natgillin/translations-raw huggingface dataset:
What is the risk associated with CaniLeish?
Kakšna tveganja so povezana z zdravilom CaniLeish?
Allergic-type reactions are uncommon and if a dog shows signs of an allergic reaction, they should be given appropriate symptomatic treatment.
Alergijske reakcije so občasne in če se pojavijo, je psu treba nuditi ustrezno simptomatsko zdravljenje.
CaniLeish is a vaccine that contains a number of proteins that are released from the Leishmania infantum parasite during its growth.
Zdravilo CaniLeish je cepivo, ki vsebuje številne beljakovine, ki jih izloča parazit Leishmania infantum med svojo rastjo.
CaniLeish contains an ‘adjuvant' (a highly purified fraction of Quillaja saponaria) to enhance the immune response.
Cepivo CaniLeish vsebuje „adjuvans“ (prečiščeni ekstrakt Quillaja saponaria), ki okrepi imunski odziv.
In dogs developing leishmaniosis (active infection or disease) despite vaccination, proceeding with vaccine injections showed no benefit.
Pri psih, pri katerih se je kljub cepljenju razvila leishmanioza (aktivna okužba ali bolezen), ponavljanje cepljenja ni pokazalo nobene koristi.
Why has CaniLeish been approved?
Zakaj je bilo zdravilo CaniLeish odobreno?
When CaniLeish is given to dogs the immune system recognises the proteins as ‘foreign' and make defences against it.
Ko pes prejme cepivo CaniLeish, imunski sistem prepozna beljakovine kot „tujek“ in proti njim začne tvoriti protitelesa.
After vaccination transient antibodies against leishmania detected by immunofluorescence antibody test (IFAT) may appear but do not reflect an active infection.
Po cepljenju se lahko razvijejo prehodna protitelesa proti parazitu Leishmania, ki jih odkrije imunofluorescenčni test za ugotavljanje protiteles (IFAT), vendar to še ne pomeni, da gre za aktivno okužbo.
Dogs that have been infected may show no signs of infection, but some do (fever, hair and weight loss, skin sores) and in the latter case the outcome of active infection can be fatal.
Okuženi psi morda ne bodo kazali znakov okužbe, kadar pa jih (zvišana telesna temperatura, izpadanje dlake in izguba telesne mase, rane na koži) je to znak, da utegne biti aktivna okužba za psa usodna.
CaniLeish is used to vaccinate dogs from six months of age to reduce the risk of developing an active infection and clinical disease after contact with Leishmania infantum.
Zdravilo CaniLeish se uporablja za cepljenje psov, starejših od šest mesecev, za zmanjšanje tveganja za razvoj aktivne okužbe in kliničnih znakov po stiku s parazitom Leishmania infantum.
The studies showed that the vaccine is safe for both leishmania-negative and leishmania-infected dogs.
Študije so pokazale, da je cepivo varno za pse, ki so negativni na parazit Leishmania, in tudi tiste, ki so okuženi s tem parazitom.
The CVMP concluded that the benefits of CaniLeish outweigh the risks for the active immunisation of leishmania-negative dogs from six months of age to reduce the risk to develop an active infection and clinical disease after contact with Leishmania infantum and recommended that CaniLeish be given a marketing authorisation.
Odbor za zdravila za uporabo v veterinarski medicini (CVMP) je zaključil, da koristi zdravila CaniLeish odtehtajo tveganja aktivne imunizacije psov, starejših od šest mesecev, ki niso okuženi s parazitom Leishmania, za zmanjšanje tveganja za razvoj aktivne okužbe in kliničnih znakov bolezni po stiku s parazitom Leishmania infantum, in priporočil, da se za zdravilo CaniLeish odobri dovoljenje za promet.
The number of dogs developing an active infection and a symptomatic disease was significantly reduced in the vaccinated group.
V skupini cepljenih psov je bilo število psov, pri katerih se je razvila aktivna okužba in simptomatska bolezen, znatno zmanjšano.
Canine vaccine against Leishmania infantum adjuvanted
Cepivo za pse proti parazitu Leishmania infantum, z adjuvansom
It contains Leishmania infantum excreted secreted proteins (ESP).
Vsebuje ekskrecijsko-sekrecijske proteine (ESP) parazita Leishmania infantum.
