natgillin/translations-raw huggingface dataset:
The total volume of the administration should be delivered in approximately 3-4 hours. 
Ukupni volumen lijeka mora se primijeniti tijekom približno 3-4 sata.
• increased body temperature 
• povišena tjelesna temperatura
The number of these reactions decreased the longer that patients were on Aldurazyme. 
Broj tih reakcija se smanjivao što su bolesnici dulje primali Aldurazyme.
Other medicines and Aldurazyme 
Drugi lijekovi i Aldurazyme
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. 
Zbog nedostatka ispitivanja kompatibilnosti ovaj lijek se ne smije miješati s drugim lijekovima, osim onih navedenih u dijelu 6.6.
This patient tested positive for IgE. 
Bolesnik je bio pozitivan na IgE.
They accumulate in many tissues in the body, which causes the symptoms of MPS I. 
One se nakupljaju u mnogim tkivima u tijelu, što uzrokuje pojavu simptoma bolesti MPS I.
Laronidase may be excreted in milk. 
Laronidaza se može izlučivati u mlijeko.
Shoulder flexion Range Of Motion (degrees) 
Raspon pokretljivosti ramena u fleksiji (stupnjevi)
• cold sweat, heavy sweating 
• hladan znoj, obilno znojenje
Cmax showed an increase over time. 
Vrijednost Cmax s vremenom se povećavala.
If you are allergic (hypersensitive) to laronidase or any of the other ingredients of this medicine (listed in section 6). 
Ako ste alergični (preosjetljivi) na laronidazu ili neki drugi sastojak ovog lijeka (naveden u dijelu 6).
The activity unit (U) is defined as the hydrolysis of one micromole of substrate (4-MUI) per minute. 
Jedinica aktivnosti (U) definira se kao hidroliza jednog mikromola supstrata (4-MUI) po minuti.
Talk to your doctor before using Aldurazyme. 
Obratite se svom liječniku prije nego primite Aldurazyme.
Other side effects include the following: 
Ostale nuspojave obuhvaćaju sljedeće:
Pharmacotherapeutic group: Enzymes. 
Farmakoterapijska skupina: enzimi.
From a microbiological safety point of view, the product should be used immediately. 
S mikrobiološkog stajališta, lijek se mora odmah upotrijebiti.
The type of IARs was similar to those seen in other clinical studies. 
Vrste reakcija povezanih s infuzijom bile su slične onima koje su primijećene u drugim kliničkim ispitivanjima.
You may be given additional medication such as antihistamines and paracetamol to help prevent allergic-type reactions. 
Možda ćete dobivati dodatne lijekove poput antihistaminika i paracetamola kako bi se spriječile alergijske reakcije.
Phase 3, 26 weeks of treatment compared to placebo p value Confidence interval 
Faza III, 26 tjedana liječenja u usporedbi s placebom p-vrijednost Interval pouzdanosti
CHAQ/HAQ Disability Index 2 
CHAQ/HAQ indeks onesposobljenosti2
• cold hands or feet 
• bljedilo • hladne šake ili stopala
Genotoxic and carcinogenic potential are not expected. 
Ne očekuje se da bi lijek mogao imati genotoksičan ni karcinogen potencijal.
Remove the required vials from the refrigerator approximately 20 minutes in advance in order to allow them to reach room temperature (below 30˚C). 
Potrebne bočice izvadite iz hladnjaka otprilike 20 minuta prije pripreme kako bi se ugrijale na sobnu temperaturu (ispod 30°C).
Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonal/foetal development, parturition and postnatal development (see section 5.3). 
Istraživanja na životinjama ne ukazuju na izravne niti neizravne štetne učinke na trudnoću, razvoj embrija/fetusa, porod ili postnatalni razvoj (vidjeti dio 5.3).
Apnea/Hypopnea Index (AHI) 
Indeks apneja/hipopneja (AHI)
Aldurazyme is an artificial enzyme called laronidase. 
Aldurazyme je umjetni enzim koji se naziva laronidaza.
• influenza like illness 
• bolest nalik gripi
The occurrence of IgE antibodies was not fully explored. 
protutijela nije u potpunosti istražena.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, single dose toxicity, repeated dose toxicity and toxicity to reproduction. 
