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Purpose: The aim of this study was to explore the effects of medication therapy management in improving perception, medication adherence, and disease control in UC patients with first-stage of biotherapy. Subjects and Methods: A total of 120 patients with UC who received first-stage biotherapy participated in this study. The patients were divided into MTM group and CFU group. Both groups received three times follow-up, which were carried out at first, third, and sixth discharged month, Group A was followed with the MTM method, and Group B received conventional follow-up. MDRKT was used to assess patient perception, adherence to treatment was assessed by MMSA-8, and we also explored disease control and patient satisfaction. Results: A total of 116 patients completed the survey, the MTM group showed a significant improvement in perception, 84.2% of patients can correctly handle ADEs and 82.5% of patients knew what to do when they leak medication, 87.8% of patients in the MTM group had better adherence than 71.2% in the CFU group (P<0.05). The evaluation of disease control showed that 56.1% of patients in the Group A were in remission which was significantly higher than 32.2% in the Group B (P<0.05). Furthermore, the result of the questionnaire survey showed that perception, ADE, self-management, anxiety, and satisfaction were better in the MTM group than in the CFU group (P<0.05). Conclusion: The MTM group was effective in improving medication adherence, perception, and satisfaction in the patient with ulcerative colitis treated with first-stage biotherapy, and the disease control significantly improved

We read with great interest the publication of Messina et al 1 reporting the first case of SARS-CoV2 infection in a young patient of 32-year-old suffering from psoriasis and psoriatic arthritis treated by Guselkumab, a monoclonal antibody that targets specifically the p19 subunit of Interleukin (IL)-232 .The patient contracted the SARS-CoV2 infection after a dinner with some friends but fortunately she developed very discrete symptoms including only mild fever and rhinorrhea. These findings support the potential role of IL-23p19 inhibitors to counteract the « cytokine storm » triggered by the SARS-CoV2 and which is potentially implicated in the severity of the symptoms 3 ., SCOPUS: le.j, info:eu-repo/semantics/published

As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies.

Acrodermatitis continua of Hallopeau, first described in 1890, is an uncommon variant of pustular psoriasis. It presents as a sterile pustular eruption of the tips of fingers and toes. The condition has a chronic, relapsing course and is often resistant to many anti-psoriatic therapies. In the following case, we present our experience of etanercept use in a 61-year-old man. Although initial therapy with high-dose etanercept achieved a rapid, sustained response and remission, the lesions relapsed a few months into a lower, maintenance dosage. This result prompted the use a second biotherapeutic agent ustekinumab, which resulted in complete remission, but required a higher dosage than recommended with reduced dosing intervals.

Acrodermatitis continua of Hallopeau, first described in 1890, is an uncommon variant of pustular psoriasis. It presents as a sterile pustular eruption of the tips of fingers and toes. The condition has a chronic, relapsing course and is often resistant to many anti-psoriatic therapies. In the following case, we present our experience of etanercept use in a 61-year-old man. Although initial therapy with high-dose etanercept achieved a rapid, sustained response and remission, the lesions relapsed a few months into a lower, maintenance dosage. This result prompted the use a second biotherapeutic agent ustekinumab, which resulted in complete remission, but required a higher dosage than recommended with reduced dosing intervals.

As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies.

The need to adjust the balance of microbiocenosis - the problem is modern and relevant. It was considered a wide range of drugs (products) that affect different parts microecological process: probiotics, preparations based on inactivated microorganisms, prebiotics, sinbiotics, drugs metabolic type, functional food, nutraceuticals. Analyzed and proved ix mechanisms of action, urgency and prospects of the known and new drugs that affect endoecology and update it., Необходимость корректировать баланс микробиоценоза - проблема современная и актуальная. Был рассмотрен широкий диапазон препаратов (продуктов), которые влияют на различные звенья микроэкологического процесса: пробиотики, препараты на основе инактивированных микроорганизмов, пребиотики, синбиотики, препараты метаболического типа, продукты функционального питания, нутрицевтики. Проанализированы и обоснованы механизмы их действия, актуальность и перспективы использования известных и создание новых препаратов, которые влияют на эндоэкологию и обновляют ее., Необхідність корегувати баланс мікробіоценозу - проблема сучасна та актуальна. Було розглянуто широкий діапазон препаратів (продуктів), які впливають на різні ланки мікроекологічного процесу: пробіотики, препарати на основі інактивованих мікроорганізмів, пребіотики, сінбіотики, препарати метаболічного типу, продукти функціонального харчування, нутрицевтики. Проаналізовано та обґрунтовано механізми іх дії, актуальність та перспективи використання відомих та створення нових препаратів, які впливають на ендоекологію та оновлюють її.

