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Introduction Breast cancer and acquired immunodeficiency syndrome (AIDS) are key issues for modern medicine. The aim of the current study was to present how cytokines, in the example of IL-6 and its polymorphism, can affect these two conditions. Material and methods Thirty-one women with benign breast tumours, 42 breast cancer patients and 40 HIV-infected females were enrolled in the study. Serum IL-6 levels were determined by ELISA. The IL-6 polymorphism was genotyped by PCR-RFLP. Results Serum IL-6 in patients with benign breast tumours was significantly lower than in females with breast cancer (p = 0.017) and HIV-infected women (p = 0.032). We did not find statistically significant differences in serum IL-6 level between females with breast cancer and HIV-infected women (p = 0.749). Comparing the distribution of genotypes and frequency of the IL-6 (–174) C/G polymorphism between the three study groups – breast cancer patients, patients with benign breast tumours, and HIV-infected patients – we did not find any statistically significant differences. Conclusions IL-6 can play an important role in pathogenesis of breast cancer and HIV infection and its level is higher than in the control group irrespective of distribution of genotypes and frequency of the IL-6 (–174) C/G polymorphism.

In the course of cirrhosis, a variety of disturbances of endocrine glands occur. Degenerative changes in the testes with atrophia and fibrosis of the glandular tissue are often found in men. Twenty-one males with compensated alcoholic liver cirrhosis were studied. The age ranged from 29 to 61 years (mean 47,1). Efficiency of the liver was evaluated according to Child classification. HBC (this needs to be spelled out in parenthesis) or HBV (Hepatitis B Virus) infections were excluded. Levels of serum testosterone were determined and the volume size of the testes was measured using 7,5 MHz sector probe, B&K Medical ultrasonograph, 3535 model. Volume size of the testes was measured in 22 healthy control volunteers, as well; age ranged from 25 to 66 years (mean-46,6). All patients were interviewed about sexual function, particularly possible erectile dysfunction using IIEF-5 questionnaire. The mean testosterone level was 8,89 umol/l (ranged: 7,4–10,9 umol/l) in the study patients [the normal range interval: 8,2–34,6 umol/l]. The level was below the normal range in 4 patients, and low but within the normal range in the remaining patients. Statistically significant lower values of both testes volumes were estimated in patients with compensated alcoholic liver cirrhosis in comparison to healthy controls (p

Multi-walled and single-walled carbon nanotubes were side-wall functionalized with azobenzene and anthraquinone residues, i.e., chemical groups possessing redox activity, for potential utilization in functional catalysis and memory storage devices. Solvent-free synthesis was performed with diazonium salts generated in situ where it was found that it was simple and effective method. Nanotube functionalization was confirmed and characterized by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). It is worth noting, that single-walled carbon nanotubes (SWCNTs) functionalized with azobenzene produced Raman modes typical of substituted azobenzenes with spectral peaks at ∼1137, 1412, and 1447 cm −1 . The nanotubes containing electroactive substituents were transferred onto electrode substrates using the Langmuir–Blodgett approach and characterized by cyclic voltammetry. The amount of electroactive groups per mg of nanotubes was calculated based on the peak of cathodic current. A highly reproducible voltammetric response was obtained with a single nanotube layer or multiple nanotube/octadecanol layers. It is believed that devices such as these will be invaluable for future high-performance electrodes.

In 2005, 440 patients infected with HIV were registered in the AIDS center in Lodz, Poland. The aim of our study was to analyze the causes of death in 70 fatal cases. We analyzed the data from 70 fatal cases from 1995 through 2005. Of the fatal cases we investigated, 10 were in women and 60 in men. The most common route of HIV transmission was intravenous drug use (50%). At the time of death, the mean age of patients was 36,48 years, and the mean CD4 count was 115,14 cells per microliter. The mean time from HIV diagnosis to death was 3,75 years. The leading cause of death in the group from 1995 through 2004 was AIDS. In 2002, liver diseases resulting from hepatitis C virus (HCV) infection were the cause of death in two patients. In 2005, two patients died as a result of myocardial infarction. The prevalence of fatal cases decreased from 9,09 % in 1995 to 1,59 % in 2005. Hepatitis B surface antigen (HBsAg) was found in 4 of 62 patients (6,45%), anti-HCV in 28 patients (45,16%), and both hepatitis B virus (HBV) and HCV infection in 5 patients (8,07%). Coinfections occurred most frequently in intravenous drug users (IDUs). In conclusions: (1) AIDS is still the leading cause of death in HIV-positive patients in the Lodz region; (2) the emerging cause of death in HIV-positive patients is liver disease as the sequel of HBV and HCV coinfections; (3) heart disease is becoming an important cause of death in HIV-positive patients.

Summary In the presented multicenter study an attempt was made to evaluate the role of nevirapine used in treatment of HIV-seropositive patients in both groups: naive as well as experienced. The therapeutic effect was evaluated while analysing the HIV-RNA level and the increase in CD4 cell count. The reasons for which the new schema with nevirapine was introduced in experienced patients were as well analysed. Among these reasons were mainly side effects of different character. On the basis of the obtained results very good virologic response was reported in both groups, naive and previously treated. Immunologic response in both populations discussed was similar though the initial level of CD4 was two times lower in naive patients in comparison with experienced population.

The interactions of liquid-crystalline monoolein (GMO) cubic phase nanoparticles with various model lipid membranes spread at the air-solution interface by the Langmuir technique were investigated. Cubosomes have attracted attention as potential biocompatible drug delivery systems, and thus understanding their mode of interaction with membranes is of special interest. Cubosomes spreading at the air-water interface as well as interactions with a monolayer of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) compressed to different surface pressures were studied by monitoring surface pressure-time dependencies at constant area. Progressive incorporation of the nanoparticles was shown to lead to mixed monolayer formation. The concentration of cubosomes influenced the mechanism of incorporation, as well as the fluidity and permeability of the resulting lipid membranes. Brewster angle microscopy images reflected the dependence of the monolayer structure on the cubosomes presence in the subphase. A parameter Csat was introduced to indicate the point of saturation of the lipid membrane with the cubosomal material. This parameter was found to depend on the surface pressure showing that the cubosomes disintegrate in prolonged contact with the membrane, filling available voids in the lipid membrane. At highest surface pressures when the layer is most compact, the penetration of cubosomal material is not possible and only some exchange with the membrane lipid becomes the route of including GMO into the layer. Finally, comparative studies of the interactions between lipids with various headgroup charges with cubosomes suggest that at high surface pressure an exchange of lipid component between the monolayer and the cubosome in its intact form may occur.

The spread of HIV-1 subtypes varies considerably both worldwide and within Europe, with non-B variants commonly found across various exposure groups. This study aimed to analyse the distribution and temporal trends in HIV-1 subtype variability across Poland. For analysis of the subtype distribution, 1219 partial pol sequences obtained from patients followed up in 9 of 17 Polish HIV treatment centres were used. Subtyping was inferred using the maximum likelihood method; recombination was assessed using the bootscanning and jumping profile hidden Markov model methods. Subtype B dominated in the studied group (n=1059, 86.9%); in 160 (13.1%) sequences, non-B variants were present [A1 (n=63, 5.2%), D (n=43, 3.5%), C (n=22, 1.8%), and F1 (n=2, 0.2%)]. In 25 (2.1%) cases circulating recombinant forms (CRFs) were found. Five A1 variants (0.4%) were unique AB recombinant forms (URF) not previously identified in Poland. Non-B clades were notably more common among females (n=73, 45.6%, p

DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) Langmuir monolayers were employed as model membranes for the studies of interactions with an amphiphilic drug — ibuprofen. The mode of interactions was found to be ibuprofen concentration dependent. The maximal value of compressibility constant, 270 mN/m is obtained for ibuprofen 10− 5–10− 6 M solutions indicating that already in contact with such diluted drug solutions, the DPPC monolayer becomes more solid than in contact with pure water or saliva solutions, thus the organization of molecules is more compact or condensed. In contrary, the effect of concentrated ibuprofen solutions is opposite. Moreover, in the “diluted ibuprofen range” the molecules do not partition into the lipid layer since the limiting area for the lipid did not increase but in contrary was found to decrease upon contact with such solutions, and a disappearance of phase transition was observed. Contact with diluted solution of ibuprofen does not influence collapse pressure while making the condensed monolayer more solid. In diluted solutions of S-ibuprofen (10− 6–10− 5 M) the value of dipole moment is larger than for pure water or saliva subphases reflecting the organizing effect of ibuprofen. In concentrated ibuprofen solutions the dipole moment decreases which indicates partial compensation of charges upon incorporation of ibuprofen into the hydrophobic region of the lipid layer. Under these conditions, ibuprofen interferes with the cooperative interactions of the DPPC molecules in the layer and perturbs the structure of the monolayer.

Summary Background HIV-1 drug resistance (DR) is becoming a growing concern. It is estimated that about one out of ten newly HIV-infected persons in Europe acquires HIV-1 drug resistant strain. DR testing is now believed to play a crucial role in proper and successful treatment. The aim of the study was a retrospective analysis of the HIV-1 drug resistance patterns among Polish naive and therapy-experienced patients. Materials and methods In all cases before drug resistance testing viral load was determined as well as CD4/CD8 counts. The sequencing assay was carried out using commercially available assays according to manufacturer's protocol. Electrophoretic analysis data were verified and manually corrected. Interpretation was performed using Stanford's Genotypic Resistance Interpretation Algorithm or by a built-in algorithm included in ViroSeq System. Results In the treatment-naive group 14,1% of tested patients have acquired HIV-1 strains harbouring resistance-associated mutations. In the therapy-experienced group among 75 analyzed patients 58 (77%) were found to be carrying drug resistant mutants. In this group 14 persons (19%) had at least one resistance-associated mutation in all three drug classes. Among therapy-experienced patients the prevalence of K65R was very low (1,3%). Conclusion The results of both analysed groups indicate the necessity of resistance testing in Poland. In the group of patients never exposed to ART in 14,1% cases viral variants resistant to at least one of the drugs were identified. The problem of resistance intensifies with consecutive regimen failures limiting the remaining treatment options. A shift has been observed in the route of HIV-1 infection in Poland. The obtained data also documents a change in HIV subtype pattern in Poland. The low prevalence of K65R mutation may result in very potent salvage therapy options based on TDF. Presented data documents high prevalence of drug resistance in Poland and justifies the necessity of DR testing.

Background Atazanavir/r (ATV/r) is used in treatment-naive HIV infected patients as a component of first antiretroviral combination or is a switch option for patients experiencing tolerability problems with other drugs. Material and methods This retrospective study included 64 patients who started ATV/r-based combination antiretroviral therapy (cART) from January 2004 to June 2011. The aim of this retrospective study was to evaluate hyperbilirubinemia in patients treated with ATV/r. Long-term maintenance and safety of the ATV/r-based antiretroviral (ARV) regiment were analysed. Results In 38 ARV-experienced patients the main reason for switching to ATV/r was hyperlipidemia. During treatment with ATV/r hyperbilirubinemia was the most commonly reported adverse event. It was observed in 58.7% patients, however only in 2 patients was the reason for discontinuation of ATV/r-based therapy. Hyperbilirubinemia occurred more frequently in patients who started ATV/r treatment with CD4 count ≥200 cells/μl and those who were treated longer. Hyperbilirubinemia was not associated with age, gender, HBV/HCV coinfection and aminotransferase level before ATV/r treatment. Conclusion ATV/r-based regimen was well tolerated and we demonstrated long-term maintenance of this antiretroviral therapy. Hyperbilirubinemia occurred more frequently in patients with higher CD4 cells count and was a rare cause of discontinuation of this drug.

The aim of the study The aim of the study was to evaluate the spectrum of AIDS-defining malignancies (ADMs) and non-AIDS-defining malignancies (NADMs) in HIV-infected patients in Poland. Material and methods A retrospective observational study was conducted among HIV-infected adult patients who developed a malignancy between 1995 and 2012 in a Polish cohort. Malignancies were divided into ADMs and NADMs. Non-AIDS-defining malignancies were further categorised as virus-related (NADMs-VR) and unrelated (NADMs-VUR). Epidemiological data was analysed according to demographic data, medical history, and HIV-related information. Results were analysed by OR, EPITools package parameters and Fisher's exact test. Results In this study 288 malignancies were discovered. The mean age at diagnosis was 41.25 years (IQR20-81); for ADMs 38.05 years, and for NADMs-VURs 46.42 years; 72.22% were male, 40.28% were co-infected with HCV. The risk behaviours were: 37.85% IDU, 33.33% MSM, and 24.31% heterosexual. Mean CD4+ at the diagnosis was 282 cells/mm3 (for ADMs 232 and for NADMs-VUR 395). Average duration of HIV infection at diagnosis was 5.69 years. There were 159 (55.2%) ADMs and 129 (44.8%) NADMs, among whom 58 (44.96%) NADMs-VR and 71 (55.04%) NADMs-VUR. The most frequent malignancies were: NHL (n = 76; 26.39%), KS (n = 49; 17.01%), ICC (n = 34; 11.81%), HD (n = 23; 7.99%), lung cancer (n = 18; 6.25%) and HCC (n = 14; 4.86%). The amount of NADMs, NADMs-VURs in particular, is increasing at present. Male gender (OR = 1.889; 95% CI: 1.104–3.233; p = 0.024), advanced age: 50–60 years (OR = 3.022; 95% CI: 1.359–6.720; p = 0.01) and ≥ 60 years (OR = 15.111; 95% CI: 3.122–73.151; p < 0.001), longer duration of HIV-infection and successful HAART (OR = 2.769; 95% CI: 1.675–4.577; p = 0) were independent predictors of NADMs overall, respectively. Conclusions In a Polish cohort NHL was the most frequent malignancy among ADMs, whereas HD was the most frequent among NADMs. Increased incidence of NADMs appearing in elderly men with longer duration of HIV-infection and with better virological and immunological control was confirmed. As HIV-infected individuals live longer, better screening strategies, especially for NADMs-VUR, are needed. The spectrum of cancer diagnoses in Poland currently does not appear dissimilar to that observed in other European populations.

The surveillance of HIV-transmitted drug resistance mutations (t-DRMs), including temporal trends across subtypes and exposure groups, remains a priority in the current management of the epidemic worldwide.A cross-sectional analysis of 833 treatment-naive patients from 9 of 17 Polish HIV treatment centres. Partial pol sequences were used to analyse drug resistance with a general time reversible (GTR)-based maximum likelihood algorithm used for cluster/pair identification. Mutation frequencies and temporal trends were investigated.t-DRMs were observed in 9% of cases (5.8% for NRTI, 1.2% NNRTI and 2.0% PI mutations) and were more common among heterosexually infected (HET) individuals (13.4%) compared with MSM (8.3%, P = 0.03) or injection drug users (IDUs; 2.9%, P = 0.001) and in MSM compared with IDUs (P = 0.046). t-DRMs were more frequent in cases infected with the non-B variant (21.6%) compared with subtype B (6.6%, P0.001). With subtype B a higher mutation frequency was found in MSM compared with non-MSM cases (8.3% versus 1.8% for IDU + HET, P = 0.038), while non-B variants were associated with heterosexual exposure (30.4% for HET versus 4.8% for MSM, P = 0.019; versus 0 for IDU, P = 0.016). Trends in t-DRM frequencies were stable over time except for a decrease in NNRTI t-DRMs among MSM (P = 0.0662) and an NRTI t-DRM decrease in HET individuals (P = 0.077). With subtype B a higher frequency of sequence pairs/clusters in MSM (50.4%) was found compared with HET (P0.001) and IDUs (P = 0.015).Despite stable trends over time, patterns of t-DRMs differed notably between transmission categories and subtypes: subtype B was associated with MSM transmission and clustering while in non-B clades t-DRMs were more common and were associated with heterosexual infections.