Neklinički podaci ne ukazuju na poseban rizik za ljude na temelju konvencionalnih ispitivanja sigurnosne farmakologije, toksičnosti pojedinačne doze, toksičnosti ponovljenih doza i reproduktivne toksičnosti.
The current medical standards for emergency treatment are to be observed. 
Moraju se poštivati važeći zdravstveni standardi za hitno liječenje.
: +359 (0)2 970 53 00 Česká republika sanofi-aventis, s.r.o. 
Тел.: +359 (0)2 970 53 00 Česká republika sanofi-aventis, s.r.o.
Store at 2°C - 8°C. 
Čuvati na 2°C - 8°C.
This can replace the natural enzyme which is lacking in MPS I disease. 
On može nadomjestiti prirodni enzim koji nedostaje kod bolesnika s bolešću MPS I.
What you need to know before you are given Aldurazyme 
Što morate znati prije nego počnete primati Aldurazyme
1 The decrease in percent predicted FVC is not clinically significant over this timeframe, and absolute lung volumes continued to increase commensurate with changes in height in growing paediatric patients. 
1 Smanjenje postotka predviđenog FVC-a nije klinički značajno u tom vremenskom razdoblju, a apsolutni plućni volumen nastavio se povećavati proporcionalno promjenama visine u pedijatrijskih bolesnika u rastu.
The pharmacokinetic profile in patients less than 5 years old was similar to that of older and less severely affected patients. 
Farmakokinetički profil kod bolesnika mlađih od 5 godina bio je sličan onomu kod starijih bolesnika s manje teškim oblicima bolesti.
Aldurazyme should not be mixed with other medicinal products in the same infusion. 
Aldurazyme se ne smije miješati u istoj infuziji s drugim lijekovima.
Patients were enrolled with a Forced Vital Capacity (FVC) less than 80% of the predicted value and had to be able to stand for 6 minutes and to walk 5 meters. 
Forced Vital Capacity, FVC) iznosio manje od 80% predviđene vrijednosti i koji su mogli stajati 6 minuta te hodati 5 metara.
Therefore Aldurazyme should not be used during pregnancy unless clearly necessary. 
Aldurazyme se stoga ne smije primjenjivati tijekom trudnoće osim ako to nije izričito neophodno.
• leakage of the drug into the surrounding tissue at the site of injection, which may cause swelling or redness 
• istjecanje lijeka u okolno tkivo na mjestu injekcije koje može prouzročiti oticanje ili crvenilo
It is given to treat the non-neurological manifestations of the disease. 
Namijenjen je liječenju manifestacija te bolesti koje nisu neurološke naravi.
Instruction for use - dilution and administration 
Upute za uporabu - razrjeđivanje i primjena
Preclinical data did not reveal any significant adverse finding (see section 5.3). 
Pretklinički podaci nisu ukazali ni na kakve značajne štetne učinke (vidjeti dio 5.3).
Following 26 weeks of therapy, Aldurazyme-treated patients showed improved respiratory function and walking ability as compared to placebo as indicated below. 
Nakon 26 tjedana liječenja kod bolesnika liječenih lijekom Aldurazyme primijećeno je poboljšanje respiratorne funkcije i sposobnosti hoda u usporedbi s placebom, kao što je prikazano u nastavku.
If not used immediately, in-use storage should not be longer than 24 hours at 2°C - 8°C provided that dilution has taken place under controlled and validated aseptic conditions. 
Ako se ne upotrijebi odmah, smije se čuvati najduže 24 sata na temperaturi od 2°C - 8°C, pod uvjetom da je razrjeđivanje provedeno u kontroliranim i validiranim aseptičkim uvjetima.
As there is little experience on resumption of treatment following prolonged interruption, use caution due to the theoretical increased risk of hypersensitivity reaction after treatment interruption. 
S obzirom na malo iskustvo s nastavkom liječenja nakon duljeg prekida, nužan je oprez zbog teoretske mogućnosti povećanog rizika za reakciju preosjetljivosti nakon prekida liječenja.
The concentrate for solution for infusion has to be diluted before administration and is for intravenous use (see information for health care professionals). 
