Sulfonated octa-substituted Co(II) phthalocyanines immobilized on silica matrix as catalyst for Thiuram E synthesis

© 2018 John Wiley & Sons, Ltd. Silica nanoparticles were obtained during the work according to two different sol–gel methods. In first one Schtrober's technique and series of cobalt phthalocyanine metal complexes varying in peripheral substituents were used. Second method was performed using the same complexes but differed in applying surface-active substance (SAS) and two precursors – tetraethoxysilane (TEOS) and aminopropyltrimethoxysilane (APTMOS). All obtained hybrid materials were analyzed via SEM, the size of single particle was studied, which in all cases was about 200 nm. In order to investigate hybrid's characteristics laser diffraction and liquid nitrogen adsorption methods were applied. Distinction in pore's specific volume of differently-obtained nanoparticles was found. Catalytic activity of all obtained materials were tested in conversion of N,N-diethylcarbamodithiolate to thiuram E. Effect of peripherally substituted phthalocyanines and morphology of matrixes were manifested on catalytic activity of the hybrids

Symmetrical and difunctional substituted cobalt phthalocyanines with benzoic acids fragments: Synthesis and catalytic activity

© 2017 World Scientific Publishing Company.Difunctional and symmetric phthalonitriles were synthesized by nucleophilic substitution of brome and nitro-group in 4-bromo-5-nitro-phthalonitrile for residues 4-amino-, 4-hydroxyl- and 4-sulfanyl benzoic acid. Symmetrical and difunctional substituted cobalt phthalocyanines were obtained by template synthesis based on mentioned phthalonitriles. Their spectral properties and catalytic activity in aerobic oxidation of sodium N,N-carbomoditiolate were investigated

Symmetrical and difunctional substituted cobalt phthalocyanines with benzoic acids fragments: Synthesis and catalytic activity

© 2017 World Scientific Publishing Company Difunctional and symmetric phthalonitriles were synthesized by nucleophilic substitution of brome and nitro-group in 4-bromo-5-nitro-phthalonitrile for residues 4-amino-, 4-hydroxyl- and 4-sulfanyl benzoic acid. Symmetrical and difunctional substituted cobalt phthalocyanines were obtained by template synthesis based on mentioned phthalonitriles. Their spectral properties and catalytic activity in aerobic oxidation of sodium (Formula presented.),(Formula presented.)-carbomoditiolate were investigated

The impact of genetic polymorphisms of IL28B gene on the efficacy of antiviral therapy of the chronic hepatitis C by using the standard Interferon-<i>α</i>

Aim of the Study. To analyze the predictive value of the genetic polymorphisms in rs8099917 and rs12979860 loci of the IL28В gene for the assessment of the efficacy prognosis of the combined antiviral therapy on the basis of the standard Interferon of the patients with Chronic Hepatitis C (CHC).Materials and Methods. The study of IL28B genetic polymorphisms was conducted in 66 patients with HCV who did not receive the treatment earlier. The 24- week or 48-week antiviral therapy by standard Interferon-α2b and Ribavirin was prescribed to all patients, taking into consideration the genotype of the HCV-infection. The analysis of the efficacy of the treatment was conducted on the basis of the assessment of the normalization of the biochemical cytolysis markers during and after the treatment as well as the availability of the rapid, early and stable virology response.Results. Among the patients with 1-st HCV genotype, the favorable genotype IL28В of alleles rs12979860 and rs8099917 (СС/ТТ) were associated with consider- ably higher frequency of the stable virology response than different versions of unfavorable genotype IL28В. Among the patients who did not have 1-st genotype the polymorphisms of IL28B gene did not affect the efficacy of antiviral therapy .Conclusion. The studies of genetic polymorphisms of the regions of human genome demonstrates that the positive predictive value of IL28B polymorphisms among the patients with 1-st HCV genotype is higher than among the patients with 2nd and 3d genotypes. This kind of approach enables to take into account the pharmaco-economic aspect of the treatment of chronic HCV-infection

Prevalence of chronic HCV infection in patients with type 2 diabetes mellitus in Russia

