Раствор и крем нафтифина гидрохлорида в терапии отрубевидного лишая

Introduction & objectives: The purpose of this study was to demonstrate the efficacy comparability of 1% NH lotion vs. of 1% NH cream (exoderil, Sandoz) in the treatment of pityriasis versicolor. Material & methods. 71 patients with pityriasis versicolor were randomly allocated either to receive NH lotion once daily (NH lotion group (п = 35, 38.6 years (95% CI [33,7, 43.5]) or NH cream once daily (NH cream group (п = 36, 40.8 years (95% CI [36,6, 45.0]) for 14 days. Mycological evaluations (microscopy and culture) were performed at weeks 2 and 3, inflammation symptoms evaluations were scored at day 3, weeks 2 and 3 after start of the therapy. Overall cure rates assessment included results of mycological, clinical outcomes and safety evaluation. Results. There was no difference between groups in mycological cure rates (94% vs 92%) and inflammation regression (97% vs 97%). Overall cure rate was 91% and 92% of patients in NH lotion and NH cream groups respectively (p = 0,97). Conclusion. 1% NH lotion and 1% NH cream are effective in the treatment of pityriasis versicolor.Цель исследования. Сравнить эффективность двух лекарственных форм нафтифина гидрохлорида: 1% раствора Экзодерил® и 1% крема Экзодерил® в терапии отрубевидного лишая. Материал и методы. Обследован 71 пациент с отрубевидным лишаем. Больные рандомизированы на две группы: группу лечения раствором нафтифина гидрохлорида 1 раз в день в течение 14 дней (35 больных; средний возраст 38,6 года; 95% доверительный интервал (ДИ) 33,7-43,5 года) и группу лечения кремом нафтифина гидрохлорида 1 раз в день в течение 14 дней (36 больных; средний возраст 38,6 года; 95% ДИ 36,6-45,0 лет). Результаты. Микологическая эффективность раствора нафтифина гидрохлорида составила 94% и была сопоставима с микологической эффективностью (92%) крема нафтифина гидрохлорида. Полная эффективность раствора нафтифина в терапии отрубевидного лишая составила 91%, а полная эффективность крема нафтифина - 92%

Identification of the Staphylococcus aureus MSCRAMM clumping factor B (ClfB) binding site in the αC-domain of human fibrinogen

Clumping factor B (ClfB) of Staphylococcus aureus binds to cytokeratin 10 and to fibrinogen. In this study the binding site in human fibrinogen was localized to a short region within the C terminus of the Aα-chain. ClfB only bound to the Aα-chain of fibrinogen in a ligand-affinity blot and in solid-phase assays with purified recombinant fibrinogen chains. A variant of fibrinogen with wild-type Bβ- and γ-chains but with a deletion that lacked the C-terminal residues from 252–610 of the Aα-chain did not support adherence of S. aureus Newman expressing ClfB. A series of truncated mutants of the recombinant Aα-chain were tested for their ability to support adherence of S. aureus Newman ClfB+, which allowed the binding site to be localized to a short segment of the unfolded flexible repeated sequence within the C terminus of the Aα-chain. This was confirmed by two amino acid substititions within repeat 5 of the recombinant Aα-chain which did not support adherence of Newman ClfB+. Lactococcus lactis expressing ClfB mutants with amino acid substitutions (N256 and Q235) located in the putative ligand-binding trench between domains N2 and N3 of the A-domain were defective in adherence to immobilized fibrinogen and cytokeratin 10, suggesting that both ligands bind to the same or overlapping regions

Justified use of 5% amorolfine nail lacquer, in the treatment of toe onychomycosis

The article presents the description of three clinical cases of the successful treatment of toe onychomycosis and athlete’s foot of various etiologies using 5% amorolfine antifungal nail lacquer. The first case: a 31-year-old woman was diagnosed with white superficial onychomycosis of great toe caused by Trichophyton rubrum. The treatment with 5% amorolfine once a week for 6 months resulted in full recovery (both mycological and clinical). The second case: a 42-year-old woman developed onychomycosis after the application of decorative coating on her nails; onychomycosis was caused by Scopulariopsis brevicaulis. She was treated with itraconazole pulse therapy and 5% amorolfine lacquer. She fully recovered. The third case: a 65-year-old man with total onychomycosis of 10 toes developed the skin mycosis of the left foot and lower third of the leg. He was prescribed a therapy with sertaconazole cream and 5% amorolfine lacquer. The use of 5% amorolfine lacquer was continued to prevent from recurrent dermatomycosis. Thus, the above mentioned cases are a good example of the advantages of using 5% amorolfine lacquer in the treatment of most toe onychomycosis types caused by any pathogens (dermatophytes, yeasts or molds)

Direct Evidence for Specific Interactions of the Fibrinogen αC-Domains with the Central E Region and with Each Other †

The carboxyl-terminal regions of the fibrinogen Aα chains (αC regions) form compact αC-domains tethered to the bulk of the molecule with flexible αC-connectors. It was hypothesized that in fibrinogen two αC-domains interact intramolecularly with each other and with the central E region preferentially through its N-termini of Bβ chains, and that removal of fibrinopeptides A and B upon fibrin assembly results in dissociation of the αC regions and their switch to intermolecular interactions. To test this hypothesis, we studied the interactions of the recombinant αC region (Aα221-610 fragment) and its sub-fragments, αC-connector (Aα221-391) and αC-domain (Aα392-610), between each other and with the recombinant (Bβ1-66)2 and (β15-66)2 fragments and NDSK corresponding to the fibrin(ogen) central E region, using laser tweezers-based force spectroscopy. TheαC-domain, but not the αC-connector, bound to NDSK, which contains fibrinopeptides A and B, and less frequently to desA-NDSK and (Bβ1-66)2 containing only fibrinopeptides B; it was poorly reactive with desAB-NDSK and (β15-66)2 both lacking fibrinopeptides B. The interactions of the αC-domains with each other and with the αC-connector were also observed, although they were weaker and heterogeneous in strength. These results provide the first direct evidence for the interaction between the αC-domains and the central E region through fibrinopeptides B, in agreement with the above hypothesis, and indicate that fibrinopeptides A are also involved. They also confirm the hypothesized homomeric interactions between the αC-domains and display their interaction with the αC-connectors, which may contribute to covalent cross-linking of α polymers in fibrin