Koncentrat za otopinu za infuziju mora se prije primjene razrijediti, a namijenjen je za intravensku primjenu (vidjeti informacije za zdravstvene djelatnike).
To date there are no clinical data that demonstrate any benefit on the neurological manifestations of the disorder. 
Za sada nema kliničkih podataka koji dokazuju korisno djelovanje na neurološke manifestacije ovog poremećaja.
You should not be given this medicine after the expiry date which is stated on the label after the letters EXP. 
Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na naljepnici iza oznake „EXP“.
You should not be given Aldurazyme 
Ne smijete primiti Aldurazyme
Inform your doctor if you are using medicines containing chloroquine or procaine, due to a possible risk of decreasing the action of Aldurazyme. 
Obavijestite svog liječnika ako uzimate lijekove koji sadrže klorokin ili prokain jer postoji rizik da oni mogu smanjiti djelovanje lijeka Aldurazyme.
After intravenous infusion, laronidase is rapidly removed from the circulation and taken up by cells into lysosomes, most likely via mannose-6 phosphate receptors. 
Nakon intravenske infuzije laronidaza se vrlo brzo uklanja iz krvotoka, ulazi u stanice i prelazi u lizosome, najvjerojatnije preko receptora manoza-6 fosfata.
• feeling hot, feeling cold 
• osjećaj vrućine, osjećaj hladnoće
Consequently, impaired liver function is not expected to affect the pharmacokinetics of laronidase in a clinically significant way. 
Stoga se ne očekuje da bi oštećenje jetrene funkcije moglo utjecati na farmakokinetiku laronidaze na klinički značajan način.
Only clear and colourless solutions without visible particles should be used. 
Smiju se upotrijebiti samo bistre i bezbojne otopine bez vidljivih čestica.
The volume of distribution decreased with continued treatment, possibly related to antibody formation and/or decreased liver volume. 
Volumen distribucije smanjio se tijekom liječenja, što može biti povezano sa stvaranjem protutijela i/ili smanjenjem volumena jetre.
Because there are no data available in neonates exposed to laronidase via breast milk, it is recommended to stop breast-feeding during Aldurazyme treatment. 
Budući da nema podataka o učincima izloženosti novorođenčadi laronidazi putem majčinog mlijeka, preporučuje se prekinuti dojenje tijekom primjene lijeka Aldurazyme.
Based on the Phase 3 clinical trial, almost all patients are expected to develop IgG antibodies to laronidase, mostly within 3 months of initiation of treatment. 
Na temelju kliničkog ispitivanja faze III očekuje se da će gotovo svi bolesnici stvoriti IgG protutijela na laronidazu, većinom u roku od 3 mjeseca nakon početka liječenja.
Laronidase is a protein and is expected to be metabolically degraded through peptide hydrolysis. 
Laronidaza je protein za koji se očekuje da će se metabolički razgraditi hidrolizom peptida.
Percent Predicted FVC (percentage point) 
Postotak predviđenog FVC-a (%)1
As a result, these substances do not get broken down and processed by the body as they should. 
Zbog toga se spomenute tvari u organizmu ne razgrađuju kako bi trebalo.
The frequency of bronchospasm and respiratory arrest is unknown. 
Učestalost bronhospazma i zastoja disanja nije poznata.
No definite benefit was shown with the higher doses over the recommended dose. 
Nije utvrđena korist od primjene većih doza u odnosu na preporučenu.
Some of the symptoms of such a severe allergic reaction were life-threatening and included extreme difficulty breathing, swelling of the throat, low blood pressure, and low oxygen level in the body. 
Neki od simptoma takve teške alergijske reakcije bili su opasni po život, a uključivali su izrazito otežano disanje, oticanje grla, nizak krvni tlak i nisku razinu kisika u tijelu.
Renal elimination of laronidase is considered to be a minor pathway for clearance (see section 4.2). 
Eliminacija laronidaze bubrezima smatra se sporednim putem klirensa (vidjeti dio 4.2).
The mean urinary GAG level declined by 50% at Week 13 and was reduced by 61% at the end of the study. 
Srednja vrijednost GAG-a u mokraći bila je 50% niža u 13. tjednu, a do kraja ispitivanja smanjila se za 61%.
The clinical significance of this finding is unknown since there were no consistent relationships between IgG antibody level and clinical efficacy endpoints. 
