Temporomandibularni poremećaji – uloga neuromuskularne stomatologije

Masticatory system function disorders, known as temporomandibular disorders (TMD) represent frequently encountered problem in daily practice. Clinicians generally agree that psychosocial factors (stress), trauma (macrotrauma - any sudden force to the joint resulting in structural alteration, or microtrauma - functional overloading associated with muscular hyperactivity (bruxism) or occlusal instability), and occlusal conditions have the important role in the onset of TMD. Neuromuscular dentistry is modern approach in diagnosis and treatment of TMD. It objectively evaluates the complex relationship between teeth, masticatory muscles, temporomandibular joints and cranial nerves in order to achieve an occlusion that is based on the optimal relationship between the mandible and the skull – a neuromuscular occlusion. Neuromuscular dentistry uses computerized instrumentation to measure the patient’s jaw movements via Computerized Mandibular Scanning (CMS) or Jaw Motion Analysis (JMA), muscle activity via electromyography (EMG) and temporomandibular joint sounds via Electro-Sonography (ESG) or Joint Vibration Analysis (JVA). The fact is, however, that to date there is still no sufficient number of randomized double-blind clinical studies that could objectively help in choosing the appropriate method of diagnosis and treatment of TMD, and that in the future those studies certainly might contribute to resolving the enigma of temporomandibular disorders.Poremećaji funkcije žvačnog sustava (tzv. temporomandibularni poremećaji) problem su s kojim se sve češće susrećemo u svakodnevnoj praksi. Kliničari se uglavnom slažu u tome da najvažniju ulogu u njihovu nastanku imaju psihosocijalni čimbenici (stres), trauma – koja može biti makrotrauma, kao što je npr. udarac u čeljust, ili mikrotrauma, ona povezana s kroničnom mišićnom hiperaktivnošću (bruksizmom) ili okluzijskom nestabilnošću – te okluzijski uvjeti. Neuromuskularna stomatologija moderan je oblik dijagnostike i liječenja tih poremećaja. Ona objektivno procjenjuje kompleksan odnos između zubi, žvačnih mišića, temporomandibularnih zglobova i kranijalnih živaca kako bi među njima postigla sklad. Za razliku od standardnih dijagnostičkih metoda kliničke funkcijske analize kojima se koristi tradicionalna stomatologija, neuromuskularna stomatologija u tu se svrhu koristi različitim kompjutoriziranim suvremenim tehnikama kojima se bilježi pomicanje donje čeljusti (analiza kretnji donje čeljusti), registriraju mišićnu aktivnost (elektromiografija) i identificiraju zvukove zgloba (elektrosonografija i analiza zglobnih vibracija). Činjenica je ipak da do danas još uvijek ne postoji dovoljan broj randomiziranih dvostruko slijepih kliničkih studija koje bi nam mogle objektivno pomoći u odabiranju odgovarajućeg načina dijagnostike i liječenja, a koje će u budućnosti zasigurno doprinijeti rješavanju enigmi temporomandibularnih poremećaja

