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Since vascular calcification is considered process regulated similar as bone tissue mineralization, we investigated the participation of bone formation proteins. We analyzed correlation of serum circulating bone markers, osteoprotegerin (OPG) and receptor activator of nuclear factor ĸB ligand (RANKL) in chronic kidney disease (CKD) patients, to coronary artery calcification score. Aside of that we consifrtrf thr effect of inorganic phosphate on pro- and anti- calcifying tissue factors. We confirmed that circulating OPG is independent calcium score predictor with its high serum concentration speaking in favor of high coronary artery calcification. In tissue samples of non-diseased human renal arteries, the expression of OPG and receptor activator of nuclear factor ĸB (RANK) was positive, while expression of RANKL was absent. In atherosclerotic specimens and arteries with medial calcification most upregulated was expression of bone morphogenetic proteins, BMP- 2 and BMP-7, as well as expression of RANK and RANKL. In the diseased arteries OPG expression was present, only in areas where bone structures were formed. In atherosclerotic and medial calcification arteries loss of alpha- smooth muscle actin (α-SMA) expression was observed. These data suggest a possible regulatory role of examined proteins, especially OPG and RANKL in vascular calcification, as well as their possible clinical significance as circulating predictors of vascular calcification.

0 Spinal cord ischemia-reperfusion injury (IRI) results in overproduction of reactive oxygen species leading to tissue oxidative stress which impacts the neuronal network in the spinal cord as well as glial cells. We investigated the expression of Nuclear factor erythroid 2-related factor 2 (Nrf2) in neurons and glial cells after occlusion of the abdominal aorta followed by IRI as well as the time-dependent expression of Nrf2 in the same cells. The experimental method of transient aortic occlusion was carried out on rats by cross-clamping of the abdominal aorta for 45 minutes. The animals used for this study were sacrificed 1 h, 6 h, and 48 h after reperfusion to determine time-related changes of Nrf2 expression, as well as changes of astrocyte activity in the spinal cord. Immunofluorescence results showed an increase in the staining intensity of Nrf2 expression in the neurons following ischemia with highest intensity 48 h post-reperfusion and an increase in a number of reactive astrocytes. Western blot analysis showed that Nrf2 protein expression increased in a cytoplasmic and nuclear fraction as early as 1 h after reperfusion and remained active 48 h after, resulting in increased expression of the main Nrf2 target gene HO-1. In conclusion, substances that enhance expression of Nrf2 may have the potential to prevent cellular damage to the spinal cord caused by IRI.

Dietary intake has been shown to affect bone health via both proinflammatory and anti- inflammatory mechanisms. Some dietary constituents such as zinc, magnesium and calcium have anti-inflammatory effect and are beneficial for the bone physiology. The aim was to analyze bone mineral density (BMD), bone remodeling markers, serum vitamin D values and overall intake of the dietary minerals (calcium, magnesium, zinc and sodium) with respect to the dietary inflammatory index (DII) score. Women (N = 400) included in this study were divided in subgroups according to the adherence to DII score. Q1 indicated participants having the lowest DII values and highest adherence to anti-inflammatory diet, while Q4 were participants having pro- inflammatory diet. Kruskal–Wallis test was used to analyze the adherence of the bone status parameters to the DII score as well as the adherence of dietary minerals to DII score. Multiple regression analyses was employed to test the relationship between BMD and bone remodeling markers with the DII score and age. P\0.05 was considered as statistically significant. Our results revealed that women whose dietary habits were more in anti- inflammatory quartiles, had significantly higher values of the lumbar spine BMD (P = 0.01), left hip BMD (P\0.01) and bone alkaline phosphatase (P\0.01). They also had significantly higher intakes of dietary calcium, magnesium and zinc, P\0.01, respectively. Multiple regression analyses revealed that age and DII were significantly and inversely correlated to left hip BMD, while deoxypyridinoline was just proportional to age and DII, P\0.01, respectively. Study results suggest that anti-inflammatory diet is associated with high BMD and younger age.