How has CaniLeish been studied?
Kako je bilo zdravilo CaniLeish raziskano?
The benefit of the vaccination was assessed in zones with a high risk of infection where it has been shown in leishmania free dogs to decrease the risk of developing an active infection and a symptomatic disease after contact with the parasite.
Koristi cepiva so ocenjevali v območjih z visokim tveganjem za okužbo, pri čemer se je izkazalo, da cepivo pri psih, ki niso okuženi s parazitom Leishmania, po stiku s parazitom zmanjša tveganje za razvoj aktivne okužbe in simptomatske bolezni.
What is CaniLeish used for?
Za kaj se zdravilo CaniLeish uporablja?
Afterward a single ‘booster' should be given every year to maintain the vaccine's effect.
Za vzdrževanje učinka cepiva je treba nato vsako leto psu injicirati osvežitveni odmerek.
The safety of the vaccine was studied in two main laboratory safety studies carried out in leishmania-free dogs (overdose and single and repeated administration) and one field trial.
Varnost cepiva so proučevali v dveh glavnih laboratorijskih študijah varnosti cepiva (prekomerni odmerek in ponavljajoče se injiciranje), v kateri so bili vključeni psi, ki niso bili okuženi s parazitom Leishmania, ter v terenski študiji.
CaniLeish is to be used only in ‘leishmania-negative' dogs.
Cepivo CaniLeish se lahko uporablja samo pri psih, ki so negativni na parazit Leishmania.
The vaccine is given to dogs as three injections, three weeks apart, under the skin.
Cepivo se psu vbrizga v podkožje s tremi injekcijami, med katerimi mora biti tritedenski premor.
What is CaniLeish?
Kaj je zdravilo CaniLeish?
The detection of Leishmania infection using a rapid diagnostic test is recommended before vaccination.
Pred cepljenjem je priporočljivo izvesti hiter diagnostični test za ugotavljanje okuženosti s parazitom Leishmania.
How does CaniLeish work?
Kako zdravilo CaniLeish deluje?
Veterinarians should assess the benefit-risk balance before vaccinating dogs in areas with little or no Leishmania infantum.
Na območjih, kjer parazit Leishmania infantum ni tako pogost ali pa ga sploh ni, naj veterinar pred cepljenjem psa pretehta razmerje med koristmi in tveganji.
The company presented data from three main studies involving over 3,000 patients.
Podjetje je predstavilo podatke iz treh glavnih študij, ki so vključevale več kot 3 000 bolnikov.
The main measure of effectiveness was a reduction in symptoms of 20% or more, based on a standard rating score (ACR-20), after 16 weeks of treatment.
Glavno merilo učinkovitosti je bilo zmanjšanje simptomov za vsaj 20 % ali več po standardni ocenjevalni lestvici (ACR-20) po 16 tednih zdravljenja.
In its letter notifying the Agency of the withdrawal of the application, the company stated that, given the need for additional clinical data and the fact that other treatments blocking the action of interleukin-6 are available, it wishes to prioritise other programs in its portfolio.
Družba je v dopisu, s katerim je agencijo obvestila o umiku vloge, navedla, da zaradi potrebe po dodatnih kliničnih podatkih in ker so na voljo druga zdravljenja, ki zavirajo delovanje interlevkina-6, želi dati prednost drugim programom v svojem portfelju.
It was to be available as a solution for injection in pre-filled pens and syringes (50 mg).
Na voljo naj bi bilo v obliki raztopine za injiciranje v napolnjenih peresnikih in injekcijskih brizgah (50 mg).
Withdrawal of the marketing authorisation application for Plivensia (sirukumab) EMA/727596/2017
Umik vloge za pridobitev dovoljenja za promet z zdravilom Plivensia (sirukumab) EMA/727596/2017
The CHMP's main concern was that the long-term safety of Plivensia had not been well characterised due to limitations in the design of the main studies.
Glavni pomislek odbora CHMP je bil, da dolgoročna varnost zdravila Plivensia zaradi omejitev pri zasnovi glavnih študij ni bila dobro opredeljena.
On 26 October 2017, Janssen-Cilag International NV officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a marketing authorisation for Plivensia, for the treatment of rheumatoid arthritis.
