Warszawa, Poland
Warszawa, Poland
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Saw K.-Y.,Kuala Lumpur Sports Medicine Center | Anz A.,Andrews Research and Education Institute | Siew-Yoke Jee C.,Kuala Lumpur Sports Medicine Center | Merican S.,Kuala Lumpur Sports Medicine Center | And 3 more authors.
Arthroscopy - Journal of Arthroscopic and Related Surgery | Year: 2013

Purpose: The purpose of this study was to compare histologic and magnetic resonance imaging (MRI) evaluation of articular cartilage regeneration in patients with chondral lesions treated by arthroscopic subchondral drilling followed by postoperative intra-articular injections of hyaluronic acid (HA) with and without peripheral blood stem cells (PBSC). Methods: Fifty patients aged 18 to 50 years with International Cartilage Repair Society (ICRS) grade 3 and 4 lesions of the knee joint underwent arthroscopic subchondral drilling; 25 patients each were randomized to the control (HA) and the intervention (PBSC + HA) groups. Both groups received 5 weekly injections commencing 1 week after surgery. Three additional injections of either HA or PBSC + HA were given at weekly intervals 6 months after surgery. Subjective IKDC scores and MRI scans were obtained preoperatively and postoperatively at serial visits. We performed second-look arthroscopy and biopsy at 18 months on 16 patients in each group. We graded biopsy specimens using 14 components of the International Cartilage Repair Society Visual Assessment Scale II (ICRS II) and a total score was obtained. MRI scans at 18 months were assessed with a morphologic scoring system. Results: The total ICRS II histologic scores for the control group averaged 957 and they averaged 1,066 for the intervention group (P =.022). On evaluation of the MRI morphologic scores, the control group averaged 8.5 and the intervention group averaged 9.9 (P =.013). The mean 24-month IKDC scores for the control and intervention groups were 71.1 and 74.8, respectively (P =.844). One patient was lost to follow-up. There were no notable adverse events. Conclusions: After arthroscopic subchondral drilling into grade 3 and 4 chondral lesions, postoperative intra-articular injections of autologous PBSC in combination with HA resulted in an improvement of the quality of articular cartilage repair over the same treatment without PBSC, as shown by histologic and MRI evaluation. Level of Evidence: Level II, randomized controlled trial (RCT). © 2013 by the Arthroscopy Association of North America.

PubMed | Kuala Lumpur Sports Medicine Center, Andrews Research and Education Institute, University Putra Malaysia and Genomed Inc.
Type: Journal Article | Journal: Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association | Year: 2015

To histologically evaluate the quality of articular cartilage regeneration from the medial compartment after arthroscopic subchondral drilling followed by postoperative intra-articular injections of autologous peripheral blood stem cells (PBSCs) and hyaluronic acid with concomitant medial open-wedge high tibial osteotomy (HTO) in patients with varus deformity of the knee joint.Eight patients with varus deformity of the knee joint underwent arthroscopic subchondral drilling of International Cartilage Repair Society (ICRS) grade 4 bone-on-bone lesions of the medial compartment with concomitant HTO. These patients were part of a larger pilot study in which 18 patients underwent the same procedure. PBSCs were harvested and cryopreserved preoperatively. At 1 week after surgery, 8 mL of PBSCs was mixed with 2 mL of hyaluronic acid and injected intra-articularly into the knee joint; this was repeated once a week for 5 consecutive weeks. Three additional intra-articular injections were administered weekly at intervals of 6, 12, and 18 months postoperatively. Informed consent was obtained at the time of hardware removal for opportunistic second-look arthroscopy and chondral biopsy. Biopsy specimens were stained with H&E, safranin O, and immunohistochemical staining for type I and II collagen. Specimens were graded using the 14 components of the ICRS Visual Assessment Scale II, and a total score was obtained.Second-look arthroscopy showed satisfactory healing of the regenerated cartilage. Histologic analysis showed significant amounts of proteoglycan and type II collagen. The total ICRS Visual Assessment Scale II histologic scores comparing the regenerated articular cartilage (mean, 1,274) with normal articular cartilage (mean, 1,340) indicated that the repair cartilage score approached 95% of the normal articular cartilage score. There were no infections, delayed unions, or nonunions.Chondrogenesis with stem cells in combination with medial open-wedge HTO for varus deformity correction of the knee joint regenerates cartilage that closely resembles the native articular cartilage.Level IV, therapeutic case series.