Shock wave therapy has found its place in the medical treatment of various diseases of the locomotor system such as acute fracture, nonunion, chronic tendinitis and pseudarthrosis. Focused shock-wave enables maximum energy in the therapeutic zone, and depth of penetration can be adjusted. Radial shock wave therapy primarily affects superficial tissues, so its application in medicine is doubtful. Our study aimed to compare long bone fracture healing in regard to soft tissues, comparing the shock-wave group with controls. For this investigation, 84 female Wistar rats were divided into the focused shock- wave group (n=36), radial shock wave group (n=36) and controls (n=12). Conclusively, long bone fracture repair is enhanced in the shock- wave group. Comparison between focused shock- wave and radial shock-wave suggested that this latter strongly stimulated the processes of the healing, as 75% of vascular spaces were VEGF-A positive on the 5th day of bone healing, and 85% on the 22nd day of healing.

Nowadays, various diseases of the locomotor system are treated by extracorporeal shock wave therapy (ESWT) for instance: acute fracture and pseudoarthrosis, nonunion, chronic tendinitis. Unfocused (radial) pressure wave therapy (RPWT) primarily affects superficial tissues, so justifiability of its medicinal employment is uncertain. We aimed to observe time sequence of the long bone fracture healing using RPWT. In this vein, 48 female Wistar rats were divided in RPWT group (n=36) and controls (n=12). ESWT group had the largest cross-sectional area (CSA) of the bone trabeculae compared to controls. Post-hoc analyses revealed the largest cross- sectional area (CSA) of the bone trabeculae (1.7 mm2) and the smallest CSA of the cartilage (0.04 mm2) at 22nd day, of the RPWT group. Conclusively, long bone fracture repair is enhanced in RPWT suggesting that it strongly stimulates processes of the callus ossification.

Bone morphogenetic proteins (BMPs) are a group of growth factors primarily isolated from bone according to their osteoinductive ability. The pleotropic nature of BMPs leads them to being called the body morphogenetic proteins. BMPs are included in various processes like cellular migration, proliferation and differentiation and as TGFbeta family members in epithelial- mesenchymal transition. In that way BMPs influence many physiological and pathological conditions. The aim of this study was to investigate the expression of BMPs in colorectal cancer (CRC) samples of patients who underwent the CRC surgery. The expression of BMPs was examined in frequently diagnosed stages of CRC (Dukes’B and Dukes’C stage) by RT-qPCR . Furthermore or also, we have analyzed BMP7 expression in CRC samples by immunohistochemistry using a polyclonal anti- BMP7 antibody. The clinicopathologic data such as age, gender, Dukes’ staging and differentiation grade are also analyzed. Our results showed that colorectal cancer occurred most frequently in men (75%) and in elderly people (more than 60 years ; 85%). The most common site of primary carcinoma was sigmoid colon and rectum (75%) and moderately differentiated (55%). In both stages of CRC, we found the downregulation of BMP4 and BMP7 expression in comparison to the normal colon samples which is significantly higher in Dukes’B stage for BMP4 and in Dukes’C stage for BMP7. The expression of BMP6 was slightly upregulated and showed no statistically significant difference in these stages of CRC. BMP7 expression determined by immunohistochemistry decreased also progressively by higher tumor stage. These results suggest that BMPs beside their importance in bone metabolism have a prominent role in the carcenogenesis and the alterations of their expression could be associated with cancer aggressiveness and progression.

