Search for predictors of psoriatic arthritis in patients with psoriasis

Background. Psoriatic arthritis is a chronic inflammatory disease of the joints, spine and entheses that can occur in patients with psoriasis. The prevalence of psoriatic arthritis is 19.7%. In 70% of cases, psoriasis precedes the development of arthritis. It has been proven that a delay in the diagnosis of psoriatic arthritis even by 6 months is associated with a deterioration in long-term radiological and functional results, leading to disability. The problem of early diagnosis of joint damage can be solved by identifying predictors of the risk of developing psoriatic arthritis in patients with psoriasis. Aims. To determine possible predictors for the development of psoriatic arthritis in patients with psoriasis. Methods. The open, uncontrolled, prospective study enrolled 250 patients. The main group consisted of 190 patients diagnosed with plaque psoriasis. The control group consisted of 60 patients with psoriatic arthritis. In order to identify associations of clinical and genetic (HLA-B27 carriage) parameters with the development of psoriatic arthritis, we compared the frequency of occurrence of these parameters in patients with psoriatic arthritis and without. Results. Among 190 patients with plaque psoriasis 128 (67.4%) men, 62 (32.6%) women, aged 18 to 84 years (40.30 ± 15.56), the average duration of psoriasis was 10.09 ± 11.08 years (0–57). Among 60 patients with psoriatic arthritis 39 (65%) men, 21 (35%) women aged 18 to 86 years (44.43 ± 14.15), the average duration of psoriasis was 20.47 ± 13.22 years (2–57), the average duration of psoriatic arthritis was 7.97 ± 9.95 years (0–47). Сlinical predictors for the development of psoriatic arthritis in patients with psoriasis: nail psoriasis (OR = 2.244 [95% CI: 1.245–4.045]); severe psoriasis (PASI ≥ 20) (OR = 2.148 [95% CI: 1.161–3.975]); arterial hypertension (OR = 1.982 [95% CI: 1.031–3.812]); duration of psoriasis over 25 years (OR = 3.365 [95% CI: 1.676–6.756]), р 0,05. Conclusions. The joint consideration of informative predictors will allow us to develop an original multi-parameter mathematical model for calculating the risk of developing psoriatic arthritis in patients with psoriasis

A rare form of leishmaniasis, identified in the Russian Federation

Diffuse cutaneous leishmaniasis is a rare form of cutaneous leishmaniasis characterized by an inadequate immune response of the host cells to parasitic invasion (weak T-helper (Th)1 response or Th2 response with the production of interleukin IL-4 and IL-10). The characteristic features of the disease include diffuse nodular eruption, masquerading as leprosy and a frequent association with immunosuppression (HIV co-infection, for example). The Russian Federation is a non-endemic country for leishmaniasis, but this disease can be brought into the country by tourists, immigrants, refugees and military personnel. A clinical case of diffuse cutaneous leishmaniasis and HIV co-infection is presented. The patient was a citizen of Uzbekistan, a country endemic for leishmaniasis. The authors were unable to find domestic scientific publications describing cases of diffuse cutaneous leishmaniasis detected in the Russian Federation. The presented clinical case of diffuse cutaneous leishmaniasis in a patient with HIV is the first in the Russian literature

The effect of apremilast therapy on skin cytokine levels in patients with psoriasis

Objective — Assessment of phosphodiesterase-4 inhibitor (apremilast) therapy’s influence on skin cytokine levels in patients with moderate-to-severe and severe psoriasis. Material and Methods — An open, uncontrolled study was conducted. 16 patients with plaque psoriasis (13 men, 3 women; mean ± standard deviation (SD) age 35.1±9.7 years, range 21-60) were enrolled. The mean Psoriasis Area and Severity Index (PASI) was 20.7±8.93 (range 10-47). All patients were prescribed apremilast 30 milligrams (mg) per os (PO) Bis In Die (BID). The efficacy of therapy was evaluated by PASI at 14 and 26 weeks of therapy. Lesional skin samples were collected at baseline and weeks 14 and 26. Levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL -33, interferon (INF)-γ, Soluble CD40-ligand (sCD40L), tumor necrosis factor (TNF)-α were measured by microsphere-based suspension array technology (Luminex® xMAP™ system). Results — Levels of cytokines (except IL-4 and IL-33) in lesional skin samples were found to have decreased at week 14 compared with those at baseline. Similar decreases were seen for IL-23, IL-25, IL-31, sCD40L at week 26. In contrast, the levels of other cytokines increased again at week 26, in comparison with baseline. Levels of IL-4 and IL-33 rose throughout the follow-up period. Cytokine levels in lesional skin samples were compared with those of healthy controls both at baseline and during therapy. Conclusion — The results of our study show that administering apremilast therapy to patients with psoriasis can bring the levels of cytokines involved in the IL-23/IL-17 axis in the lesional skin to the level of cytokine in non-lesional skin and to the levels in the skin of healthy individuals

Harnessing the Technological Potential of Chia Seeds in the Technology of Cream-whipped Candy Masses

