Drug-Eluting Stents and Balloons-Materials, Structure Designs, and Coating Techniques: A Review.

Controlled drug delivery is a matter of interest to numerous scientists from various domains, as well as an essential issue for society as a whole. In the treatment of many diseases, it is crucial to control the dosing of a drug for a long time and thus maintain its optimal concentration in the tissue. Heart diseases are particularly important in this aspect. One such disease is an obstructive arterial disease affecting millions of people around the world. In recent years, stents and balloon catheters have reached a significant position in the treatment of this condition. Balloon catheters are also successfully used to manage tear ducts, paranasal sinuses, or salivary glands disorders. Modern technology is continually striving to improve the results of previous generations of stents and balloon catheters by refining their design, structure, and constituent materials. These advances result in the development of both successive models of drug-eluting stents (DES) and drug-eluting balloons (DEB). This paper presents milestones in the development of DES and DEB, which are a significant option in the treatment of coronary artery diseases. This report reviews the works related to achievements in construction designs and materials, as well as preparation technologies, of DES and DEB. Special attention was paid to the polymeric biodegradable materials used in the production of the above-mentioned devices. Information was also collected on the various methods of producing drug release coatings and their effectiveness in releasing the active substance.

Endoplasmic reticulum aminopeptidase 1 polymorphism Ile276Met is associated with atopic dermatitis and affects the generation of an HLA-C associated antigenic epitope in vitro.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease of complex aetiology, with interactions between susceptibility genes and environmental factors. We have previously described a protective effect of the KIR2DS1 gene encoding the natural killer cell receptor, whose ligands are HLA-C molecules. Here, we found an association of HLA-C*05:01 allele with AD. KIR-HLA-C interactions are affected by peptides presented by HLA-C. The generation of these peptides is strongly influenced by endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2). Expression and activity of ERAP molecules depend on the polymorphisms of their genes. OBJECTIVE: Possible associations of several single nucleotide polymorphisms (SNPs) in the ERAP1 and ERAP2 genes with susceptibility to AD. METHODS: Peripheral blood DNA isolation from 318 patients and 549 controls. PCR-SSO or PCR-SSP for HLA-C typing; TaqMan Genotyping Assay for ERAP typing. RESULTS: Only one SNP in the ERAP1 gene, rs26618T>C, causing the amino acid change Ile276Met, had an association with AD. To gain insight on the functional role of this SNP, we produced recombinant variants differing only at position 276 (Ile or Met) and tested their aminopeptidase activity against a N-terminally extended precursor LIVDRPVTLV of the HLA-C*05:01 epitope IVDRPVTLV. Both ERAP1 variants were able to efficiently generate the epitope, although the 276Ile allotype was able to do this about 50% faster. Furthermore, both variants were quite inefficient in further degradation of the mature epitope. Finally, we found that the effect of 276Met on susceptibility to AD was seen only in KIR2DS1-negative individuals, not protected by this KIR. CONCLUSION: Associations of HLA-C*05:01 allele and rs26618T>C (Ile276Met) ERAP1 polymorphism with AD, and a significant difference between these two ERAP1 variants in their ability to generate an epitope for the HLA-C*05:01 molecule was found.

Evaluation of sex-related changes in skin topography and structure using innovative skin testing equipment.

BACKGROUND: Evaluation of skin condition on the basis of parametrization and objective measurements of the parameters has become obligatory. The aim of this study was to assess sex-related changes in skin topography and structure using the skin testing equipment. MATERIALS AND METHODS: The study was carried out on the group of 40 volunteers (20 females and 20 males) of the mean age 24 ± 3 years. The skin parameters were measured using 3 devices: Visioscan®  VC 98 (skin topography), Visioline® VL 650 (skin macro relief) and Ultrascan UC22 (ultrasound imaging of the skin). All measurements were performed on the inner part of the left forearm. RESULTS: The skin parameters measured revealed significant differences in skin surface and structure between females and males. The skin of all women subjects was more homogenous in its structure with the presence of more abundant superficial skin lines and wrinkles in comparison to male skin. The higher number of skin furrows in the skin of women is in agreement with literature reports claiming that men's skin has lower number of wrinkles which are deeper and more pronounced. Ultrasound imaging of the skin indicated greater thickness and lower density of the dermis of men subjects compared to those of females. CONCLUSION: Non-invasive methods of skin testing using new and advanced equipment have provided a possibility of objective parametrization and evaluation of sex-related changes in skin topography and structure.