A Modular Fibrinogen Model that Captures the Stress-Strain Behavior of Fibrin Fibers

We tested what to our knowledge is a new computational model for fibrin fiber mechanical behavior. The model is composed of three distinct elements: the folded fibrinogen core as seen in the crystal structure, the unstructured α-C connector, and the partially folded α-C domain. Previous studies have highlighted the importance of all three regions and how they may contribute to fibrin fiber stress-strain behavior. Yet no molecular model has been computationally tested that takes into account the individual contributions of all these regions. Constant velocity, steered molecular dynamics studies at 0.025 Å/ps were conducted on the folded fibrinogen core and the α-C domain to determine their force-displacement behavior. A wormlike chain model with a persistence length of 0.8 nm (Kuhn length = 1.6 nm) was used to model the mechanical behavior of the unfolded α-C connector. The three components were combined to calculate the total stress-strain response, which was then compared to experimental data. The results show that the three-component model successfully captures the experimentally determined stress-strain behavior of fibrin fibers. The model evinces the key contribution of the α-C domains to fibrin fiber stress-strain behavior. However, conversion of the α-helical coiled coils to β-strands, and partial unfolding of the protein, may also contribute

Oviduct-specific expression of tissue plasminogen activator in laying hens

Egg-laying hens are important candidate bioreactors for pharmaceutical protein production because of the amenability of their eggs for protein expression. In this study, we constructed an oviduct-specific vector containing tissue plasminogen activator (tPA) protein and green fluorescent protein (pL-2.8OVtPAGFP) and assessed its expression in vitro and in vivo. Oviduct epithelial and 3T3 cells were cultured and transfected with pL-2.8OVtPAGFP and pEGP-N1 (control vector), respectively. The pL-2.8OVtPAGFP vector was administered to laying hens via a wing vein and their eggs and tissues were examined for tPA expression. The oviduct-specific vector pL-2.8OVtPAGFP was expressed only in oviduct epithelial cells whereas pEGP-N1 was detected in oviduct epithelial and 3T3 cells. Western blotting detected a 89 kDa band corresponding to tPA in egg white and oviduct epithelial cells, thus confirming expression of the protein. The amount of tPAGFP in eggs ranged 9 to 41 ng/mL on the third day after vector injection. The tPA expressed in egg white and oviduct epithelial cells showed fibrinolytic activity, indicating that the protein was expressed in active form. GFP was observed only in oviducts, with no detection in heart, muscle, liver and intestine. This is the first study to report the expression of tPA in egg white and oviduct epithelial cells using an oviduct-specific vector

Crystal Structures Reveal the Multi-Ligand Binding Mechanism of Staphylococcus aureus ClfB

Staphylococcus aureus (S. aureus) pathogenesis is a complex process involving a diverse array of extracellular and cell wall components. ClfB, an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family surface protein, described as a fibrinogen-binding clumping factor, is a key determinant of S. aureus nasal colonization, but the molecular basis for ClfB-ligand recognition remains unknown. In this study, we solved the crystal structures of apo-ClfB and its complexes with fibrinogen α (Fg α) and cytokeratin 10 (CK10) peptides. Structural comparison revealed a conserved glycine-serine-rich (GSR) ClfB binding motif (GSSGXGXXG) within the ligands, which was also found in other human proteins such as Engrailed protein, TCF20 and Dermokine proteins. Interaction between Dermokine and ClfB was confirmed by subsequent binding assays. The crystal structure of ClfB complexed with a 15-residue peptide derived from Dermokine revealed the same peptide binding mode of ClfB as identified in the crystal structures of ClfB-Fg α and ClfB-CK10. The results presented here highlight the multi-ligand binding property of ClfB, which is very distinct from other characterized MSCRAMMs to-date. The adherence of multiple peptides carrying the GSR motif into the same pocket in ClfB is reminiscent of MHC molecules. Our results provide a template for the identification of other molecules targeted by S. aureus during its colonization and infection. We propose that other MSCRAMMs like ClfA and SdrG also possess multi-ligand binding properties

GroEL-Assisted Protein Folding: Does It Occur Within the Chaperonin Inner Cavity?

The folding of protein molecules in the GroEL inner cavity under the co-chaperonin GroES lid is widely accepted as a crucial event of GroEL-assisted protein folding. This review is focused on the data showing that GroEL-assisted protein folding may proceed out of the complex with the chaperonin. The models of GroEL-assisted protein folding assuming ligand-controlled dissociation of nonnative proteins from the GroEL surface and their folding in the bulk solution are also discussed

ЭВОЛЮЦИЯ ПРОГРАММЫ ТРАНСПЛАНТАЦИИ ПЕЧЕНИ В РОССИЙСКОМ НАУЧНОМ ЦЕНТРЕ РАДИОЛОГИИ И ХИРУРГИЧЕСКИХ ТЕХНОЛОГИЙ

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