Družba Janssen-Cilag International NV je 26. oktobra 2017 uradno obvestila Odbor za zdravila za uporabo v humani medicini (CHMP), da želi umakniti vlogo za pridobitev dovoljenja za promet z zdravilom Plivensia, namenjenim zdravljenju revmatoidnega artritisa.
The company informed the CHMP that it will discontinue the ongoing long-term extension study with Plivensia in patients with rheumatoid arthritis.
Družba je odbor CHMP obvestila, da bo prekinila potekajočo dolgoročno podaljšano študijo zdravila Plivensia pri bolnikih z revmatoidnim artritisom.
Withdrawal of the marketing authorisation application for Plivensia (sirukumab)
Umik vloge za pridobitev dovoljenja za promet z zdravilom Plivensia (sirukumab)
The active substance in Plivensia, sirukumab, is a monoclonal antibody, a type of protein which has been designed to block a molecule called interleukin-6.
Zdravilna učinkovina zdravila Plivensia, sirukumab, je monoklonsko protitelo, tj. vrsta beljakovine, ki je bila zasnovana tako, da zavre molekulo, imenovano interlevkin-6.
Therefore, at the time of the withdrawal, the CHMP was of the opinion that, because of lack of proven long-term safety, the benefits of Plivensia did not outweigh its risks, and that further studies were needed.
Zato je odbor CHMP ob umiku vloge menil, da koristi zdravila Plivensia zaradi pomanjkanja dokazov o njegovi dolgoročni varnosti ne odtehtajo z njim povezanih tveganj in da so potrebne nadaljnje študije.
What is Plivensia?
Kaj je zdravilo Plivensia?
What was Plivensia expected to be used for?
Za kaj naj bi se zdravilo Plivensia uporabljalo?
By blocking interleukin-6, sirukumab reduces inflammation and other symptoms associated with rheumatoid arthritis.
Z zaviranjem interlevkina-6 sirukumab zmanjša vnetje in simptome, povezane z revmatoidnim artritisom.
Plivensia was to be used with methotrexate (a DMARD) or alone if the patient could not take methotrexate.
Zdravilo Plivensia naj bi se uporabljalo z metotreksatom (zdravilom DMARD) ali samostojno, če bolnik ne more jemati metotreksata.
Based on the review of the data and the company's response to the CHMP lists of questions, at the time of the withdrawal the CHMP had some concerns and was of the provisional opinion that Plivensia could not have been approved for the treatment of moderate to severe rheumatoid arthritis.
Odbor CHMP je na podlagi pregleda podatkov in odgovorov družbe na sezname vprašanj, ki jih je zastavil, ob umiku vloge izrazil določene zadržke in je začasno menil, da zdravila Plivensia ni mogoče odobriti za zdravljenje zmernega do hudega revmatoidnega artritisa.
How does Plivensia work?
Kako zdravilo Plivensia deluje?
The medicine was to be used in patients when treatment with one or more medicines known as disease-modifying anti-rheumatic drugs (DMARDs) had not worked well enough or had led to troublesome side effects.
Uporabljalo naj bi se, kadar zdravljenje z enim ali več zdravili, znanimi kot imunomodulirajoča antirevmatična zdravila (DMARD), ni dovolj dobro delovalo ali je povzročilo problematične neželene učinke.
Plivensia was expected to be used in adults with moderate to severe rheumatoid arthritis, a disease that causes inflammation of the joints.
Zdravilo Plivensia naj bi se uporabljalo za zdravljenje odraslih z zmernim do hudim revmatoidnim artritisom, boleznijo, ki povzroča vnetje sklepov.
Plivensia is a medicine that contains the active substance sirukumab.
Plivensia je zdravilo, ki vsebuje zdravilno učinkovino sirukumab.
Two studies compared Plivensia with placebo (a dummy treatment) in patients with moderate to severe rheumatoid arthritis for whom treatment with a DMARD or with an anti-TNF agent (another type of medicine for rheumatoid arthritis) had not worked well enough or had led to troublesome side effects.
Dve študiji sta primerjali zdravilo Plivensia s placebom (zdravilom brez zdravilne učinkovine) pri bolnikih z zmernim do hudim revmatoidnim artritisom, pri katerih zdravljenje z zdravili DMARD ali s sredstvom proti TNF (drugo vrsto zdravila za revmatoidni artritis) ni bilo dovolj uspešno ali pa je povzročilo problematične neželene učinke.