Jurecka A.,University of Gdansk | Jurecka A.,The Childrens Memorial Health Institute | Piotrowska E.,University of Gdansk | Cimbalistiene L.,Vilnius University | And 7 more authors.
Molecular Genetics and Metabolism | Year: 2012

Mucopolysaccharidosis VI (MPS VI) is a rare autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB). Over 130 ARSB gene mutations have been identified thus far and most mutations are unique to individual families. We aimed to analyze the spectrum of mutations in the ARSB gene responsible for the disorder in Poland, Belarus and Baltic States. Twenty one families with MPS VI patients, in whom diagnosis was confirmed biochemically and enzymatically, were studied. Direct sequencing of patient genomic DNA was used to identify ARSB mutations. In total, fourteen different disease-causing mutations were found. Three novel mutations included insertion c.375_376insT, a missense mutation c.499G>A (p.G167R) and deletion/insertion c.750_754delinsCCTGAAGTCAAG. We also report 11 previously described mutations (p.A33V, p.W57C, p.Q88X, p.T92K, p.Q97X, p.R152W, p.R160Q, p.R160X, p.Y210C, p.Y266S, p.G302R). The mutation p.R152W was present at a high prevalence of 50% (21/42) the mutated alleles in this group of patients. High prevalence of p.R152W mutation in Poland, Belarus and Baltic States indicates a possible founder effect and suggests that screening for this mutation may be appropriate in MPS VI patients from this region. Our study has also provided evidence to support genotype-phenotype correlation. © 2011 Elsevier Inc.

Stankiewicz-Drogon A.,Polish Academy of Sciences | Dorner B.,University of Vienna | Erker T.,University of Vienna | Boguszewska-Chachulska A.M.,Genomed Inc. | Boguszewska-Chachulska A.M.,Warsaw University of Technology
Journal of Medicinal Chemistry | Year: 2010

A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC 50 from 1.5 to 20 μM). The acridone derivatives probably act via intercalation into double-stranded nucleic acids with a strong specificity for double-stranded RNA, although an interaction with the enzyme cannot be excluded. Testing in the subgenomic HCV replicon system revealed that compounds 10 and 13 are efficient RNA replication inhibitors, with EC50 of 3.5 and 1 μM and therapeutic indexes of >28 and 20, respectively. Compound 16, with EC50 < 1 μM and TI > 1000, is extremely specific and practically noncytotoxic at the concentrations tested, proving that the acridone derivatives may be regarded as potential antiviral agents. Although the mechanism of action of 16 in the replicon system remains unclear, it is the key lead compound for further development of anti-HCV drugs. © 2010 American Chemical Society.

Teper S.J.,Okregowy Szpital Kolejowy | Nowinska A.,Okregowy Szpital Kolejowy | Pilat J.,Okregowy Szpital Kolejowy | Palucha A.,Genomed Inc. | Wylegala E.,Okregowy Szpital Kolejowy
Molecular Vision | Year: 2010

Purpose: To determine whether gene polymorphisms of the major genetic risk factor for age-related macular susceptibility 2 (ARMS2 A69S) and the complement factor H Y402H influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration. Methods: This prospective cohort study included 90 patients (90 eyes) with exudative age related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (Mitchell et al.). Injections were administered monthly when a patient lost five letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness (CSRT). Genotypes (rs10490924 and rs1061170) were analyzed using gene sequence analysis. Best-corrected visual acuity (BCVA) and CSRT values were compared between ARMS2 and complement factor H genotypes. Multiple regression analysis was used to assess the statistical significance. Results: Mean increase in visual acuity was 4.44±8.12 letters with a 103.63±94.7 μm decrease in CSRT. BCVA improvement was statistically significant in all genotype groups except in homozygous 69S in the AMRS2 gene. CSRT and BCVA changes were correlated (r=0.2521; 95% CI: 0.04746-0.4364, p=0.0165). Multiple regression analysis revealed a significant impact of 69S (p=0.015) on the change in BCVA. Conclusions: Visual acuity did not improve during the study in patients homozygous for ARMS2 69S, despite a decrease in CSRT. Further investigation is needed to confirm our findings and understand the mechanisms involved. © 2010 Molecular Vision.

Sobczynska-Tomaszewska A.,Institute of Mother and Child | Sobczynska-Tomaszewska A.,Genomed Inc. | Oltarzewski M.,Institute of Mother and Child | Czerska K.,Institute of Mother and Child | And 8 more authors.
European Journal of Human Genetics | Year: 2013

Newborn screening for cystic fibrosis (NBS CF) in Poland was started in September 2006. Summary from 4 years' experience is presented in this study. The immunoreactive trypsin/DNA sequencing strategy was implemented. The group of 1 212 487 newborns were screened for cystic fibrosis during the programme. We identified a total of 221 CF cases during this period, including, 4 CF cases were reported to be omitted by NBS CF. Disease incidence in Poland based on the programme results was estimated as 1/4394 and carrier frequency as 1/33. The frequency of the F508del was similar (62%) to population data previously reported. This strategy allowed us to identify 29 affected infants with rare genotypes. The frequency of some mutations (eg, 2184insA, K710X) was assessed in Poland for the first time. Thus, sequencing assay seems to be accurate method for screening programme using blood spots in the Polish population. © 2013 Macmillan Publishers Limited All rights reserved.

