Profi vybavení pro pizzerie

Češi milují pizzu – je to nepopiratelné! Není překvapením, že to vede k otevírání nových pizzerie. Nové pizzerie potřebují kvalitní vybavení pro pizzerie, aby mohli nabídnout skutečně vynikající pizzu.

Takže, pokud jste jedním z podnikatelů, kteří chtějí prodat svou první pizzu, zde je seznam vybavení potřebného pro pizzerii, s sebou nebo do restaurace.

Pizza pec

Pec na pizzu je absolutní nezbytnou složkou na spuštění seznamu zařízení pro pizzerie, ačkoli existují různé typy pecí na pizzu, které umožňují zahájit svou pravost od základny. Malé nebo velké, cihla nebo dopravník, je tu pec na pizzu, která je pro váš nový podnik ideální. Nezapomeňte také, že musí být schopen vyhovět vašim potřebám kapacity.

Stanice pro přípravu pizzy

Pizzu je třeba někde přepracovat a profesionální počítadlo na přípravu pizzy vám umožní udržovat správné hygienické postupy a připravovat pizzu profesionálním a rychlým způsobem. Pokud máte vážné problémy s prací na svém podnikání, je jediným způsobem, jak udělat toto prohlášení, investování do profesionálních předmětů.

Míchač na těsto

Míchání cesta je základním kamenem každé restaurace na pizzu, ale brzy ho budete naštvaný, pokud vyrábíte pouze malé dávky. A co víc, výroba malých šarží zbytečně ztrácí čas a riskuje, že vaši zákazníci vyšli ze dveří. Seznam zařízení na pizzu by proto měl obsahovat mixér těsta s hmotností asi 25 kg, aby bylo dosaženo optimální výsledky.

Misky na těsto

Po smíchání tohoto cesta je třeba někde ochladit, odpočívat a vstát dříve, než se upeče. Profesionální misky na těsto na pizzu jsou nejlepším způsobem, jak toho dosáhnout, v neposlední řadě proto, že jsou stohovatelné a šetří místo. Pokud je vaše restaurace malá nebo si berete pizzu na cestách v dodávce, budete potřebovat veškerou vynalézavost, kterou můžete získat.

Deska na podávání pizzy

Po tom, co se pizza odloupla z trouby, co se stane dál? Pokud připravujete kontrolní seznam vybavení pro pizzerii, budete si jisti, že budete potřebovat něco, abyste mohli pizzu sloužit. Jistě, můžete si ji vzít na talíř, ale estetika je všechno a desky na servírování pizzy vám pomohou učinit prohlášení o kvalitě vašeho jídla.

Destičky na pizzu

Pokud se rozhodnete pro servírování pizzy na talířích, nezapomeňte použít speciální talíře na pizzu, které usnadňují přístup k pizzy, a ne ji chytíte na standardní nádobí. Nikdo nechce jíst pizzu z talíře, ke kterému nemá snadný přístup bez použití nože a vidličky. Další tip – nemusíte vařit pizzu talíře úplně jinak. Bílá je populární, protože pomáhá předvádět kvalitu jídla a to je přesně ta reakce, kterou chcete od svých zákazníků.

Comments

  1. Jasonjouri

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  2. AndrewWhima

    I’m selling Aged 2012 Twitter accounts with verified email address only for 4$

    All accounts come with full access to the original email that was used to create the account!
    FAQ.

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    Discord : CongMMO#9766
    Skype & Telegram : congmmo
    ICQ : @652720497
    Thank you!

  3. AndrewWhima

    Premium Aged Twitters 2007-2013

    – all come with the original email, means they’re as good as your own, will last a long time!
    – long 1 week replacement policy
    – responsive after-sales support

    Prices:
    2007 – $20
    2008 – $15
    2009 – $10
    2010 – $8
    2011 – $7
    2012 – $6
    2013 – $5
    MAJOR bulk discounts when ordering 10+ accounts! deal here]

    Where you can contact me,PM me here!

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

    Payments Accepted:
    BTC,ETH,ETC,LTC or Payoneer or Paypal
    Paypal fees will be paid by the buyer
    No refunds allowed, if you’re having issues with an account you’ve bought I will gladly replace within the first hour of purchase!
    Thank you!

  4. AndrewWhima

    HQ Twitter 2007 – 2019 Aged Accounts Starting from 1$
    Prices:
    2017,2018,2019-1$ per account
    2015,2016-4$ per account
    2013,2014 – 5$ per account
    2012 – 6$ per account
    2011 – 7$ per account
    2010 – 8$ per account
    2009 – 10$ per account
    2008 – 20$ per account ( limited stock)

    The Accounts
    Have zero or less than 50 followers.
    Gender can be both male and female.
    May or may not have profile pic and tweets.
    I have full access to the accounts,
    Accounts are delivered instant after paying.
    My Contact Info

    Email – congmmo@gmail . com

    https://sellaccs.net

    Discord : CongMMO#9766
    Skype & Telegram : congmmo
    ICQ : @652720497

    Please don’t PM here on this website , i rarely check it
    For quick response contact me on discord or email.

    Join my discord server to buy instantly – Link

    Instant Buy from the below link
    Buy link

    Due to timezone difference it might take some time to get back to you. Please wait patiently.

    I am verified seller here and have 100% positive feedback

    Payments Methods Accepted- BTC, Paypal (additional transaction/miner fee )

    Please don’t waste my time if u r not serious.

    Terms
    All sales are final, once accounts delivered, no refunds
    Twitter rules are becoming very strict everyday so I will not be held responsible for the suspension or banning of account in the near future.

    I also sell accounts with followers, check my other threads.

  5. AgedTwitter-alupt

    Selling Aged 2012 Twitter accounts

    General Information

    ☑️ Email Address Verified
    ☑️ All accounts come with full access to the original email that was used to create the account!
    ☑️8 years old
    ☑️Comes with little or no followers, following
    ☑️Comes with bio or profile picture

    Price
    $5 Only!

    Interested? – click buy now button.