The third study compared Plivensia with adalimumab (a monoclonal antibody targeting a chemical messenger called tumour necrosis factor - TNF) in patients who could not take methotrexate or whose condition had not responded adequately to methotrexate; the study looked at the improvement in how patients' joints worked (based on a standard rating score called DAS28-ESR) after 24 weeks of treatment.
V tretji študiji so zdravilo Plivensia primerjali z zdravilom adalimumab (monoklonskim protitelesom, ki cilja kemični prenašalec, imenovan tumorje nekrotizirajoči faktor (TNF)) pri bolnikih, ki niso mogli jemati metotreksata ali pri katerih se njihovo stanje ni ustrezno odzvalo na metotreksat.
These changes returned to normal within two weeks.
Te spremembe so se normalizirale v dveh tednih.
Invented name Name
Izmišljeno ime Ime
Avalox was initially approved in June 1999.
Zdravilo Avalox je bilo prvič odobreno junija 1999.
However it was questioned that this might not be compatible with clinical practice.
Vendar pa se je pojavilo vprašanje, da to morda ne bi bilo združljivo s klinično prakso.
5 - 10 days
5 do 10 dni
The duration of treatment depends upon the type of infection.
Trajanje zdravljenja je odvisno od vrste okužbe.
The absolute bioavailability amounts to approximately 91%.
Absolutna biološka uporabnost je približno 91 %.
It is important that you complete the course of treatment, even if you begin to feel better after a few days.
Pomembno je, da zdravljenje v celoti zaključite, tudi če se po nekaj dneh počutite bolje.
This Mutual Recognition variation procedure was started on 7 December 2006.
Ta postopek medsebojnega priznavanja za prijavljeno spremembo se je pričel 7. decembra 2006.
It is recommended that you take the tablet at approximately the same time each day.
Priporočamo, da tableto vzamete vsak dan približno ob istem času.
Interference with culture test
Vpliv na test kulture
- The Committee considered that no additional safety concerns were expected with the claimed indication in comparison to the previously approved indications.
- Odbor je menil, da pri zahtevani indikaciji v primerjavi s predhodno odobrenimi indikacijami ni pričakovati dodatnih varnostnih pomislekov.
The tablets have to be taken orally once daily for up to 10 days, depending on the indication.
Tablete je treba jemati peroralno enkrat dnevno največ 10 dni, odvisno od indikacije.
M1 and M2 are the only metabolites relevant in humans, both are microbiologically inactive.
M1 in M2 sta edina pomembna presnovka pri ljudeh, oba pa sta mikrobiološko neaktivna.
In view of these concerns, during the Mutual Recognition Procedure, Belgium considered that a positive benefit / risk balance had not been demonstrated and more robust evidence should be submitted in order to grant the indication applied for.
Ob upoštevanju teh pomislekov je Belgija med postopkom medsebojnega priznavanja izrazila mnenje, da pozitivno razmerje med koristmi in tveganji ni bilo dokazano ter da je treba predložiti tehtnejše dokaze, na podlagi česar bi bilo mogoče odobriti zahtevano indikacijo.
Absorption and Bioavailability
Absorpcija in biološka uporabnost
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Upoštevati je treba uradne smernice o pravilni uporabi protimikrobnih zdravil.
H. influenzae and M. catarrhalis
H. influenzae in M. catarrhalis
Moxifloxacin is contraindicated in children and adolescents (< 18 years).
Moksifloksacin je kontraindiciran pri otrocih in mladostnikih (< 18 let).
The recommended dose and duration of treatment should not be exceeded (see section 2.
Priporočenega odmerka in trajanja zdravljenja ne smete prekoračiti (glejte poglavje 2.
As these concerns were not resolved during the course of the variation procedure, a notification of an official referral for Arbitration, under Article 6(12) of Commission Regulation EC No 1084/2003, to the CHMP was made by Belgium on 19 October 2007.
Ker ti pomisleki med postopkom za odobritev spremembe niso bili razrešeni, je Belgija 19. oktobra 2007 obvestila odbor CHMP o uradni napotitvi na arbitražo v skladu s členom 6(12) Uredbe Komisije (ES) št. 1084/2003.
