Nanoplastics Penetrate Human Bronchial Smooth Muscle and Small Airway Epithelial Cells and Affect Mitochondrial Metabolism.

Micro- and nanoplastic particles, including common forms like polyethylene and polystyrene, have been identified as relevant pollutants, potentially causing health problems in living organisms. The mechanisms at the cellular level largely remain to be elucidated. This study aims to visualize nanoplastics in bronchial smooth muscle (BSMC) and small airway epithelial cells (SAEC), and to assess the impact on mitochondrial metabolism. Healthy and asthmatic human BSMC and SAEC in vitro cultures were stimulated with polystyrene nanoplastics (PS-NPs) of 25 or 50 nm size, for 1 or 24 h. Live cell, label-free imaging by holotomography microscopy and mitochondrial respiration and glycolysis assessment were performed. Furthermore, 25 and 50 nm NPs were shown to penetrate SAEC, along with healthy and diseased BSMC, and they impaired bioenergetics and induce mitochondrial dysfunction compared to cells not treated with NPs, including changes in oxygen consumption rate and extracellular acidification rate. NPs pose a serious threat to human health by penetrating airway tissues and cells, and affecting both oxidative and glycolytic metabolism.

Articular Cartilage Reconstruction with Hyaluronate-Based Scaffold Significantly Decreases Pain and Improves Patient's Functioning.

Articular cartilage lesions negatively affect patients' well-being, causing severe pain and significantly limiting functioning. The purpose of this study was to evaluate the effectiveness of a one-stage reconstruction, performed arthroscopically using a hyaluronate-based scaffold. Pain reduction and functional improvement were assessed. The study also evaluated if postoperative vitamin D supplementation and rehabilitation protocol impact obtained outcomes. A group of 29 patients was included in a retrospective study. All the participants underwent arthroscopic reconstruction of osteochondral lesions using hyaluronate-based scaffolds. The study group used standard questionnaires to self-assess their condition before surgery and at the time of completion. Despite the aforementioned, all the participants fulfilled two original questionnaires on postoperative rehabilitation and vitamin D supplementation. Significant pain reduction (mean NRS 1.83 vs. 7.21, p < 0.0001) and functional improvement (mean Lysholm score 82.38 vs. 40.38, p < 0.0001; mean OKS 40.2 vs. 23.1, p < 0.0001) were found. No differences in pain reduction and functional improvement were seen between genders. The impact of post-operative rehabilitation and vitamin D supplementation on clinical outcomes was found to be statistically nonsignificant. The results obtained in this study clearly confirm the effectiveness of osteochondral reconstruction using hyaluronate-based scaffolds. The outcomes were equally favorable, regardless of postoperative rehabilitation and vitamin D supplementation.

Structural Patterns Enhancing the Antibacterial Activity of Metallacarborane-Based Antibiotics.

Healthcare systems heavily rely on antibiotics to treat bacterial infections, but the widespread presence of multidrug-resistant bacteria puts this strategy in danger. Novel drugs capable of overcoming current resistances are needed if our ability to treat bacterial infections is to be maintained. Boron clusters offer a valuable possibility to create a new class of antibiotics and expand the chemical space of antibiotics beyond conventional carbon-based molecules. In this work, we identified two promising structural patterns providing cobalta bis(dicarbollide)(COSAN)-based compounds with potent and selective activity toward Staphylococcus aureus (including clinical strains): introduction of the α-amino acid amide and addition of iodine directly to the metallacarborane cage. Furthermore, we found that proper hydrophilic-lipophilic balance is crucial for the selective activity of the tested compounds toward S. aureus over mammalian cells. The patterns proposed in this paper can be useful in the development of metallacarborane-based antibiotics with potent antibacterial properties and low cytotoxicity.

Case report: Unusual patient with dermatomyositis associated with SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a major challenge for clinicians. SARS-CoV-2 infection results in coronavirus disease 2019 (COVID-19), and it is best known for its respiratory symptoms. It can also result in several extrapulmonary manifestations such as neurological complications potentially experienced during the course of COVID-19. The association of dermatomyositis (DM) with COVID-19 pathogenesis has not been well-studied. This study aimed to present a previously healthy 37-year-old man, a soldier by profession, with symptoms of DM on the 4th day from the onset of COVID-19. The patient presented DM symptoms with both skin and muscle manifestations. The patient suffered from cough, fever, and fatigue to begin with, and reverse-transcription polymerase chain reaction (RT-PCR) reported positive for SARS-CoV-2 infection. The laboratory findings showed, intra alia, elevated muscle enzymes CK 8253 U/l (N: <145 U/l), a positive test for myositis-specific autoantibodies (anti-Mi-2), electrodiagnostic tests exhibited features of myopathy, with the presence of muscle and skin symptoms. The patient improved with corticosteroids and immunosuppressive agent therapy. In summary, the association between COVID-19 and the development of multi-system autoimmune disorders such as DM remains unclear. Nevertheless, viral infections such as SARS-CoV-2 may likely serve as a trigger.

The Influence of Comorbidities on Chemokine and Cytokine Profile in Obstructive Sleep Apnea Patients: Preliminary Results.

INTRODUCTION: Obstructive sleep apnea (OSA) is frequently associated with a chronic inflammatory state and cardiovascular/metabolic complications. The aim of this study was to evaluate the influence of certain comorbidities on a panel of 45 chemokines and cytokines in OSA patients with special regard to their possible association with cardiovascular diseases. MATERIAL AND METHODS: This cross-sectional study was performed on 61 newly diagnosed OSA patients. For the measurement of the plasma concentration of chemokines and cytokines, the magnetic bead-based multiplex assay for the Luminex® platform was used. RESULTS: In the patients with concomitant COPD, there were increased levels of pro-inflammatory cytokines (CCL11, CD-40 ligand) and decreased anti-inflammatory cytokine (IL-10), while in diabetes, there were increased levels of pro-inflammatory cytokines (IL-6, TRIAL). Obesity was associated with increased levels of both pro-inflammatory (IL-13) and anti-inflammatory (IL-1RA) cytokines. Hypertension was associated with increased levels of both pro-inflammatory (CCL3) and anti-inflammatory (IL-10) cytokines. Increased daytime pCO2, low mean nocturnal SaO2, and the oxygen desaturation index were associated with increased levels of pro-inflammatory cytokines (CXCL1, PDGF-AB, TNF-α, and IL-15). CONCLUSIONS: In OSA patients with concomitant diabetes and COPD, elevated levels of certain pro-inflammatory and decreased levels of certain anti-inflammatory cytokines may favor the persistence of a chronic inflammatory state with further consequences. Nocturnal hypoxemia, frequent episodes of desaturation, and increased daytime pCO2 are factors contributing to the chronic inflammatory state in OSA patients.

Polymorphisms within Genes Coding for IL-17A and F and Their Receptor as Clinical Hallmarks in Ankylosing Spondylitis.

IL-17A and IL-17F together with their coreceptor (IL-17RA/RC) were reported to play a significant role in the pathogenesis of spondyloarthritis. The group of axial spondyloarthritis comprises ankylosing spondylitis (AS), a rheumatic disease characterized by chronic inflammation of the joints in the spine. This study is aimed at investigating IL-17A, IL-17F, IL-17RA, and IL-17RC polymorphisms as potential biomarkers of disease susceptibility, clinical parameters, and anti-TNF treatment outcome in a cohort of Polish ankylosing spondylitis patients. In total, 328 subjects, including 138 AS patients and 190 healthy volunteers, participated in the study. Genotyping of IL-17A rs2275913 (G/A), IL-17F rs763780 (A/G), IL-17RA rs4819554 (A/G), and IL-17RC rs708567 (G/A) was performed on real-time PCR instrument using LightSNiP assays. No significant differences were revealed in genotype and allele distribution between patients and controls despite the association of the IL-17RC rs708567 AA homozygosity with the earlier onset of the disease. Moreover, some relationships between IL-17F rs763780 and IL-17RA rs4819554 polymorphisms with clinical parameters related to the disease activity and anti-TNF treatment outcome were observed. IL-17F rs763780 G allele was found to be associated with high disease activity and BASDAI after 6 months and poor response to the treatment while higher VAS values were more common among IL-17RA rs4819554 G variant carriers. In conclusion, the IL-17F rs763780 polymorphism should be considered as a promising biomarker of disease activity and anti-TNF treatment outcome. The IL-17RA rs48419554 G allele may serve as a potential marker of disease severity in Polish AS patients.

Decreased Thrombospondin-1 and Bone Morphogenetic Protein-4 Serum Levels as Potential Indices of Advanced Stage Lung Cancer.