    For Bulk 2012 Accounts only, Contact us @:

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

  6. AgedTwitter-alupt

    All of the accounts were opened in Turkey. It is delivered together with the first mails. (hotmail)

    Per account Prices :

    2016-2017 = 1$
    2014-2015 = 3$
    2013 = 4$
    2012 = 5$
    2011 = 6$
    2010 = 7$

    Accounts detail :

    – Have 0 or less than 75 followers.
    – Gender can be male or female.
    – There may be no tweets.
    – May not be profile photo
    – Accounts are seamless.
    – Instant delivery at the end of payment.

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

    Conditions :

    – I do not accept responsibility after submitting the account.
    – There is no refund.

  7. AgedTwitter-alupt

    HQ Twitter 2007 – 2019 Aged Accounts Starting from 1$
    Prices:
    2017,2018,2019-1$ per account
    2015,2016-4$ per account
    2013,2014 – 5$ per account
    2012 – 6$ per account
    2011 – 7$ per account
    2010 – 8$ per account
    2009 – 10$ per account
    2008 – 20$ per account ( limited stock)

    The Accounts
    Have zero or less than 50 followers.
    Gender can be both male and female.
    May or may not have profile pic and tweets.
    I have full access to the accounts,
    Accounts are delivered instant after paying.
    My Contact Info

    Email – congmmo@gmail . com

    https://sellaccs.net

    Discord : CongMMO#9766
    Skype & Telegram : congmmo
    ICQ : @652720497

    Please don’t PM here on this website , i rarely check it
    For quick response contact me on discord or email.

    Join my discord server to buy instantly – Link

    Instant Buy from the below link
    Buy link

    Due to timezone difference it might take some time to get back to you. Please wait patiently.

    I am verified seller here and have 100% positive feedback

    Payments Methods Accepted- BTC, Paypal (additional transaction/miner fee )

    Please don’t waste my time if u r not serious.

    Terms
    All sales are final, once accounts delivered, no refunds
    Twitter rules are becoming very strict everyday so I will not be held responsible for the suspension or banning of account in the near future.

    I also sell accounts with followers, check my other threads.

  8. AgedTwitter-alupt

    Aged Twitter Accounts (2009.-2015.)

    M Package (25 accounts) – 70$

    S Package (10 accounts) – 30$
    M Package (25 accounts) – 70$
    L Package (50 accounts) – 130$
    XL Package (100 accounts) – 250$

    Accounts have random amount of tweets and followers, registered in 2009-2013.

    Where you can contact me,PM me here!

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com
    Thanks

  9. Randalljousa

    Selling Aged 2012 Twitter accounts

    General Information

    ?? Email Address Verified
    ?? All accounts come with full access to the original email that was used to create the account!
    ??8 years old
    ??Comes with little or no followers, following
    ??Comes with bio or profile picture

    Price
    $5 Only!

    Interested? – click buy now button.

    For Bulk 2012 Accounts only, Contact us @:

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

  10. Keithsmask

    HQ Twitter 2007 – 2019 Aged Accounts Starting from 1$
    Prices:
    2017,2018,2019-1$ per account
    2015,2016-4$ per account
    2013,2014 – 5$ per account
    2012 – 6$ per account
    2011 – 7$ per account
    2010 – 8$ per account
    2009 – 10$ per account
    2008 – 20$ per account ( limited stock)

    The Accounts
    Have zero or less than 50 followers.
    Gender can be both male and female.
    May or may not have profile pic and tweets.
    I have full access to the accounts,
    Accounts are delivered instant after paying.
    My Contact Info

    Email – congmmo@gmail . com

    https://sellaccs.net

    Discord : CongMMO#9766
    Skype & Telegram : congmmo
    ICQ : @652720497

    Please don’t PM here on this website , i rarely check it
    For quick response contact me on discord or email.

    Join my discord server to buy instantly – Link

    Instant Buy from the below link
    Buy link

    Due to timezone difference it might take some time to get back to you. Please wait patiently.

    I am verified seller here and have 100% positive feedback

    Payments Methods Accepted- BTC, Paypal (additional transaction/miner fee )

    Please don’t waste my time if u r not serious.

    Terms
    All sales are final, once accounts delivered, no refunds
    Twitter rules are becoming very strict everyday so I will not be held responsible for the suspension or banning of account in the near future.

    I also sell accounts with followers, check my other threads.

  11. Keithsmask

    Selling Aged 2012 Twitter accounts

    General Information

    ☑️ Email Address Verified
    ☑️ All accounts come with full access to the original email that was used to create the account!
    ☑️8 years old
    ☑️Comes with little or no followers, following
    ☑️Comes with bio or profile picture

    Price
    $5 Only!

    Interested? – click buy now button.

    For Bulk 2012 Accounts only, Contact us @:

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

  12. Keithsmask

    Premium Aged Twitters 2007-2013

    – all come with the original email, means they’re as good as your own, will last a long time!
    – long 1 week replacement policy
    – responsive after-sales support

    Prices:
    2007 – $20
    2008 – $15
    2009 – $10
    2010 – $8
    2011 – $7
    2012 – $6
    2013 – $5
    MAJOR bulk discounts when ordering 10+ accounts! deal here]

    Where you can contact me,PM me here!

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

    Payments Accepted:
    BTC,ETH,ETC,LTC or Payoneer or Paypal
    Paypal fees will be paid by the buyer
    No refunds allowed, if you’re having issues with an account you’ve bought I will gladly replace within the first hour of purchase!
    Thank you!

  13. Keithsmask

    Selling Aged 2009 Twitter accounts ​

    ☀️☀️☀️☀️
    General Information

    ☑️ Email Address Verified
    ☑️ All accounts come with full access to the original email that was used to create the account!
    ☑️ 11 years old
    ☑️Comes with little or no followers, following
    ☑️Comes with/without bio or profile picture​


    ☀️☀️☀️☀️
    Price
    $10 Bitcoins/Middleman Only!​


    Interested? – click buy now button/Contact Us to send bitcoins
    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

  14. Keithsmask

    Aged Twitter Accounts (2009.-2015.)