Genetic polymorphisms and expression of HLA-G and its receptors, KIR2DL4 and LILRB1, in non-small cell lung cancer.

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule absent from most normal tissues but detected in many malignant tumors. It is recognized by cells of the immune system using LILRB1, KIR2DL4 and LILRB2 receptors. We attempted to find out whether some polymorphisms of HLA-G, LILRB1 and KIR2DL4 genes are associated with susceptibility to nonsmall cell lung cancer (NSCLC). Four polymorphisms in HLA-G, i.e. -964A>G (rs1632947), -725C>G>T (rs1233334), -716T>G (rs2249863) in the promoter, and a 14 base pair insertion/deletion (14 bp indel) in the 3'-untranslated region (3'UTR), and five in LILRB1 - 5651G>A (rs41308748) in intron 14, 5717C>T L622L (rs1061684), 5724G>A E625K (rs16985478), 5774 C>A P641P (rs41548213) in exon 15, and 5806C>T (rs8101240) in 3'UTR - as well as 9620 9A/10A (rs11410751) polymorphism in exon 7 of KIR2DL4 were typed using different laboratory techniques. Only one single nucleotide polymorphism (SNP) in HLA-G (-964A>G) and one in LILRB1 (5724G>A) were found to influence the risk of NSCLC. In addition, 5724G>A was associated with protection from tumor cell infiltration of regional lymph nodes. Most importantly, we detected HLA-G and LILRB1 expression in tumor specimens, but no correlation with genetic polymorphisms was observed. HLA-G and LILRB1 protein expression levels in tumor tissue were significantly correlated with tumor stage.

Genetic polymorphism of KIR2DL4 in the Polish population.

The KIR2DL4 gene is characterized by alleles with either 9 or 10 consecutive adenines in exon 7, which encodes the transmembrane domain. The 9A variant produces either a protein with a truncated cytoplasmic tail or one lacking the transmembrane region. This causes a lack of KIR2DL4 expression. In contrast, 10A alleles encode receptors that may be expressed at the cell surface. We tested 438 healthy individuals for polymorphism of the KIR2DL4 gene. KIR2DL4 9A/10A alleles were distinguished by the high resolution melting (HRM) method, and restriction fragment length polymorphism (RFLP) was used for genotyping of three other single nucleotide polymorphisms (SNPs) spanning the near vicinity of the poly-adenine fragment. We found a weak difference between males and females in 9769 C/A genotypes and alleles. In addition, we observed complete linkage disequilibrium (LD) between 9A insertion/deletion in the 9620 position and the 9571T/C position of the gene (r(2) = 1) both in females and males and almost complete LD with the 9797G/A position (r(2) = 0.963 for females and r(2) = 0.892 for males). Most importantly, we detected, in a group of fertile women, a high frequency (30.2%) of homozygosity for the defective 9A variant, which suggests that KIR2DL4 as a functional cell surface receptor is not absolutely necessary for reproduction. On the other hand, lower representation of 10A/10A homozygotes and high frequency of 10A/9A heterozygotes indicates a need for both cell membrane-anchored and soluble KIR2DL4 molecules. Finally, cost-reducing RFLP instead of HRM is proposed for typing 9A and 10A variants.

Stability determination of the formulations containing hyaluronic acid.

OBJECTIVES: The aim of this work was to investigate the long-term stability of four emulsions (creams and ointments) developed for carrying hyaluronic acid (HA) for dermal penetration. METHODS: The stability of obtained formulations was analysed by multiple light scattering and laser diffraction methods. RESULTS: The experimental results showed that the moisturizing creams were more stable than the ointments containing HA. The migration phenomenon of particles was observed in soft ointment with HA and the flocculation phenomenon was detected in ointment based on lanolin. The larger the water content, the more stable formulation can be, due to hygroscopic properties of HA. CONCLUSIONS: The identification of instability phenomena was shortened dramatically using optical method such as multiple light scattering. Even small changes in the stability of emulsion were determined very early. We suggest that the moisturizing creams may be more suitable than ointments to carry HA for dermal absorption. These studies are a significant first step towards further exploration into what form of HA would assure maximum effect, give consumers satisfaction and guarantee safety during application.