INTRODUCTION: Lung cancer belongs to the most common carcinoma worldwide and is the leading cause of cancer-related death. Bone morphogenetic protein-4 (BMP-4) is extracellular signaling molecule involved in many important processes, including cell proliferation and mobility, apoptosis and angiogenesis. Thrombospondin-1 (TSP-1) belongs to the extracellular matrix proteins. It participates in the cell-to-cell and cell-to-matrix interactions and thus plays important role in tumor microenvironment for cancer development and metastasis formation. AIM: To investigate serum levels of TSP-1 and BMP-4 together with BMP-4 polymorphism in lung cancer patients. MATERIAL AND METHODS: A total of 111 patients (76 men) with newly diagnosed lung cancer, including 102 patients with non-small cell lung cancer and 9 patients with small-cell lung cancer. Advanced stage of lung cancer was diagnosed in 99 (89%) of patients: stage IV-in 48, stage IIIB-in 33, stage IIIA-in 18 patients; there were six patients with stage II and six patients with stage I. The control group consisted of 61 healthy persons. In all the subjects, serum levels of BMP-4 and TSP-1 were measured by ELISA. With a Real-Time PCR system genotyping of BMP-4 was performed. RESULTS: BMP-4 and TSP-1 serum levels were significantly lower in the patients with lung cancer than in the controls (TSP-1:10,109.2 ± 9581 ng/mL vs. 11,415.09 ± 9781 ng/mL, p < 0.05; BMP-4: 138.35 ± 62.59 pg/mL vs. 226.68 ± 135.86 pg/mL p < 0.001). In lung cancer patients TSP-1 levels were lower in advanced stages (9282.07 ± 4900.78 ng/mL in the stages III-IV vs. 16,933.60 ± 6299.02 ng/mL in the stages I-II, p < 0.05) and in the patients with than without lymph nodes involvement (10,000.13 ± 9021.41 ng/mL vs. 18,497.75 ± 12,548.25 ng/mL, p = 0.01). There was no correlation between TSP-1 and BMP-4 serum levels. BMP-4 gene polymorphism did not influence the results of the study. CONCLUSION: Decreased levels of TSP-1 and BMP-4 may serve as potential indices of lung cancer, with additional importance of low TSP-1 level as a marker of advanced stage of the disease.

IL-33 Gene Polymorphisms as Potential Biomarkers of Disease Susceptibility and Response to TNF Inhibitors in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Patients.

Objective: Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) belong to inflammatory rheumatic diseases, the group of conditions of unknown etiology. However, a strong genetic component in their pathogenesis has been well established. A dysregulation of cytokine networks plays an important role in the development of inflammatory arthritis. Interleukin 33 (IL-33) is a recently identified member of the IL-1 family. To date, the significance of IL-33 in inflammatory arthritis has been poorly studied. This research aimed to investigate the potential of IL-33 gene polymorphisms to serve as biomarkers for disease susceptibility and TNF inhibitor response in RA, AS, and PsA patients. Materials and Methods: In total, 735 patients diagnosed with RA, AS, and PsA and 229 healthy individuals were enrolled in the study. Genotyping for three single nucleotide polymorphisms (SNPs) within the IL-33 gene, namely, rs16924159 (A/G), rs10975519 (T/C), and rs7044343 (C/T), was performed using polymerase chain reaction amplification employing LightSNiP assays. Results: In the present study, the IL-33 rs10975519 CC genotype was associated with a decreased risk of developing RA in females, while the IL-33 rs16924159 polymorphism was associated with the efficacy of anti-TNF therapy and clinical parameters for RA and AS patients. The IL-33 rs16924159 AA genotype correlated with higher disease activity and worse clinical outcomes in RA patients treated with TNF inhibitors, and AS patients carrying the IL-33 rs16924159 AA genotype had higher disease activity and a worse response to anti-TNF therapy. That indicates a deleterious role of the IL-33 rs16924159 AA genotype in the context of RA, as well as AS. Conclusions: The obtained results suggest that IL-33 gene polymorphisms might be potential candidate biomarkers of disease susceptibility and anti-TNF treatment response in patients with inflammatory rheumatic diseases.

Polymorphisms within the RANK and RANKL Encoding Genes in Patients with Rheumatoid Arthritis: Association with Disease Progression and Effectiveness of the Biological Treatment.