    M Package (25 accounts) – 70$

    S Package (10 accounts) – 30$
    M Package (25 accounts) – 70$
    L Package (50 accounts) – 130$
    XL Package (100 accounts) – 250$

    Accounts have random amount of tweets and followers, registered in 2009-2013.

    Where you can contact me,PM me here!

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com
    Thanks

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  18. Patrickroday

    Selling Aged Twitter Accounts for Cheap 2008-2015

    Hello! I will sell Aged Twitter Accounts for Cheap 2008-2015

    Accounts Prices:
    2008 – 10$ Per Account
    2009 – 9$ Per Account
    2010 – 8$ Per Account
    2011 – 7$ Per Account
    2012 – 6$ Per Account
    2013 – 5$ Per Account
    2014 – 4$ Per Account
    2015 – 3$ Per Account

    Buy for testing accept!
    Discounts available if you buy in bulk

    with Format
    Username:Password Twitter:Live Emai:Password Email,
    joindate,tweets,following,followers and likes.

    Accounts Info:
    Gender can either be female or male.
    Accounts can be either empty with photos or without photos, or with already added entries, for example: tweets, retweets, likes, comments and followers.

    Where you can contact me,PM me here!
    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

    Payments Accepted:
    BTC,ETH,ETC,LTC or Payoneer or Paypal
    Paypal fees will be paid by the buyer
    No refunds allowed, if you’re having issues with an account you’ve bought I will gladly replace within the first hour of purchase!
    Thank you!

  19. Patrickroday

    Premium Aged Twitters 2007-2013

    – all come with the original email, means they’re as good as your own, will last a long time!
    – long 1 week replacement policy
    – responsive after-sales support

    Prices:
    2007 – $20
    2008 – $15
    2009 – $10
    2010 – $8
    2011 – $7
    2012 – $6
    2013 – $5
    MAJOR bulk discounts when ordering 10+ accounts! deal here]

    Where you can contact me,PM me here!

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com

    Payments Accepted:
    BTC,ETH,ETC,LTC or Payoneer or Paypal
    Paypal fees will be paid by the buyer
    No refunds allowed, if you’re having issues with an account you’ve bought I will gladly replace within the first hour of purchase!
    Thank you!

  20. Patrickroday

    HQ Twitter 2007 – 2019 Aged Accounts Starting from 1$
    Prices:
    2017,2018,2019-1$ per account
    2015,2016-4$ per account
    2013,2014 – 5$ per account
    2012 – 6$ per account
    2011 – 7$ per account
    2010 – 8$ per account
    2009 – 10$ per account
    2008 – 20$ per account ( limited stock)

    The Accounts
    Have zero or less than 50 followers.
    Gender can be both male and female.
    May or may not have profile pic and tweets.
    I have full access to the accounts,
    Accounts are delivered instant after paying.
    My Contact Info

    Email – congmmo@gmail . com

    https://sellaccs.net

    Discord : CongMMO#9766
    Skype & Telegram : congmmo
    ICQ : @652720497

    Please don’t PM here on this website , i rarely check it
    For quick response contact me on discord or email.

    Join my discord server to buy instantly – Link

    Instant Buy from the below link
    Buy link

    Due to timezone difference it might take some time to get back to you. Please wait patiently.

    I am verified seller here and have 100% positive feedback

    Payments Methods Accepted- BTC, Paypal (additional transaction/miner fee )

    Please don’t waste my time if u r not serious.

    Terms
    All sales are final, once accounts delivered, no refunds
    Twitter rules are becoming very strict everyday so I will not be held responsible for the suspension or banning of account in the near future.

    I also sell accounts with followers, check my other threads.

  21. Patrickroday

    Aged Twitter Accounts (2009.-2015.)

    M Package (25 accounts) – 70$

    S Package (10 accounts) – 30$
    M Package (25 accounts) – 70$
    L Package (50 accounts) – 130$
    XL Package (100 accounts) – 250$

    Accounts have random amount of tweets and followers, registered in 2009-2013.

    Where you can contact me,PM me here!

    https://sellaccs.net

    Skype & Telegram : congmmo
    ICQ : @652720497
    Email : congmmo@gmail . com
    Thanks