The technological properties of chia seeds have been studied. It has been established that the degree of their swelling depends on the type of a medium (water, albumin solution, fat) and the state of seeds (whole seeds or ground seeds). It was noted that the whole seeds have a higher capacity to retain water than the ability to retain an albumin solution or fat, by 1.87 and 17.28 times, and the ground seeds – by 1.75 and 17.49 times, respectively. Their capacity to swell improves after grinding regardless of the type of a medium. In addition, the ground seeds have a better fat-emulsifying ability but they do not demonstrate the foaming properties. The whole chia seeds have good foaming properties. It is possible to obtain a whipped protein mass, which is not worse than the control sample in terms of stability and foaming capacity, in case of replacing 40 % of dry albumin with whole chia seeds.We recommend adding the whole chia seeds at the stage of the whipping of protein mass, and the ground seeds – at the stage of obtaining a fat emulsion semi-finished product in the production of cream-whipped candy masses. Thus, the formulation amount of dry albumin and fat decreases. The addition of 30 % of whole seeds and 30 % of ground seeds helps reduce the density of structured cream-whipped candy mass by 6.7 %. A further increase in the dosage of the additive leads to a slight increase in the value of the density indicator. In addition, an increase in the content of chia seeds causes an increase in the strength indicator of samples. The organoleptic analysis showed that the structured cream-whipped candy masses with the most studied dosage of chia seeds have the densified structure, uneven porosity, and strong, viscous consistency. It was found that the dosage of whole seeds should equal 40 % by weight of egg albumin, and the dosage of ground seeds – 40 % by weight of fat to ensure the high quality of cream-whipped candy masses.The obtained results are of practical importance for improving the technology of cream-whipped candy masses towards decreasing the formulation amount of albumin and margarine. The addition of chia seeds would improve the nutritional and biological values of cream-whipped candie

Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis

One of the target drugs for plaque psoriasis treatment is apremilast, which is a selective phosphodiesterase 4 (PDE4) inhibitor. In this study, 34 moderate-to-severe and severe plaque psoriasis patients from Russia were treated with apremilast for 26 weeks. This allowed us to observe the effectiveness of splitting patient cohorts based on clinical outcomes, which were assessed using the Psoriasis Area Severity Index (PASI). In total, 14 patients (41%) indicated having an advanced outcome with delta PASI 75 after treatment; 20 patients indicated having moderate or no effects. Genome variability was investigated using the Illumina Infinium Global Screening Array. Genome-wide analysis revealed apremilast therapy clinical outcome associations at three compact genome regions with undefined functions situated on chromosomes 2, 4, and 5, as well as on a single single-nucleotide polymorphism (SNP) on chromosome 23. Pre-selected SNP sets were associated with psoriasis vulgaris analysis, which was used to identify four SNP-associated targeted therapy efficiencies: IL1β (rs1143633), IL4 (IL13) (rs20541), IL23R (rs2201841), and TNFα (rs1800629) genes. Moreover, we showed that the use of the global polygenic risk score allowed for the prediction of onset psoriasis in Russians. Therefore, these results can serve as a starting point for creating a predictive model of apremilast therapy response in the targeted therapy of patients with psoriasis vulgaris

Mass spectrometry and biochemical analysis of RNA polymerase II: Targeting by protein phosphatase-1

Transcription of eukaryotic genes is regulated by phosphorylation of serine residues of heptapeptide repeats of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII). We previously reported that protein phosphatase-1 (PP1) dephosphorylates RNAPII CTD in vitro and inhibition of nuclear PP1-blocked viral transcription. In this article, we analyzed the targeting of RNAPII by PP1 using biochemical and mass spectrometry analysis of RNAPII-associated regulatory subunits of PP1. Immunoblotting showed that PP1 co-elutes with RNAPII. Mass spectrometry approach showed the presence of U2 snRNP. Co-immunoprecipitation analysis points to NIPP1 and PNUTS as candidate regulatory subunits. Because NIPP1 was previously shown to target PP1 to U2 snRNP, we analyzed the effect of NIPP1 on RNAPII phosphorylation in cultured cells. Expression of mutant NIPP1 promoted RNAPII phosphorylation suggesting that the deregulation of cellular NIPP1/PP1 holoenzyme affects RNAPII phosphorylation and pointing to NIPP1 as a potential regulatory factor in RNAPII-mediated transcription. © 2010 Springer Science+Business Media, LLC

Mass spectrometry and biochemical analysis of RNA polymerase II: targeting by protein phosphatase-1

Transcription of eukaryotic genes is regulated by phosphorylation of serine residues of heptapeptide repeats of the carboxyterminal domain (CTD) of RNA polymerase II (RNAPII). We previously reported that protein phosphatase-1 (PP1) dephosphorylates RNAPII CTD in vitro and inhibition of nuclear PP1-blocked viral transcription. In this article, we analyzed the targeting of RNAPII by PP1 using biochemical and mass spectrometry analysis of RNAPII-associated regulatory subunits of PP1. Immunoblotting showed that PP1 co-elutes with RNAPII. Mass spectrometry approach showed the presence of U2 snRNP. Co-immunoprecipitation analysis points to NIPP1 and PNUTS as candidate regulatory subunits. Because NIPP1 was previously shown to target PP1 to U2 snRNP, we analyzed the effect of NIPP1 on RNAPII phosphorylation in cultured cells. Expression of mutant NIPP1 promoted RNAPII phosphorylation suggesting that the deregulation of cellular NIPP1/PP1 holoenzyme affects RNAPII phosphorylation and pointing to NIPP1 as a potential regulatory factor in RNAPII-mediated transcription