This procedure is a referral following a Mutual Recognition Procedure concerning the above variation application which was submitted for Avalox film-coated tablets to Germany as Reference Member State (RMS) and the Concerned Member States (CMS) AT, BE, CY, CZ, DK, EE, EL, ES, FI, FR, HU, IE, IT, LT, LU, LV, MT, NL, PL, PT, SE, SI, SK and UK on 5 December 2006.
Ta postopek je napotitev na podlagi postopka medsebojnega priznavanja v zvezi z zgornjo vlogo za spremembo, ki je bila za zdravilo Avalox - filmsko obložene tablete Nemčiji kot referenčni državi članici in zadevnim državam članicam AT, BE, CY, CZ, DK, EE, EL, ES, FI, FR, HU, IE, IT, LT, LU, LV, MT, NL, PL, PT, SE, SI, SK in UK predložena dne 5. decembra 2006.
As necessary, expert advice should be sought where the local prevalence of resistance is such that utility of the agent in at least some types of infections is questionable.
Nasvet izvedenca je nujno potreben, kjer je lokalna prevalenca odpornosti tolikšna, da je koristnost uporabe učinkovine pri vsaj nekaterih vrstah okužb dvomljiva.
In this situation adequate therapeutic measures should be initiated immediately.
V tem primeru moramo takoj pričeti z ustreznim zdravljenjem.
30588 Murcia
30588 Murcia Španija
- The Committee considered the Referral made under Article 6(12) of Commission Regulation (EC) No 1084/2003, for Avalox and associated names (See Annex 1).
- Odbor je preučil napotitev, pripravljeno v skladu s členom 6(12) Uredbe Komisije (ES) št. 1084/2003, za zdravilo Avalox in z njim povezana imena (glejte Dodatek I).
Women with PID are generally young women with few underlying diseases and concomitant medications.
Ženske s pelvičnimi vnetnimi boleznimi so običajno mlade ženske z malo osnovnimi boleznimi in sočasnimi zdravljenji.
The Referral procedure was initiated on 15 November 2007 with the adoption of a CHMP List of Questions to be addressed by the MAHs.
Napotitveni postopek se je pričel 15. novembra 2007 s sprejetjem seznama vprašanj CHMP, naslovljenih na imetnike dovoljenja za promet z zdravilom.
- Quinolone antibiotics may make your skin become more sensitive to sunlight or UV light.
- Kinolonski antibiotiki lahko povzročijo večjo občutljivost vaše kože na sončno ali UV svetlobo.
If you are affected in this way do not drive or operate machinery.
V tem stanju ne vozite ali upravljajte strojev.
In this situation, you should not take medicines that stop or slow down bowel movement.
V tem primeru ne jemljite zdravil, ki prekinejo ali zavirajo gibanje črevesja.
On the basis of the pharmacokinetic studies carried out so far in patients with liver failure (Child Pugh A, B), it is not possible to determine whether there are any differences compared with healthy volunteers.
Na podlagi do sedaj opravljenih farmakokinetičnih študijah pri bolnikih z okvaro jeter (Child-Pugh A, B), ni mogoče dokazati, ali obstajajo kakršnekoli razlike v primerjavi z zdravimi prostovoljci.
BAYER SANTE 13, rue Jean Jaurès 92807 PUTEAUX CEDEX France
BAYER SANTE 13, rue Jean Jaurès 92807 PUTEAUX CEDEX Francija
Although it is acknowledged that approximately 95% of the women with a PID might be ‘overtreated' by this combination therapy this fact outweighs the potential risk of not treating approximately 5% of a mainly very young population which could develop serious long-term sequelae.
Čeprav je znano, da je pri približno 95 % žensk s pelvičnimi vnetnimi boleznimi to kombinirano zdravljenje „prekomerno“, to dejstvo ne odtehta možnega tveganja nezdravljenja približno 5 % pretežno zelo mlade populacije, pri kateri bi lahko prišlo do resnih dolgoročnih posledic.
At steady-state the exposure within the dosing interval is approximately 30% higher than after the first dose.
Pri dinamičnem ravnovesju je izpostavljenost v intervalu odmerjanja približno za 30 % večja kot po prvem odmerku.
The steady-state volume of distribution (Vss) is approximately 2 l/kg.
Razporeditveni volumen pri dinamičnem ravnovesju (Vss) je približno 2 l/kg.