Klinički značaj tog nalaza nije poznat jer nema dosljedne veze između razine IgG protutijela i mjera ishoda kliničke djelotvornosti.
The safety and efficacy of Aldurazyme in patients older than 65 years have not been established and no dosage regimen can be recommended in these patients. 
Sigurnost i djelotvornost lijeka Aldurazyme kod bolesnika starijih od 65 godina nisu ustanovljene pa se ne može preporučiti režim doziranja za te bolesnike.
Aldurazyme should not be administered simultaneously with chloroquine or procaine due to a potential risk of interference with the intracellular uptake of laronidase. 
Aldurazyme se ne smije primjenjivati istodobno s klorokinom ili prokainom zbog mogućeg rizika od ometanja unutarstaničnog pohranjivanja laronidaze.
The majority of these reactions were mild or moderate in intensity. 
Te su reakcije većinom bile blagog do umjerenog intenziteta.
Several patients showed an increase in height (n=7) and weight (n=3) for age Z-score. 
Kod nekoliko je bolesnika zabilježeno povećanje tjelesne visine (n=7) i težine (n=3) za Z-vrijednost dobi.
Patients treated with Aldurazyme should be closely monitored and all cases of infusion-associated reactions, delayed reactions and possible immunological reactions reported. 
Treba pažljivo nadzirati bolesnike koji se liječe lijekom Aldurazyme i prijaviti sve slučajeve reakcija povezanih s infuzijom, odgođenih reakcija i mogućih imunoloških reakcija.
Paediatric population No dose adjustment is necessary for the paediatric population. 
Nije potrebno prilagođavati dozu u pedijatrijskoj populaciji.
The infusion can be restarted with a reduction of the infusion rate to 1/2 - 1/4 the rate of the infusion at which the reaction occurred. 
Infuzija se može ponovno započeti nakon što se njezina brzina smanji na 1/2 - 1/4 brzine pri kojoj se reakcija pojavila.
Body temperature increased, oxygen saturation decreased 
Pretrage povišena tjelesna temperatura, smanjena zasićenost kisikom
The rationale for enzyme replacement therapy is to restore a level of enzymatic activity sufficient to hydrolyse the accumulated substrate and to prevent further accumulation. 
Svrha enzimske nadomjesne terapije je vraćanje enzimske aktivnosti na razinu dostatnu za hidrolizu nakupljenog supstrata te za sprječavanje daljnjeg nakupljanja.
Aldurazyme was well tolerated at both dosages. 
Bolesnici su dobro podnosili Aldurazyme u obje ispitivane doze.
One study mainly assessed the safety and pharmacokinetics of Aldurazyme in patients less than 5 years old, but some efficacy measurements were included as well. 
Drugo je ispitivanje uglavnom ocjenjivalo sigurnost i farmakokinetiku lijeka Aldurazyme kod bolesnika mlađih od 5 godina, no obuhvaćalo je i neke pokazatelje djelotvornosti.
Aldurazyme is used to treat patients with MPS I disease (Mucopolysaccharidosis I). 
Aldurazyme se koristi za liječenje bolesnika koji boluju od MPS I (mukopolisaharidoze I).
As with any intravenous protein product, severe allergic-type hypersensitivity reactions are possible. 
Kao i kod svakog proteinskog lijeka koji se primjenjuje intravenski, moguće su teške alergijske reakcije.
Preparation of the Aldurazyme Infusion (Use Aseptic Technique) Determine the number of vials to be diluted based on the individual patient's weight. 
Priprema infuzije lijeka Aldurazyme (primijeniti aseptički postupak) Odredite broj bočica koje treba razrijediti na temelju tjelesne težine pojedinog bolesnika.
The younger patients with the severe phenotype (< 2.5 years) and all 4 patients with the intermediate phenotype exhibited a normal rate of mental development, whereas the older patients with a severe phenotype made limited or no gains in cognition. 
Kod mlađih bolesnika s teškim fenotipom (< 2,5 godina) i kod sva 4 bolesnika s intermedijarnim fenotipom primijećen je normalan mentalni razvoj, dok je kod starijih bolesnika s teškim fenotipom zabilježeno malo ili nikakvo kognitivno poboljšanje.
