natgillin/translations-raw huggingface dataset:
Additionally, although some patients (39 out of 53) responded to the combination Arzerra plus bendamustine, only a few patients (6 out of 53) had a complete response, and these data were not supported by further study results.
Poleg tega so se sicer nekateri bolniki (39 bolnikov od 53) odzvali na kombinacijo zdravila Arzerra in bendamustina, vendar se je nanjo popolnoma odzvalo samo nekaj bolnikov (6 bolnikov od 53), teh podatkov pa nadaljnji rezultati študije niso podprli.
It can also be used in patients whose disease has not responded to previous treatment with fludarabine and a medicine called alemtuzumab1.
Prav tako se lahko uporablja pri bolnikih, ki se niso odzvali na predhodna zdravljenja s fludarabinom in zdravilom, imenovanim alemtuzumab1.
What is happening with Arzerra for the treatment of other diseases?
Kaj to pomeni za nadaljnjo uporabo zdravila Arzerra za zdravljenje drugih bolezni?
The company presented the results from a study involving 53 patients with relapsed CLL.
Družba je predložila rezultate študije, ki je vključevala 53 bolnikov s ponovljeno KLL.
There are no consequences on the use of Arzerra in its authorised indications.
Umik vloge nima nobenih posledic za uporabo zdravila Arzerra pri odobrenih indikacijah.
The application was withdrawn after the CHMP had evaluated the documentation provided by the company and formulated a list of questions.
Vlogo so umaknili po tem, ko je odbor CHMP že ocenil začetno dokumentacijo, ki jo je predložila družba, in oblikoval seznam vprašanj.
On 8 November 2016, Novartis Europharm Ltd officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for Arzerra to be used in a new combination with bendamustine for the treatment of relapsed chronic lymphocytic leukaemia (CLL).
Družba Novartis Europharm Ltd je dne 8. novembra 2016 uradno obvestila Odbor za zdravila za uporabo v humani medicini (CHMP), da želi umakniti vlogo za pridobitev dovoljenja za promet z zdravilom Arzerra, ki naj bi se uporabljalo v novi kombinaciji z bendamustinom, namenjenim zdravljenju ponovljene kronične limfocitne levkemije (KLL).
In its letter notifying the Agency of the withdrawal of application, the company stated that its decision was based on the objections raised by the CHMP with regard to the design of the study and its patient population.
Družba je v dopisu, s katerim je agencijo obvestila o umiku vloge, navedla, da njena odločitev temelji na ugovorih odbora CHMP v zvezi z zasnovo študije in vključeno populacijo bolnikov.
It contains the active substance ofatumumab and is available as a concentrate that is made up into a solution for infusion (drip) into a vein.
Vsebuje zdravilno učinkovino ofatumumab in je na voljo v obliki koncentrata za pripravo raztopine za infundiranje (kapalne infuzije) v veno.
The company informed the CHMP that there are no consequences for patients currently included in or who may be joining clinical trials using Arzerra.
Družba je odbor CHMP obvestila, da umik nima nobenih posledic za bolnike, ki trenutno sodelujejo ali bodo morda sodelovali v kliničnih preskušanjih zdravila Arzerra.
Arzerra is a cancer medicine used to treat adults with chronic lymphocytic leukaemia (CLL), a cancer of a type of white blood cells called lymphocytes.
Arzerra je zdravilo za zdravljenje raka, ki se uporablja za zdravljenje odraslih s kronično limfocitno levkemijo (KLL), rakom vrste belih krvnih celic, imenovanih limfociti.
It is used together with the cancer medicines chlorambucil or bendamustine in previously untreated patients who cannot be given treatment based on another medicine, fludarabine.
Uporablja se skupaj z drugim zdravilom za zdravljenje raka, klorambucilom ali bendamustinom, pri predhodno nezdravljenih bolnikih, ki ne morejo prejemati zdravljenja na osnovi drugega zdravila, fludarabina.
Arzerra was also expected to be used in combination with bendamustine to treat adults with relapsed CLL (CLL that came back after previous treatment).