The aim of this study is to assess the efficacy of an initial dose of ribavirin administered before a 48-week course of treatment with peg-IFN + ribavirin in treatment-naïve patients and in patients after previous failure of CHC treatment.A total of 103 patients with chronic hepatitis C infected with genotype 1 HCV were qualified to the study. Study patients were randomised to receive one of two treatments: A- RBV for 4 weeks followed by combined therapy with peg-IFN alpha-2a +RBV for 48 weeks (n = 73), or B- combined therapy with peg-IFN alpha-2a +RBV for 48 weeks (n = 30).SVR 24 was observed in 44% patients in group A and in group 40% patients in group B (40%), p0.05. Comparing subgroups of the naive patients, it was found that the SVR24 value was higher in group A than group B (57% vs. 47%, p0.05). In the re-therapy subgroups, higher treatment response rates in patients not responding earlier was found in group A than group B (39% vs. 16%, p0.05).No significant advantage was found in the use of a priming method over a standard regimen. However, it could be recommended in patients with a total lack of response to peg-IFN and ribavirin when no other therapeutic options are available.

Introduction : In Poland, the HIV epidemic has shifted recently from being predominantly related to injection drug use (IDU) to being driven by transmissions among men-who-have-sex-with-men (MSM). The number of new HIV cases has increased in the recent years, while no current data on the transmitted drug resistance associated mutations (tDRM) frequency trend over time are available from 2010. In this study, we analyze the temporal trends in the spread of tDRM from 2008 to 2013. Materials and Methods : Partial pol sequences from 833 antiretroviral treatment-naive individuals of European descent (Polish origin) linked to care in 9 of 17 Polish HIV treatment centres were analyzed. Drug resistance interpretation was performed according to WHO surveillance recommendations, subtyping with REGA genotyping 2.0 tool. Time trends were examined for the frequency of t-DRM across subtypes and transmission groups using logistic regression (R statistical platform, v. 3.1.0). Results : Frequency of tDRM proved stable over time, with mutation frequency change from 11.3% in 2008 to 8.3% in 2013 [OR: 0.91 (95% CI 0.80–1,05), p=0.202] (Figure 1a). Also, no significant differences over time were noted for the subtype B (decrease from 8.4% 2008 to 6.2% in 2013 [OR: 0.94 (95% CI 0.79–1.11), p=0.45] and across non-B variants [change from 22.6% 2008 to 23.1% in 2013, OR: 0.94 (95% CI 0.75–1.19), p=0.62]. When patient groups were stratified according to transmission route, in MSM there was a trend for a NNRTI t-DRM decrease (from 6.8% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34–1.02), p=0.0655, slope −0.74%/year) (Figure 1b), related to the subtype B infected MSM (decrease from 7% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34–1.03), p=0.0662, slope −0.75%/year). Overall tDRM frequency decrease was also noted for the heterosexually infected patients [from 17.6% 2008 to 10.3% in 2013, OR: 0.83 (95% CI 0.67–1.02, p=0.077, slope −2.041%/year)] but did not associate with drug class (Figure 1c). In IDUs, the trends in t-DRM frequency were not significant over time (change from 1.9% in 2008 to 0 in 2013 [OR:1.24 (95% CI 0.73–2.26), p=0.4)]. Conclusions : The frequency of t-DRM in Poland is generally stable over time. Decrease in the overall tDRM frequency in heterosexual infected cases and NNRTI resistance in subtype B infected MSM may be related to the higher treatment efficacy of current cART. (Published: 2 November 2014) Citation: Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Parczewski M et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19753 http://www.jiasociety.org/index.php/jias/article/view/19753 | http://dx.doi.org/10.7448/IAS.17.4.19753