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Das Vorhandensein von Fluor im MolekГјl verringert die Mineralocorticoid-Eigenschaften, ist jedoch mit dem Risiko einer Myopathie verbunden. Dies ist die Grundlage fГјr die Empfehlung, die Verwendung von Dexamethason, Triamcinolon und Betamethason bei Patienten mit Dermatomyositis oder bekannter Myopathie zu vermeiden. Synthetische HA sind aktiver als natГјrliche Hormone und wirken daher in geringeren Dosen. Mit einem Г¤hnlichen Wirkungsschwerpunkt zeichnen sich synthetische HAs durch ein unterschiedliches VerhГ¤ltnis der Glukokortikoid- und Mineralokortikoid-Eigenschaften aus – die Schwere der entzГјndungshemmenden Wirkung und die Profile der Nebenwirkungen unterscheiden sich. Basierend auf diesen Unterschieden wurden Tabellen zur relativen Wirksamkeit und zu Г¤quivalenten HA-Dosen erstellt (Tabellen 2, 3). 5 mg Prednison entsprechen 4 mg Methylprednisolon, 0,75 mg Dexamethason oder Betamethason. Die Mineralocorticoid-AktivitГ¤t (die FГ¤higkeit, Natrium zurГјckzuhalten, Schwellungen und Bluthochdruck zu verursachen) ist in Methylprednisolon, Dexamethason und Betamethason praktisch nicht vorhanden, in Prednisolon leicht exprimiert und in Cortison und Hydrocortison am hГ¶chsten. In dieser Hinsicht werden Cortison und Hydrocortison, die vor 70 Jahren den therapeutischen Triumph von HA begannen, derzeit zur Behandlung von Krankheiten mit Nebennierenunterfunktion und nicht zu entzГјndungshemmenden Zwecken eingesetzt. GCs werden auch nach Wirkdauer klassifiziert, die von der Eliminationshalbwertszeit abhГ¤ngt (Tabelle 2). Cortison und Cortisol werden am schnellsten aus dem KГ¶rper ausgeschieden. Mittelfristige Arzneimittel umfassen Prednison, Methylprednisolon und Triamcinolon, und langwirksame Arzneimittel umfassen Dexamethason und Betamethason. Es wird nicht empfohlen, eine HA mit einer langen Halbwertszeit fГјr die Langzeitverabreichung zu verschreiben, um eine Hemmung der Produktion ihrer eigenen Glukokortikoidhormone zu vermeiden. Daher werden Dexamethason und Betamethason hauptsГ¤chlich zum Starten und zur Intensivpflege eingesetzt. Wenn eine Langzeittherapie erforderlich ist, werden Prednison und Methylprednisolon bevorzugt, die sich durch ein optimales Gleichgewicht zwischen entzГјndungshemmender Wirkung und Nebenwirkungen auszeichnen. Wirkmechanismen FГјr den rationalen Einsatz von HA ist es notwendig, eine Vorstellung von den Wirkmechanismen und ihren Merkmalen bei verschiedenen Vertretern dieser Gruppe von Arzneimitteln zu haben. Bisher ist bekannt, dass sich HA in der Art und Weise unterscheidet, wie sie ihr immunsuppressives und entzГјndungshemmendes Potenzial entfalten. Es werden zwei Wirkmechanismen von HA unterschieden: genomisch und nicht genomisch (F. Buttgereit et al., Ann. Rheum. Dis. 2002; 61 (8): 718-22). Die genomischen Wirkungen von HA werden in Dosen von ≥ 2,5 mg PrednisonГ¤quivalent durch Bindung an intrazellulГ¤re cytosolische О±-Rezeptoren (GRО±) realisiert. Die therapeutische Wirkung entwickelt sich frГјhestens 30 Minuten nach der Bildung des Hormon-Rezeptor-Komplexes. Durch die Bindung an GRО± wirken GAs auf intrazellulГ¤re Signalwege von der Membran zum Zellkern und vermitteln die Expression von Genen fГјr die proinflammatorische Faktorsynthese sowie regulieren lebenswichtige Stoffwechselprozesse in der Zelle. HA stimuliert die Produktion von Lipocortin, das die Phospholipase A2 blockiert. Infolgedessen wird der Abbau von Phospholipiden unter Bildung von ArachidonsГ¤ure blockiert und daher die Synthese von proinflammatorischen Leukotrienen und Prostaglandinen gestГ¶rt. Die Blockade des Kerntranskriptionsfaktors Kappa B (NF-ОєB) hemmt die Synthese der Interleukine 1 und 6, des Tumornekrosefaktors-О± (TNF-О±) und der Metalloproteinasen. NF-ОєB beeinflusst auch die AktivitГ¤t der induzierbaren NO-Synthase, die mit der Entwicklung von zytotoxischem oxidativem Stress und systemischer EntzГјndungsreaktion verbunden ist. Aufgrund der komplexen Modulation von Zytokinen, Interleukinen und AdhГ¤sionsmolekГјlen sowie der StГ¶rung der Proliferation und Synthese von Proteinen blockiert HA die Гјbermäßige Aktivierung fast aller zellulГ¤ren Einheiten der ImmunentzГјndungsreaktion, einschlieГџlich Makrophagen, Monozyten, Endothelzellen, Basophilen, Fibroblasten und Lymphozyten. Somit werden die entzГјndungshemmenden und immunmodulierenden Wirkungen von HA auf mehrere parallele Arten realisiert. Nicht-genomische Effekte treten in den ersten Sekunden und Minuten nach der EinfГјhrung von hochdosiertem HA auf. Sie werden durch die direkte Wechselwirkung von HA-MolekГјlen mit Biomembranen sowie steroidselektiven Membranrezeptoren erklГ¤rt. Es gibt vier Hauptgruppen nichtgenomischer Effekte: 1) Stabilisierung von Zellmembranen und Organellenmembranen, Abnahme der PermeabilitГ¤t des Kapillarendothels, Schutz der Zellen vor zytotoxischen Wirkungen; 2) Hemmung der AktivitГ¤t von phagozytischen mononukleГ¤ren Zellen; 3) UnterdrГјckung der Leukozytenmigration zum EntzГјndungsherd; 4) eine Abnahme der