The need to adjust the balance of microbiocenosis - the problem is modern and relevant. It was considered a wide range of drugs (products) that affect different parts microecological process: probiotics, preparations based on inactivated microorganisms, prebiotics, sinbiotics, drugs metabolic type, functional food, nutraceuticals. Analyzed and proved ix mechanisms of action, urgency and prospects of the known and new drugs that affect еndoecology and update it., Необходимость корректировать баланс микробиоценоза - проблема современная и актуальная. Был рассмотрен широкий диапазон препаратов (продуктов), которые влияют на различные звенья микроэкологического процесса: пробиотики, препараты на основе инактивированных микроорганизмов, пребиотики, синбиотики, препараты метаболического типа, продукты функционального питания, нутрицевтики. Проанализированы и обоснованы механизмы их действия, актуальность и перспективы использования известных и создание новых препаратов, которые влияют на эндоэкологию и обновляют ее., Необхідність корегувати баланс мікробіоценозу - проблема сучасна та актуальна. Було розглянуто широкий діапазон препаратів (продуктів), які впливають на різні ланки мікроекологічного процесу: пробіотики, препарати на основі інактивованих мікроорганізмів, пребіотики, сінбіотики, препарати метаболічного типу, продукти функціонального харчування, нутрицевтики. Проаналізовано та обґрунтовано механізми іх дії, актуальність та перспективи використання відомих та створення нових препаратів, які впливають на ендоекологію та оновлюють її.

Affibody molecules are a class of engineered affinity proteins with proven potential for therapeutic, diagnostic and biotechnological applications. Affibody molecules are small (6.5 kDa) single domain proteins that can be isolated for high affinity and specificity to any given protein target. Fifteen years after its discovery, the Affibody technology is gaining use in many groups as a tool for creating molecular specificity wherever a small, engineering compatible tool is warranted. Here we summarize recent results using this technology, propose an Affibody nomenclature and give an overview of different HER2-specific Affibody molecules. Cumulative evidence suggests that the three helical scaffold domain used as basis for these molecules is highly suited to create a molecular affinity handle for vastly different applications., QC 20101214

The major goal of this research project was to optimize the conjugation procedures used in the preparation of the EGF-Gen conjugates in order to overcome the major limitations of this technology, including (1) instability of the conjugates; (2) presence of Gen-free modified EGF in the conjugate preparations; (3) slow kinetics of cell kill; and (4) low yield of intact conjugate. The research did not lead to a solution for any of the above listed problems/limitations of the technology. It is therefore unlikely that the Genistein conjugates of EGF will be clinically useful. We have explored the potential of EGF conjugates containing other more active inhibitors of the EGF tyrosine kinase. While these conjugates have not been tested in animal models of breast cancer during the term of this grant, they are unlikely to offer significant advantages over the unconjugated small molecule tyrosine kinase inhibitors.

Our proposed research plan involves laboratory studies using a SCID mouse model of human metastatic breast cancer, as well as in vitro MTT(3- 4,5- DIMETHYLTHIAZOL-2-YL -2,5-diphenyl tetrazolium bromide) and colony assays, using established breast cancer cell lines, to examine the potency and toxicity of various EGE-Genistein conjugates. In an effort to generate more effective conjugates, we have employed a variety of crosslinking agents and photolysis conditions. Furthermore, we have established HPLC(high performance liquid chromatography) procedures to characterize and isolate the EGF components of the reaction mixture. We have also conjugated EGF to other small molecules which by themselves have been shown to possess anti-cancer activity. The knowledge gained from these studies is expected to lead to more effective biotherapy and combined biochemotherapy regimens for the treatment of breast cancer patients.