* Non-species related breakpoints have been determined mainly on the basis of pharmacokinetic/pharmacodynamic data and are independent of MIC distributions of specific species.
* Mejne vrednosti za nespecifične vrste so določili zlasti na podlagi farmakokinetičnih/farmakodinamičnih podatkov in so neodvisne od MIK za specifične vrste.
- If you have a severe liver disease or increased liver enzymes (transaminases) higher than 5 times the upper normal limit.
- če imate hudo jetrno bolezen ali zvečano vrednost jetrnih encimov (transaminaz), ki za več kot petkrat presega zgornjo normalno mejo.
and fastidious organisms (M100-S17, 2007) and MIC breakpoints for anaerobes (M11-A7, 2007):
in občutljive mikroorganizme (M100-S17, 2007) in mejne vrednosti glede na preskušanje MIK za anaerobne mikroorganizme (M11-A7, 2007):
Anaphylactic reactions can progress to a life-threatening shock, even after the first administration.
Anafilaktične reakcije lahko privedejo do življenjsko ogrožujočega šoka celo po prvi uporabi.
There is no indication of oxidative metabolism.
Znakov oksidacijske presnove ni bilo.
Contact your doctor if you are not sure if you belong to a patient group described below.
Posvetujte se z zdravnikom, če ste negotovi, ali spadate v katero od skupin, ki so opisane v nadaljevanju.
Minimum bactericidal concentrations (MBC) were found to be in the range of the minimum inhibitory concentrations (MIC).
Ugotovili so, da so minimalne baktericidne koncentracije (MBK) v razponu minimalnih inhibicijskih koncentracij (MIK).
Streptococcus milleri group* (S. anginosus, S. constellatus and S. intermedius) Streptococcus pneumoniae*
Streptococcus skupine milleri* (S. anginosus, S. constellatus in S. intermedius) Streptococcus pneumoniae*
Drugs inhibiting peristalsis are contraindicated in this situation.
Zdravila, ki zavirajo peristaltiko, so v tem primeru kontraindicirana.
Due to the potential risk of adverse effects on the cartilage in patients under the age of 18 years, and the fact that PID mostly affects young women, the existing wording of the contraindication in children and adolescents was further specified namely that it is contraindicated in patients below 18 years of age.
Zaradi možnega tveganja neželenih učinkov na hrustanec pri bolnikih, mlajših od 18 let, in dejstva, da pelvične vnetne bolezni prizadenejo zlasti mlade ženske, je bilo obstoječe besedilo kontraindikacije pri otrocih in mladostnikih podrobneje opredeljeno, in sicer tako, da je zdravilo kontraindicirano pri bolnikih, mlajših od 18 let.
Bayer BV Energieweg 1
NL - Nizozemska Bayer BV Energieweg 1
Bayer Hungária Kft Alkotás ut.50
HU - Madžarska Bayer Hungária Kft Alkotás ut.50
In these cases moxifloxacin should be discontinued and suitable treatment (e.g. treatment for shock) initiated.
V teh primerih je treba z uporabo moksifloksacina prekiniti in začeti z ustreznim zdravljenjem (npr. zdravljenje šoka).
ANNEX I LIST OF THE NAMES, PHARMACEUTICAL FORM(S), STRENGTH(S) OF THE MEDICINAL PRODUCT(S), ROUTE(S) OF ADMINISTRATION, APPLICANT(S) MARKETING AUTHORISATION HOLDER(S) IN THE MEMBER STATES
DODATEK I SEZNAM IMEN, FARMACEVTSKIH OBLIK, JAKOSTI ZDRAVILA, POTI UPORABE ZDRAVILA, PREDLAGATELJEV, IMETNIKOV DOVOLJENJA ZA PROMET Z ZDRAVILOM V DRŽAVAH ČLANICAH
Swallow the tablet as a whole (to mask the bitter taste) and with plenty of liquid.
Tableto pogoltnite celo (da bi prikrili grenek okus) z veliko tekočine.
Moraxella (Branhamella) catarrhalis* Anaerobic micro-organisms
Moraxella (Branhamella) catarrhalis* anaerobni mikroorganizmi
Avenue Louise 143 B-1050 Bruxelles
Avenue Louise 143 B-1050 Bruxelles Belgija