funktionellen AktivitГ¤t von Endotheliozyten, Monozyten, Makrophagen, neutrophilen Granulozyten und Fibroblasten. Die ausgeprГ¤gtesten nicht-genomischen Wirkungen haben Dexamethason und Methylprednisolon. Sie werden ab 60 mg PrednisonГ¤quivalent verkauft. Daher werden diese Medikamente in hohen Dosen fГјr die Pulstherapie in der Rheumatologie eingesetzt. Es sollte beachtet werden, dass HA die EntzГјndungskaskade auf einem hГ¶heren Niveau blockiert als nichtsteroidale entzГјndungshemmende Medikamente (NSAIDs). Wenn wir die HA mit anderen entzГјndungshemmenden Arzneimitteln vergleichen, die zur Behandlung von rheumatischen Erkrankungen eingesetzt werden (Sulfasalazin, Goldsalze, Methotrexat, Cyclosporin, AntikГ¶rper gegen TNF-О±), ist die Wirkung von HA auf die Synthese von Zytokinen und anderen EntzГјndungsfaktoren sowie die Funktionen immunkompetenter Zellen universeller und universeller umfassend. Die Untersuchung der Mechanismen zur Umsetzung zahlreicher intrazellulГ¤rer Wirkungen von HA ist noch nicht abgeschlossen. Es besteht Grund zu der Annahme, dass einige Unterschiede zwischen HA auf die Eigenschaften ihrer Rezeptorinteraktion zurГјckzufГјhren sind. Die Existenz von zwei Arten von Glukokortikoidrezeptoren – GRО± und GRОІ, die im Zytoplasma fast aller KГ¶rperzellen exprimiert werden, ist belegt. О±-Rezeptoren werden als die Hauptrezeptoren in der Kette der Realisierung von HA-Effekten erkannt, wГ¤hrend die physiologische Rolle von ОІ-Rezeptoren lange Zeit unklar geblieben ist. GRОІ sind in kleineren Mengen vorhanden und binden kein HA. In einigen, aber nicht allen Studien wurde festgestellt, dass GR & bgr; einen dominanten negativen Effekt auf die GR & agr; -induzierte Transaktivierung von HA-abhГ¤ngigen Genen hat (CM Bamberger et al., J. Clin. Invest. 1995; 95: 2435–2441. PJ Hauk et al. Am. J. Respir. Cell. Mol. Biol. 2002; 27: 361-367. RH Oakley et al., J. Biol. Chem. 1999; 274: 27857-27866). Mit anderen Worten, GRОІ wirkt wahrscheinlich der Realisierung der bekannten genomischen Wirkungen von HA durch GRО± entgegen. Bei entzГјndlichen Autoimmunerkrankungen ist eine Гњberexpression von GRОІ mГ¶glich, was hГ¤ufig zur Entwicklung einer Resistenz gegen HA fГјhrt. Das heiГџt, die Existenz von GR & bgr; kann das therapeutische Versagen der HA-Therapie erklГ¤ren. Es gibt jedoch Hinweise darauf, dass die GRОІ-Reaktion unter dem Einfluss verschiedener HAs nicht dieselbe ist. Nach O. Fruchter et al. UnterdrГјckt GRОІ die durch TrО±cinolon, Dexamethason, Hydrocortison und Betamethason stimulierte GRО±-induzierte Transaktivierung um 96, 68, 62 bzw. 49%, dies wurde jedoch bei Verwendung von Methylprednisolon nicht beobachtet (O. Fruchter et al. J. Clin. Endocrinol. Metab. 2005; 90: 3505 & ndash; 3509). Die erhaltenen Daten zeigen, dass Methylprednisolon das Medikament der Wahl fГјr die Entwicklung einer Resistenz gegen andere HA sein kann. Pulstherapie 1976 stellten ES Cathcart et al. berichteten Гјber einen positiven Effekt von Infusionen mit ultrahohen Dosen von Methylprednisolon bei Patienten mit Lupusglomerulonephritis und einer raschen Verschlechterung der Nierenfunktion. Von diesem Moment an begann die Entwicklung des Konzepts der Impulstherapie bei HA. Pulstherapie – intermittierende Verabreichung von Arzneimitteln in suprapharmakologischen Dosen, um die therapeutische Wirkung zu verstГ¤rken und das Risiko von Nebenwirkungen zu verringern. Gleichzeitig Гјberschreiten die HA-Dosen 250 bis 1 Tage lang 5 mg / Tag PrednisonГ¤quivalent (F. Buttgerent et al., Ann. Rheum. Dis. 2002; 61: 718-722). FГјr die Impulstherapie werden HA sowohl unabhГ¤ngig als auch in Kombination mit Zytostatika (meistens Cyclophosphamid), Plasmapherese oder intravenГ¶sem Immunglobulin verwendet. Indikationen fГјr eine Impulstherapie sind schwere rheumatische Erkrankungen und systemische Erkrankungen des Bindegewebes mit dem Risiko lebensbedrohlicher Folgen (rheumatoide Vaskulitis, schwerer refraktГ¤rer Verlauf der Spondylitis ankylosans, Lupusnephritis, LГ¤sionen des Zentralnervensystems, schwere Vaskulitis, Dermatomyositis usw.). Bei systemischer Vaskulitis ist die Impulstherapie insbesondere in den frГјhen Stadien der Entwicklung entzГјndlicher VerГ¤nderungen in der Gefäßwand vor dem Einsetzen irreversibler ischГ¤mischer, nekrotischer VerГ¤nderungen in Organen und Geweben (im Stadium der Remissionsinduktion) angezeigt. Die Pulstherapie ist kontraindiziert, wenn der Patient an einer Infektionskrankheit, einem MagengeschwГјr, einem Glaukom, einer schlecht kontrollierten arteriellen Hypertonie (AH) und einem dekompensierten Diabetes mellitus (DM) leidet. Alle Kontraindikationen sind jedoch relativ, wenn es darum geht, Leben zu retten. Bei der Realisierung der ausgeprГ¤gten therapeutischen Wirkung hoher HA-Dosen spielen schnelle nicht-genomische Wirkungen eine wichtige Rolle – Stabilisierung von Zellmembranen und Organellenmembranen, verminderte kapillare EndothelpermeabilitГ¤t und Zellschutz vor zytotoxischen Wirkungen. In der klinischen Praxis wird Methylprednisolon, das durch eine