Inconsistency of the results regarding the genetic variability within genes coding for receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) in rheumatoid arthritis (RA) prompted us to study the RANK and RANKL polymorphisms as potential biomarkers associated with disease predisposition and response to anti-TNF treatment in a group of Polish patients with RA. This study enrolled 318 RA patients and 163 controls. RANK (rs8086340, C > G; rs1805034, C > T) and RANKL (rs7325635, G > A; rs7988338 G > A) alleles were determined by real-time PCR with melting curve analysis and related with clinical parameters. In addition, RANKL serum levels were measured by ELISA. The RANK rs8086340-G allele was overrepresented among patients as compared to controls (OD = 1.777, p = 0.038). C-reactive protein (CRP) levels were significantly (p < 0.05) associated with RANK rs8086340 polymorphism and were higher in the CC-homozygotes at the baseline while lower in the GG-carriers at the 12th week of the treatment. At the latter time point RANKL rs7325635-GG-positive patients also showed significantly lower CRP concentrations. Higher alkaline phosphatase levels before induction of anti-TNF therapy were observed in RANK rs8086340 and RANK rs1805034 CC homozygotes (p = 0.057 and p = 0.035, respectively). The GG homozygosity of both RANKL single nucleotide polymorphisms was significantly associated with the number of swollen joints (rs7988338 and rs7325635, before and at the 12th week of therapy, respectively, p < 0.05 in both cases). These results imply that polymorphisms within the RANK and RANKL genes affect RA susceptibility and anti-TNF treatment outcome.

Genetic basis of sleep bruxism and sleep apnea-response to a medical puzzle.

Sleep bruxism (SB) and obstructive sleep apnea (OSA) are co-occurring sleep conditions. The study aimed to evaluate the association of selected single-nucleotide polymorphisms (SNPs) occurring within the genes of the serotonin and dopamine pathways in SB and OSA and investigate the relationship between them. The study group included 100 Caucasian patients. SB and OSA were diagnosed in 74 and 28 patients, respectively. In addition, 125 unrelated Caucasian healthy blood donors served as randomly selected controls to enable comparison of polymorphisms. The following SNPs were analyzed: rs2770304 and rs6313 within the serotonin receptor encoding gene (HTR2A), rs4680 polymorphism of the catechol-O-methyltransferase (COMT) gene, and rs686 within the dopamine receptor (DRD1) encoding gene. The prevalence of the DRD1 rs686 G variant (GG homozygosity) was found to be high in the study group compared to the control group. Bruxism episode index (BEI) was found to be significantly increased in the HTR2A rs6313 TT homozygotes compared to the heterozygous patients. Moreover, within a group of the HTR2A rs2770304 TT homozygous cases, a statistically significant correlation was observed between BEI and apnea-hypopnea index. These results indicate that DRD1 rs686 may potentially affect predisposition to SB, that HTR2A rs6313 SNP may be involved in SB pathogenesis, and that HTR2A rs2770304 polymorphism might contribute to the association between SB and OSA. This suggests a possible genetic contribution to the etiology of primary SB.

ECCR1 and NFKB2 Polymorphisms as Potential Biomarkers of Non-small Cell Lung Cancer in a Polish Population.

BACKGROUND/AIM: Although genetic factors are presumed to account only for a part of the inter-individual variation in lung cancer susceptibility, the results are conflicting and there are no data available regarding the Polish population. We, therefore, performed a case-control study to investigate the association of seven selected single nucleotide polymorphisms (SNPs), in genes coding for excision repair cross-complimentary group 1 (ERCC1: rs11615, rs3212986, rs2298881), nuclear factor ĸB (NFKB2: rs7897947, rs12769316), bone morphogenetic protein 4 (BMP4: rs1957860), complement receptor 1 (CR1: rs7525160) and del/ins polymorphism in the family hypoxia inducible factor 2 gene (EGLN2: rs10680577), with non-small cell lung cancer (NSCLC) risk. MATERIALS AND METHODS: Real-time PCR with melting curve analysis was used for genotyping of NSCLC patients and healthy individuals of Polish origin. RESULTS: The ERCC1 rs11615 T allele and rs3212986 GG homozygosity were found to be associated with a higher risk of developing NSCLC. In addition, NFKB2 rs12769316 GG homozygosity was more frequently detected among male patients than controls, while no significant differences were found between the five polymorphisms. CONCLUSION: ERCC1 polymorphisms may affect NSCLC risk in the Polish population, while the NFKB2 variant may be a possible marker of the disease in males.