Najda-Bernatowicz A.,Polish Academy of Sciences | Krawczyk M.,Polish Academy of Sciences | Krawczyk M.,Genomed Inc. | Stankiewicz-Drogon A.,Polish Academy of Sciences | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2010

We synthesized new tropolone derivatives substituted with cyclic amines: piperidine, piperazine or pyrrolidine. The most active anti-helicase compound (IC 50= 3.4 μM), 3,5,7-tri[(4′-methylpiperazin-1′-yl) methyl]tropolone (2), inhibited RNA replication by 50% at 46.9 μM (EC 50) and exhibited the lowest cytotoxicity (CC 50) >1 mM resulting in a selectivity index (SI = CC 50/EC 50) >21. The most efficient replication inhibitor, 3,5,7-tri[(4′-methylpiperidin- 1′-yl)methyl]tropolone (6), inhibited RNA replication with an EC 50 of 32.0 μM and a SI value of 17.4, whereas 3,5,7-tri[(3′- methylpiperidin-1′-yl)methyl]tropolone (7) exhibited a slightly lower activity with an EC 50 of 35.6 μM and a SI of 9.8. © 2010 Elsevier Ltd. All rights reserved.

Rachwal K.,Maria Curie Sklodowska University | Matczynska E.,Jagiellonian University | Matczynska E.,Genomed Inc. | Janczarek M.,Maria Curie Sklodowska University
BMC Genomics | Year: 2015

Background: Rhizobium leguminosarum bv. trifolii is a soil bacterium capable of establishing a symbiotic relationship with red clover (Trifolium pratense). The presence of surface polysaccharides and other extracellular components as well as motility and competitiveness are essential traits for both adaptation of this bacterium to changing environmental conditions and successful infection of host plant roots. The R. leguminosarum bv. trifolii rosR gene encodes a protein belonging to the family of Ros/MucR transcriptional regulators, which contain a Cys2His2-type zinc-finger motif and are involved in the regulation of exopolysaccharide synthesis in several rhizobial species. Previously, it was established that a mutation in the rosR gene significantly decreased exopolysaccharide synthesis, increased bacterial sensitivity to some stress factors, and negatively affected infection of clover roots. Results: RNA-Seq analysis performed for the R. leguminosarum bv. trifolii wild-type strain Rt24.2 and its derivative Rt2472 carrying a rosR mutation identified a large number of genes which were differentially expressed in these two backgrounds. A considerable majority of these genes were up-regulated in the mutant (63.22%), indicating that RosR functions mainly as a repressor. Transcriptome profiling of the rosR mutant revealed a role of this regulator in several cellular processes, including the synthesis of cell-surface components and polysaccharides, motility, and bacterial metabolism. Moreover, it was established that the Rt2472 strain was characterized by a longer generation time and showed an increased aggregation ability, but was impaired in motility as a result of considerably reduced flagellation of its cells. Conclusions: The comparative transcriptome analysis of R. leguminosarum bv. trifolii wild-type Rt24.2 and the Rt2472 mutant identified a set of genes belonging to the RosR regulon and confirmed the important role of RosR in the regulatory network. The data obtained in this study indicate that this protein affects several cellular processes and plays an important role in bacterial adaptation to environmental conditions. © 2015 Rachwal et al.

Krawczyk M.,Polish Academy of Sciences | Stankiewicz-Drogon A.,Polish Academy of Sciences | Haenni A.-L.,Institute Jacques Monod | Boguszewska-Chachulska A.,Genomed Inc.
Methods in Molecular Biology | Year: 2010

The development of techniques based on fluorescence has made it possible to create new types of assays that represent an advantageous alternative to old tests relying on radioactivity. Such a novel approach has been applied to develop a high-throughput assay to measure the helicase activity of the hepatitis C virus (HCV) NS3 protein and the inhibitory potential of several classes of compounds. The NS3 helicase is one of the most promising targets of anti-HCV-oriented screening of compounds due to the urgent need for more effective and tolerable drugs. The 96- or 384-well microplate assay that we developed is based on the use of a quenched double-stranded DNA substrate labeled with a fluorophore (Cy3 or FAM) and with a Black Hole Quencher 1 or 2. It allows for direct (real-time) measurements of substrate unwinding and inhibition of unwinding by anti-helicase compounds. After a few modifications of buffers and assay conditions this method can be applied to various variants of HCV helicase and other proteins with helicase activities. © 2009 Humana Press, a part of Springer Science+Business Media, LLC.

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