Zdravilo Arzerra naj bi se uporabljajo v kombinaciji z bendamustinom za zdravljenje odraslih s ponovljeno KLL (KLL, ki se je po predhodnem zdravljenju vrnila).
Therefore, at the time of the withdrawal, the CHMP was of the opinion that the results of the study were not considered to be robust and the CHMP concluded that the medicine could not have been approved based on the data presented by the company.
Zato je odbor CHMP ob umiku vloge menil, da rezultati študije niso robustni, in sklenil, da zdravila Arzerra na podlagi podatkov, ki jih je predložila družba, ni mogoče odobriti.
Arzerra was designated an ‘orphan medicine' (a medicine to be used in rare diseases) on 7 November 2008 for CLL.
Zdravilo Arzerra je bilo dne 7. novembra 2008 določeno kot „zdravilo sirota“ (zdravilo za zdravljenje redkih bolezni) za zdravljenje KLL.
The CHMP was concerned that the study did not compare Arzerra with any other medicine and only included 53 patients with relapsed CLL.
Odbor CHMP je izrazil zadržke, ker v študiji zdravila Arzerra niso primerjali z nobenim drugim zdravilom in ker je študija vključevala samo 53 bolnikov s ponovljeno KLL.
What is Arzerra?
Kaj je zdravilo Arzerra?
The active substance in Arzerra, ofatumumab, is a monoclonal antibody, a protein that has been designed to recognise and attach to another protein called CD20 on the surface of lymphocytes, including the cancerous lymphocytes seen in CLL.
Zdravilna učinkovina v zdravilu Arzerra, ofatumumab, je monoklonsko protitelo, beljakovina, zasnovana za prepoznavo in vezavo na drugo beljakovino, imenovano CD20 na površini limfocitov, tudi na rakavih limfocitih, ki se pojavijo pri KLL.
What was Arzerra expected to be used for?
Za kaj naj bi se zdravilo Arzerra uporabljalo?
Based on the review of the data, at the time of the withdrawal the CHMP had some concerns and was of the provisional opinion that Arzerra could not have been approved for the treatment of relapsed CLL in combination with bendamustine.
Odbor CHMP je na podlagi pregleda podatkov ob umiku vloge izrazil določene zadržke in je začasno menil, da zdravila Arzerra ni mogoče odobriti za zdravljenje ponovljene KLL v kombinaciji z bendamustinom.
All patients received Arzerra plus bendamustine; Arzerra was not compared with any other treatment in this study.
Zdravila Arzerra v tej študiji niso primerjali z nobenim drugim zdravilom.
• have cancer.
• imate raka.
Date of latest renewal: 15 January 2015
Datum zadnjega podaljšanja: 15. januar 2015
It must be used within this 30 days period.
Uporabiti ga morate v 30 dneh.
Specific radiographic findings characterise these events.
Za te dogodke so značilni specifični radiografski izvidi.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 26 May 2010
DATUM PRIDOBITVE/PODALJŠANJA DOVOLJENJA ZA PROMET Z ZDRAVILOM Datum prve odobritve: 26. maj 2010
The study was not powered to show a difference in fractures.
Študija ni bila zasnovana tako, da bi pokazala razliko v zlomih.
Long-term antiresorptive treatment
Dolgoročno antiresorpcijsko zdravljenje
Oestrogen helps keep bones healthy.
Estrogen pomaga ohranjati zdrave kosti.
• are a smoker (as this may increase the risk of dental problems).
• ste kadilec (to lahko poveča tveganje za zobozdravstvene težave),
These events have also occurred without antiresorptive therapy.
Ti dogodki so se pojavili tudi brez antiresorpcijskega zdravljenja.
These cases were predominantly cellulitis.
V teh primerih je šlo v glavnem za celulitis.
The bones become weaker and break more easily.
Kosti postanejo šibkejše in se lažje zlomijo.
• hair loss (alopecia).
• izguba las in dlak (alopecija).
Bone is a living tissue and is renewed all the time.
Kost je živo tkivo in se ves čas obnavlja.
DO NOT use it if the date has passed the last day of the month shown.
NE uporabite je, če je že pretekel zadnji dan navedenega meseca.