G-CSF administration favours SDF-1 release and activation of neutrophils and monocytes in recipients of autologous peripheral blood progenitor cells.

G-CSF is a growth factor widely used to mobilise CD34+ progenitor cells for clinical applications. The present study aimed to assess expression of G-CSF receptor (CSF3R) on neutrophils and monocytes, as well as SDF-1 and G-CSF serum levels in relation to efficacy of G-CSF-induced mobilisation for autologous transplantation. For this purpose, 105 patients with haematological disorders and 46 healthy controls were investigated. Before mobilisation patients were characterised with significantly higher percentage of CSF3R expressing neutrophils (p < 0.001) and monocytes (p = 0.002), than controls. G-CSF administration resulted in a decrease of CSF3R+ neutrophils (p < 0.001) and monocytes (p < 0.001), while presence of G-CSF receptor on neutrophils tended to negatively affect mobilisation yield (p = 0.075). G-CSF concentration increased during mobilisation (p < 0.001). On the 5th day of mobilisation a positive correlation was observed between G-CSF and SDF-1 serum levels (p < 0.001) and the number of CD34+ cells released from bone marrow seemed to be related to both G-CSF (p = 0.036) and SDF-1 levels (p = 0.084). As compared to Hodgkin's lymphoma patients, those with multiple myeloma had lower basal percentage of CSF3R+ neutrophils (p = 0.014) while Non-Hodgkin's lymphoma cases exhibited higher G-CSF (p = 0.026) and SDF-1 (p = 0.006) concentration on mobilisation day 5. Hodgkin's lymphoma patients were also characterised with worse mobilisation efficacy than multiple myeloma (p = 0.022) and Non-Hodgkin's lymphoma (p = 0.013) patients. These results suggest that both SDF-1 and G-CSF play a role in HSC release into peripheral blood and show that G-CSF administration affects expression of CSF3R on monocytes and neutrophils, implying potential role of these cell subpopulations in mobilisation process.

Genetically determined enlargement of carotid body evaluated using computed angiotomography.

It has recently been established that carotid bodies play a significant role in the regulation of activities of the cardiovascular system as well as in the pathogenesis of arterial hypertension, heart failure and diabetes. Aim of study was to determinate the influence of polymorphisms within genes of the renin-angiotensin-aldosterone system (RAAS) on the volume of the carotid bodies (CB) in patients with hypertension (HTA). The study group consisted of 77 patients with HTA. All patients were genotyped for single-nucleotide polymorphisms of genes coding for: angiotensinogen: rs4762, rs5049, rs5051 and rs699; angiotensin-converting enzyme: rs4343; angiotensin receptor type 1 gene (AGTR1): rs5182 and rs5186; and the aldosterone synthase: rs1799998. The estimation of volumes of CB (VrCB+lCB) was based on computed tomography angiography. Among individuals with essential hypertension certain relationships were documented between rs5182 and rs5186 polymorphisms of AGTR1 gene and rs1799998 polymorphism of CYP11B2 gene on one hand and the volume of carotid bodies on one other. Patients carrying the C alleles within the rs5182 and rs5186 of AGTR1 gene was associated with higher values of VrCB+lCB. The carriage of the T allele in the rs5182 locus of the AGTR1 gene determine lower values of VrCB+lCB. In summary, in patients with HTA a higher volume of CB may be resulted from the presence of specific genotypes in RAAS.

The renin-angiotensin-aldosterone system (RAAS) - physiology and molecular mechanisms of functioning.

Secretion of renin juxtaglomerular cells into bloodstream initiates activation of an enzymatic-hormonal cascade known as the RAAS (renin - angiotensin - aldosterone system). As a result, blood pressure is increased by the means several interrelated mechanisms. Mechanism of Zjednoczoaction of this system has been known for decades, but a few previously unknown components were recently added, such as ACE-2 and Ang(1-7), and their role often seems to be opposite to that of the conventional components. Local tissue systems also have important biological functions. They operate largely independently of the systemic activity, and their activity is observed primarily in the kidney, heart, in blood vessels, adrenal gland and nervous system. Angiotensin-2 (Ang-2), the main RAAS effector, has a wide scope of action, and thus abnormalities in its functioning have many consequences. Excessive activation is accompanied by chronic inflammation, as Ang-2 stimulates inflammatory mediators. As a result, degenerative processes and atherosclerosis are initiated. RAAS imbalance is associated with the most common diseases of civilization, such as cardio-vascular diseases, diabetes, kidney diseases, preeclampsia, osteoporosis and even neurodegenerative diseases. Many of these pathological processes are attributed to the excessive activation of tissue RA system. Therapeutic strategies based on inhibition of the RAAS are commonly used mainly in the treatment of hypertension and other cardiovascular disorders. The benefits of this class of drugs is primarily a decrease in blood pressure, but also the suppression of inflammatory processes and other pathological phenomena resulting from excessive activation of the RAAS. For that reason, some consider to use RAAS inhibitors in other diseases, e.g. Parkinson's disease. Further studies give hope for the improvement of RAAS inhibitor therapy and the development of new therapeutic strategies.