Temporomandibularni poremećaji – uloga neuromuskularne stomatologije

Masticatory system function disorders, known as temporomandibular disorders (TMD) represent frequently encountered problem in daily practice. Clinicians generally agree that psychosocial factors (stress), trauma (macrotrauma - any sudden force to the joint resulting in structural alteration, or microtrauma - functional overloading associated with muscular hyperactivity (bruxism) or occlusal instability), and occlusal conditions have the important role in the onset of TMD. Neuromuscular dentistry is modern approach in diagnosis and treatment of TMD. It objectively evaluates the complex relationship between teeth, masticatory muscles, temporomandibular joints and cranial nerves in order to achieve an occlusion that is based on the optimal relationship between the mandible and the skull – a neuromuscular occlusion. Neuromuscular dentistry uses computerized instrumentation to measure the patient’s jaw movements via Computerized Mandibular Scanning (CMS) or Jaw Motion Analysis (JMA), muscle activity via electromyography (EMG) and temporomandibular joint sounds via Electro-Sonography (ESG) or Joint Vibration Analysis (JVA). The fact is, however, that to date there is still no sufficient number of randomized double-blind clinical studies that could objectively help in choosing the appropriate method of diagnosis and treatment of TMD, and that in the future those studies certainly might contribute to resolving the enigma of temporomandibular disorders.Poremećaji funkcije žvačnog sustava (tzv. temporomandibularni poremećaji) problem su s kojim se sve češće susrećemo u svakodnevnoj praksi. Kliničari se uglavnom slažu u tome da najvažniju ulogu u njihovu nastanku imaju psihosocijalni čimbenici (stres), trauma – koja može biti makrotrauma, kao što je npr. udarac u čeljust, ili mikrotrauma, ona povezana s kroničnom mišićnom hiperaktivnošću (bruksizmom) ili okluzijskom nestabilnošću – te okluzijski uvjeti. Neuromuskularna stomatologija moderan je oblik dijagnostike i liječenja tih poremećaja. Ona objektivno procjenjuje kompleksan odnos između zubi, žvačnih mišića, temporomandibularnih zglobova i kranijalnih živaca kako bi među njima postigla sklad. Za razliku od standardnih dijagnostičkih metoda kliničke funkcijske analize kojima se koristi tradicionalna stomatologija, neuromuskularna stomatologija u tu se svrhu koristi različitim kompjutoriziranim suvremenim tehnikama kojima se bilježi pomicanje donje čeljusti (analiza kretnji donje čeljusti), registriraju mišićnu aktivnost (elektromiografija) i identificiraju zvukove zgloba (elektrosonografija i analiza zglobnih vibracija). Činjenica je ipak da do danas još uvijek ne postoji dovoljan broj randomiziranih dvostruko slijepih kliničkih studija koje bi nam mogle objektivno pomoći u odabiranju odgovarajućeg načina dijagnostike i liječenja, a koje će u budućnosti zasigurno doprinijeti rješavanju enigmi temporomandibularnih poremećaja

Pilocarpine-Hydrocloride Has a Short-Time Effect on Reducing Xerostomia

Kserostomija, tj. suhoća usta jest stanje uglavnom uzrokovano uzimanjem lijekova, imunološkim bolestima (Sy. Sjoegren) ili radioterapijom tumora usta i glave. Postoje mnogi ali ne dovoljno učinkoviti terapijski postupci, uključujući i uporabu agonista muskarinskih receptora pilokarpin- hidroklorida. U Hrvatskoj liječenje salivarne hipofunkcije polikarpin-hidrokloridom još nije uvedeno. U ovome istraživanju cilj je bio ocijeniti učinak peroralne uporabe pilokarpina na male žlijezde slinovnice i ukupnu salivaciju te nadzirati moguće neželjene pojave i subjektivni odgovor bolesnika na terapiju. Bio je to jednostruko slijepi placebo pokus. Deset bolesnika s kserostomijom sudjelovalo je u pokusu. Isključeni su bolesnici sa srčanim i plućnim bolestima te oni kojima se tijekom uključenog ispitivanja 7 dana prije pokusa kemijskom stimulacijom C-vitaminom nije povećao salivarni tok. Pokus je obuhvaćao 7 uzastopnih mjerenja količine sline u vremenskim razmacima od 15 do 30 min, od vremena neposredno prije i nakon jedinstvene doze 5 mg pilokarpin- hidroklorida (5 kapi otopine, Pilokarpin 2%, Pliva, hrvatska). Sekrecija malih slinovnica mjerena je na donjoj usni i nepcu s pomoću Periotrona (Oraflow, Plainview, SAD), a ukupna salivacija mjerna je s piomoću graduiranih epruveta. Svaki je ispitanik ispunio jednostavan upitnik o subjektivnoj percepciji liječenja i o možebitnim nuspojavama. Sljedeći je tjedan procedura ponovljena, ali tada je umjesto pilokarpina upotrebljena dekspantenolna otopina (D-panthenol, Ljekarne Zagreb, Hrvatska) kao placebo. Pilokarpin je povećao slivaciju i poboljšao simptome u svakog bolesnika. Razlike u sekreciji sline bile su statistički znatne i u usporedbi sa stanjem prije ordiniranja pilokarpina i u usporedbi s placebom (p = 0,01). Nije bilo zabilježenih nepoželjnih pojava ni nakon ordiniranja pilokarpina ni nakon placeba. Nakon poboljšanja salivacije učinak pilokarpina se vremenom smanjuje, što je zabilježeno tijekom promatranja bolesnika. Uzimajući u obzir kontraindikacije i neželjene učinke, rezultati našeg ispitivanja upućuju da bi se pilokarpin trebao redovito upotrebljavati u liječenju kserostomije.Xerostomia, i.e. oral dryness, is mainly caused by side effects of medications, immunologic diseases, e.g. Sy. Sjoegren, and radiation treatment for oral and neck cancer. There are variable, although far from satisfactory, treatment options, including that of muscarinic receptor agonist pilocarpine-hydrochloride. Pilocarpine treatment of salivary hypofunction is not yet an established method in croatia. The aim of this preliminary study was to assess the autcome of oral administration of pilocarpin on minor salivary glands and whole saliva production, as well as to monitor possible side effects and patients subjective responses to treatment. Is was a single blind-placebo controlled trial. Ten patients suffering from xerostomia underwent this trial. Patients with cardiac or pulmonary diseases were excludet, as well as those that did not show any increase in salivary flow rate after administration of ascorbic acid solution (chemical stimulant) at inclusion testing one week prior to the experiment. The experiment comprised 7 repeated measurements in time intervals of 15-30 min., from the baseline up to 2 h after single oral administration of 5 mg of pilocarpine hydrochloride ( 5 drops of slution, Pilokarpin 2%, pliva, Croatia). The flow rate of minor salivary glands was measured on the lower lip and palate by means of Periotron (Oraflow Inc., Plainview, USA) and whole saliva was collected in calibrated test tubes . A simple questionnaire was filled in to record patients subjective perception of treatment. The same procedure was repeated one week later, when dexpanthenol drops (DPanthenol, Ljekarne Zagreb, Croatia) were used as placebo instead of pilocarpine. Pilocarpine increased salivary output and gave symptomatic relief in every patient. The differences in salivary output were significant both compared to baseline and to placebo controls (p = 0,01). There were no side effects during the trial, either after administration of pilocarpine; or placebo. After increasing salivary flow rate the action of pilocarpine decrease in time, which was recordable during the observation session. Respecting possible contraindications and side effects, according to our finding pilocarpine should be regulary used in treatment of xerostomia