Lack of KIR2DL4 gene in a fertile Caucasian woman.

Killer cell immunoglobulin-like receptor (KIR2DL4) gene is present in virtually all humans. It encodes a receptor present on uterine and decidual natural killer (NK) cells and some peripheral blood NK cells. Its only known ligand is human leukocyte antigen-G molecule expressed on extravillous trophoblasts invading the decidua. Therefore, KIR2DL4 has been regarded as a molecule important for successful pregnancy. However, a multiparous woman from Africa, lacking KIR2DL4 gene, was described suggesting that this gene is not absolutely required for successful human reproduction. Here, we describe a Polish woman who delivered a child and who is not only lacking KIR2DL4 gene, but also possessing a KIR genotype virtually identical to that of the African woman mentioned above. Their genotypes are compared with few other KIR2DL4-negative genotypes and haplotypes described so far.

Association of the HLA-G gene polymorphism with multiple sclerosis in a Polish population.

Summary In this study, three polymorphic sites in the HLA-G gene: -725C>G>T, -716T>G and 14bp(indel) were genotyped. Significant differences were found between patients and controls in the alleles and genotypes for -725C>G>T and in three-point haplotypes. We observed also a significant difference in the age of disease onset between patients positive and negative for 14bp(ins). The results suggest that single nucleotide polymorphisms in the promoter of the HLA-G gene (mainly -725C>G>T), and 14bp(indel), or some genetic marker in tight linkage disequilibrium with them are associated with multiple sclerosis.

Sequential recovery of NK cell receptor repertoire after allogeneic hematopoietic SCT.

Alloreactivity of natural killer (NK) cells contributes to the GVL reaction after allogeneic hematopoietic SCT (allo-HSCT). However, various procedure-related factors may affect NK cell maturation and their ability to recognize and kill leukemic cells. In this study, we prospectively evaluated expression of NK cell inhibitory receptors in 83 adults treated with myeloablative, killer cell Ig-like receptor (KIR)-ligand-matched allo-HSCT. NK cell maturation was evaluated by comparing the phenotypic patterns after allo-HSCT with the donor ones. The frequencies of KIR3DL1 were comparable to the donor ones on day +28, while they decreased significantly starting from day +100. The expression of KIR2DL2/3 was significantly lower in patients compared with donors up to day +100. The expression of KIR2DL1, despite continues growth, remained significantly decreased for 1 year after allo-HSCT. NKG2A was over-expressed up to day +180. Within 1 year after allo-HSCT, the NK cell phenotypic pattern tended to recapitulate the donor type. The process was disturbed by the use of steroids with significant differences observed on days +56 (P=0.01) and +100 (P=0.04). Up to day +100, reconstitution of NK cell receptor repertoire correlated with the absolute numbers of circulating CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells. Our observations should be taken into account when trying to predict potential benefit from NK cell alloreactivity.

Frequencies of killer immunoglobulin-like receptor genotypes influence susceptibility to spontaneous abortion.

Natural killer (NK) cells are the most abundant lymphocyte population in the decidua. These cells express killer immunoglobulin-like receptors (KIRs), which upon recognition of HLA class I molecules on trophoblasts may either stimulate NK cells (activating KIRs) or inhibit them (inhibitory KIRs) to produce soluble factors necessary for the maintenance of pregnancy. KIR genes exhibit extensive haplotype polymorphism; individuals differ in both the number and kind (activating vs. inhibitory) of KIR genes. This polymorphism affects NK cell reactivity and susceptibility to diseases, including gynecological disorders. Therefore we KIR-genotyped 149 spontaneously aborting women and 117 control multiparae (at least 2 healthy-born children). Several genotypes (i.e. combinations of various KIR genes) were differently distributed among the patients and control subjects. Differences were observed in the numbers and the ratios of activating to inhibitory KIRs between patients and healthy women: (i) genotypes containing 6 activating KIR genes were less frequent and those containing 6 inhibitory KIR genes were more frequent in patients than in control subjects, and (ii) an excess of inhibitory KIRs (activating-to-inhibitory KIR gene ratios of 0.33 to 0.83) was associated with miscarriage, whereas ratios close to equilibrium (0.86-1.25) seemed to be protective. In addition, the results suggest for the first time that sporadic and recurrent spontaneous abortions as well as miscarriage in the presence or absence of autoantibodies may have different KIR genotypic backgrounds.

