- MeSH
- cílená molekulární terapie klasifikace metody MeSH
- humanizované monoklonální protilátky farmakologie klasifikace terapeutické užití MeSH
- inhibitory TNF farmakologie klasifikace terapeutické užití MeSH
- interleukin-17 antagonisté a inhibitory MeSH
- interleukin-23 antagonisté a inhibitory MeSH
- lidé MeSH
- psoriáza * diagnóza farmakoterapie imunologie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Hidradenitis suppurativa (HS) je chronické onemocnění terminálních pilosebaceózních žláz primárně se projevující bolestivými zánětlivými recidivujícími noduly a abscesy, které opakovaně praskají, a vedou tak k tvorbě píštělí a jizev. Projevy HS lze rozdělit na dvě formy – zánětlivou a nezánětlivou –, které pak určují způsob léčby pacienta. Hidradenitis suppurativa je spojena s četnými komorbiditami, jako jsou např. obezita, kouření, deprese, idiopatické střevní záněty, axiální spondyloartritida aj., proto je klíčová multioborová spolupráce.
Hidradenitis suppurativa (HS) is a chronic disease of the terminal pilosebaceous glands, manifesting primarily by recurrent painful inflammatory nodules and abscesses that tend to rupture and thus form fistulas and scars. Two distinct forms of HS – inflammatory and non‐inflammatory – require different clinical approach. HS is associated with multiple comorbidities including obesity, smoking, depression, inflammatory bowel disease, axial spondylarthritis, etc. Cooperation of various specialists in the management of patients suffering from HS is mandatory.
- MeSH
- antibakteriální látky klasifikace terapeutické užití MeSH
- hidradenitis suppurativa * chirurgie diagnóza farmakoterapie klasifikace MeSH
- klindamycin terapeutické užití MeSH
- komorbidita MeSH
- lidé MeSH
- management nemoci MeSH
- obezita komplikace MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- tetracykliny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Chronic venous disease (CVD) is a common disorder of lower extremities. OBJECTIVES: The study was scheduled to investigate the relationship between polymorphisms in major proinflammatory genes TNF α (-238 A/G; -308 A/G), TNF β (NcoI), IL-1β (+3953 T/C); IL-6 (-174 G/C; -596 G/C) and ADAM17 (3'TACE) and CVD risk. Genotype-phenotype study was calculated to test possible association between examined genotypes and phenotypes of CVD. METHODS: Finally, 150 CVD patients and 227 control subjects were enrolled to the study. Genotypes in proinflammatory gene polymorphisms were identified from isolated DNA by PCR method and restriction analysis. RESULTS: Significant differences in genotype distribution/allelic frequencies in TNF β gene, IL-1 β gene and in ADAM17 gene polymorphisms were found between CVD women and control ones. In the genotype-phenotype study, identified genotypes were associated with arterial hypertension (ADAM17, IL-6-men), ischaemic heart disease (TNF α and β genes), diabetes mellitus (ADAM17-women, TNF β-men), age of CVD onset (TNF α and IL-6), ulceration (ADAM17), duration of ulceration (ADAM17), ulceration recurrence (ADAM17-women), home care necessity (TNF α), varices surgery (TNF α), erysipelas development (ADAM17-men) and tumour development (TNF α). CONCLUSION: Studying of these polymorphisms associations can help us better identify patients at higher risk of developing severe CVD.
- MeSH
- chronická nemoc MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- interleukin-1beta genetika MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus MeSH
- kardiovaskulární nemoci * genetika MeSH
- lidé MeSH
- lymfotoxin-alfa genetika MeSH
- protein ADAM17 genetika MeSH
- TNF-alfa * genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Cardiovascular diseases, such as myocardial infarction, ischemic stroke, and pulmonary embolism, are the most common causes of disability and death worldwide. Blood clot hydrolysis by thrombolytic enzymes and thrombectomy are key clinical interventions. The most widely used thrombolytic enzyme is alteplase, which has been used in clinical practice since 1986. Another clinically used thrombolytic protein is tenecteplase, which has modified epitopes and engineered glycosylation sites, suggesting that carbohydrate modification in thrombolytic enzymes is a viable strategy for their improvement. This comprehensive review summarizes current knowledge on computational and experimental identification of glycosylation sites and glycan identity, together with methods used for their reengineering. Practical examples from previous studies focus on modification of glycosylations in thrombolytics, e.g., alteplase, tenecteplase, reteplase, urokinase, saruplase, and desmoteplase. Collected clinical data on these glycoproteins demonstrate the great potential of this engineering strategy. Outstanding combinatorics originating from multiple glycosylation sites and the vast variety of covalently attached glycan species can be addressed by directed evolution or rational design. Directed evolution pipelines would benefit from more efficient cell-free expression and high-throughput screening assays, while rational design must employ structure prediction by machine learning and in silico characterization by supercomputing. Perspectives on challenges and opportunities for improvement of thrombolytic enzymes by engineering and evolution of protein glycosylation are provided.
- MeSH
- bércové vředy * diagnostické zobrazování terapie MeSH
- hojení ran MeSH
- kompresní obvazy MeSH
- lidé MeSH
- žilní insuficience diagnostické zobrazování komplikace terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Stroke burden is substantially increasing but current therapeutic drugs are still far from ideal. Here we highlight the vast potential of staphylokinase as an efficient, fibrin-selective, inexpensive, and evolvable thrombolytic agent. The emphasis is escalated by new recent findings. Staphylokinase nonimmunogenic variant was proven noninferior to alteplase in a clinical trial, with decreased risk of intracranial hemorrhage and the advantage of single bolus administration. Furthermore, our detailed kinetic analysis revealed a new staphylokinase limiting bottleneck whose elimination might provide up to 1000-fold higher activity than the clinically approved alteplase. This knowledge of limitations unlocks new possibilities for improvements that are now achievable by the community of protein engineers who have the required expertise and are ready to transform staphylokinase into a powerful molecule. Collectively, the noninferiority and safety of nonimmunogenic staphylokinase together with the newly identified effectivity limitation make staphylokinase a perfect candidate for further exploration, modification, and advancement to make it the next-generation widely accessible thrombolytic drug effectively treating stroke all around the world, including middle- and low-income countries.
- MeSH
- cévní mozková příhoda * farmakoterapie MeSH
- fibrin MeSH
- fibrinolytika * terapeutické užití MeSH
- kinetika MeSH
- lidé MeSH
- metaloendopeptidasy metabolismus terapeutické užití MeSH
- tkáňový aktivátor plazminogenu terapeutické užití MeSH
- trombolytická terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- antiinfekční látky lokální aplikace a dávkování terapeutické užití MeSH
- bércové vředy * etiologie terapie MeSH
- chronická bolest MeSH
- debridement metody MeSH
- kompresní obvazy MeSH
- lidé MeSH
- vazokonstriktory aplikace a dávkování terapeutické užití MeSH
- žilní insuficience terapie MeSH
- Check Tag
- lidé MeSH