Summary Background A wide clinical spectrum of kidney diseases has been recognized in individuals with HIV (human immunodeficiency virus). The aim of this retrospective study was to assess renal function in HIV patients before the introduction of combined antiretroviral therapy (cART). Material and Methods The study group consisted of 106 HIV-positive patients (72 males, 34 females). The level of serum creatinine and creatinine clearance using the Cockcroft-Gault formula were assessed. Urine analysis for proteinuria was performed. The relationship between HIV infection including CD4 cells count, CD4 nadir and renal function was determined. Results The correlation between the creatinine clearance and CD4 nadir and CD4 cells count before the introduction of cART was found (p = 0.037, p = 0.036). Conclusion: The kidney dysfunction measured with the creatinine clearance before the introduction of cART was associated with the immunodeficiency.

Combination of surface analytical techniques was employed to investigate the interfacial behavior of the two designed lipids-N-stearoylglycine (1) and its bulky neutral headgroup-containing derivative N-stearoylvaline ethyl ester (2)-at the air-solution interface and as transferred layers on different substrates. Formation of monolayers at the air-water interface was monitored on pure water and on aqueous solutions of different pH. Crystallization effects were visualized at pure water by recording the hystereses in the Langmuir-Blodgett (LB) isotherms and by transferring the layers onto mica, gold (111), and ITO (indium-tin oxide on glass) electrodes. Subphase pH affects the morphology and patch formation in monolayers of 1, as evidenced by BAM measurements. At pH 8.2, formation of well-ordered crystallites is observed, which upon compression elongate according to predominantly 1-D growth mechanism to form a dense layer of crystallites. This effect is not observed in monolayers of 2, whose headgroup is not protonated. The orientation of layers of 1 transferred to the solid supports is also pH dependent, and their stability can be related to formation of a hydrogen-bonded networks. AFM images of 1 exhibited platelets of multilayer phase. The IR spectra of the ITO substrates covered by 1 indicated formation of hydrogen bonds between the amide groups. The nature of the adsorption layer and its organization as a function of potential were studied in-depth by EC STM using Au(111) as the substrate. A model showing the arrangement of hydrogen bonds between adsorbed molecules is presented and related to the observed organization of the layer.

The aim of this study was to determine the presence of kidney tubular damage in the absence of overt evidence of glomerular dysfunction (GFR>60 ml/min without proteinuria) in HIV-infected patients receiving antiretroviral therapy. Urine kidney injury molecule-1 (KIM-1) and liver-type fatty acid-binding protein (L-FABP) levels were measured by ELISA and expressed as a ratio to creatinine. Sixty-six patients (median age 38 years) and 10 healthy controls (median age 35.5 years) were included in the study. Patients with chronic diseases such as diabetes, hypertension, heart disease, or kidney disease were excluded from the study. All patients received tenofovir/emtricitabine combined with one of three other components, namely efavirenz, atazanavir/norvir, or lopinavir/norvir. A lower concentration of L-FABP/creatinine was observed in HIV-infected as compared to healthy individuals (p=0.0353); KIM-1/creatinine was also lower in comparison with healthy controls but not statistically significantly. Patients receiving efavirenz had higher levels of L-FABP/creatinine in comparison to healthy controls (p=0.0039). Patients with anti-HCV had higher concentrations of L-FABP/creatinine as compared to the HIV-monoinfected individuals (not statistically significant) and to healthy subjects (p=0.0356). All four patients with L-FABP>17.5 μg/g creatinine were HIV/HCV coinfected. On multivariate logistic regression urine L-FABP above 5.5 μg/g creatinine was independently associated with body weight (OR=0.93 p=0.039). This study suggests that HIV/HCV-coinfected patients with lower body weight treated with tenofovir may be at an increased risk of tubular dysfunction and should be monitored more closely. The use of protease inhibitors was not associated with an increased risk of tubular disorders.