Cereblon and IRF4 Variants Affect Risk and Response to Treatment in Multiple Myeloma.

Multiple myeloma (MM) is a plasma-cell malignancy derived from an early precursor of the B-cell lineage characterised by bone-marrow infiltration, lytic bone lesions, and the presence of a monoclonal protein in serum and/or urine. Interferon regulatory factor 4 (IRF4) is a critical transcriptional regulator in B-cell development and function that is required during immune response for lymphocyte activation and the generation of immunoglobulin-secreting plasma cells. Immunomodulatory drugs, derivatives of thalidomide, are commonly used in therapy against MM. They are known to target a protein called cereblon (CRBN); however, the exact mechanism remains unknown. The present study aimed to assess the association of two (rs12203592 and rs872071) polymorphisms within the IRF4 gene and two (rs711613 and rs1045433) in the CRBN gene with MM susceptibility, progression, and response to treatment. For this purpose, 144 MM patients and 126 healthy individuals were genotyped for the IRF4 and CRBN alleles. The presence of the IRF4 (rs872071) G allele was more frequently detected in patients than healthy individuals (OR 1.78; P = 0.034), and this relationship was especially pronounced in women (OR 2.83; P = 0.012). The CRBN (rs711613) A allele-carriers were better responders to the treatment (P = 0.012), in particular to thalidomide including therapy (P = 0.023). These results underline the prognostic significance of the IRF4 and CRBN polymorphisms in patients with MM.

Liposomal formulation of 5-fluorocytosine in suicide gene therapy with cytosine deaminase--for colorectal cancer.

It is generally accepted that successful gene therapy depends on two major factors: tumor-specific expression of a therapeutic gene and the efficient transfer of a therapeutic gene to tumor cells. For gene-directed enzyme prodrug therapy (GDEPT) involving Escherichia coli cytosine deaminase (CD) and 5-fluorocytosine (5-FC), several tumor-specific promoters and virus-based vectors were used. No attention whatsoever was paid to the way of 5-FC delivery to solid tumors, despite the fact that the delivery of drugs to such tumors is generally low because of their insufficient transfer from the blood. To compare the effectiveness of GDEPT with free and liposomal 5-FC, the prodrug was encapsulated in liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (1:1). When the liposomal form of 5-FC was administered i.v., mice treated with a dose of 5mg of liposomal 5-FC/kg body weight for 10 days, showed complete regression of transplanted tumors and complete cure was observed, whereas in animals treated with the same amounts of the free prodrug, 50% tumor regression and only insignificantly prolonged median survival were found. In summary, these results showed a remarkable enhancement of the antitumor effects of the liposomal form of 5-FC in comparison with the free prodrug. Therapy with liposomal 5-FC thus represents a new approach to achieving a high local concentration of the prodrug for suicide gene therapy using E. coli CD.

Plasmid condensation induced by cationic compounds: hydrophilic polylysine and amphiphilic cationic lipid.

The construction of an efficient carrier for genetic material is a major research objective that needs to be achieved before gene therapy can become a viable pharmacological approach. Artificial aggregates containing nucleic acids are one of the options for the systemic delivery of genetic information. The diversity of functions the aggregate is expected to fulfill necessitates its complex architecture. In order to obtain a complex supramolecular aggregate, formed from elements that are themselves complex molecules, appropriate procedures based on the detailed understanding of processes at the molecular level are required. In this study, we investigated how the various properties of cationic compounds affect nucleic acid condensation. The combination of two condensing agents, differing in their affinity towards water, when mixed with plasmids, resulted in aggregates which are resistant to enzymatic digestion and which form particles with well-defined size distributions. Such uniform and well-defined complexes may subsequently be further modified in order to obtain a fully functional genetic material carrier.