Distribution of killer cell immunoglobulin-like receptor genes in Poles.

Killer cell immunoglobulin-like receptors (KIRs) present on natural killer cells and minor subpopulations of T cells recognize class I human leucocyte antigen (HLA) molecules on the surface of target cells. Humans differ by the presence or absence of some KIR genes on their chromosomes. As KIRs are important for the outcome of tissue transplantation (particularly for haematopoietic stem cell transplantation) and possibly for pregnancy and autoimmune diseases, knowledge of the KIR gene distribution in a given human population is of practical value. Therefore, we tested 363 healthy individuals from Western Poland for the presence or absence of KIR genes. Results are compared with those published for other human populations. KIR gene frequencies in Poles are close to these in other Caucasoids but different from those in Asian and African populations, and particularly distant from those in Australian Aborigines.

The introduction of the SENTINEL influenza surveillance system in Poland--experiences and lessons learned from the first three epidemic seasons.

Influenza surveillance provides information on virus activity and is necessary for the selection of vaccine strains and early warning. To improve this surveillance in Poland, a sentinel surveillance system was introduced in 2004-5 influenza season (SENTINEL). This paper presents results from SENTINEL during three seasons of its existence. Voivodship Sanitary-Epidemiological Stations (VSESs), physicians and the National Influenza Center (NIC) participate in SENTINEL. Laboratory course was performed by the NIC for VSESs. Stations were provided with procedures, report forms, etc. Physicians register number of influenza-like illnesses (ILI) and collect swabs. VSESs perform diagnostic tests. On the basis of information from VSESs, the NIC prepares weekly reports for the entire country. In 2004-5 epidemiological reports were received from 50% of VSESs, while in 2005-6 and 2006-7 from all VSESs. Virological reports were obtained from 37.5% of VSESs (2004-5), 75% (2005-6) and 94% (2006-7). Weekly number of reporting physicians ranged in three consecutive seasons from 165 to 219, 98 to 949 and 696 to 1,054. A total of 399 specimens were tested during the 2004-5 winter; 63 (16%) were positive for influenza and 21 (5%) for other respiratory viruses. In 2005-6, 949 specimens were tested. Influenza infections were confirmed in 47 cases (5%) and infections with other respiratory viruses in 36 cases (4%). A total of 1,195 specimens were tested during the 2006-7 winter; 37 (3%) were positive for influenza and 26 (2%) for other respiratory viruses. SENTINEL provided improvement of influenza surveillance when compared with seasons before 2004. Nevertheless, due to decreasing rate of positive specimens, virological surveillance is the most important part to improve in the next years.

Distribution of the CTLA-4 single nucleotide polymorphisms CT60G>A and +49A>G in psoriasis vulgaris patients and control individuals from a Polish Caucasian population.

Psoriasis vulgaris is a multifactorial disease with an autoimmune component, and T lymphocytes seem to be involved in its aetiology. CTLA-4 molecule is an important down-regulator of T-lymphocyte activation, and several polymorphisms of the CTLA-4 gene were found to be associated with some autoimmune diseases. We examined whether single nucleotide polymorphisms (SNPs) in the CTLA-4 gene, CT60A>G and +49A>G, are associated with psoriasis vulgaris. Alleles of these two SNPs were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Both the CT60G>A and the +49A>G alleles and genotypes were distributed similarly in patients and controls. Although the two SNPs studied here in Poles were in linkage disequilibrium, all four possible two-locus haplotypes were found, one of them rare; of the remaining three, the haplotype +49G, CT60G was significantly (P = 0.019, OR = 0.58, 95%CI = 0.37-0.91) less frequent in the patient group with disease onset between the ages of 21 and 40 years than in controls and the other patient groups, whereas the frequencies of the other haplotypes were similar in patients and controls. To the authors' knowledge, this is the first study on CTLA-4 CT60 allele frequencies in psoriasis.

Associations of killer cell immunoglobulin-like receptor genes with complications of rheumatoid arthritis.