verlГ¤ngerte Wirkung (24 bis 72 Stunden nach der Infusion) und eine lineare Bindung an Blutplasmaproteine ​​(die Konzentration von Methylprednisolon im Blutplasma entspricht der Dosis des verabreichten Arzneimittels) gekennzeichnet ist, in der klinischen Praxis am hГ¤ufigsten zur DurchfГјhrung einer Impulstherapie von HA verwendet. Die entzГјndungshemmende Wirkung von Methylprednisolon ist in ihrer Schwere der von Cortison, Hydrocortison, Prednisolon und Prednison Гјberlegen, wГ¤hrend das Mineralocorticoid praktisch nicht auftritt. AbhГ¤ngig von den individuellen Merkmalen des Patienten und der klinischen Situation kann der Arzt eine der Optionen fГјr die Impulstherapie von HA verwenden (V. A. Nasonova, E. L. Nasonov et al., 2012): – klassisch – Methylprednisolon in einer Dosis von 1000 mg / Tag 3 Tage hintereinander intravenГ¶s abtropfen lassen; – mittlere IntensitГ¤t (“Midi” -Pulstherapie) – Methylprednisolon in einer Dosis von 500 mg / Tag 3 Tage hintereinander intravenГ¶s abtropfen lassen; – geringe IntensitГ¤t (“Mini” -Pulstherapie) – Methylprednisolon in einer Dosis von 250 mg / Tag tropft 3 Tage hintereinander intravenГ¶s ab. Es gibt keine speziellen Indikationen fГјr die Mini-, Midi- und klassische Impulstherapie. Das Regime wird individuell unter BerГјcksichtigung der Schwere der Erkrankung, des Risikos von Nebenwirkungen und Kontraindikationen festgelegt. Um Nebenwirkungen zu vermeiden, sollte eine zu schnelle Verabreichung von HA vermieden und der Zustand des Patienten wГ¤hrend und nach der Infusion Гјberwacht werden. Die meisten Nebenwirkungen treten wГ¤hrend der Verabreichung des Arzneimittels oder nach einigen Stunden auf, sehr selten am zweiten oder dritten Tag. Aufgrund der Tatsache, dass Nebenwirkungen eine schnelle Korrektur erfordern (z. B. HyperglykГ¤mie), sollte die Impulstherapie nur in einem Krankenhaus durchgefГјhrt werden. GK Nebenwirkungen und Sicherheitsprobleme Die Intervention von synthetischem HA, das zu therapeutischen Zwecken in verschiedenen Stoffwechselwegen fast aller KГ¶rperzellen verwendet wird, fГјhrt zu einer Vielzahl unerwГјnschter Wirkungen (Tabelle 4). In den Empfehlungen der EuropГ¤ischen Antirheumatischen Liga (EULAR) zur Anwendung systemischer HA zur Behandlung rheumatischer Erkrankungen (Ann. Rheum. Dis. 2007; 66: 1560-1567) wurde die Inzidenz von Nebenwirkungen nach randomisierten kontrollierten Studien eingestuft (Tabelle 5). Alle Nebenwirkungen von HA sind dosisabhГ¤ngig, was auch im niedrigen Dosisbereich beobachtet werden kann – von 5 bis 7,5 mg / Tag in PrednisonГ¤quivalent. Einige Autoren identifizieren minimale gefГ¤hrliche Dosen, unterhalb derer die Entwicklung einer Nebenwirkung unwahrscheinlich oder unbedeutend ist (G. Ruiz-Irastorza et al. Rheumatology, 2012 Jul; 51 (7): 1145-53). Anderen Daten zufolge gibt es fГјr die meisten Effekte jedoch keine untere Dosisgrenze, und beispielsweise tritt ein Verlust der Knochenmineraldichte auf, wenn HA lГ¤nger als 6 Monate in einer beliebigen Dosis eingenommen wird (A. Kavanaugh et al. Rheumatology, 2014; 53 (10): 1742-1751) ) Auch Nebenwirkungen von HA werden nach Zeitpunkt des Auftretens klassifiziert. Beispielsweise werden Osteoporose, HyperglykГ¤mie und Cushing-Syndrom frГјh in den ersten Monaten der Behandlung beobachtet, und Katarakte stehen im Zusammenhang mit den verzГ¶gerten kumulativen Folgen einer lГ¤ngeren Verabreichung von HA. In der klinischen Praxis sollten wirklich gefГ¤hrliche und inakzeptable Nebenwirkungen von Voreingenommenheit und Stereotypen unterschieden werden, die die Compliance verschlechtern und das Risiko eines Therapieversagens bergen. Die Bedeutung einiger Nebenwirkungen neigt dazu, sowohl Patienten als auch Г„rzte zu Гјbertreiben und zu dramatisieren. Mit dem Aufkommen fortgeschrittener HA-MolekГјle (insbesondere Methylprednisolon) und neuen Forschungsergebnissen wurde jedoch eine Reihe von Mythen Гјber Nebenwirkungen von HA zerstreut. Es ist unmГ¶glich, Daten Гјber das schlechte Toleranzprofil hoher HA-Dosen automatisch an Patienten zu Гјbertragen, die niedrige Dosen einnehmen. DarГјber hinaus ist es in der klinischen Praxis manchmal schwierig, zwischen Nebenwirkungen und Anzeichen eines Fortschreitens oder von Komplikationen der Krankheit, fГјr die sie verschrieben werden, zu unterscheiden. Somit wird die Zunahme des KГ¶rpergewichts, die fГјr hohe HA-Dosen charakteristisch ist, durch die Verwendung niedriger Dosen moderner HA-MolekГјle minimiert und kann weniger mit den metabolischen Wirkungen von HA als vielmehr mit einer Abnahme der EntzГјndungsaktivitГ¤t und einer Abnahme der Wirkungen der rheumatoiden Kachexie verbunden sein. Eine Г¤hnliche Gewichtszunahme wurde auch bei Patienten beobachtet, die TNF-О±-Inhibitoren erhielten (MS Jurgens et al., Arthritis Care Res. 2013; 65 (1): 88-93). Nach Piper et al. HA verursacht weniger schwere SchГ¤den im Magen-Darm-Trakt als NSAIDs. Ein zweifacher Anstieg des Risikos fГјr die Entwicklung von MagengeschwГјren, der wГ¤hrend der Behandlung mit HA beschrieben wird, ist mГ¶glicherweise mit der kombinierten Verwendung von NSAIDs verbunden (JM Piper et al., Ann. Intern. Med. 1991; 114: 735-740). Studien zufolge betrГ¤gt das Risiko fГјr osteoporotische Frakturen bei Patienten mit RA, die HA in einer durchschnittlichen Dosis von 8,6 mg / Tag fГјr Prednison einnehmen, 33 Jahre lang 5%. Die entzГјndliche AktivitГ¤t von RA und die EinschrГ¤nkung der kГ¶rperlichen AktivitГ¤t von Patienten mit dieser Krankheit sind jedoch nicht weniger wichtige Risikofaktoren fГјr die Entwicklung von Osteoporose als die osteoresorbierende Wirkung von HA (MC Van der Goes. Osteop. Int. 2013; 24: 1429-36). Eine der gefГ¤hrlichen Nebenwirkungen von HA ist die HyperglykГ¤mie, die bei Menschen ohne eine solche Diagnose zur Manifestation von Diabetes oder bei Patienten mit einer Diagnose von Diabetes, der eine Behandlung erhГ¤lt, zu einem Versagen der Kompensation fГјhren kann. Bei sorgfГ¤ltiger Гњberwachung des glykГ¤mischen Profils kann diese unerwГјnschte Wirkung von HA jedoch erfolgreich durch eine ErhГ¶hung der Dosis von Insulin oder oralen hypoglykГ¤mischen Arzneimitteln kompensiert werden. Das Problem der Bewertung des RisikoverhГ¤ltnisses von Nebenwirkungen und der Vorteile der Verschreibung von HA fГјr die systemische Therapie bleibt relevant und wird ausfГјhrlich diskutiert. Auf dem EULAR-Kongress 2016 wurde ein vielversprechendes Instrument zur Risikobewertung vorgestellt – der GC-ToxizitГ¤tsindex (GTI), ein zusammengefasster Indikator fГјr die Wirkung von GC auf verschiedene Organe und Systeme (EM Miloslavsky et al. Ann. Rheum. Dis. 2017; 76 ( 3): 543-546). 19 Experten von 11 Fachgebieten zur Verwendung von HA als Ergebnis von Informationsanalysen und Konsensentscheidungen entwickelten und schlugen vor, die ToxizitГ¤t von HA anhand von 31 Indikatoren zu bewerten. Die Komponenten dieses Indikators sind SchГ¤tzungen des Body-Mass-Index, der Glukosetoleranz, des Bluthochdrucks, der Daten zum Lipidstoffwechsel, der Knochenmineraldichte, der Schwere der Steroidmyopathie, HautverГ¤nderungen, neuropsychiatrischen VerГ¤nderungen und Infektionen. Г„nderungen in jedem dieser Systeme unter Verwendung mathematischer Koeffizienten werden als Verbesserung, Fehlen von Г„nderungen, mäßiger Grad der Verletzung, schwere Verstöße eingestuft. Es ist geplant, eine auf dem GTI basierende Online-Schnittstelle zu erstellen, um diesen Indikator sowohl in klinischen Studien als auch in der realen klinischen Praxis zu verwenden. In der Zwischenzeit wird die Entwicklung und Validierung eines solchen klinischen Instruments fortgesetzt. Expertengesellschaften bieten einen pragmatischen Ansatz fГјr die Verwendung von HA in der rheumatologischen Praxis. Moderne Prinzipien der Verwendung von HA In den Empfehlungen von EULAR (2007) zur Verwendung von HA zur Behandlung von rheumatischen Erkrankungen werden 10 Grundprinzipien formuliert, die in den Grundprinzipien kurz zusammengefasst werden kГ¶nnen: – individuelle Auswahl der HA-Dosis in AbhГ¤ngigkeit von der Krankheit, der EntzГјndungsaktivitГ¤t, den Risikofaktoren und dem Ansprechen auf die Behandlung; – Minimierung der Dosis und Dauer der Verabreichung so weit wie mГ¶glich; – BerГјcksichtigung von Begleiterkrankungen und Risikofaktoren; – die Ernennung einer zusГ¤tzlichen Therapie, um den Nebenwirkungen von HA entgegenzuwirken oder diese zu kompensieren. Zum Beispiel Calcium und Vitamin D wГ¤hrend der Therapie mit HA in Dosen von ≥ 7,5 mg / Tag fГјr Prednison fГјr mehr als 3 Monate. Im Jahr 2013 verГ¶ffentlichte EULAR evidenzbasierte und gemeinsame Richtlinien fГјr Expertenmeinungen zur Behandlung von rheumatischen Erkrankungen mit mittleren und hohen HA-Dosen (Ann. Rheum. Dis. Doi: 10.1136 / annrheumdis – 2013-203249). Vor der Verschreibung mittlerer / hoher HA-Dosen sollten Begleiterkrankungen und -zustГ¤nde untersucht werden, die das Risiko von Nebenwirkungen von HA erhГ¶hen kГ¶nnen, wie Diabetes, beeintrГ¤chtigte Glukosetoleranz, kardiovaskulГ¤re Pathologie, MagengeschwГјr, wiederkehrende Infektionen, Immunsuppression, Glaukom und Osteoporose. Gleichzeitig sollten zusГ¤tzliche Faktoren berГјcksichtigt werden: Beispielsweise sind eine gesunde ErnГ¤hrung und kГ¶rperliche AktivitГ¤t bei Herz-Kreislauf-Erkrankungen vorbeugende Faktoren und verringern das Gesamtrisiko, und ein langer Krankheitsverlauf, schlecht kontrollierte Hypertonie und DyslipidГ¤mie erhГ¶hen das Risiko. Angesichts des Risikos eines Therapieversagens sollte eine angemessene Anfangsdosis von HA ausgewГ¤hlt werden, um das erforderliche therapeutische Ansprechen zu erzielen. In Zukunft sollte die Notwendigkeit einer weiteren HA- und Dosisanpassung in AbhГ¤ngigkeit von der therapeutischen Reaktion und den Nebenwirkungen stГ¤ndig ГјberprГјft werden. Befund Angesichts der Empfehlungen von EULAR zur DurchfГјhrung einer HA-Therapie bei Patienten mit rheumatischen Erkrankungen ist es ratsam, die folgenden Schritte durchzufГјhren, um eine sicherere Anwendung von HA in der tГ¤glichen klinischen Praxis zu gewГ¤hrleisten. Der Patient sollte vor Beginn der HA-Therapie Гјber die mГ¶glichen