Transmitted drug resistance (TDR) is an important public health issue, because it may affect the outcome of antiretroviral treatment. The prevalence of human immunodeficiency virus type 1 (HIV-1) with TDR mutations defined according to the list of the World Health Organization was investigated among 53 therapy-naïve persons with confirmed recent HIV-1 infection diagnosed in Poland, in the years 2008-2010. Proviral DNA was amplified, sequenced, and screened for the TDR mutations in the pol gene fragments coding for the whole protease and the initial 256 residues of the reverse transcriptase. The frequency of sequences with at least one TDR mutation was 11.3%. In four (7.5%) sequences at least one resistance mutation related to reverse transcriptase inhibitors was identified, and in further two (3.8%) sequences one mutation related to protease inhibitors' resistance was present. The moderate rate of TDR highlights the need for a continuous surveillance and resistance testing among treatment-naïve individuals to optimize treatment effects within a country.

Introduction Hepatitis C virus (HCV) infection is a global health problem which can lead to liver cirrhosis or hepatocellular carcinoma in one-fifth of chronically infected patients. Materials and methods The study group consisted of 123 patients: 90 with HCV mono- and 33 with HIV/HCV co-infection, who were treated with pegylated interferon alfa (Peg-IFN-α) and ribavirin. We analyzed selected pretreatment factors: age, sex, HIV/HCV co-infection, grade of inflammation, necrotic changes and fibrosis in histological analysis of liver bioptates, HCV viral load, HCV genotypes, and single nucleotide polymorphisms (SNPs) of IL28B and tried to find out which of them influence sustained virological response (SVR). The IL28B SNP C/T (rs12979860) was analyzed using Custom(®) SNP Genotyping Assays (Applied Biosystems). Results Multivariate analysis demonstrated that after adjusting for the other variables three predictors independently influence SVR, namely genotype 3 of HCV, presence of the CC genotype and age >40 years (OR respectively 15.14, 3.62, and 0.36). HCV mono-infected patients were infected with HCV genotype 3 or 4 less frequently (p=0.0001) compared to HIV/HCV co-infected individuals. In patients with HIV/HCV co-infection the CC variant occurred more frequently whereas CT was found less frequently (p=0.001, p=0.0146, respectively). In patients with HIV/HCV co-infection, 3 and 4 genotype of HCV occurred more frequently compared to patients with HCV mono-infection (p=0.0001). Conclusions These data suggest that age, HCV genotype and IL28B polymorphism are useful for prediction of the response to treatment with Peg-IFN-α and ribavirin. The more frequent occurrence of HCV genotypes 3 or 4 in patients with HIV/HCV co-infection could be associated with the route of transmission.

The aim of the study was to determine the rate of transmission of drug resistant human immunodeficiency virus-1 (HIV-1) variants among therapy-naive HIV positive patients in Poland in the year 2008, to compare the data with the results from the years 2000 to 2007 and to monitor patterns of HIV-1 subtypes present in Polish population and their evolution. Complete protease and part of reverse transcriptase regions were sequenced from the sera of patients directed to the laboratory for drug resistance testing. The Stanford's HIVdb program was used for the interpretation of results and subtyping. The variants scoring at least “intermediate resistance” for at least one drug were considered as resistant. The results obtained were compared to those obtained in the years 2000–2007. A total of 95 patients were enrolled in the 2008 study. Homosexual transmission of infection was documented in more than 55% of all cases. The overall prevalence of transmitted drug resistance (TDR) was 5.3% (3.9% in 2007, 5.8% in 2006, and 14.1% in the years 2002–2005). The study from the years 2000 to 2001 revealed 28.7% prevalence. Preliminary analysis of the first half of 2009 shows the ratio of 7.8%. In four (4.2%) cases drug resistance was associated with protease inhibitors class, in one case (1.1%) with resistance to non-nucleoside reverse transcriptase inhibitors class. In four cases (4.2%) non-B subtype was identified (C, G, CRF01_AE, CRF02_AG). An increase of percentage of drug resistant mutants—from 3.9% (2007) to 5.3% (2008)—was recognized. In this study, TDR was limited to single classes of antiretroviral drugs. HIV-1 subtype B prevails in Poland. J. Med. Virol. 82:1291–1294, 2010. © 2010 Wiley-Liss, Inc.