ADHERENCE TO »AMERICAN EUROPEAN CONSENSUS GROUP« CLASSIFICATION CRITERIA FOR SJÖGREN’S SYNDROME IN DIFFERENTIAL DIAGNOSIS OF XEROSTOMIA

Svrhe rada su dobiti epidemiološke i etiološke podatke o problemu kserostomije u dijelu hrvatske populacije i utvrditi dosljednost pridržavanja klasifikacijskih kriterija American European Consensus Group (AECG) za Sjögrenov sindrom (SSj), s ciljem identificiranja moguće potrebe za poboljšanjem dijagnostičkog postupka u diferencijalnoj dijagnostici kserostomije. Retrospektivno istraživanje provedeno je u Zavodu za oralnu medicinu među bolesnicima primljenima zbog osjećaja suhih usta. Uključne kriterije zadovoljilo je 395 bolesnika. Napravljena je baza epidemioloških, kliničkih i sijalometrijskih podataka, nalaza seroloških, scintigrafskih, ultrazvučnih i patohistoloških pretraga žlijezda slinovnica te podataka o farmakoterapiji. Rabili su se deskriptivni statistički postupci. Salivarna hipofunkcija dokazana je u 74% bolesnika. Najčešći vjerojatni uzrok kserostomije bila je farmakoterapija. SSj je dokazan u 6,7% ispitanika sa kserostomijom, dok u 8% postoji visoka sumnja, ali biopsija labijalnih slinovnica nije učinjena, što upućuje na nepridržavanje kriterija AECG za dijagnostiku SSj-a. Nužno je provoditi kriterije AECG u obradi bolesnika sa suhim ustima i provesti edukaciju liječnika opće prakse, stomatologa i bolesnika o kserogenim nuspojavama farmakoterapije.The aims were to obtain epidemiological and etiological data on xerostomia in cross section of Croatian population, and to evaluate adherence to »American European Consensus Group« (AECG) classification criteria for Sjögren’s syndrome (SSj), in order to identify possible need for improvements in differential diagnosis of xerostomia. A retrospective study among patients seen at the Department of oral medicine for complaints of dry mouth was performed. Three hundred and ninety-five patients met inclusion criteria. A data base was formed, comprising epidemiological, clinical and sialometric data, immunological, scintigraphic, ultrasonographic and histopathological findings of salivary glands, coupled with drug intake listings. Descriptive statistics were used for data analysis. Objective salivary hypofunction was found in 74% of our patients. The most common probable cause of xerostomia was side effect of pharmacotherapy. SSj was diagnosed in 6.7% of patients with xerostomia, whereas in another 8% of patients Sjögren’s syndrome was strongly suspected, but labial gland biopsy wasn’t performed, indicating a lack of adherence to AECG criteria for SSj diagnosis. Application of AECG criteria in differential diagnosis of patients with dry mouth is mandatory, as well as educating general practitioners, dentists and patients on xerogenic side effects of pharmacotherapy