Our proposed research plan involves laboratory studies using an in vivo severe combined immunodeficiency (SCID) mouse model of human metastatic breast cancer as well as cynomologous monkeys to examine the anti-breast cancer activity, toxicity, and pharmacodynamic features of EGF-Gen. Our primary goal in the proposed animal studies is to determine whether systemic exposure levels of EGF-Gen found to be therapeutically effective in SCD mouse models of human breast cancer can be achieved in cynomologous monkeys without excessive toxicity. The knowledge gained from these studies is expected to facilitate the design of effective biotherapy and combined biochemotherapy regimes for breast cancer patients. The proposed research is directly relevant to a critical issue in the treatment of breast cancer.

De toenames van eosinofiele granulocyten en IgE concentraties in Toxocara canis geinfecteerde BALB/c muizen werden geblokkeerd door behandeling met ratte-hybridoma cellen die respectievelijk anti-interleukine-5 (anti-IL-5) en anti-IL-4 produceerden. Doel was het effect te bestuderen van deze blokkade op het verloop van de door de migrerende larven veroorzaakte ontstekingen in het longweefsel. Anti-IL-5 producerende cellen (1 x 1000000) toegediend twee dagen voor en vijf dagen na infectie (p.i.) blokkeerden volledig de toename van eosinofiele granulocyten in het bloed en de infiltratie hiervan in de longen tot 28 p.i.. Het totaal aantal ontstekingscellen in het bronchoalveolair lavaat (BAL) was afgenomen ten opzichte van niet behandelde of met isotype behandelde en geinfecteerde dieren. Deze afname was geheel toe te schrijven aan de remming op de infiltratie van eosinofielen in de longen. Het albumine gehalte in het BAL was significant toegenomen in de geinfecteerde dieren. Behandeling met anti-IL-5 of isotype controle cellen bracht hierin geen verandering. Dit duidde er op dat eosinofielen de vaatdoorlaatbaarheid niet belangrijk beinvloedden. Onderzoek naar IL-5 en IFN-gamma positieve cellen in het longweefsel toonde aan dat deze afwezig waren in niet geinfecteerde dieren. Geinfecteerde dieren behandeld met anti-IL-5 hadden geen IL-5 positieve cellen terwijl deze wel werden aangetroffen in de met isotype behandelde dieren. Opmerkelijk was dat het aantal IFN-gamma positieve cellen in combinatie met anti-IL-5 behandeling sterk en met isotype behandeling in mindere mate waren toegenomen. De resultaten suggereren dat toediening van ratte-eiwitten aan T.canis geinfecteerde dieren de toename van IFN-gamma positieve cellen bevordert en daarmee dus de stimulatie van T helper 1 cellen. De behandeling met anti-IL-4 leek niet succesvol. Toediening van 1,5 x 1000000 cellen op dag 0 en 1 x 1000000 cellen op dag 7 p.i. had geen effect op de celpopulaties in het BAL. Anti-IL-4 beh, Toxocara canis-infected BALB/c mice were treated with rat hybridoma cells producing either anti-interleukin-5 (anti-IL-5) or anti-IL-4 to inhibit increases in eosinophils and immunoglobulin E respectively. The aim of the investigation was to study the effect of this inhibition on the course of pulmonary inflammation caused by T.canis migrating larvae. Anti-IL-5 producing cells administered i.p. (1 x 1000000) two days before and 5 days after infection inhibited completely the eosinophil increases in blood and bronchoalveolar lavage fluid (BALF). The albumin concentration in the BALF of infected mice increased significantly. Treatment with anti-IL-5 or with isotype control did not affect this increase, showing that eosinophils apparently played a minor role in the observed change in microvascular permeability. Lung tissue sections stained to demonstrate IL-5 and IFN-gamma positive cells showed their absence in non-infected mice and in infected mice treated with anti-IL-5. In the lungs of isotype and saline-treated infected controls IL-5 positive cells were present although their number was low. Remarkable was that anti-IL-5 treatment, and to a less extent isotype treatment, of infected mice caused a huge increase in IFN-gamma positive cells. These results suggested that administration of rat proteins to T.canis-infected animals promoted the increase of IFN-gamma positive cells and apparently stimulated T helper 1 cells. Anti-IL-4 treatment seemed unsuccessful. Administration of 1,5 x 1000000 cells at day 0 and 1 x 1000000 at day 7 p.i. did not have any effect on the cell populations in the BALF. Anti-IL-4 inhibited the IgE increase in infected mice with about 70% in both, serum and BALF at 14 days p.i. but no inhibition was observed at 28 days p.i.. Isotype treatment even stimulated IgE production in infected mice. The persisting presence of larvae and thus of antigen caused a continuous stimulation of the immune response with emphasis on the T helper 2 cells. Prolong