The crown ethers with electro- and photoactive azo moieties containing substituents with mobile protons such as in the –COOH groups of histidine, show unique effect of pH switched on/off presence of the azo form. The differences observed for the electrochemical behavior of azocrown ethers with N-acetylhistidine and imidazole moieties reveal the interference of a chemical reduction pathway in strongly acidified solutions. This chemical reduction process leads to the formation of a hydrazine derivative which can be detected by its further electroreduction on the electrode surface. The involvement of chemical reduction is seen clearly in the presence of mobile protons of the –COOH group and mercury as the electrode substrate. The behaviour of the N-acetylhistidine azomacrocyle is similar to that of compounds known to exist in quinone– hydrazone tautomeric equilibria.

AIM: To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and lipid profile. METHODS: The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects. Total levels of adiponectin, leptin, resistin, visfatin, omentin, osteopontin and insulin were measured using an ELISA kit. The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method. RESULTS: Homeostasis model assessment for insulin resistance (HOMA-IR) values were significantly higher in hepatitis C virus (HCV) infected patients without metabolic disorders compared to healthy controls (2.24 vs 0.59, P = 0.0003). Hepatic steatosis was observed in 32.2% of patients with HCV infection and was found in patients with increased HOMA-IR index (2.81 vs 1.99, P = 0.05) and reduced adiponectin level (5.96 vs 8.37, P = 0.04). Inflammatory activity (G ≥ 2) was related to increased osteopontin concentration (34.04 vs 23.35, P = 0.03). Advanced liver fibrosis (S ≥ 2) was associated with increased levels of omentin and osteopontin (436.94 vs 360.09, P = 0.03 and 32.84 vs 20.29, P = 0.03) and reduced resistin concentration (1.40 vs 1.74, P = 0.047). No correlations were reported between adipokine profile, HOMA-IR values and hepatic expression of the SOCS-3 gene. CONCLUSION: We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself. Some adipokines appear to be biochemical markers of steatosis, inflammation and fibrosis in patients with chronic HCV infection. © 2014 Baishideng Publishing Group Inc. All rights reserved.

The effect of a lipolytic enzyme, pork pancreatic phospholipase A(2), on hybrid bilayer membranes was monitored using voltammetry, impedance spectroscopy and surface plasmon resonance. The hybrid bilayers were prepared by Langmuir-Schaefer transfer of lipid monolayers onto gold electrodes modified with self-assembled alkanethiol monolayers, or by liposome spreading. The electrodes were immersed in the phospholipase aqueous solution to allow adsorption of the enzyme and cleavage of the ester bond in the sn-2 position of phospholipids in the outer leaflet of the hybrid layers. The action of phospholipase A(2) led to perforation of the lipid films. Impedance spectroscopy and surface plasmon resonance were used for monitoring enzyme adsorption, phospholipid hydrolysis and product desorption. The results obtained show that transport efficiency of an electroactive probe, ferrocyanate, and of an electroactive drug, doxorubicin, through the bilayer depends on the action of the enzyme; the state of the lipid layer covering the electrode surface depends on the latter as well. Cyclic voltammetry and electrochemical impedance spectroscopy were used to study this effect. The doxorubicin reduction/oxidation signals appearing at potentials close to those observed using a bare gold electrode indicated facilitated penetration of the drug into the layer. The results obtained were interpreted in terms of pore formation in the lipid matrix; phospholipase A(2) can be considered as a nano-device for high precision perforation of the lipid layer.