0-2 years
0-2 leti
Use the peel-off stickers to mark the next injection date on your personal calendar and/or the reminder card to keep a record of the next injection date.
Uporabite odlepne nalepke, da boste na svojem osebnem koledarju označili datum naslednje injekcije, in/ali opomnilno kartico za evidenco o datumu naslednje injekcije.
If any of these apply to you, tell your doctor immediately.
Če kaj od naštetega velja za vas, to takoj povejte zdravniku.
To avoid bending the needle, gently pull the cover from the needle straight off without twisting, as shown in pictures 1 and 2.
Da ne boste zvili igle, previdno snemite pokrovček igle naravnost z nje, ne da bi ga upogibali, tako kot prikazujeta sliki 1 in 2.
• painful urination, frequent urination, blood in the urine, inability to hold your urine,
• boleče uriniranje, pogosto uriniranje, kri v urinu, nezmožnost zadrževanja urina,
Concomitant glucocorticoid treatment is an additional risk factor for hypocalcaemia.
Sočasno glukokortikoidno zdravljenje je dodaten dejavnik tveganja za hipokalciemijo.
• if you are allergic to denosumab or any of the other ingredients of this medicine (listed in section 6).
• če ste alergični na denosumab ali katero koli sestavino tega zdravila (navedeno v poglavju 6).
Before receiving treatment, tell your doctor or nurse (health care professional) if you:
Preden dobite zdravilo, morate zdravniku ali medicinski sestri (zdravstvenemu delavcu) povedati, če:
It is important to tell your doctor if you are pregnant; think you may be pregnant; or plan to get pregnant.
Pomembno je, da zdravniku poveste, če ste noseči, menite, da bi lahko bili noseči, ali načrtujete zanositev.
0-3 years *p < 0.0001, **p < 0.0001 - exploratory analysis
0-3 leta *p < 0,0001, **p < 0,0001 - eksploratorna analiza
Thereafter, injections should be scheduled every 6 months from the date of the last injection.
Nato morate injekcije dobivati na 6 mesecev od datuma zadnje injekcije.
• don't receive routine dental care or have not had a dental check-up for a long time.
• niste deležni redne zobozdravstvene oskrbe ali dlje časa niste opravili zobozdravniškega pregleda,
Hypocalcaemia (see section 4.4).
Hipokalciemija (glejte poglavje 4.4).
It allows continued monitoring of the benefit-risk balance of the medicinal product.
Omogoča namreč stalno spremljanje razmerja med koristmi in tveganji zdravila.
Prolia is not recommended for children and adolescents under 18 years of age.
Zdravilo Prolia ni priporočljivo za otroke in mladostnike, mlajše od 18 let.
Always wash your hands before every injection.
Vedno si umijte roke pred injiciranjem.
How do you give the injection?
Kako dati injekcijo?
The carcinogenic potential of denosumab has not been evaluated in long-term animal studies.
Kancerogenega potenciala denosumaba v dolgoročnih študijah na živalih niso ocenili.
Patients who did not complete the study for any reason had higher on-treatment fracture rates.
Bolnice, ki študije zaradi katerega koli razloga niso zaključile, so imele večjo pogostnost zlomov med zdravljenjem.
Although this imbalance was identified via a pooled analysis, it was not identified via a stratified analysis.
Čeprav so to razliko ugotovili s kumulativno analizo, pa se ni pokazala pri stratificirani analizi.
Temporary interruption of treatment should be considered until the condition resolves and contributing risk factors are mitigated where possible.
Razmisliti je treba o začasnem prenehanju zdravljenja, dokler se to stanje ne razreši in se sovpleteni dejavniki tveganja ublažijo, če je mogoče.
Low calcium in the blood may also lead to a change in heart rhythm called QT prolongation which is seen by electrocardiogram (ECG).
Nizek kalcij v krvi lahko povzroči tudi motnjo srčnega ritma, imenovano podaljšanje QT, ki je vidna na elektrokardiogramu (EKG).
This can eventually lead to a condition called osteoporosis.
Končna posledica je lahko bolezen, ki jo imenujemo osteoporoza.
It is especially important that you tell your doctor if you are being treated with another medicine containing denosumab.
Posebej pomembno je, da zdravniku poveste, če se zdravite z drugim zdravilom, ki vsebuje denosumab.
The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of denosumab on an individual patient basis, particularly after 5 or more years of use (see section 4.4).
Priporočljivo je, da se potreba po nadaljevalnem zdravljenju občasno ponovno oceni na podlagi koristi in možnih tveganj denosumaba pri individualnem bolniku, posebno po 5 ali več letih uporabe (glejte poglavje 4.4).
The instructions for use, handling and disposal are given in section 6.6.
Za navodila glede uporabe, ravnanja z zdravilom in odstranjevanja glejte poglavje 6.6.
Osteoporosis can also occur in men due to a number of causes including ageing and/or a low level of the male hormone, testosterone.
Osteoporoza se lahko pojavi tudi pri moških, in sicer iz številnih razlogov, med katerimi sta staranje in/ali nizka koncentracija moškega hormona testosterona.
Standard tests to investigate the genotoxicity potential of denosumab have not been evaluated, since such tests are not relevant for this molecule.
Standardni testi za preučevanje genotoksičnega potenciala denosumaba niso bili opravljeni, ker takšni testi za to molekulo niso pomembni.
• The used syringe should be disposed of in accordance with local requirements.
• Uporabljeno brizgo je treba zavreči v skladu z lokalnimi predpisi.
Prolia n = 3,902
Zdravilo Prolia n = 3.902
Sodium hydroxide (for pH adjustment)* Sorbitol (E420)
Natrijev hidroksid (za prilagoditev pH)* Sorbitol (E420)
Administration should be performed by an individual who has been adequately trained in injection techniques.
Zdravilo mora aplicirati oseba, ki se je za injiciranje ustrezno usposobila.
MedDRA system organ class Frequency category
Organski sistem po MedDRA Kategorija pogostnosti
Prolia is not recommended in paediatric patients (age < 18) as the safety and efficacy of Prolia in these patients have not been established.
Uporaba zdravila Prolia ni priporočljiva za pediatrične bolnike (stare < 18 let), ker njegovi učinkovitost in varnost pri teh bolnikih nista dokazani.
It is important to identify patients at risk for hypocalcaemia.
Pomembno je, da identificirate bolnike s tveganjem za hipokalciemijo.
• Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit-risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.
• ob vsakršni spremembi sistema za obvladovanje tveganj, zlasti kadar je tovrstna sprememba posledica prejema novih informacij, ki lahko privedejo do znatne spremembe razmerja med koristmi in tveganji, ali kadar je ta sprememba posledica tega, da je bil dosežen pomemben mejnik (farmakovigilančni ali povezan z zmanjševanjem tveganja).
Effect on all clinical fractures Prolia significantly reduced fractures across all fracture types/groups (see table 3).
Učinek na vse klinične zlome Zdravilo Prolia je znatno zmanjšalo število zlomov po vseh vrstah/skupinah (glejte tabelo 3).
It is important to try to prevent ONJ developing as it may be a painful condition that can be difficult to treat.
Pomembno si je prizadevati, da bi preprečili nastanek osteonekroze čeljustnice, ker gre za stanje, ki lahko boli in ga je težko zdraviti.
In a study of 55 patients with varying degrees of renal function, including patients on dialysis, the degree of renal impairment had no effect on the pharmacokinetics of denosumab.
V študiji 55 bolnikov z različno stopnjo delovanja ledvic, vključno z bolniki na dializi, stopnja okvare ledvic ni vplivala na farmakokinetiko denosumaba.
The optimal total duration of antiresorptive treatment for osteoporosis (including both denosumab and bisphosphonates) has not been established.
Optimalno trajanje antiresorpcijskega zdravljenja osteoporoze (vključno z denosumabom in bisfosfonati) še ni bilo potrjeno.
Proportion of women with fracture (%)+
Delež žensk z zlomom (%)+
Problems with your mouth, teeth or jaw
Težave z usti, zobmi ali čeljustnico
Please talk to your doctor before you consider stopping the treatment.
Posvetujte se z zdravnikom, preden se odločite za prenehanje zdravljenja.