We investigated whether killer cell immunoglobulin-like receptor (KIR) genes are risk factor(s) for rheumatoid arthritis (RA) and its clinical manifestations. One hundred and seventy-seven RA patients and 243 healthy individuals were tested for the presence of 11 KIR genes using PCR-SSP method. The frequencies of KIRs in patients with RA were similar to the frequencies in controls. However, RA patients positive for KIR2DL3 and negative for KIR2DS3 had earlier disease diagnosis. Additionally, KIR2DL2 and KIR2DS2 were significantly more frequent among RA patients with extra-articular manifestations and in its subgroup with vasculitis than in controls and in patients without these complications. Furthermore, the frequencies of KIR2DS1 and KIR3DS1 were lower in patients without bone erosions compared with healthy individuals. Relationships between the presence or absence of autoantibodies (rheumatoid factor and anti-cyclic citrullinated peptide) and KIR frequencies were also evaluated, but no significant differences were observed. These results suggest that particular clinical manifestations of RA may have different genetic backgrounds with respect to KIR genotype.

Antibody response to influenza vaccination in patients suffering from asthma.

The aim of the study was to assess humoral response to influenza vaccination in 20 children with bronchial asthma vaccinated with split inactivated vaccine. Response to influenza hemagglutinin was assessed before vaccination and after 1 month by hemagglutination inhibition test. Antibody titers were significantly higher after vaccination than before vaccination. The mean fold increase of antibody levels ranged after vaccination from 12.2 to 53.7. The post-vaccination percentage of patients with protective antihemagglutinin antibody titers>or=40 ranged from 95% to 100%. The percentage of patients with at least a 4-fold increase of anthemagglutinin antibody titers ranged after vaccination from 90% to 100%. The results confirmed the immunogenicity and safety of inactivated influenza vaccine in children with asthma. The registered values of all parameters of the immunological response (mean fold increase, protection rate, response rate) fulfilled the requirements of the Committee for Proprietary Medicinal Products established for healthy people vaccinated against influenza.

Antibody response to inactivated subunit influenza vaccine in patients with Wegener's granulomatosis.

In the present study we investigated the humoral response to inactivated subunit influenza vaccine in patients with Wegener's granulomatosis, who were in clinical and serological remission after immunosuppressive treatment (Group I). The results were compared with patients with Wegener's granulomatosis who were treated immunosuppressively, but were not vaccinated (Group II) and with healthy persons who received the vaccine (Group III). After vaccination, antihemagglutinin and antineuraminidase antibody titers significantly increased in Groups I and Group III subjects when compared with the pre-vaccination values. Post-vaccination protection rates ranged from 51.4% to 74.3% in Group I patients and from 65.7% to 94.3% in Group III subjects. In Group II, the protection rates were between 0% and 21.4%. The response rates ranged from 60% to 74.3% in Group I patients and from 71.4% to 88.6% in Group III subjects. In Group II, the response rates were between 7.1% and 21.4%. The study confirmed the immunogenicity of influenza vaccine in patients with Wegener's granulomatosis and showed similar response in the patients to those present in healthy people.

Inhibitory and activatory KIR gene frequencies in the Polish population.

Killer cell immunoglobulin-like receptors (KIRs) present on natural killer cells and minor subpopulations of T cells recognize class I human leukocyte antigen (HLA) molecules on the surface of target cells. Human individuals differ by the presence or absence of some KIR genes on their chromosomes (haplotypic polymorphism). As KIRs (especially two-immunoglobulin-domain-like containing, or KIR2D, molecules) are important for the outcome of tissue (particularly for haematopoietic stem cell) transplantation and possibly for pregnancy, the knowledge of KIR gene distribution in a given human population is of practical value. Therefore, we tested 175 healthy individuals from Poland for the presence or absence of these KIR genes which show haplotypic polymorphism and are expressed. Results were compared with those published for other human populations, showing close relations with other Caucasoids.

CTLA-4 gene polymorphisms and natural soluble CTLA-4 protein in psoriasis vulgaris.

CTLA-4 molecule is an important inhibitor of T-lymphocyte activation. Several single nucleotide polymorphisms (SNPs) in the CTLA-4 gene were found, and their associations with many human diseases were described. So far, however, such studies have not been performed in psoriasis vulgaris in Caucasoids. Therefore, we examined the distribution of three CTLA-4 SNPs: -1147C/T, -318C/T and +49 A/G in 116 patients with psoriasis vulgaris and 123 healthy blood donors using the polymerase chain reaction-restriction fragment length polymorphism method. For all three SNPs, the frequencies of alleles, genotypes and three-point haplotypes were very similar in patients and controls, suggesting no contribution of these genetic variants to psoriasis.