There are no clinical data on the effects of laronidase on fertility. 
Nema kliničkih podataka o učincima laronidaze na plodnost.
The third study was conducted to evaluate the pharmacodynamics and safety of different dose regimens of Aldurazyme. 
Treće ispitivanje provedeno je u svrhu ocjenjivanja farmakodinamike i sigurnosti različitih režima doziranja lijeka Aldurazyme.
Aldurazyme is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis I (MPS I; α-L-iduronidase deficiency) to treat the nonneurological manifestations of the disease (see section 5.1). 
Aldurazyme je indiciran kao dugotrajna enzimska nadomjesna terapija kod bolesnika s potvrđenom dijagnozom mukopolisaharidoze I (MPS I; nedostatak α-L-iduronidaze) za liječenje manifestacija bolesti koje nisu neurološke naravi (vidjeti dio 5.1).
The safety and efficacy of Aldurazyme was assessed in a randomised, double-blind, placebo controlled, Phase 3 Study of 45 patients, ranging in age from 6 to 43 years. 
Sigurnost i djelotvornost lijeka Aldurazyme procijenjene su u randomiziranom, dvostruko slijepom, placebom kontroliranom ispitivanju faze III u kojemu je sudjelovalo 45 bolesnika u dobi od 6 do
Although patients representing the full range of the disease spectrum were enrolled, the majority of the patients were of the intermediate phenotype, with only one patient exhibiting the severe phenotype. 
Iako su u ispitivanje uključeni bolesnici koji su predstavljali cjelokupan raspon spektra ove bolesti, većina je bolesnika imala intermedijarni fenotip, a samo je jedan bolesnik imao težak fenotip.
After intravenous administration of laronidase with an infusion time of 240 minutes and at a dose of 100 U/kg body weight pharmacokinetic properties were measured at Weeks 1, 12 and 26. 
Nakon primjene laronidaze intravenskom infuzijom u trajanju od 240 minuta te u dozi od 100 U/kg tjelesne težine, farmakokinetička svojstva mjerena su u 1., 12. i 26. tjednu.
Four patients (three in the Phase 3 study and one in the Phase 2 study) showed marginal to low level in vitro inhibition of laronidase enzymatic activity, which did not appear to impact clinical efficacy and/or urinary GAG reduction. 
Kod četiri bolesnika (tri u ispitivanju faze III i jednog u ispitivanju faze II) uočena je zanemariva do niska razina inhibicije enzimske aktivnosti laronidaze in vitro, što nije imalo utjecaja na kliničku djelotvornost i/ili smanjenje koncentracije GAG-a u mokraći.
Severe hypersensitivity (e.g. anaphylactic reaction) to the active substance or to any of the excipients listed in section 6.1 (see sections 4.4 and 4.8). 
Teška preosjetljivost (npr. anafilaktička reakcija) na djelatnu tvar ili neku od pomoćnih tvari navedenih u dijelu 6.1 (vidjeti dijelove 4.4 i 4.8).
Upon study completion, all patients showed reductions in liver size and 50% (9/18) had normal liver size. 
Do završetka ispitivanja, kod svih se bolesnika veličina jetre smanjila, a kod 50% (9/18) bila je normalne veličine.
It is recommended to stop breast-feeding during treatment with Aldurazyme. 
Preporučuje se prekinuti dojenje tijekom liječenja lijekom Aldurazyme.
No case of overdose has been reported. 
Nije prijavljen niti jedan slučaj predoziranja.
Side effects were mainly seen while patients were being given the medicine or shortly after (infusionassociated reactions). 
Nuspojave su se uglavnom javljale dok su bolesnici primali lijek ili neposredno nakon toga (reakcije povezane s infuzijom).
Almost all patients developed IgG antibodies to laronidase. 
Gotovo su svi bolesnici stvorili IgG protutijela na laronidazu.
The primary efficacy endpoints were changes in percent of predicted normal FVC and absolute distance travelled in the six-minute walk test (6MWT). 
Primarne mjere ishoda djelotvornosti bile su promjene postotka predviđenog normalnog FVC-a i apsolutne udaljenosti koju su mogli prijeći u šestominutnom ispitivanju hoda (engl. six-minute walk test, 6MWT).