ADHERENCE TO »AMERICAN EUROPEAN CONSENSUS GROUP« CLASSIFICATION CRITERIA FOR SJÖGREN’S SYNDROME IN DIFFERENTIAL DIAGNOSIS OF XEROSTOMIA

Svrhe rada su dobiti epidemiološke i etiološke podatke o problemu kserostomije u dijelu hrvatske populacije i utvrditi dosljednost pridržavanja klasifikacijskih kriterija American European Consensus Group (AECG) za Sjögrenov sindrom (SSj), s ciljem identificiranja moguće potrebe za poboljšanjem dijagnostičkog postupka u diferencijalnoj dijagnostici kserostomije. Retrospektivno istraživanje provedeno je u Zavodu za oralnu medicinu među bolesnicima primljenima zbog osjećaja suhih usta. Uključne kriterije zadovoljilo je 395 bolesnika. Napravljena je baza epidemioloških, kliničkih i sijalometrijskih podataka, nalaza seroloških, scintigrafskih, ultrazvučnih i patohistoloških pretraga žlijezda slinovnica te podataka o farmakoterapiji. Rabili su se deskriptivni statistički postupci. Salivarna hipofunkcija dokazana je u 74% bolesnika. Najčešći vjerojatni uzrok kserostomije bila je farmakoterapija. SSj je dokazan u 6,7% ispitanika sa kserostomijom, dok u 8% postoji visoka sumnja, ali biopsija labijalnih slinovnica nije učinjena, što upućuje na nepridržavanje kriterija AECG za dijagnostiku SSj-a. Nužno je provoditi kriterije AECG u obradi bolesnika sa suhim ustima i provesti edukaciju liječnika opće prakse, stomatologa i bolesnika o kserogenim nuspojavama farmakoterapije.The aims were to obtain epidemiological and etiological data on xerostomia in cross section of Croatian population, and to evaluate adherence to »American European Consensus Group« (AECG) classification criteria for Sjögren’s syndrome (SSj), in order to identify possible need for improvements in differential diagnosis of xerostomia. A retrospective study among patients seen at the Department of oral medicine for complaints of dry mouth was performed. Three hundred and ninety-five patients met inclusion criteria. A data base was formed, comprising epidemiological, clinical and sialometric data, immunological, scintigraphic, ultrasonographic and histopathological findings of salivary glands, coupled with drug intake listings. Descriptive statistics were used for data analysis. Objective salivary hypofunction was found in 74% of our patients. The most common probable cause of xerostomia was side effect of pharmacotherapy. SSj was diagnosed in 6.7% of patients with xerostomia, whereas in another 8% of patients Sjögren’s syndrome was strongly suspected, but labial gland biopsy wasn’t performed, indicating a lack of adherence to AECG criteria for SSj diagnosis. Application of AECG criteria in differential diagnosis of patients with dry mouth is mandatory, as well as educating general practitioners, dentists and patients on xerogenic side effects of pharmacotherapy

Temporomandibular Dysfunctions (TMD) in Contemporary Practice

Temporomandibularne disfunkcije u svim svojim patološkim oblicima čine sve češći problem u suvremenoj stomatološkoj praksi. Sustavan pristup dijagnostici s obzirom na prikupljanje i interpretaciju podataka o pacijentu jedan je od primarnih ciljeva u tretmanu znakova i simptoma TMD-a. Prema W. Bellu dijagnoza TMD-a mora obuhvatiti: • pravilnu identifikaciju i klasifikaciju poremećaja • razumijevanje mehanizma nastanka i mjesta boli • utvrđivanje etioloških čimbenika, ako je moguće • bazirati prognozu s obzirom na djelotvornost terapije. Temeljem navedenih načela temporomandibularna disfunkcija ne može se smatrati jedinstvenim patološkim entitetom već skupinom bolesti koja se javlja sličnim preklapajućim simptomima. Posljedično, terapija svih oblika TMD-a nikako ne može biti ista. Osim uobičajenih kliničkih postupaka u dijagnostici TMD-a upotrebljavaju se i računalni postupci poput elektromiografije, elektrosonografije elektrokinetička i aksiografska mjerenja koja omogućuju da se lakše postavi pravilna dijagnoza i izabere prikladna terapija.Temporomandibular dysfunction in al its variety tends to present a problem with high morbidity and increasing prevalence in the dental office. A systematic approach to gathering and interpreting clinical evidence must be the primary goal when dealing with patients who suffer from TMD signs and symptoms. According to W. Bell diagnosis of TMD must: • Properly identify and classify the disorder. • Establish the mechanism of dysfunction and the source of pain. • Determine the etiology, if possible. • Provide a basis prognosis in the light of effective therapy. As a result of these principles we can canclude that TMD is not an acceptable diagnosis. It refers to a group of diseases with overlapping and similar signs and symptomatologies and cannot be solely used to determine appropriate therapy. Apart from good clinical judgement the patient can benefit from any inanimate objective measuring device which improves the clinician’s sensory acuity. Information obtained from electomyography, electrosonography, electrokinetic and axiographic tracings analyzed properly can aid in assessing what a specific TM disorder does to a patient and the effect treatment has on that disorder

Electromyographic Evaluation of Masticatory Muscle Activity in Patients with Temporomandibular Dysfunction

Pojam temporomandibularna disfunkcija (TMD) obuhvaća mnoge poremećaje u vezi sa žvačnim mišićima i temporomandibularnim zglobovima. U vezu s nastankom TMD-a najčešće se dovode okluzalni, traumatski, psihosocijalni i sustavski čimbenici. Svrha ovoga istraživanja bila je ustanoviti postoji li promijenjena aktivnost žvačnih mišića u ispitanika s poremećajem te utvrditi mogućnosti dijagnostike temporomandibularnih poremećaja metodom elektromiografije. U ispitivanju je sudjelovalo 40 ispitanika: 13 ispitanika sa simptomima temporomandibularne disfunkcije i 27 asimptomatskih ispitanika, usporedivih po spolu i dobi. Elektromiografska mjerenja provedena su na šest mišića (desni i lijevi prednji temporalis, maseter i digastrikus) u osam referentnih položaja. Ispitivanje odnosa vrijednosti mioelektričkih signala pojedinog mišića desne i lijeve strane u skupini zdravih ispitanika u lateralnim okluzijskim položajima i u maksimalnim lateralnim položajima pokazalo je znatno veću aktivnost temporalnoga mišića radne strane (p0,05). Razlika u vrijednosti mioelektričkih signala između asimptomatske i simptomatske skupine pronađena je za desni i lijevi maseter u maksimalnoj interkuspidaciji s 50% MVC (p<0,05), kod kojih su veće vrijednosti nađene u simptomatskoj skupini. Rezultati ovoga istraživanja pokazali su postojanje promjena aktivnosti žvačnih mišića u ispitanika s TMD-om te potvrdili mogućnost uporabe elektromiografije u dijagnostici temporomandibularnih poremećaja.The term temporomandibular dysfunction (TMD) encompasses a group of disorders of the masticatory muscles and temporomandibular joints. Major precipitating factors are occlusal, traumatic, psychosocial and systemic factors. The aim of this investigation was to determine possible altered muscular function in patients with TMD, as well as to determine the need for EMG application in TMD diagnosis. Forty young adults participated in this study: 13 subjects with signs and symptoms of TMD and 27 asymptomatic subjects, sex and age matched. Surface EMG recordings were obtained from left and right anterior temporal muscle, left and right masseter muscle and from left and right digastric muscle in eight mandibular positions. Right side to left side ratio of examined muscles myoelectrical signals in lateral occlusal and maximal lateral positions for the asymptomatic group showed significantly higher activity of the working side anterior temporal muscle (p0.05). Comparison of myoelectrical signals in the position of maximal intercuspation of teeth between the patients and the controls, showed significantly higher activity in right and left masseter muscle at 50% MVC (p<0.05) in the symptomatic group. Results of this investigation showed the presence of altered masticatory muscle activity in TMD patients and confirmed the use of electromyography in TMD diagnosis

The Effect of Nonaromatic Naphthalane on Mice Oral Planocellular Carcinoma - a Pilot Study

Nearomatski visokosteranski naftalan (NAVS) posebna je frakcija hrvatske nafte, iznimno bogata steranima, iz koje je odstranjen aromatski sastav. Steranima se pripisuje bioaktivnost slična steroidnim hormonima, modulatorima tumorskoga rasta. Potaknuti rezultatima prijašnjih in vitro i in vivo studija o inhibitornom efektu NAVS-a na rast planocelularnog karcinoma, proveli smo studiju o njegovu učinku na oralni planocelularni karcinom (OPCC) u miševa. Ciljevi: 1) ispitati valjanost jednostavnog eksperimentalnog modela OPCC-a; 2) ispitati mogući antiproliferativni učinak NAVS-a na postavljenome modelu praćenjem tumorskoga rasta; 3) ispitati antineoangiogeni učinak NAVS-a kao objašnjenje mogućeg antiproliferativnog učinka, te za tu prigodu procijeniti mogućnost križne reaktivnosti anti-humanih imunohistokemijskih markera s mišjim tkivom. Suspenzija od 100 μl s 105 SCC VII stanica inokulirana je intraoralnim putem pod bukalnu sluznicu u 48 singeničnih C3H miševa. Sedam dana nakon inokulacije životinje su podijeljene u 6 jednakih skupina, te se miševima, ovisno o skupini, intratumorski injiciralo po 100 μl sljedećih tvari: parafinsko ulje (PO) kao negativna kontrola, NAVS (u jednoj skupini 7 dana, a u drugoj skupini 14 dana nakon inokulacije tumora), 1, 25 dihidroksiergotamin (1,25-D3) kao pozitivna kontrola, te kombinacije NAVS s 1,25-D3 i PO s 1,25-D3. Rast tumora praćen je tjednim mjerenjem s pomoću kalipera. Životinje su žrtvovane 1., 2., 3. i 4. tjedna nakon aplikacije ispitivanoga sredstva. Histološki pripravci eksplantiranih tumora bojeni su hematoksilin-eozinom te imunohistokemijski s anti-CD34 protutijelima radi procjene tumorske neoangiogeneze. U usporedbi s PO skupinom, tumorski rast i angiogeneza bili su sniženi u 1,25-D3 i NAVS skupinama. NAVS vjerojatno smanjuje rast OPCC-a inhibicijom vaskularne proliferacije potrebne za tumorski rast.Nonaromatic naphthalane (NAVS) is a specific fraction of Croatian oil, extremely rich in steranes from which the aromatic system is removed. Steranes are attributed with bioactivity similar to steroid hormones, modulators of tumour growth. Encouraged by the results of earlier in vitro and in vivo studies on the inhibitory effect of NAVS on the growth of planocellular carcinoma, we carried out a study on its effect on oral planocellular carcinoma (OPCC) in mice. Aims: 1) To test the validity of the simple experimental model OPCC, 2) to test possible antiproliferative effect of NAVS on the above model by monitoring tumour growth, 3) to test the antineoangiogenic effect of NAVS to explain the possible antiproliferative effect, and to estimate the possibility of crisis reactivity of anti-human immunohistochemical markers with mice tissue. A suspension of 100 μl s 105 SCC VII cell was inoculated intraorally under the buccal mucous membrane in 48 syngeneic C3H mice. Seven days after inoculation the animals were divided in six equal groups and the mice, depending on the group, were intratumorously injected with 100 μl of the following substances: paraffin oil (PO) as a negative control, NAVS (in one group 7 days, and in the second group 14 days, after inoculation of the tumour), 1.25 dihydroxyergotamine (1.25-D3) as a positive control, and a combination of NAVS with 1.25 D3 and PO with 1.25- D3. Tumour growth was monitored weekly by measuring with callipers. The animals were sacrificed 1, 2, 3 and 4 week after application of the tested substance. Histological specimens of explanted tumours were stained with hematoxylin-eozine, and immunohistochemically with anti-CD34 antibodies for estimation of tumour neoangiogenesis. Compared with the PO group, tumour growth and angiogenesis were decreased in the 1.25-D3 and NAVS groups. NAVS probably reduced growth by OPCC inhibition of vascular proliferation, needed for tumour growth