BACKGROUND: The poor outcomes of chronic hepatitis C (CHC) and type 2 diabetes determine the socio-economic significance of the combined pathology since they lead to premature death. The proportion of patients with type 2 diabetes with markers of viral hepatitis (VH) in the Russian Federation is not known, which does not allow us to estimate the burden for the state of this medical problem.OBJECTIVE: Assessment of the prevalence of concomitant pathology, HCV infection and type 2 diabetes, as well as the proportion of severe liver damage in its structure, according to the analysis of the primary medical records of four Moscow hospitals.MATERIALS AND METHODS: A retrospective analysis of the medical records of patients with HCV infection and diabetes mellitus, who admitted at different periods to four hospitals in Moscow, was carried out, as well as a total examination for the presence of anti-HCV in the blood of all patients with diabetes who were admitted within a certain period to the endocrinology department of a multidisciplinary hospital. Additionally, to determine the proportion of patients with liver cirrhosis (LC), an additional examination of patients with this combined pathology was carried out in accordance with the standards for the diagnosis of hepatitis C.RESULTS: In total, according to data from 4 hospitals in Moscow, over a certain period, 2% (105/5298) of diabetes patients with anti-HCV in their blood were identified. Sex ratio for men: women = 54 (51%): 51 (49%). Patients aged 50–69 years prevailed — 70% (74/105). Seroprevalence of HCV in cohorts of patients with type 2 diabetes according to the analysis in 3 health facilities: 0.9% (20/2196), 1.9% (8/432), 1.9% (28/1500). A significant drawback was revealed that did not allow assessing the true seroprevalence of HCV: not all patients were hospitalized with the results of a VH test, and not all of them were assigned an examination for VH markers if it was not performed before hospitalization. The proportion of type 2 diabetes patients with anti-HCV in the blood according to the results of total screening (3.7%; 16/432) became comparable to the proportion of type 2 diabetes patients among patients with CHC admitted to an infectious hospital (4.2%; 49 / 1170). The proportion of patients with LC according to the analysis of the medical records of the infectious hospital is 65% (32/49), in the group of endocrinological patients with additional examination it is 18% (13/71).CONCLUSION: For the first time in the Russian Federation, data were obtained on the prevalence of HCV infection in combination with type 2 diabetes. The results of the study indicate the need to develop effective screening programs to detect active HCV infection in the group of patients with diabetes, as well as patients among them with severe hepatic fibrosis for the timely conduct of highly effective antiviral therapy, which will prevent poor outcomes in a separate perspective

Treatment of chronic hepatitis C by cepeginterferon alpha-2b in combination to ribavirin

Aim of investigation. Comparative study of efficacy and safety of Algeron in dozes of 1,5 and 2,0 mkg/kg and PegIntron in combination to ribavirin within combined mode of treatment of patients with chronic hepatitis C (CHC) with subsequent assessment of therapeutic doze of Algeron.Material and methods. In open randomized «noninferiority» clinical study of II–III phase 150 previously untreated by interferon adult CHC patients (genotypes 1, 2, 3) were randomized in three medical groups: Algeron 1,5 mkg/kg, Algeron 2,0 mkg/kg and active control group — PegIntron 1,5 mkg/kg. All patients received ribavirin 800-1400 mg/day for 24-48 wks in relation to genotype. Early virologic response (EVR) rate was used as a primary endpoint of efficacy. Intentto-treat the analysis was applied at rating of obtained results.Results. The comparative analysis has demonstrated, that EVR at the 12-th week in group of Algeron 1,5 mkg/kg was observed in 100 % of patients with genotypes 2/3 and in 88,5% of patients with genotype 1. In Algeron 2,0 mkg/kg group it was registered at 95,7 and 92,6 % of patients respectively, in control group – in 95,5 and 82,1% (р&gt; 0,05 in comparison of all scores between groups). As no distinctions in Algeron efficacy were revealed, at more favorable safety profile of low doze, the therapeutic doze of 1,5 mkg /kg/wk has been chosen. After the first 12 wks of treatment all patients of the 1-st and 2-nd groups received Algeron in the chosen doze of 1,5 mkg/kg up to termination of the treatment course. Therefore the response at the end of treatment (direct virologic response, DVR) and sustained virologic response (SVR) were estimated for patients of the 1-st and 2-nd groups in common (n=100). Among patients with HCV 2/3 genotypes, receiving Algeron, DVR was observed in 93,6%, in control group – in 81,8%, in patients with the 1-st virus genotype — in 83 and 71,4 % of cases respectively (р&gt;0,05 at comparison of all scores between groups). In patients with 2/3 genotypes HCV, at Algeron therapy, SVR was reached in 83 % of cases, in PegIntron group — in 81,8 %. In patients with the 1-st virus genotype it was observed in 67,9 and 57,1 % respectively (p&gt; 0,05). The adverse events were registered during treatment by Algeron, in dose-dependent manner, however their frequency had did not exceed that in patients receiving standard PegIntron dozes.Conclusions. Study results prove high efficacy and safety of Algeron in suppression of hepatitis C virus replication and allow to recommend its application at previously untreated patients with CHC in a doze of 1,5 mkg/kg/wk for 24-48 wks in relation to genotype HCV

Diet-Induced Muscle Insulin Resistance Is Associated With Extracellular Matrix Remodeling and Interaction With Integrin α2β1 in Mice