The frequency of severe allergic reaction (anaphylactic reaction) and swelling of the face is considered common and may affect up to 1 in 10 people. 
Teška alergijska reakcija (anafilaktička reakcija) i oticanje lica smatraju se čestim nuspojavama i mogu se javiti u manje od 1 na 10 osoba.
For information on pre-treatment, see section 4.4. 
Za podatke o premedikaciji vidjeti dio 4.4.
Pack sizes: 1, 10 and 25 vials. 
Veličine pakiranja: 1, 10 i 25 bočica.
When you experience such a reaction, you should immediately contact your doctor. 
Kad osjetite takvu reakciju, morate se odmah obratiti svom liječniku.
This medicinal product contains sodium and is administered in 0.9% sodium chloride intravenous solution (see section 6.6). 
Ovaj lijek sadrži natrij i primjenjuje se u intravenskoj 0,9%-tnoj otopini natrijeva klorida (vidjeti dio 6.6).
Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs). 
Poremećaji odlaganja mukopolisaharida prouzročeni su nedostatkom određenih lizosomskih enzima potrebnih za katabolizam glikozaminoglikana (GAG).
Aldurazyme/Aldurazyme Placebo/Aldurazyme At 208 weeks 
Aldurazyme/Aldurazyme Placebo/Aldurazyme
In addition 60 patients in the Phase 2 and 3 studies were tested for in-vitro neutralising effects. 
Osim toga, u ispitivanjima faze II i faze III 60 je bolesnika ispitano na in vitro neutralizirajuće učinke.
Patients treated with Aldurazyme may develop infusion-associated reactions (IARs), defined as any related adverse event occurring during the infusion or until the end of the infusion day (see section 4.8). 
Kod bolesnika liječenih lijekom Aldurazyme mogu se razviti reakcije povezane s infuzijom, definirane kao bilo koji povezani štetni događaj koji se javi za vrijeme infuzije ili do kraja dana u kojem bolesnik primi infuziju (vidjeti dio 4.8).
Marketing Authorisation Holder: Genzyme Europe B.V. 
Nositelj odobrenja za stavljanje lijeka u promet: Genzyme Europe B.V.
QUALITATIVE AND QUANTITATIVE COMPOSITION 1 ml contains 100 U (approximately 0.58 mg) of laronidase. 
1 ml sadrži 100 U (približno 0,58 mg) laronidaze.
You should not be given Aldurazyme during pregnancy unless clearly necessary. 
Aldurazyme tijekom trudnoće, osim ako je to izričito neophodno.
The molecule contains 6 N-linked oligosaccharide modifications sites. 
Molekula ima 6 mjesta za reakciju s oligosaharidima vezanima s dušikom.
Due to the small patient population, an ADR reported in a single patient is classified as common. 
Zbog male populacije bolesnika, nuspojava koja se pojavila u samo jednog bolesnika kategorizira se kao česta.
Most patients seroconverted within 3 months of initiation of treatment; although seroconversion in patients under 5 years old with a more severe phenotype occurred mostly within 1 month (mean 26 days versus 45 days in patients 5 years and older). 
Kod većine bolesnika do serokonverzije je došlo unutar 3 mjeseca nakon početka liječenja, iako je kod bolesnika mlađih od 5 godina s težim fenotipom serokonverzija nastupila uglavnom u roku od mjesec dana (srednja vrijednost 26 dana u odnosu na 45 dana kod bolesnika u dobi od 5 ili više godina).
If you miss an infusion of Aldurazyme If you have missed an Aldurazyme infusion, please contact your doctor. 
Ako ste propustili infuziju lijeka Aldurazyme, molimo obratite se svom liječniku.
MPS I is a heterogeneous and multisystemic disorder characterised by the deficiency of α-L-iduronidase, a lysosomal hydrolase which catalyses the hydrolysis of terminal α-L-iduronic residues of dermatan sulfate and heparan sulfate. 
MPS I je heterogeni i multisustavni poremećaj obilježen nedostatkom α-L-iduronidaze, lizosomske hidrolaze koja katalizira hidrolizu terminalnih α-L-iduronskih ostataka dermatan sulfata i heparan sulfata.