Calcium and Vitamin D supplementation
Dodajanje kalcija in vitamina D
Age (28-87 years), race and disease state (low bone mass or osteoporosis; prostate or breast cancer) do not appear to significantly affect the pharmacokinetics of denosumab.
Kaže, da starost (28 - 87 let), rasa in stanje bolezni (majhna kostna masa ali osteoporoza; rak na prostati ali dojki) ne vplivajo pomembno na farmakokinetiko denosumaba.
DO NOT touch the needle or push the plunger.
NE dotikajte se igle in ne pritiskajte bata.
The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.
Upoštevati je treba aditivni učinek sočasnega dajanja zdravil, ki vsebujejo sorbitol (ali fruktozo), in prehranskega vnosa sorbitola (ali fruktoze).
These effects were sustained with continued treatment.
Ti vplivi so se med nadaljevanjem zdravljenja ohranili.
A trend was observed between higher body weight and lower exposure based on AUC and Cmax.
Opazili so povezanost med večjo telesno maso in manjšo izpostavljenostjo, ocenjeno z AUC in Cmax.
Elderly (age ≥ 65) No dose adjustment is required in elderly patients.
Starejši (stari ≥ 65 let) Starejšim bolnikom odmerka ni treba prilagoditi.
Many patients with osteoporosis have no symptoms, but they are still at risk of breaking bones, especially in the spine, hips and wrists.
Številni bolniki z osteoporozo nimajo simptomov, a jih kljub temu ogrožajo zlomi kosti, zlasti hrbtenice, kolkov in zapestij.
The following convention has been used for the classification of the adverse reactions (see table 1): very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).
Za razvrstitev neželenih učinkov (glejte tabelo 1) je uporabljen naslednji dogovor: zelo pogosti (≥ 1/10), pogosti (≥ 1/100 do < 1/10), občasni (≥ 1/1.000 do < 1/100), redki (≥ 1/10.000 do < 1/1.000), zelo redki (< 1/10.000) in neznana pogostnost (pogostnosti ni mogoče oceniti iz razpoložljivih podatkov).
You must inject the entire content (1 mL) of the Prolia pre-filled syringe and it should be injected once every 6 months as instructed by your doctor.
Injicirati morate celotno vsebino (1 ml) napolnjene injekcijske brizge Prolia in injicirati jo morate enkrat vsakih 6 mesecev, kot vam je naročil zdravnik.
Following subcutaneous administration of a 1.0 mg/kg dose, which approximates the approved 60 mg dose, exposure based on AUC was 78% as compared to intravenous administration at the same dose level.
Po subkutanem dajanju odmerka 1,0 mg/kg, ki približno ustreza odobrenemu odmerku 60 mg, je bila izpostavljenost ocenjena na podlagi AUC 78 % tiste po intravenskem dajanju enakega odmerka.
While being treated, you should maintain good oral hygiene and receive routine dental check-ups.
Med zdravljenjem morate vzdrževati dobro ustno higieno in opravljati redne zobozdravniške preglede.
Subjects with an eGFR < 30 mL/min/1.73 m2 were excluded from the study.
Preiskovanci z ocenjeno hitrostjo glomerularne filtracije < 30 ml/min/1,73 m2 so bili izključeni iz študije.
What Prolia is and how it works
Kaj je zdravilo Prolia in kako deluje
• if you have low calcium levels in the blood (hypocalcaemia).
• če imate nizko koncentracijo kalcija v krvi (hipokalciemijo).
Injecting the solution with the air bubble is harmless.
Injiciranje raztopine z mehurčkom zraka je neškodljivo.
Bone turnover markers generally reached pre-treatment levels within 9 months after the last dose.
Označevalci prenove kosti so na splošno dosegli raven, kakršna je bila pred zdravljenjem, v 9 mesecih po zadnjem odmerku.
It can also occur in patients receiving glucocorticoids.
Pojavi se lahko tudi pri bolnikih, ki prejemajo glukokortikoide.
Only use each pre-filled syringe for one injection.
Vsako napolnjeno injekcijsko brizgo uporabite samo za eno injiciranje.
Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma.
Med možne dejavnike tveganja za osteonekrozo zunanjega slušnega kanala spadajo uporaba steroidov in kemoterapija in/ali lokalni dejavniki tveganja, kot sta okužba ali poškodba.
No specific study in patients with hepatic impairment was performed.
Specifičnih študij pri bolnikih z okvaro jeter ni bilo.
A no observed adverse effect level for reproductive effects was not established.
Ravni odmerka brez ugotovljenih neželenih učinkov niso ugotovili.
• Belly, except for a 5 cm (2-inch) area right around your belly button.
• trebuh, razen v predelu 5 cm okrog popka.
Efficacy and safety of Prolia once every 6 months for 1 year were investigated in 242 men aged 31-84 years.
Učinkovitost in varnost zdravila Prolia, uporabljenega enkrat na 6 mesecev v obdobju 1 leta, so raziskali pri 242 moških, starih od 31 do 84 let.
• Inject the entire contents of the pre-filled syringe.
• Injicirajte celotno vsebino napolnjene injekcijske brizge.
Bone biopsy results showed bone of normal architecture and quality with no evidence of mineralisation defects, woven bone or marrow fibrosis.
Rezultati biopsije kosti so pokazali normalno kostno arhitekturo in kakovost, brez znakov mineralizacijskih defektov, prepletene kostnine ali fibroze kostnega mozga.
Any effects of Prolia are likely to be greater during the second and third trimesters of pregnancy since monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester.
Za vse učinke zdravila Prolia je verjetno, da so večji v drugem ali tretjem trimesečju nosečnosti, kajti monoklonska protitelesa prehajajo skozi placento linearno, kot napreduje nosečnost, s tem da jih največja količina preide v tretjem trimesečju.
Prolia has no or negligible influence on the ability to drive and use machines.
Prolia ne vpliva ali pa le zanemarljivo vpliva na sposobnost vožnje in upravljanja strojev.
• bone, joint, and/or muscle pain which is sometimes severe, • arm or leg pain (pain in extremity).
• bolečina v kosteh, sklepih in/ali mišicah, ki je včasih huda, • bolečina v rokah ali nogah (bolečina v udih).
Other medicines and Prolia
Druga zdravila in zdravilo Prolia
In the post-marketing setting, severe symptomatic hypocalcaemia (including fatal cases) has been reported (see section 4.8), with most cases occurring in the first weeks of initiating therapy, but it can occur later.
V obdobju trženja zdravila so poročali o hudi simptomatski hipokalciemiji (vključno s smrtnimi primeri) (glejte poglavje 4.8), večina primerov se je pojavila v prvih tednih po uvedbi zdravljenja, a pojavi se lahko tudi pozneje.
• concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to head and neck.
• sočasna zdravljenja: kortikosteroide, kemoterapijo, zaviralce angiogeneze, radioterapijo glave in vratu,
Once your syringe has been left to reach room temperature (up to 25°C), it must be used within 30 days.
Ko brizga enkrat doseže sobno temperaturo (do 25 °C), jo morate uporabiti v 30 dneh.
A total of 2,626 subjects (58% of the women included in the extension study i.e. 34% of the women included in the pivotal study) completed the extension study.
Podaljšanje študije je dokončalo skupaj 2.626 bolnic (58 % žensk, vključenih v podaljšanje študije, to je 34 % žensk, ki so bile vključene v ključno študijo).
• have previously been treated with a bisphosphonate (used to treat or prevent bone disorders).
• ste predhodno dobivali zdravilo iz skupine bisfosfonatov (uporabljajo se za zdravljenje ali preprečevanje kostnih bolezni),
DO NOT warm it in any other way, for example, in a microwave or in hot water.
NE ogrevajte zdravila kako drugače, npr. v mikrovalovni pečici ali vroči vodi.
INFORMATION IN BRAILLE Prolia
PODATKI V BRAILLOVI PISAVI Prolia
In general, monoclonal antibodies are not eliminated via hepatic metabolic mechanisms.
Na splošno se monoklonska protitelesa ne odstranijo z jetrnimi presnovnimi mehanizmi.