10.1038/labinvest.2010.58DOI Listing
June 2010

Blocking angiogenesis with peptides that inhibit the activity of procollagen C-endopeptidase.

Pharmacol Rep 2009 May-Jun;61(3):468-76

Department of General and Molecular Biology and Genetics, Centre of Excellence for Research and Teaching of Molecular Biology of Matrix and Nanotechnology, BioMedTech Silesia, Medical University of Silesia in Katowice, Medyków 18, Bldg C-1, PL 40-752 Katowice, Poland.

Procollagen C-endopeptidase (BMP-1) is one of two key enzymes crucial for conversion of fibrillar procollagens to self-assembling collagen monomers. Recently, we have reported inhibition of the largest variant of BMP-1, a recombinant mammalian tolloid (mTld) in vitro, on procollagen type I using peptides with amino acid sequences in chordin conserved across different species. Here, we tested the same peptides as potent blockers of angiogenesis ex vivo in cultured rings of rat aorta, in vivo in chick embryos, and in vitro in cell cultures. Our results revealed that the peptides inhibited the angiogenic activity in rat aorta explants at micromolar concentrations; they also blocked blood vessel growth in chick embryos. The peptides were also tested on three types of human cells, e.g., umbilical vein endothelium, skin fibroblasts, and tumor HT-1080 cells. Since the three types of cells proliferated at a significantly lower rate or did not proliferate at all, we conclude that the anti-angiogenic effect observed in rat aorta ring explants and in chick embryos was related to inhibition of cell proliferation. In conclusion, we showed the ability to inhibit angiogenesis by blocking the activity of procollagen C-endopeptidase. The results strongly indicate crucial role(s) of this metalloproteinase in the formation of new blood vessels and maintenance of their growth.
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http://dx.doi.org/10.1016/s1734-1140(09)70088-xDOI Listing
November 2009

Mutations in mammalian tolloid-like 1 gene detected in adult patients with ASD.

Eur J Hum Genet 2009 Mar 1;17(3):344-51. Epub 2008 Oct 1.

Swietokrzyskie Center for Cardiology, Regional Hospital, Kielce, Poland.

Atrial septal defect (ASD) is an incomplete septation of atria in human heart causing circulatory problems. Its frequency is estimated at one per 10 000. Actions of numerous genes have been linked to heart development. However, no single gene defect causing ASD has yet been identified. Incomplete heart septation similar to ASD was reported in transgenic mice with both inactive alleles of gene encoding mammalian zinc metalloprotease a mammalian tolloid-like 1 (tll1). Here, we have screened 19 ASD patients and 15 healthy age-matched individuals for mutations in TLL1 gene. All 22 exons were analyzed exon by exon for heteroduplex formation. Subsequently, DNA fragments forming heteroduplexes were sequenced. In four nonrelated patients, three missense mutations in coding sequence, and one single base change in the 5'UTR have been detected. Two mutations (Met182Leu, and Ala238Val) were detected in ASD patients with the same clinical phenotype. As the second mutation locates immediately upstream of the catalytic zinc-binding signature, it might change the enzyme substrate specificity. The third change, Leu627Val in the CUB3 domain, has been found in an ASD patient with interatrial septum aneurysm in addition to ASD. The CUB3 domain is important for substrate-specific recognition. In the remaining 15 patients as well as in 15 reference samples numerous base substitutions, deletions, and insertions have been detected, but no mutations changing the coding sequence have been found. Lack of mutations in relation to ASD of these patients could possibly be because of genetic heterogeneity of the syndrome.
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http://dx.doi.org/10.1038/ejhg.2008.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2986167PMC
March 2009

Two novel COL1A1 mutations in patients with osteogenesis imperfecta (OI) affect the stability of the collagen type I triple-helix.

J Appl Genet 2008 ;49(3):283-95

Department of General and Molecular Biology and Genetics, Medical University of Silesia, Katowice, Poland.

Osteogenesis imperfecta (OI) is a bone dysplasia caused by mutations in the COL1A1 and COL1A2 genes. Although the condition has been intensely studied for over 25 years and recently over 800 novel mutations have been published, the relation between the location of mutations and clinical manifestation is poorly understood. Here we report missense mutations in COL1A1 of several OI patients. Two novel mutations were found in the D1 period. One caused a substitution of glycine 200 by valine at the N-terminus of D1 in OI type I/IV, lowering collagen stability by 50% at 34 degrees C. The other one was a substitution of valine 349 by phenylalanine at the C-terminus of D1 in OI type I, lowering collagen stability at 37.5 degrees C. Two other mutations, reported before, changed amino residues in D4. One was a lethal substitution changing glycine 866 to serine in genetically identical twins with OI type II. That mutated amino acid was near the border of D3 and D4. The second mutation changed glycine 1040 to serine located at the border of D4 and D0.4, in a proband manifesting OI type III, and lowered collagen stability at 39 degrees C (2 degrees C lower than normal). Our results confirm the hypothesis on a critical role of the D1 and D4 regions in stabilization of the collagen triple-helix. The defect in D1 seemed to produce a milder clinical type of OI, whereas the defect in the C-terminal end of collagen type caused the more severe or lethal types of OI.
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http://dx.doi.org/10.1007/BF03195625DOI Listing
October 2008

Specific inhibition of procollagen C-endopeptidase activity by synthetic peptide with conservative sequence found in chordin.

Acta Biochim Pol 2008 7;55(2):297-305. Epub 2008 Jun 7.

Department of General and Molecular Biology, Center of Excellence for Research and Teaching of Molecular Biology of Matrix and Nanotechnology, Silesian Medical University in Katowice, Katowice, Poland.

Procollagen C-endopeptidase (BMP-1) and N-endopeptidase (ADAMTS-2) are key enzymes for correct and efficient conversion of fibrillar procollagens to their self assembling monomers. Thus, they have an essential role in building and controlling the quality of extracellular matrices (ECMs). Here, we tested inhibition of activity of the largest variant of BMP-1, a recombinant mammalian tolloid (mTld), in vitro by three synthetic peptides with conservative amino-acid sequences found in chordin using procollagen type I as a substrate. We also verified the specific action of best inhibitory 16 amino-acid peptide in the procollagen type I cleavage assay with the use of ADAMTS-2 (procollagen N-endopeptidase). Subsequently, we determined the critical residues and minimal sequence of six amino acids in the original 16 amino-acid peptide required to maintain the inhibitory potential. Studies on the interactions of 6 and 16 amino acid long peptides with the enzyme revealed their binding to non-catalytic, regulatory domains of mTld; the inhibitory activity was not due to the competition of peptides with the substrate for the enzyme active center, because mTld did not cleave the peptides. However, in the presence of mTld both peptides underwent cyclization by disulfide bond formation. Concluding, we have shown that procollagen C-endopeptidase may be specifically blocked via its non-catalytic domains by synthetic peptide consisting of 6 amino acids in the sequence found in highly conservative region of chordin. Thus, we hypothesize that the 6 amino-acid peptide could be a good candidate for anti-fibrotic drug development.
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September 2008