Nebenwirkungen informiert werden. Die Wahl der Anfangsdosis des Arzneimittels sowie die anschlieГџende Taktik fГјr die Langzeit-HA-Therapie werden unter BerГјcksichtigung der Art der rheumatischen Erkrankung, der AktivitГ¤t des pathologischen Prozesses, des Vorhandenseins von Risikofaktoren und der Merkmale des individuellen Ansprechens des Patienten auf die Behandlung durchgefГјhrt. Der Zeitpunkt der HA-Einnahme kann im Hinblick auf den zirkadianen Aktivierungsrhythmus der Nebennierenrinde wichtig sein. Bei der PrГјfung der Machbarkeit der Verschreibung von HA sollten das Vorhandensein von Begleiterkrankungen und Risikofaktoren fГјr Nebenwirkungen sowie die Notwendigkeit therapeutischer Interventionen zur Vorbeugung dieser berГјcksichtigt werden. Bei lГ¤ngerer GC-Therapie sollten die Dosen der Arzneimittel minimal sein, und im Falle einer Remission oder einer geringen AktivitГ¤t der Krankheit ist es ratsam, die Dosis zu reduzieren. AbhГ¤ngig vom individuellen Risiko des Patienten sollten die Dosis und Dauer der HA-Einnahme wГ¤hrend der Behandlung, die Гњberwachung des KГ¶rpergewichts, der Hypertonie, des Augeninnendrucks, der Blutfette und der Glukose, das Vorhandensein von Г–demen und die Entwicklung von Symptomen einer Herzinsuffizienz Гјberwacht werden. Zur Bewertung der Nebenwirkungen der HA-Therapie kann ein neuer HA-ToxizitГ¤tsindex (GTI) verwendet werden. Bei einer anfГ¤nglichen Prednisontherapie mit einer Dosis von ≥ 7,5 mg / Tag und einer Behandlungsdauer von mehr als 3 Monaten sollten Calcium- und Vitamin D-PrГ¤parate verschrieben werden. Die antiresorptive Therapie mit Bisphosphonaten zur Vorbeugung von HC-induzierter Osteoporose sollte auf einer Bewertung von Risikofaktoren einschlieГџlich Daten beruhen Studien zur Knochenmineraldichte. Patienten, die HA und nicht selektive NSAIDs erhalten, sollten sich einer gastroprotektiven Therapie unterziehen oder eine alternative Behandlung mit selektiven Cyclooxygenase-2-Inhibitoren anwenden. Es muss betont werden, dass keine Studien durchgefГјhrt wurden, um gastroprotektive MaГџnahmen bei Patienten zu bewerten, die HA einnehmen. Daher ist die Verwendung der sichersten Mittel, insbesondere Methylprednisolon, wichtig fГјr die PrГ¤vention von gastrointestinalen Komplikationen bei der Anwendung von HA und NSAIDs. Bei allen Patienten, die lГ¤nger als 1 Monat eine GC-Therapie erhalten haben, ist es bei Anzeichen fГјr einen chirurgischen Eingriff erforderlich, eine angemessene Ersatztherapie durchzufГјhren, um eine mГ¶gliche Nebenniereninsuffizienz auszugleichen. Die Einnahme von HA wГ¤hrend der Schwangerschaft ist nicht mit einem zusГ¤tzlichen Risiko fГјr Mutter und Kind verbunden (die Dosis fГјr Prednison sollte 10 mg / Tag nicht Гјberschreiten). Die Medikamente der Wahl fГјr Patienten in dieser Kategorie sind Methylprednisolon und Prednisolon. Diese Medikamente werden in der Plazenta intensiv metabolisiert und gelangen in geringen Konzentrationen (10% der eingenommenen Dosis) in das fetale Blut, wГ¤hrend die Konzentration von Dexamethason im fetalen Blut recht hoch sein kann. Daher ist ihre Verwendung ratsam, wenn die Lungenreifung stimuliert werden muss der FГ¶tus und mit der Zuversicht, dass der erwartete Nutzen fГјr die Mutter das potenzielle Risiko fГјr den FГ¶tus Гјberwiegt. Bei Kindern, die HA einnehmen, sollte das Wachstum regelmäßig beurteilt und im Falle einer VerzГ¶gerung eine Ersatztherapie mit Somatotropin verschrieben werden. GegenwГ¤rtig bleibt die Verwendung von HA ein wichtiger Bereich bei der Behandlung von rheumatischen Erkrankungen, die eine rechtzeitige Identifizierung von Risikofaktoren und eine sorgfГ¤ltige Гњberwachung des Zustands der Patienten wГ¤hrend der Behandlung sowie die strikte Umsetzung von Empfehlungen zur rationellen Anwendung dieser Arzneimittel erfordern. Diese MaГџnahmen werden dazu beitragen, die Sicherheit einer HA-Langzeittherapie zu verbessern, die Dauer zu verlГ¤ngern und die LebensqualitГ¤t von Patienten mit rheumatischen Erkrankungen zu verbessern. Thematische Ausgabe “Kardiologie, Rheumatologie, Kardiologie” Nr. 1 (56) lyutiy 2018 p. Um zu verhindern, dass Diabetes mellitus in eine komplexe Form Гјbergeht, die eine konstante Insulinaufnahme erfordert, muss gelernt werden, wie man die Krankheit kontrolliert. Das neueste Medikament Insumed trГ¤gt dazu bei , das hilft, Diabetes „auf zellulГ¤rer Ebene“ loszuwerden: Das Medikament stellt die Insulinproduktion wieder her (die bei Typ-2Diabetes beeintrГ¤chtigt ist) und reguliert die Synthese dieses Hormons (wichtig ist das fГјr Typ-1Diabetes ). Alle Bestandteile der Zubereitung werden auf der Basis von Pflanzenmaterialien unter Verwendung der Biosynthesetechnik hergestellt und sind mit dem menschlichen KГ¶rper verwandt. Sie werden von Zellen und Geweben gut absorbiert, da es sich um AminosГ¤uren handelt, aus denen Zellstrukturen bestehen. Kapselkomponenten Insumed normalisieren die Insulinproduktion und regulieren den Blutzucker. ErhГ¶hter Blutzucker 7 wichtige Symptome

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