OBJECTIVE: The hypothesis that high-fat (HF) feeding causes skeletal muscle extracellular matrix (ECM) remodeling in C57BL/6J mice and that this remodeling contributes to diet-induced muscle insulin resistance (IR) through the collagen receptor integrin α(2)β(1) was tested. RESEARCH DESIGN AND METHODS: The association between IR and ECM remodeling was studied in mice fed chow or HF diet. Specific genetic and pharmacological murine models were used to study effects of HF feeding on ECM in the absence of IR. The role of ECM-integrin interaction in IR was studied using hyperinsulinemic-euglycemic clamps on integrin α(2)β(1)-null (itga2(-/-)), integrin α(1)β(1)-null (itga1(-/-)), and wild-type littermate mice fed chow or HF. Integrin α(2)β(1) and integrin α(1)β(1) signaling pathways have opposing actions. RESULTS: HF-fed mice had IR and increased muscle collagen (Col) III and ColIV protein; the former was associated with increased transcript, whereas the latter was associated with reduced matrix metalloproteinase 9 activity. Rescue of muscle IR by genetic muscle-specific mitochondria-targeted catalase overexpression or by the phosphodiesterase 5a inhibitor, sildenafil, reversed HF feeding effects on ECM remodeling and increased muscle vascularity. Collagen remained elevated in HF-fed itga2(-/-) mice. Nevertheless, muscle insulin action and vascularity were increased. Muscle IR in HF-fed itga1(-/-) mice was unchanged. Insulin sensitivity in chow-fed itga1(-/-) and itga2(-/-) mice was not different from wild-type littermates. CONCLUSIONS: ECM collagen expansion is tightly associated with muscle IR. Studies with itga2(-/-) mice provide mechanistic insight for this association by showing that the link between muscle IR and increased collagen can be uncoupled by the absence of collagen-integrin α(2)β(1) interaction

Long-Term Monitoring of Liver Fibrosis and Steatosis in Patients with Chronic Hepatitis C after Achieving a Sustained Virologic Response to Antiviral Therapy

Aim: to analyze the dynamics of fibrosis and steatosis of the liver according to fibroelastometry in patients with chronic hep-atitis C (CHC) after ≥ 6 months from transient elastometry (TE) achieving a sustained virologic response (SVR) to antiviral therapy.Materials and methods. At baseline, a prospective observational study included 628 CHC patients with known stage of liver fibrosis (F) before AVT, some of whom were phased out due to non-compliance with the inclusion criteria. The final analysis included 297 patients who had transient elastometry (TE) data with CAP™ technology on the severity of liver fibrosis (± steatosis) before treatment and after ≥ 6 months after reaching SVR (67 % – interferonfree regimens of therapy). Median follow-up from the moment SVR was confirmed was 3 years [2; 6].Results. At the end of the study, the average age of patients was 49 ± 12 years, of which 53 % were men. In the long-term period after reaching SVR, regression of liver fibrosis was diagnosed in 80 % of cases (including in patients with cirrhosis), and the progression of fibrosis was in 3 % of patient. At the same time, regression of liver steatosis was detected only in 31 % of the patient, worsening of the results was in 23 % (26 % of them had the appearance of steatosis (S) of the liver of 1–3 degrees in persons with no fatty liver before the start of AVT). In the group of patients with liver steatosis, the proportion of men was significantly higher (p = 0.004). Clinically significant stages of fibrosis F3–F4 were significantly more often recorded in patients with hepatic steatosis, both before treatment (46 % S1–S3 and 22 % S0, p &lt; 0.001) and after ≥ 6 months after reaching SVR (19 % S1–S3 and 9 % S0, p = 0.023).Conclusion. In patients with chronic hepatitis C with SVR achieved in the long term, despite a significant regression of liver fibrosis, a high prevalence of hepatic steatosis remains. The data obtained indicate the feasibility of routine diagnosis of both fibrosis and steatosis of the liver in the management of patients with chronic HCV infection before and after successful antiviral therapy

Efficacy of pegylated interferon alfa-2b «Algeron» in the treatment of chronic hepatitis C

Aim of the study. To compare efficacy and safety of Algeron 1.5 and 2.0 μg/kg with PegIntron in combination with ribavirin in the treatment of chronic hepatitis C and to determine therapeutic dose of Algeron.Materials and Methods. 150 adult treatment-naive patients with HCV (all genotypes)were randomized into 3 groups. In the two main groups the patients received Algeron in the dosage of 1.5 or 2.0 μg/kg/week, in the active control group – PegIntron 1.5 μg/kg/week in combination with ribavirin. Primary efficacy endpoints were rapid and early virologic response (RVR and EVR).Results. Comparative analysis of virologic response rate after 4th and 12th weeks of the therapy and biochemical response did not show any statistically significant differences between the groups. RVR was observed in 64% and 56% of patients receiving Algeron 1.5 and 2.0 μg/kg, respectively, in the PegIntron group – in 66% (mITTanalysis, p&gt;0,05).The frequency of EVR in Algeron groups after 12 weeks of treatment (regardless of a dose – 1.5 or 2.0 μg/kg) was 94%, in the reference group (PegIntron) – 88% (p&gt;0,05). RVR and EVR rate analysis according to HCV genotype also did not showed statistically significant differences between the groups. Safety profiles of Algeron and PegIntron were similar. The complex assessment of the efficacy and safety allowed to make the conclusion about the optimal therapeutic dose of Algeron, equal to 1.5 μg/kg/week.Conclusions. Results of the study provide evidence of the high efficacy and safety of Algeron for suppression of HCV replication and make it possible to recommend Algeron 1.5 μg/kg weekly in combination with ribavirin for the treatment of chronic hepatitis C in treatment-naÏve patients for 24–48 weeks depending on the HCV genotype

Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors