Provider: - Institution: - Data provided by Europeana Collections- Kosti su stalno u procesu trošenja i obnavljanja, a ravnoteža razgradnje i izgradnje
preduvjet je za zdravo koštano tkivo. ...Slabljenje kvalitete kosti posljedica je poremećaja te
ravnoteže. Za razgradnju su odgovori osteoklasti dok su za izgradnju odgovorni osteoblasti.
Osteopenija je stanje smanjene gustoće kosti, a do nje može doći i zbog dugotrajne primjene
glukokortikosteroida.
Glukokortikosteroidi su protuupalni lijekovi koji se, između ostalog, koriste za
sprečavanje upale dišnih puteva kod astme. Budući je astma česta kronična bolest u djece
potrebno je pratiti metaboličke i koštane učinke glukokortikosteroida tijekom terapije. Cilj
ovog rada je uspostava modela hipoplazije fize izazvane glukokortikosteroidima i odabir
optimalnih biljega njihovih metaboličkih i koštanih učinaka.
Istražen je učinak 3 glukokortikosteroida na rast i promjenu metabolizma kosti te na
ostale sustavne učinke u štakora. Beklometazon dipropionat, prednizolon i ciklezonid, davani
mladim muškim Sprague-Dawley štakorima 7 dana u dozama od 0,3-10 mg/kg dnevno, s.c.,
su ovisno o dozi inhibirali indeks tjelesne mase timusa (za 57%, 44% i 76% s 3 mg/kg).
Ciklezonid i manje učinkovit prednizolon su utjecali na ploču rasta glave femura inhibirajući
rast femura (za 41% i 18% s 10 mg/kg), značajno smanjujući povećanje tjelesne mase (oboje
za 100% s 10 mg/kg), te serumske koncentracije kisele fosfataze i tartarat rezistentne kisele
fosfataze (za >30% s 10 mg/kg); oba su povećala serumske razine glukoze i triglicerida.
Beklometazon dipropionat je imao slab učinak na ove dodatne varijable. Ciklezonid pokazuje
izraženo inhibirajuće djelovanje na rast kosti u štakora. Možemo zaključiti da je ovo dobar
model za ispitivanje utjecaja glukokortikosteroida na metabolizam kosti.- Bone in children is structurally different from adult bone. It is weaker but less brittle.
Bone growth starts with cartilage formation. Then vessels invade the cartilage, delivering
pluripotent stem cells, which initiate the formation of a primary center of ossification.
Secondary ossification centers are formed at each end of long bone, and between the primary
and secondary ossification centers the growth plate, or physis, develops. Bone grows as
secondary and primary ossification centers unite.
Bone tissue is in dinamic process of constant deteriorating and regeneration.
Weakening of bone quality is a result of imbalance in a process of bone remodelling. Bone
remodelling has two stages: bone resorption with the osteoclasts, bone cells which resorb the
bone, and bone formation with osteoblasts, bone cells which form the bone. The bone
remodelling cycle ends with bone mineralisation. The content of mineral in bones is defined
as bone density. Osteopenia is a condition with decreased bone density. Apart being a sign of
normal aging, osteopenia can be induced with prolonged use of glucocorticosteroids.
Glucocorticosteroids are antiinflammatory medications prescribed, among others, for
reducing and prevention inflammation of respiratory pathways in asthma. Since asthma is the
most common chronic disease in children, need for monitoring metabolic and bone effects of
glucocorticosteroids during therapy is appearing. Although inhaled glucocorticoids are known
to have systemic effects on bone metabolism, there is little comparative information on their
relative potencies.
The goal of this work is establishment of glucocorticosteroid induced hypoplasia of
the physis and finding the optimal markers of their metabolic and bone effects.
The effects of three standard glucocorticoids, beclomethasone dipropionate,
prednisolone and ciclesonide, in causing changes in bone metabolism and growth were
investigated in relation to other systemic effects in the rat.
Male, specific pathogen-free, Sprague-Dawley rats, 4,5–5,5 weeks old (at the
beginning of the experiments), were used in the study.
The rat femur model of glucocorticosteroid-induced hypoplasia of the physis was
established according to Belvisi et al., using subcutaneous (s.c.) drug administration to allow
for future parenteral comparison with novel compounds. Briefly, rats were randomly assigned
to experimental groups of 8 animals each. In total, three experiments were performed for each
glucocorticoid; beclomethasone dipropionate, prednisolone and ciclesonide, at doses of 0,3–
10 mg/kg daily for 7 days. Animals in the control groups received s.c. the volume of 10 ml/kg
of vehicle (4% DMSO in 0,125% CMC) daily, for 7 days. Twenty-four hours after the last
treatment, animals were anaesthetized with sodium thiopental and the blood was collected at
exsanguination in order to obtain serum. Also, thymus weights were recorded and the femoral
bones removed (for measurement of the thickness of the proliferating zone). Animal body
weights were correspondingly documented at the beginning and at the end of each
experiment. Body weight gain was calculated as the change in body weight from day 1 until
24 h after treatment on day 7.
Biochemical analyses were performed on rat sera. Serum concentrations of glucose
and triglycerides, alkaline and acid phosphatases, and tartrate-resistant acid phosphatase were
determined on the biochemical analyzer. Concentration of osteocalcin, as a biochemical
marker for bone formation, and TRACP 5b, as a biochemical marker for bone resorption,
were also determined using ELISA.
The thymus was dissected free of connective tissue and immediately weighed.
Thymus body mass index (BMI) was calculated according to the following formula: BMI
(thymus)=thymus weight (mg)/body mass (mg). The left femur was exposed and removed
with the head intact in the acetabulum by cutting through the pelvic girdle and through the
femur shaft above the knee joint. The tissue was then fixed in 10% neutral buffered formalin
for histological assessment.
For the purpose of quantitative histology of the femoral head proliferating zone femurs
were fixed, decalcified and processed to paraffin using the unit for tissue processing. Threemicrometer-
thick sections were cut in a way to include femoral head and stained. The femoral
head growth plate was examined under a light microscope. Images of the growth plate were
captured onto a computer. One image was captured from each tissue section, five
measurements of the growth plate width being obtained from each calibrated image.
Measurements involved drawing a line perpendicular to the growth plate between the edge of
the hypertrophic zone, distal to the articular cartilage and the end of the proliferating zone.
Daily treatment for 7 days with standard glucocorticoids resulted in significant
increases in serum glucose and triglycerides concentrations at the highest doses (10 mg/kg) of
prednisolone and ciclesonide. The most pronounced changes were observed with ciclesonide,
which also significantly increased serum triglycerides at a daily dose of 3 mg/kg.
None of the standard glucocorticoids had any significant effect on serum ALP, over
the tested dose range, given daily for 7 days. However, at the highest dose (10 mg/kg),
prednisolone and ciclesonide significantly inhibited both serum ACP and TRACP. The most
pronounced changes were observed with ciclesonide, which also significantly decreased
serum ACP and TRACP at a daily dose of 3 mg/kg. Beclomethasone dipropionate was less
effective, causing a slight but significant decrease in serum ACP (but not TRACP) at doses of
0,3 and 1 mg/kg.
The comparative potency of the three glucocorticoids in influencing non-specific
serum parameters of bone metabolism was also reflected in their effects on the proliferating
zone thickness of the femoral bone head. While beclomethasone dipropionate had no
significant effect, ciclesonide and prednisolong decreased physeal growth plate width.
Prednisolone reduced median bone growth by 18% at the highest dose (10 mg/kg) and
ciclesonide caused a dosedependent reduction in median bone growth, with significant
inhibition of up to 41% over the whole tested dose range (0,3–10 mg/kg).
All three standard glucocorticoids exerted significant, dose related inhibitory effects
on median body weight gain and thymus body mass indices after daily treatment for 7 days.
Beclomethasone dipropionate was the least growth inhibitory; although it caused statistically
significant inhibition of thymus BMIs by 50% at dose of 1 mg/kg per day, it caused
statistically significant 23% inhibition of median body weight gain only at 10 mg/kg per day.
Prednisolone affected thymus BMIs causing statistically significant inhibition by 44% at dose
of 3 mg/kg per day and body weight gain causing statistically significant inhibition by 33% at
dose of 1 mg/kg per day. Ciclesonide exerted the most pronounced inhibition of body weight
gain and thymus BMIs, causing statistically significant inhibition by 34% and 55%,
respectively, already at the lowest dose of 0,3 mg/kg per day.
In order to see how examined glucocorticoids effected bone markers results showed
that prednisolone had no statistical effect on bone formation while ciclesonide significantly
reduced osteocalcin concentration in doses of 3 and 10 mg/kg per day (157 ng/mL and 88
ng/mL, respectively) vs. control (453 ng/mL).
On the other hand, ciclesonid showed no significant effect on bone resorption while
prednisolone significantly reduced TRACP 5b concentration at the highest dose of 10 mg/kg
per day compared to negative control group (10,6±0,9 U/L vs. 19,7±3,1 U/L).
Ciclesonide, although a pro-drug, still has potent systemic activity in the rat, causing
typical glucocorticoid effects, including inhibition of bone growth. Prednisolone exhibits a
similar, though less potent, spectrum of systemic activity, while beclomethasone dipropionate
has weak activity in causing systemic metabolic effects, but retains thymus inhibiting
potency. However, although the distinction between the effect of glucocorticoids on bone
growth was observed in this stud
Provider: - Institution: University of Zagreb. Faculty of Pharmacy and Biochemistry. Department of pharmacology. - Data provided by Europeana Collections- Novi dokazi ukazuju da je antinociceptivno ...djelovanje botulinum toksina tipa A (BT-A) središnjeg porijekla. U ovom doktorskom radu smo provjerili ovu pretpostavku u ranije nedovoljno istraženim oblicima boli, istraživali interakciju sa središnjim neurotransmitorima kao mogući mehanizam djelovanja te pokušali pobliže utvrditi mjesto djelovanja toksina u središnjem živčanom sustavu (SŽS).
Ispitivanja su izvedena na mužjacima Wistar štakora. U upalnoj, neuropatskoj i bilateralnoj mišićnoj boli ispitan je učinak selektivnih i neselektivnih antagonista opioidnih i GABAA receptora, primijenjenih sistemski, spinalno ili supraspinalno, na antinociceptivno djelovanje periferno (supkutano u šapu) primijenjenog BT-A. U tkivu kralješnične moždine ispitana je aktivacija neuronalnih i glija stanica, ekspresija mRNA proupalnih citokina i μ-opioidnih receptora te ekspresija Leu/Met-enkefalina metodama imunofluorescencije i lančane reakcije polimerazom s reverznom transkripcijom. Istraživano je antinociceptivno djelovanje BT-A nakon periferne, spinalne i supraspinalne primjene te je imunofluorescencijom ispitana enzimska aktivnost BT-A u tkivu SŽS-a.
Opioidni i GABAA antagonisti su ovisno o dozi, sistemski i intratekalno, ali ne i supraspinalno, poništili antinociceptivno djelovanje BT-A u svim ispitanim modelima. Učinak antagonista bio je kratkotrajan. BT-A je smanjio neuronalnu aktivaciju u dorzalnom rogu kralješnične moždine, što su antagonisti blokirali. BT-A je smanjio bol u dosad neistraženim modelima visceralne boli (peritonitis, kolitis). Bilateralno antinociceptivno djelovanje BT-A posljedica je prisutnosti toksina samo na ipsilateralnoj strani. BT-A je smanjio bol nakon periferne i intratekalne primjene, dok primijenjen supraspinalno (cisterna magna, moždane komore) nije djelovao, unatoč nalazu njegove enzimske aktivnosti u pojedinim regijama mozga uključenima u nocicepciju.
BT-A ima segmentalno antinociceptivno djelovanje spinalnoj razini, uz neizravnu aktivaciju endogenog opioidnog i GABA-ergičkog sustava. Ovi bi nalazi mogli biti važni za klinička ispitivanja potencijalno korisnih sinergističkih interakcija s konvencionalnim analgeticima i drugim lijekovima te usmjeriti klinička ispitivanja na nove indikacije i nove načine primjene, poput intratekalne.- Novel evidence suggests that the antinociceptive effect of botulinum toxin type A (BT-A) is of central origin. In this doctoral thesis, we verified this assumption in previously insufficiently investigated types of pain, investigated the interaction with central neurotransmitters as the possible mechanism of action and tried to determine the site of the toxin’s action within the central nervous system (CNS).
Male Wistar rats were used in experiments. We examined the effect of selective and nonselective opioid and GABAA antagonists, applied systemically, spinally and supraspinally, on antinociceptive effect of peripherally (subcutaneously into hind paw) applied BT-A in inflammatory, neuropathic, and bilateral pain. Neuronal and glial cells’ activation, proinflammatory cytokines’ and μ-opioid receptors mRNA expression, and Leu/Met-enkephalin protein expression were analyzed using immunofluorescence and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in lumbar spinal cord tissue. Further, we investigated the antinociceptive effect of BT-A following peripheral, spinal and supraspinal application. In parallel, enzymatic activity of BT-A in CNS tissue was examined using immunofluorescence.
Opioid and GABAA antagonists, applied systemically and intrathecally, dose-dependently abolished the antinociceptive effect of peripheral BT-A in all tested models, while no effect was observed following their supraspinal application. The effect of antagonists was short-lasting. BT-A reduced neuronal activation in dorsal horn, which was abolished by both, opioid and GABAA antagonist. BT-A diminished pain in, yet uninvestigated, models of visceral pain (peritonitis and colitis). BT-A’s bilateral antinociceptive action occurs after toxin’s presence on ipsilateral side only. BT-A reduced pain after peripheral and intrathecal application, but not after application in cisterna magna or cerebral ventricles, despite of its enzymatic activity in brain regions involved in nociception.
BT-A has segmental antinociceptive effect at the spinal level, which involves an indirect activation of endogenous opioid and GABA-ergic systems. These findings might guide clinical investigations of potentially useful additive or synergistic effects with conventional analgesics and direct clinical trials for novel indications and the routes of application, like intrathecal.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: University of Zagreb. Faculty of Pharmacy and Biochemistry. Department of medical biochemistry and haematology. - Data provided by Europeana Collections- U fiziološkom ...odgovoru na stres i kontroli stresnog odgovora uglavnom sudjeluju dvije komponente neuroendokrinog sustava, simpatičko-medularna (SAM) os, koja regulira prvi odgovor na stres i os hipotalamus-adenohipofiza-kora nadbubrežne žlijezde (HPAC), čija se aktivacija uočava 15 do 20 minuta nakon stresnog podražaja. Cilj ovog istraživanja bilo je ispitati bazalnu, fiziološku aktivnost SAM i HPAC osi te njihovu povezanost s nizom kovarijabli (spol, tip škole, turnus pohađanja nastave, ritam spavanja i budnosti te demografska, akademska i društvena obilježja) u zdravih učenika koji pohađaju završne razrede srednjih škola. Specifični ciljevi uključivali su ispitivanje koncentracije kortizola i aktivnosti alfa-amilaze kao salivarnih biljega odgovora na stres te istraživanje njihove povezanosti sa subjektivnim procjenama razine stresa i sa strategijama suočavanja sa stresom, kao i s polimorfizmima jednog nukleotida (SNP) gena za mineralokortikoidni i glukokortikoidni receptor (rs5522, rs6189, rs6190) te za vezni protein 5 za FK506 (rs1360780). U istraživanje su bila uključena 903 maturanta gimnazija i strukovnih škola iz četiri najveća grada u Hrvatskoj (Zagreb, Split, Rijeka i Osijek). Uzorci sline prikupljeni kod kuće, tijekom jednog radnog dana u tri vremenske točke (po buđenju, 30 do 45 minuta nakon buđenja i neposredno prije lijeganja), uzeti su za analizu koncentracija kortizola dok se aktivnost alfa-amilaze mjerila samo u jednom uzorku, neposredno po buđenju. Kako bi se ispitao cirkadijalni ritam lučenja kortizola analizirani su i indeksi lučenja kortizola (CAR, DCD, AUCG). Učenice su imale statistički značajno veće koncentracije kortizola u jutarnjim satima, dok se koncentracije kortizola neposredno prije lijeganja nisu razlikovale među spolovima. Učenice imaju različite obrasce priprema za izazove koji ih očekuju tijekom nadolazećeg dana u odnosu na učenike, imaju značajno viši CAR, izraženiji DCD, veći AUCG u odnosu na učenike koji su imali statistički značajno veću aktivnost alfa-amilaze. Turnus pohađanja nastave, koji svakako posljedično utječe na ritam spavanja i trajanje budnosti, pokazao se kao prediktor lučenja kortizola. Statistički značajne razlike većine varijabli kortizola potvrđene su između učenika koji pohađaju različite turnuse nastave (SCC30-45, CAR, DCD i AUCG). Učenici koji su se budili ranije i imali duže trajanje budnosti imali su veći CAR, niži DCD i veći AUCG. Nisu potvrđene statistički značajne razlike niti jedne ispitivane varijable u učenika koji pohađaju različite tipove škola (gimnazije vs. strukovne škole). Također, statistički značajne razlike između učenika i učenica bile su uočene i u subjektivnoj procjeni stresa, suočavanju te njihovoj povezanosti s koncentracijama i indeksima kortizola. Zabrinutost za budućnost su oba spola procijenila kao najstresniju domenu života, dok su učenice imale statistički značajno veću razinu ukupnog stresa u odnosu na učenike te su više koristile aktivno suočavanje sa stresom. U ovom su istraživanju pronađene statistički značajne razlike povezanosti alela G polimorfizma rs 5522 s višom koncentracijom kortizola po buđenju (P=0,036), nižim CAR-om (P=0,021), dok je povezanost s DCD-om bila granična (P=0,050). Može se pretpostaviti kako učenici s dokazanim alelom G imaju niži CAR te zbog toga pokazuju lošiju pripremljenost za stresne izazove u nadolazećem danu, unatoč nešto izraženijim vrijednostima DCD-a. Ovo istraživanje ukazuje na potrebu definiranja protokola prikupljanja uzoraka sline u nekliničkim uvjetima i metodoloških smjernica za populacijska istraživanja, ponajprije zbog postojanja niza kovarijabli koje utječu na mjerenje koncentracije kortizola i aktivnosti alfa-amilaze. Dobiveni rezultati doprinose saznanjima o spolnim razlikama u funkciji HPAC osi, koje bi se trebale primijeniti i tijekom provedbe preventivnih mjera u adolescenata te ranijeg otkrivanja skupina koje su posebno osjetljive na stresne poticaje.- Physiological response to stress and the control of the stress response is mediated by two major components of the neuroendocrinological systems, sympathetic nervous (SAM) system and hypothalamic-pituitary-adrenal (HPA) axis. In the stress response, the SAM axis is first activated. About fifteen to twenty minutes following the SAM activation, the HPA axis is activated. The aim of the study was to examine basal, physiologically activity of the SAM and HPAC axis activity and to determine associations of various covariates (gender, school type, school shift, sleep-wake rhythm, demographic, academic and life style characteristics) with altered daily salivary cortisol profiles in healthy students attending finishing grades of secondary schools. Specific aims of the study were to analyse concentration of cortisol and activity of alpha- amylase, as salivary markers of stress reaction, to determine association of salivary markers of stress with stress perception and coping, and to determine associations of salivary markers of stress with single nucleotide polymorphisms (SNP) in the genes for the mineralocorticoid and glucocorticoid receptors (rs5522, rs6189, rs6190) and FK506 binding protein 5 (rs1360780). The study included 903 secondary school students enrolled in the finishing classes of gymnasiums and vocational schools from the four largest cities in Croatia (Zagreb, Split, Rijeka and Osijek). The saliva samples were collected at students’ homes, over the course of one weekday. Salivary cortisol was sampled at three time points: at awakening, 30 to 45 after wakening and at bedtime. Salivary alpha-amylase was sampled at awakening. In order to analyse the circadian rhythm of salivary cortisol secretion, three indexes were analysed (CAR, DCD and AUCG).Females had higher morning concentrations of salivary cortisol than males, whereas bedtime cortisol concentrations were not different in females and males. Females had different salivary cortisol profile and different mechanisms for preparing for the anticipated stress of the upcoming day, higher CAR, steeper DCD and larger AUCG than males. On the other side, males had higher activity of salivary alpha-amylase. School shift, and therefore the sleep-wake up rhythm, was an important predictor of the secretion of salivary cortisol. There were statistically significant differences in two school shifts with respect to the majority of salivary cortisol measures (SCC30-45, CAR, DCD and AUCG). Students who woke-up earlier and were longer awake had larger CAR, flatter DCD and larger AUCG. Students from two types of schools (gymnasiums vs. vocational schools) did not differ in any of the measured salivary variables. Furthermore, female and male students differed significantly in stress perception, coping and associations between stress perception, coping and salivary cortisol concentrations and indexes. Future was rated as the most stressful problem domain in both sexes. The perception of total stress was higher in females than males, and females used more active coping than males. Finally, we found statistically significant differences in associations between G allele of rs 5522 polymorphism and higher cortisol concentration at awakening (P=0.036), lower CAR (P=0.021) and higher DCD (P=0.050), but at borderline. It can be hypothesized that the G allele is associated with the lower CAR and therefore, decreased ability of preparing for the anticipated stress (despite borderline association with the steeper DCD). This study points to the need for defining the protocol for salivary sampling in non-clinical conditions and developing methodological guidelines for population-based research, primarily due to the number of co-variables that affect the concentration of salivary cortisol and the activity of salivary alpha-amylase. Obtained results contribute to better understanding of sex differences in the functioning of the HPA axis, which should be considered in the prevention of various psychopathological conditions in adolescence and used for earlier identification of vulnerable groups at high risk of stress-related health problems.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: University of Zagreb. Faculty of Pharmacy and Biochemistry. Department of medicinal chemistry. - Data provided by Europeana Collections- U okviru ovog doktorskog rada, koji ...predstavlja nastavak istraživanja o mogućnostima derivatizacije antimalarijskog lijeka primakina (PQ) u Zavodu za farmaceutsku kemiju Farmaceutsko-biokemijskog fakulteta Sveučilišta u Zagrebu, sintetizirane su bis-uree PQ 11 te uree i semikarbazoni 12 s velikim arilnim i hidroksialkilnim supstituentima, konjugati PQ i derivata cimetne kiseline (DCK) amidnog 15 i acilsemikarbazidnog tipa 16 te ureidoamidi PQ 20. Većina derivata PQ pripremljena je koristeći benzotriazolsku metodu – klorid 1-benzotriazolkarboksilne kiseline (BtcCl) s nukleofilima daje cijeli niz vrlo reaktivnih prekursora koji su upotrijebljeni u sintezi navedenih derivata PQ. Za pripremu bis-urea 11 primijenjena su dva sintetska pristupa. U prvom pristupu produkti su „rasli” sa semikarbazidne strane, a PQ je ulazio u molekulu zadnji, dok su u drugom pristupu produkti sintetizirani iz zajedničkog prekursora semikarbazida PQ 9. Drugi pristup bio je prikladniji za pripremu cijele serije bis-urea. Derivati PQ 12 sintetizirani su iz benzotriazolida 8, 2c ili 2d i odgovarajućih amina ili izravno iz PQ i izocijanata. PQ-DCK amidi 15 i acilsemikarbazidi 16 pripremljeni su iz odgovarajućih klorida 14 i PQ ili semikarbazida PQ 9. Amidi 15d,e,g pripremljeni su dodatno aminolizom benzotriazolida DCK 13 primakinom. Derivati PQ i aminokiselina ureidoamidi 20 pripravljeni su iz PQ i odgovarajućih amida N-(1-benzotriazolkarbonil)aminokiselina 19.
Svi sintetizirani spojevi karakterizirani su uobičajenim analitičkim i spektroskopskim metodama te im je in vitro ispitano citostatsko djelovanje, kao i antioksidativno djelovanje na temelju sposobnosti redukcije 1,1-difenil-2-pikrilhidrazila (DPPH) te inhibicije lipidne peroksidacije linolne kiseline i lipooksigenaze. Najbolje citostatsko djelovanje na staničnu liniju MCF-7 adenokarcinoma dojke pokazao je spoj 16j, a slijedio ga je 11f s povoljnijim omjerom citostatske aktivnosti i citotoksičnosti. Najjaču sposobnost redukcije DPPH pokazali su spojevi 16d,g,i,j,k, najjači inhibitori lipidne peroksidacije bili su spojevi 20c i 12d, a najsnažniji inhibitor lipooksigenaze bio je spoj 16d. Iz dobivenih rezultata može se zaključiti da su bis-uree i acilsemikarbazidni derivati primakina aktivniji od urea i amida te mogu poslužiti kao vodeći spojevi u razvoju novih citostatika i antioksidansa.- This doctoral thesis describes synthesis of various primaquine (PQ) derivatives: bis-ureas 11, ureas and semicarbazones 12 with bulky aryl or hydroxyalkyl substituents, PQ-cinnamic acid conjugates (PQ-CAD) of the amide 15 and acylsemicarbazide type 16, and ureidoamides 20, as a continuation of the previous work on the derivatization of the antimalarial drug PQ developed at the Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry in Zagreb. Most PQ derivatives were prepared utilizing benzotriazole as a synthetic auxiliary – 1-benzotriazolecarboxylic acid chloride (BtcCl) reacts readily with nucleophiles affording a variety of highly reactive synthetic precursors for the synthesis of the title compounds. Two synthetic approaches for the preparation of the PQ bis-ureas 11 were applied. In the first approach, the products grew from the semicarbazide part, and PQ entered the molecule at the final stage. In the second approach, one common precursor PQ semicarbazide 9 was introduced, from which various PQ bis-ureas were prepared. Derivatives 12 were obtained in the reaction of benzotriazolide 8, 2c or 2d with corresponding amines or directly from PQ and isocyanate. PQ-CAD amides 15 and acylsemicarbazides 16 were prepared from the corresponding chlorides 14 and PQ or PQ semicarbazide 9, respectively. Additionally, amides 15d,e,g were obtained by aminolysis of CAD benzotriazolide 13 with PQ. Ureidoamide derivatives of PQ and amino acids 20 were synthesized in the reaction of PQ and corresponding N-(1-benzotriazolecarbonyl)amino acid amides 19.
Common analytical and spectroscopic methods for the characterization of the synthesized compounds were used. Their cytostatic activity, antioxidative activity by DPPH reducing ability, and inhibition of linoleic acid lipid peroxidation and lipoxygenase were evaluated in vitro. The most prominent cytostatic activity on MCF-7 breast adenocarcinoma cell line was exerted by compound 16j, followed by 11f having more favourable ratio of antiproliferative activity and cytotoxicity. Compounds 16d,g,i,j,k had the strongest DPPH reducing ability, whereas compounds 20c and 12d showed the highest inhibition of linoleic acid lipid peroxidation. The most potent lipoxigenase inhibitor was compound 16d. The obtained results indicate that PQ bis-ureas and acylsemicarbazides are more active than ureas and amides, and therefore could be considered as lead compounds in development of novel cytostatics and antioxidants.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: University of Zagreb. Faculty of Pharmacy and Biochemistry. Department of medical biochemistry and haematology. - Data provided by Europeana Collections- Oralni antikoagulans ...varfarin se već desetljećima koristi u terapiji i/ili prevenciji tromboembolijskih stanja različite
etiologije. Varfarin ima uzak terapijski raspon i pokazuje veliku interindividualnu varijabilnost u odgovoru na terapiju,
što može potencijalno rezultirati i po život opasnim komplikacijama uslijed prekomjernog antikoagulacijskog učinka i
krvarenja.
Cilj ovoga istraživanja bio je ispitati utjecaj polimorfizama VKORC1 -1639G>A, VKORC1 1173C>T, CYP2C9*2,
CYP2C9*3, CYP4F2*3 i GGCX 12970C>G te kliničkih i okolišnih čimbenika na stabilnu dozu održavanja i nuspojave
terapije varfarinom. U istraživanju su sudjelovala 204 bolesnika na terapiji varfarinom i 420 zdravih ispitanika. Rezultati
genotipizacije na zdravim ispitanicima pokazuju kako je učestalost polimorfizama VKORC1 1639G>A i VKORC1
1173>T u populaciji Hrvatske u skladu s učestalošću u europskim populacijama. Rezultati istraživanja na skupini
bolesnika na terapiji varfarinom ukazuju na statistički značajnu povezanost stabilne doze održavanja varfarina sa
sljedećim čimbenicima: genotipovima CYP2C9, VKORC1 i CYP4F2, zatim s fizičkom aktivnošću, tjelesnom
površinom, te uzimanjem lijekova koji utječu na metabolizam varfarina. Algoritam za predviđanje doze dobiven
višestrukom linearnom regresijom u stanju je objasniti 49,8 % varijabilnosti doze varfarina. Dokazana je statistički
značajna povezanost vremena potrebnog za postizanje stabilne doze varfarina s polimorfizmom CYP4F2*3 te
povezanost udjela vremena provedenog unutar terapijskog raspona i pojave nuspojava terapije varfarinom u obliku
prekomjerne antikoagulacije s polimorfizmima VKORC1 -1639G>A i/ili VKORC1 1173C>T. Isto tako, utvrđena je
statistički značajna povezanost VKORC1 -1639G>A i/ili VKORC1 1173C>T te CYP4F2*3 s nuspojavama terapije
varfarinom u obliku krvarenja.- Warfarin is the most commonly used oral anticoagulant worldwide. It is used for over a half of century for prevention
of thromboembolic disorders. Dosage of warfarin is difficult due to a very narrow therapeutic index (with lifethreatening
overdose complications) and wide interindividual variability.
Aim of this study was to investigate association of VKORC1 -1639G>A, VKORC1 1173C>T, CYP2C9*2, CYP2C9*3,
CYP4F2*3 and GGCX 12970C>G genetic polymorphisms, along with some clinical and environmental factors, on
warfarin maintenance dose and adverse effects of warfarin therapy. This study included 204 patients on warfarin therapy
and 420 healthy volunteers. Results of genotyping study on healthy population confirms that allele frequencies for
VKORC1 -1639G>A and VKORC1 1173C>T polymorphisms in Croatian population are in good agreement with other
populations of European ancestry. Results obtained on warfarin patient population indicate that warfarin maintenance
dose was significantly associated with following variables: CYP2C9, VKORC1 and CYP4F2 genotype, physical activity,
body surface area and concomitant usage of drugs that influence warfarin metabolism. Dosage prediction algorithm
obtained with multiple regression could explain 49,8 % of dose variability. Time to warfarin stable dose was significantly
associated with CYP4F2*3 genetic polymorphism. Time in therapeutic range was significantly associated with VKORC1
-1639G>A and VKORC1 1173C>T polymorphisms. VKORC1 -1639G>A and VKORC1 1173C>T polymorphisms were
also significantly associated with time to first overanticoagulation in warfarin therapy. VKORC1 -1639G>A, VKORC1
1173C>T and CYP4F2*3 polymorphisms were significantly associated with bleedings encountered during warfarin
therapy.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: - Data provided by Europeana Collections- Kardiovaskularne bolesti uzrokovane aterosklerozom predstavljaju značajan uzrok smrtnosti u hemodijaliziranih
(HD) bolesnika. ...Bolesnici koji se liječe HD imaju i do 30 puta veću stopu smrtnosti uzrokovanu kardiovaskularnim
bolestima. Rizični čimbenici uključeni u patogenezu ateroskleroze u HD bolesnika pacijenata uključuju dijabetes,
hipertenziju, dislipidemiju, pušenje, oksidativni stres, upalu te endotelnu disfunkciju. Budući da ateroskleroza ima
dugačku subkliničku fazu veoma je važno da patološki procesi budu otkriveni čim ranije, dok je bolest još u
asimptomatskoj fazi. Povećana debljina intime-medije (IMT) prepoznata je kao rani indikator subkliničke
ateroskleroze, kako u općoj populaciji tako i u HD-ih bolesnika te je povezana s tradicionalnim i novijim
kardiovaskularnim čimbenicima rizika. Nekoliko je studija dokazalo da je karotidna ateroskleroza povezana s
adhezijskim molekulama te omentin-1 proteinom. Ciljevi ovog rada bili su sljedeći: a) istražiti povezanost sICAM-1,
sVCAM-1, omentin-1 proteina te ostalih netradicionalnih rizičnih čimbenika sa subkliničkom aterosklerozom; b)
ispitati dijagnostičku vrijednost ovih specifičnih markera u otkrivanju subkliničke ateroskleroze i c) ispitati njihovu
ulogu kao prediktora smrtnosti u asimptomatskih bolesnika.
Počevši od studenog 2011. godine, kohorta od 210 HD-ih bolesnika sudjelovala je u trogodišnjem istraživanju.
Ispitanici su bili podijeljeni u tri skupine ovisno o prisutnosti ateroskleroze. Ateroskleroza je dijagnosticirana na
temelju mjerenja debljine intima-medija karotidne arterije. Uzorkovanje krvi izvršeno je na početku studije te svakih
12 mjeseci iza toga sve do kraja istraživanja. Ehokardiografska mjerenja učinjena su na početku i na kraju studije.
Dokazana je slaba korelacije između IMT i sICAM-1 (r=0,39, P=0,001), sVCAM-1 (r=0,27, P=0,015) i omentin-1
proteina (r=-0,25, P=0,020). Omentin-1 protein je pokazao dobru korelaciju s parametrima sistoličke i dijastoličke
funkcije lijeve klijetke (r=0,52, P=0,001 i r=0,51, P=0,001). Multivarijantna analiza je pokazala kako su koncentracije
sICAM-1 i omentin-1 proteina snažni neovisni pretkazatelji IMT (P=0,031 i P=0,010). Coxova analiza
proporcionalnih rizika pokazala je da su koncentracija sICAM-1 i omentin-1 proteina snažni pretkazatelji
kardiovaskularne smrti (HR=1,85, CI=1,18-2,32, P=0,021 i HR=4,14, CI=1,38-12,1, P=0,004,) te da uzastopno
mjerenje koncentracija sICAM-1 i omentin-1 proteina predstavlja jake prediktore IMT progresije (HR=1,98, 95%
CI=1,21-2,38, P<0,002 i HR=2,91, 95% CI=1,57-4,72, P<0,001).
Naša studija je pokazala kako su koncentracije ICAM-1 I omentin-1 proteina jaki pretkazatelji kardiovaskularne
smrti u asimptomatskih HD bolesnika. Porast koncentracije ICAM-1 te pad koncentracije omentin-1 proteina imaju
ključnu ulogu u ranoj progresiji ateroskleroze.- Atherosclerotic cardiovascular complications represent significant cause of mortality in hemodialysis (HD)
patients. Patients undergoing HD have up to 30 times higher incidence of cardiovascular disease mortality. Risk
factors involved in pathogenesis of atherosclerosis in patients undergoing HD include diabetes, hypertension,
dyslipidemia, smoking, oxidative stress, inflammation and endothelial dysfunction. Since atherosclerosis has a long
subclinical phase it is important that pathogenic processes are identified while disease is still asymptomatic. Increased
carotid intima-media thickness (cIMT) is well recognized as an early indicator of subclinical atherosclerosis both in
the general population and in HD patients and it is associated with traditional and emerging CV risk factors. Several
studies have shown that carotid atherosclerosis is associated with circulating concentrations of soluble adhesion
molecules (CAMs) and omentin-1 protein. The aims of this study were to: a) investigate association of sICAM-1,
sVCAM-1, omentin-1 and other non-traditional risk factors with subclinical atherosclerosis; b) examine the diagnostic
value of these specific markers in the early detection of subclinical atherosclerosis and c) examine their role as
predictors of mortality in group of patients with subclinical atherosclerosis on regular HD.
Starting from November 2011, a cohort of 210 HD patients participated in this three-year follow-up study. The
subjects were divided into three groups according to the presence of atherosclerosis. Atherosclerotic disease was
assessed by measuring carotid intima-media thickness (IMT). Samplings were withdrawn at baseline and thereafter
every 12 months until the end of follow-up. Echocardiography was performed at baseline and at the end of follow-up.
IMT showed weak correlation with sICAM-1 (r=0.39, P=0.001), sVCAM-1 (r=0.27, P=0.015), and omentin-1 (r=-
0.25, P=0.020), also omentin-1 showed good correlation with parameters of systolic and diastolic function (r=0.52,
P=0.001 and r=0.51, P=0.001). Multivariate analysis showed that sICAM-1 and sVCAM-1 concentrations were a
strong independent correlate of IMT (P=0.031 and P=0.010, respectively). The Cox proportional analysis showed that
sICAM-1 and omentin-1 concentrations were strong predictors of cardiovascular death (HR=1.85, CI=1.18-2.32,
P=0.021 and HR=4.14, CI=1.38-12.1, P=0.004, respectively) and that serial measurements of these markers predict
IMT progression (HR=1.98, 95% CI=1.21-2.38, P<0.002 and HR=2.91, 95% CI=1.57-4.72, P<0.001, respectively).
Our study demonstrated that sICAM-1 and omentin-1 levels are strong predictors of cardiovascular death in HD
patients with subclinical atherosclerosis. . We believe that an increase in sICAM-1 and decrease in omentin-1 levels
could play an important role in the early progression of atherosclerosis.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: University of Zagreb. Faculty of Pharmacy and Biochemistry. Department of medical biochemistry and haematology. - Data provided by Europeana Collections- Stresni proteini ...(HSP) pripadaju skupini unutarstaničnih proteina koji su eksprimirani konstitutivno i
kao odgovor na fizikalni odnosno biološki stres. U staničnom odgovoru na stres HSP imaju ulogu stabiliziranja
proteina i peptida čime promoviraju preživljenje stanice. Hsp27 i Hsp70 inhibitori su različitih čimbenika
apoptoze, dok je glavna uloga Hsp90 osiguravanje aktivnost čimbenika uključenih u proliferaciju stanica.
Sposobnost stresnih proteina da zaustave proces programirane stanične smrti i potaknu proliferaciiju predstavlja
bitan aspekt njihove povezanosti s malignom proliferacijom.
Glavni cilj ovog istraživanja bio je procijeniti ulogu Hsp70 u zaštiti od programirane stanične smrti u
tumorskim stanicama. U tom smislu ispitana je uloga inducibilnog oblika Hsp70 u fiziološkim i stresnim
uvjetima. Hsp70, induciran stresom, pokazao je značajnu ulogu u zaštiti tumorskih stanica od stanične smrti
izazvane staurosporinom. U svrhu utišavanja ekspresije Hsp70 pri fiziološkim uvjetima korištena je tehnologija
koja počiva na RNA interferenciji, specifičnoj razgradnji ciljne mRNA pomoću kratke siRNA uklopljene u
nanočestice. Dizajnirane su kitozanske nanočestice za dostavu Hsp70 sljedno-specifične siRNA. U uvjetima in
vitro kitozanske nanočestice pokazale su nisku toksičnost, učinkovito uklapanje Hsp70 siRNA te učinkovito
utišavanje Hsp70. U staničnim linijama Jurkat i U251N utišavanje Hsp70 omogućeno pomoću Hsp70 siRNA
uklopljene u kitozanske nanočestice, prouzročilo je smanjenje vijabilnosti ovih tumorskih staničnih linija.
U radu je ispitana i antitumorska učinkovitost istovremene inhibicije Hsp90, pomoću celastrola, i
Hsp70 pomoću kitozanskih nanočestica s uklopljenom Hsp70 siRNA. Učinkovitost ovog pristup bila je značajna
u dvodimenzionalnim modelima tumorskih staničnih linija, dok su u trodimenzionalnim modelima bile potrebne
povećane koncentracije oba spoja/sustava kako bi se postiglo značajno smanjenje vijabilnosti tumorskih stanica.
Rad predstavlja temelje za daljnja istraživanja optimalnih nanosustava za dostavu sljedno-specifičnih
siRNA za HSP te moguća ispitivanja istovremene inhibicije Hsp70 i Hsp90 u tumorskim modelima in vivo.- Stress proteins (HSP) are intracellular proteins expressed constitutively but can also be induced by
various types of stress including environmental changes and non-stress conditions such as cell cycle, growth
factors, development and differentiation. Under physiological conditions these proteins function as molecular
chaperones that enable the function of different proteins. Hsp27 and Hsp70 appear to function at key regulatory
control points in apoptotic process, whereas the major role of Hsp90 is protection from degradation for the major
factors responsible for cell proliferation. The promotion of tumor cell survival is closely related to the ability of
Hsp to inhibit programmed cell death during malignant proliferation.
The purpose and the main goal of the proposed study was to explore Hsp70's role in protection against
programmed cell death in tumor cells. The role of stress induced Hsp70 and the role of Hsp70 within
physiological levels was explored. Stress induced Hsp70 was found to efficiently protect tumor cells against cell
death promoted with staurosporin. Hsp70 silencing was accomplished using the technology based on RNA
interference, specific degradation of mRNA after binding with siRNA delivered into the cells with nanoparticles.
Chitosan based nanoparticles for Hsp70 siRNA delivery were prepared. These showed low toxicity, efficient
siRNA entrapment and efficient Hsp70 silencing. In Jurkat and U251N cell lines Hsp70 silencing with Hsp70
siRNA delivered in chitosan nanoparticles significantly decreased cell viability.
The antitumor efficiency of simultaneous inhibition of Hsp90 with celastrol and Hsp70 with chitosan
nanoparticles entrapping Hsp70 siRNA was also explored. Significant reduction in cell viability was observed in
two-dimensional cell cultures, while for the induction of comparable effect in three-dimensional cell cultures,
U251N spheroids, higher concentration of both celastrol and Hsp70 siRNA were necessary.
The results of this work present important findings that could lead into the development of optimal
delivery systems for siRNA and possible in vivo research of Hsp70/Hsp90 inhibition approach.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: - Data provided by Europeana Collections- Hrana je glavni izvor izloženosti ljudi esencijalnim i toksičnim metalima, uključujući kadmij (Cd). Cilj istraživanja je bio ...procijeniti učinke peroralne izloženosti Cd tijekom skotnosti štakorice na razdiobu kadmija i stanje mikronutrijenata u majčinom organizmu i fetusu te funkcije posteljice u prijenosu nutrijenata i sintezi steroidnih hormona. Hipoteze istraživanja su bile da se tijekom graviditeta povećava želučanocrijevna apsorpcija Cd koji se nakuplja u posteljici i može poremetiti prijenos nutrijenata do fetusa i sintezu posteljičnih hormona. Pokusne štakorice (Wistar) su nakon parenja izlagane dozi od 50 mg Cd/l (u obliku CdCl2xH2O) u vodi za piće od 1. do 19. ili 20. dana skotnosti. Neskotne štakorice su istodobno izlagane pod jednakim uvjetima izloženosti tijekom 20 dana. Posljednjeg dana pokusa je svim štakoricama u općoj anesteziji izvađena krv iz srca i uzorkovani unutrašnji organi, posteljice i fetusi, koji su pripremljeni za analize mikroelemenata (metodom AAS). Progesteron i testosteron su analizirani imunokemijski izravno u serumu (metodom IEMA) i u uzorcima pripremljenim iz posteljičnog tkiva (metodama IEMA i/ili ELISA). U svih izloženih štakorica su nađena povećanja Cd u svim izmjerenim uzorcima i cinka u jetri. Količine željeza u fetusu i cinka u fetusu i/ili posteljici su bile smanjene. U izloženih skotnih vs. izložene neskotne štakorice su bila izraženija povećanja koncentracije Cd u krvi i količina Cd u jetri i bubregu kao i smanjenja količina željeza u jetri i bubregu te cinka i bakra u bubregu. U svih skotnih vs. neskotne štakorice su bile veće koncentracije Cd u krvi i količine bakra u bubregu te manje količine željeza u jetri i bubregu i bakra u jetri. Nije bilo promjena u steroidnim hormonima ni u serumu, ni u posteljici, u kojoj su vrijednosti svakog hormona izmjerene dvjema imunokemijskim metodama značajno korelirale. U zaključku, ovim radom su dobiveni izvorni podaci o vrijednostima progesterona i testosterona (kao prekusora za sintezu estradiola u jajniku) u serumu i posteljici štakorice blizu roka okoćenja. Novi i izvorni znanstveni rezultati su da peroralna izloženost štakorica dozi od 6,5 mg Cd/kg tjelesne mase otopinom za napajanje tijekom skotnosti povećava razine Cd u krvi, jetri i bubregu s posljedičnim biokemijskim promjenama mikronutrijenata u većoj mjeri nego u neskotnih štakorica što istodobno s nakupljanjem Cd u posteljici remeti transplacentarni prijenos željeza i cinka te može predstavljati opasnost za rast i razvoj fetusa in utero.- Food is the main source of human exposure to essential and toxic metals, including cadmium (Cd). This investigation aimed to assess the effects of oral Cd exposure during rat pregnancy on Cd distribution and micronutrient status in a maternal organism and foetus and placental functions in nutrient transport and steroid hormone synthesis. Research hypotheses were that Cd gastrointestinal absorption increases during pregnancy and Cd accumulates in the placenta where it may interfere with nutrient transport to the foetus and placental hormone biosynthesis. Female rats (Wistar) were mated and exposed to 50 mg Cd/l (as CdCl2xH2O) in drinking water from gestation day 1 through 19 or 20. Non-pregnant rats were concurrently exposed during 20 days under the same exposure conditions. On the last experimental day, under general anaesthesia, blood was taken by cardiac puncture from all of the rats and internal organs, placentas and foetuses were dissected and prepared for element analysis (by AAS). Progesterone and testosterone were assayed by immunochemical methods directly in sera (by IEMA) and in placental tissue-derived samples (by IEMA and/or ELISA). All of the exposed rats exhibited increases in Cd in all of the analysed samples and zinc in the liver. Contents of iron in the foetus and zinc in the foetus and/or placenta were decreased. In exposed pregnant vs. exposed non-pregnant rats, more pronounced increases in Cd concentration in the blood and Cd contents in the liver and kidney, decreases in iron contents in the liver and kidney, and decreases in zinc and copper contents in the kidney were recorded. In all pregnant vs. non-pregnant rats, higher Cd concentrations in the blood and copper content in the kidney and lower iron contents in the liver and kidney and copper content in the liver were found. Steroid hormones did not change in either the serum or placenta; in the latter the values of either hormone measured by two immunochemical assays were correlated. In conclusion, this work provides original evidence on progesterone and testosterone (as the precursor for the ovarian oestradiol synthesis) in rat serum and placenta at term. New and original research results are that oral Cd exposure to 6.5 mg Cd/kg body mass in drink during rat pregnancy increases levels of Cd in the blood, liver and kidney with consequent biochemical changes of micronutrients more pronouncedly than in non-pregnant rats, which together with accumulation of Cd in the placenta disrupts the transplacental handover of iron and zinc and may put at risk foetal growth and development in utero.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: - Data provided by Europeana Collections- Problemi u funkciji hoda u pacijenata nakon moždanog udara svode se na problem balansa, na smanjenje brzine hoda, smanjenje dužine i ...ciklusa koraka te oblik asimetričnog uzorka što smanjuje njihovu sposobnost u obavljanju svakodnevnih aktivnosti, a time i njihovo zadovoljstvo samom kvalitetom života.
Cilj istraživanja bio je utvrditi učinkovitost neurofacilitacijskog programa prema Bobath konceptu, kao i kombiniranog tretmana neurofacilitacijske terapije sa dodatnim tretmanom specifičnih mobilizacija na balans i funkciju hoda, te razliku u učinkovitosti provedenih programa.
Ispitanici su raspoređeni u dvije ispitivane skupine po 20 ispitanika. Prva skupina ispitanika bila je u programu neurofacilitacijske terapije kroz pet tjedana, dok je druga skupina ispitanika bila uključena u isti program s dodatnim tretmanom specifičnih mobilizacija mekih tkiva. Razlike kod ispitanika u pojedinim varijablama unutar grupa i između grupa ispitanika u inicijalnom i finalnom mjerenju obrađene su univarijantnom analizom varijance - ANOVA. Uspoređeni su rezultati učinaka dvaju programa neurofacilitacijskog tretmana sa i bez specifičnih mobilizacija mekih tkiva testovima „Berg balance scale“, „Timed up and go testa“ i aktivnog pokreta dorzalne fleksije stopala, fleksije i ekstenzije koljena.
Istraživanje je pokazalo da je u prvoj skupini ispitanika koja je imala neurofacilitacijski tretman u 83,4% varijabli statistički značajnih rezultata u finalnom mjerenju na razini od p<0.05. U drugoj skupini ispitanika tretman neurofacilitacijske terapije kombiniran s tretmanom specifičnih mobilizacija mekih tkiva, pokazao se ključnim za poboljšanje aktivnosti u pokretima stopala i koljena što je značajno doprinijelo učinkovitosti onih varijabli koje u prvoj skupini nisu bile značajne, a to su hod, ustajanje, sjedanje, pa je tako učinkovitost bila značajna gotovo u svim varijablama statičkog i dinamičkog balansa.
Rezultati dobiveni ovim istraživanjem pokazali su značajan doprinos kombiniranog tretmana na sve varijable balansa, funkciju hoda kao i na povećanje fleksibilnosti mišića i tetiva koji su važni za funkciju koljena i skočnog zgloba, a time i na funkciju hoda.- Introduction: Problems in the function of the stroke patient gait are balance problems, slower walking speed, reducing the step length and the gait cycle, and the asymmetrical gait pattern. They all reduce the patient’s ability to perform everyday activities and result in the patient’s dissatisfaction with the quality of their life. Finding new programmes to improve the quality of the previously used rehabilitation procedures is imperative for members of the team included in movement and gait re-education of stroke patients.
Subjects and methods: The aim of this study is to determine the effectiveness of the neurofacilitaton programme according to the Bobath concept, and a combined treatment consisting of the neurofacilitation therapy and an additional treatment with specific mobilization to improve balance and gait, as well as determining the difference in the effectiveness of the implemented programmes.
40 subjects, successfully tested initially, at least 3 months after suffering a stroke, and after a one-year period, were diagnosed by magnetic resonance imaging. They were suffering from hemiparesis, classified as level 3 according to the Medical Research Council paresis classification. The subjects were randomly divided into two groups consisting of 20 patients. The first experimental group was in the programme of neurofacilitation therapy for 5 weeks, undergoing 45-minute sessions 5 times a week, while the second group was included in the same programme with an additional specific mobilization programme with 20-minute sessions 3 times a week, during 5 weeks. The STATISTICA for Windows ver. 10 StatSoft Inc. statistical software packet was used for data processing. Differences between the respondents in individual variables within groups and between groups in both initial and final measurements were processed by ANOVA, the univariate analysis of variance.
Results: Effects of the two neurofacilitation treatment programmes, with and without specific mobilization of soft tissues, were compared by the Berg Balance Scale, the Timed Up and Go Test and active dorsiflexion of the foot, flexion and extension of the knee. The study showed statistically significant results in the final measurement in 83.4% of variables at the level of p<0.05 in the tested group of patients who only had a neurofacilitation treatment. The variables which did not show significant results were complex activities, such as getting up, walking, rotation, and sitting down, which clearly required additional treatment. The neurofacilitation therapy combined with the specific mobilization of soft tissues, which the second tested group of patients underwent, greatly contributed to the improvement of foot and knee movements resulting in better walking, standing up and sitting down activities, as well as other variables of static and dynamic balance. Results also suggested that there are no statistically significant differences between the two tested groups in the final measurement of the given variables. However, the additional statistical analysis which took into account the period between the initial and final measurements demonstrated a statistical significance and a high tendency to significance in almost 61% of variables indicating the benefit of the combined therapy programme.
Conclusion: Results obtained in this study showed a significant contribution of the combined treatment to all the variables of the static and dynamic balance and gait function, as well as an increase in the muscle and tendon flexibility which is important for knee and ankle functions, thus influencing the gait function, too.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Analize često otkriju neujednačenost sastava tableta ecstasyja od čistoga 3,4-metilendioksimetamfetamina (MDMA) do mješavina njegovih derivata, amfetamina i drugih neutvrđenih tvari. Stoga je za ...kvalitetnu toksikološku analizu potreban uvid u sve korake sinteze MDMA, s obzirom na to da se ondje vjerojatno kriju izvori nečistoće (prekursori, katalizatori). Cilj ovog ispitivanja bio je sintetizirati derivate MDMA te napraviti njihovu kemijsko-fi zikalnu i biološku in vitro karakterizaciju. 3,4-metilendioksifenil-2-nitropropen (MDNP) dobiven je kondenzacijom piperonala u suvišku nitroetana uz
dodatak amonijeva acetata. Njegovom redukcijom s pomoću LiAlH3 dobiven je 3,4-metilendioksiamfetamin
(MDA). Svi spojevi iz pojedinih koraka sinteze karakterizirani su s pomoću tekućinske kromatografi je visoke djelotvornosti (HPLC) i spektroskopskih tehnika Ramanove spektroskopije, nuklearne magnetske rezonancije (NMR-a) te infracrvene spektroskopije (IR-a). Usto je ocijenjen i njihov biološki učinak in vitro mjerenjem (i) koefi cijenta raspodjele krvna stanica/puna krv, (ii) vezanja za bjelančevine u plazmi (Fbp) te (iii) adsorpcije na membranu. Kemijska je struktura utvrđena s pomoću fl uorescentnoga polarizacijskog imunokemijskog testa (FPIA). Analiza je u konačnim proizvodima utvrdila prisutnost krutih nečistoća, napose spojeva neurotoksičnog aluminija (Al3+). FPIA je prepoznao aminoetansku skupinu blizu supstituiranoga benzenskog prstena, ali ne i dva glavna prekursora za MDMA: MDNP i piperonal. Posebno je zanimljiva Ramanova spektroskopija budući da (i) pruža privlačnu alternativu za karakterizaciju sastava tableta ecstasyja te (ii) može otkriti stereoizomerne cis/trans-oblike spoja poput cis-MDNP-a odnosno
trans-MDNP-a, čiji se signal vidi na 1650 cm-1 odnosno 1300 cm-1.
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