RIVM rapport:De toenames van eosinofiele granulocyten en IgE concentraties in Toxocara canis geinfecteerde BALB/c muizen werden geblokkeerd door behandeling met ratte-hybridoma cellen die respectievelijk anti-interleukine-5 (anti-IL-5) en anti-IL-4 produceerden. Doel was het effect te bestuderen van deze blokkade op het verloop van de door de migrerende larven veroorzaakte ontstekingen in het longweefsel. Anti-IL-5 producerende cellen (1 x 1000000) toegediend twee dagen voor en vijf dagen na infectie (p.i.) blokkeerden volledig de toename van eosinofiele granulocyten in het bloed en de infiltratie hiervan in de longen tot 28 p.i.. Het totaal aantal ontstekingscellen in het bronchoalveolair lavaat (BAL) was afgenomen ten opzichte van niet behandelde of met isotype behandelde en geinfecteerde dieren. Deze afname was geheel toe te schrijven aan de remming op de infiltratie van eosinofielen in de longen. Het albumine gehalte in het BAL was significant toegenomen in de geinfecteerde dieren. Behandeling met anti-IL-5 of isotype controle cellen bracht hierin geen verandering. Dit duidde er op dat eosinofielen de vaatdoorlaatbaarheid niet belangrijk beinvloedden. Onderzoek naar IL-5 en IFN-gamma positieve cellen in het longweefsel toonde aan dat deze afwezig waren in niet geinfecteerde dieren. Geinfecteerde dieren behandeld met anti-IL-5 hadden geen IL-5 positieve cellen terwijl deze wel werden aangetroffen in de met isotype behandelde dieren. Opmerkelijk was dat het aantal IFN-gamma positieve cellen in combinatie met anti-IL-5 behandeling sterk en met isotype behandeling in mindere mate waren toegenomen. De resultaten suggereren dat toediening van ratte-eiwitten aan T.canis geinfecteerde dieren de toename van IFN-gamma positieve cellen bevordert en daarmee dus de stimulatie van T helper 1 cellen. De behandeling met anti-IL-4 leek niet succesvol. Toediening van 1,5 x 1000000 cellen op dag 0 en 1 x 1000000 cellen op dag 7 p.i. had geen effect op de celpopulaties in het BAL. Anti-IL-4 beh, Toxocara canis-infected BALB/c mice were treated with rat hybridoma cells producing either anti-interleukin-5 (anti-IL-5) or anti-IL-4 to inhibit increases in eosinophils and immunoglobulin E respectively. The aim of the investigation was to study the effect of this inhibition on the course of pulmonary inflammation caused by T.canis migrating larvae. Anti-IL-5 producing cells administered i.p. (1 x 1000000) two days before and 5 days after infection inhibited completely the eosinophil increases in blood and bronchoalveolar lavage fluid (BALF). The albumin concentration in the BALF of infected mice increased significantly. Treatment with anti-IL-5 or with isotype control did not affect this increase, showing that eosinophils apparently played a minor role in the observed change in microvascular permeability. Lung tissue sections stained to demonstrate IL-5 and IFN-gamma positive cells showed their absence in non-infected mice and in infected mice treated with anti-IL-5. In the lungs of isotype and saline-treated infected controls IL-5 positive cells were present although their number was low. Remarkable was that anti-IL-5 treatment, and to a less extent isotype treatment, of infected mice caused a huge increase in IFN-gamma positive cells. These results suggested that administration of rat proteins to T.canis-infected animals promoted the increase of IFN-gamma positive cells and apparently stimulated T helper 1 cells. Anti-IL-4 treatment seemed unsuccessful. Administration of 1,5 x 1000000 cells at day 0 and 1 x 1000000 at day 7 p.i. did not have any effect on the cell populations in the BALF. Anti-IL-4 inhibited the IgE increase in infected mice with about 70% in both, serum and BALF at 14 days p.i. but no inhibition was observed at 28 days p.i.. Isotype treatment even stimulated IgE production in infected mice. The persisting presence of larvae and thus of antigen caused a continuous stimulation of the immune response with emphasis on the T helper 2 cells. Prolong

RIVM rapport:De toenames van eosinofiele granulocyten en IgE concentraties in Toxocara canis geinfecteerde BALB/c muizen werden geblokkeerd door behandeling met ratte-hybridoma cellen die respectievelijk anti-interleukine-5 (anti-IL-5) en anti-IL-4 produceerden. Doel was het effect te bestuderen van deze blokkade op het verloop van de door de migrerende larven veroorzaakte ontstekingen in het longweefsel. Anti-IL-5 producerende cellen (1 x 1000000) toegediend twee dagen voor en vijf dagen na infectie (p.i.) blokkeerden volledig de toename van eosinofiele granulocyten in het bloed en de infiltratie hiervan in de longen tot 28 p.i.. Het totaal aantal ontstekingscellen in het bronchoalveolair lavaat (BAL) was afgenomen ten opzichte van niet behandelde of met isotype behandelde en geinfecteerde dieren. Deze afname was geheel toe te schrijven aan de remming op de infiltratie van eosinofielen in de longen. Het albumine gehalte in het BAL was significant toegenomen in de geinfecteerde dieren. Behandeling met anti-IL-5 of isotype controle cellen bracht hierin geen verandering. Dit duidde er op dat eosinofielen de vaatdoorlaatbaarheid niet belangrijk beinvloedden. Onderzoek naar IL-5 en IFN-gamma positieve cellen in het longweefsel toonde aan dat deze afwezig waren in niet geinfecteerde dieren. Geinfecteerde dieren behandeld met anti-IL-5 hadden geen IL-5 positieve cellen terwijl deze wel werden aangetroffen in de met isotype behandelde dieren. Opmerkelijk was dat het aantal IFN-gamma positieve cellen in combinatie met anti-IL-5 behandeling sterk en met isotype behandeling in mindere mate waren toegenomen. De resultaten suggereren dat toediening van ratte-eiwitten aan T.canis geinfecteerde dieren de toename van IFN-gamma positieve cellen bevordert en daarmee dus de stimulatie van T helper 1 cellen. De behandeling met anti-IL-4 leek niet succesvol. Toediening van 1,5 x 1000000 cellen op dag 0 en 1 x 1000000 cellen op dag 7 p.i. had geen effect op de celpopulaties in het BAL. Anti-IL-4 beh, Toxocara canis-infected BALB/c mice were treated with rat hybridoma cells producing either anti-interleukin-5 (anti-IL-5) or anti-IL-4 to inhibit increases in eosinophils and immunoglobulin E respectively. The aim of the investigation was to study the effect of this inhibition on the course of pulmonary inflammation caused by T.canis migrating larvae. Anti-IL-5 producing cells administered i.p. (1 x 1000000) two days before and 5 days after infection inhibited completely the eosinophil increases in blood and bronchoalveolar lavage fluid (BALF). The albumin concentration in the BALF of infected mice increased significantly. Treatment with anti-IL-5 or with isotype control did not affect this increase, showing that eosinophils apparently played a minor role in the observed change in microvascular permeability. Lung tissue sections stained to demonstrate IL-5 and IFN-gamma positive cells showed their absence in non-infected mice and in infected mice treated with anti-IL-5. In the lungs of isotype and saline-treated infected controls IL-5 positive cells were present although their number was low. Remarkable was that anti-IL-5 treatment, and to a less extent isotype treatment, of infected mice caused a huge increase in IFN-gamma positive cells. These results suggested that administration of rat proteins to T.canis-infected animals promoted the increase of IFN-gamma positive cells and apparently stimulated T helper 1 cells. Anti-IL-4 treatment seemed unsuccessful. Administration of 1,5 x 1000000 cells at day 0 and 1 x 1000000 at day 7 p.i. did not have any effect on the cell populations in the BALF. Anti-IL-4 inhibited the IgE increase in infected mice with about 70% in both, serum and BALF at 14 days p.i. but no inhibition was observed at 28 days p.i.. Isotype treatment even stimulated IgE production in infected mice. The persisting presence of larvae and thus of antigen caused a continuous stimulation of the immune response with emphasis on the T helper 2 cells. Prolong