INTRODUCTION: Postmenopausal osteoporosis is a common, debilitating disease. The lifetime risk of a hip fracture in women is greater than the combined lifetime risks of breasts, endometrial and ovarian cancers. Postmenopausal osteoporosis is also likely to become more common in the decades ahead as the life expectancy of the population increases. Early menopause, occurring either naturally, or because of surgery, increases the risk of the development of osteoporosis. In addition, various lifestyle factors are known to increase the risk of osteoporosis, including a life-long low calcium intake, smoking, over-use of alcohol, and the lack of exercise or chronic immobility. Osteoporosis that develops secondary to other pathologies, or to medications is considered to be postmenopausal in origin, although its severity is likely to increase after the menopause if appropriate measures are not taken. AIM: The aim was to compare handgrip strength, measured by hydraulic dynamometer in the same women, at two different intervals: at the beginning of exercise program and after six months of active exercise program. We also explored weather age and anthropometric parameters significantly predict the handgrip strength, prior to exercise and after six months of exercise. PATIENTS AND METHODS: The research included women with diagnosed osteoporosis or osteopenia, mostly postmenopausal women (N=100). Examinees are active participants of the project „Exercising and proper nutrition in fight against osteoporosis”. Anthropometric parameters were measured twice: at the time when women were just enrolled in project and after six months of exercise. Handgrip strength was measured by hydraulic dynamometer, at the same two intervals as the measures for anthropometric parameters were done. RESULTS: We found that handgrip strength of the right hand was significantly higher in women, after six months of exercise, than it was prior to exercise (P=0.002). Hip circumference after six months of exercise(R=0.37, P=0.001) and body height at the beginning of exercise (R=0.34, P=0.005) were directly correlated to the handgrip strength of the right hand, while waist circumference at the beginning of exercise was indirectly proportional to the handgrip strength of the right hand (R=-0.25, P=0.04). The similar was observed when the handgrip strength of the left hand was analyzed, except for the variable hip circumference at the beginning of the exercise, which was inversely correlated to the handgrip strength of the left hand, after six months of exercise (R=-0.35, P=0.004). CONCLUSION: Regular physical exercise is thought to reduce the risk of osteoporosis and delay the physiologic decrease of bone mineral density (BMD), which occurs with aging. With this investigation we have found that time period of six months of exercise significantly increases handgrip strength at the right hand, which suggests good muscle adoption to exercise, which is an important prerequisite for maintaining existing bone mass of our study participants.

OPG – early marker for ckd-mbd diagnosis?

Bone status in correlation to BMP-9, IL-6 and adiponectin in diabetes mellitus type

Introduction. Anatomical variations of neurovascular structures of the upper limb are not uncommon. Ulnar and radial arteries terminate in palm usually forming complete superficial palmar arch. However, variations of incomplete superficial palmar arch are less frequent. Musculocutaneous nerve arises from the lateral chord of brachial plexus and passes through coracobrachialis, travels between biceps and brachialis and continues as the lateral cutaneous nerve of the forearm. Rarely, it adheres for some distance to the median nerve and passes behind biceps. Median nerve arises with two roots from the lateral and medial chord of brachial plexus, enters the arm lateral to the brachial artery and crosses in front of the artery descending to cubital fossa medial to the artery. Rarely, median nerve crosses brachial artery from behind. Material and methods. During dissection of the female specimen we found multiple neurovascular variations in the single upper limb. Results. In our specimen, we found formation of incomplete superficial palmar arch. Superficial palmar branch of radial artery didn’t anastomose with ulnar artery. Instead, it gave one common palmar digital artery (later divided into two proper palmar digital arteries for contiguous sides of index and middle fingers) and one proper palmar digital artery for lateral side of index finger. Ulnar artery gave remaining two common palmar digital arteries. The palmar digital artery for the medial side of the little finger arised from third common palmar digital artery. Musculocutaneous nerve adhered median nerve and didn’t pass through coracobrachialis. Median nerve after entering the arm lateral to the brachial artery crossed artery from behind. Conclusion. Although, anatomical variations of vessels and nerves of the upper limb are quite common, multiple neurovascular variations in the single upper limb are, probably, less frequent. However, as seen from our case, they do coexist and that should be taken into consideration during various diagnostic, surgical or other medical procedures.

Introduction. Synovial plicae in the knee joint are remnants of embryonal mesenchymal tissue which fills the space between the femur and tibia during embryonic joint development. Formation of the joint cavity begins approximately at 8th week of embryonic development as a result of programmed resorption of the mesenchymal tissue. Mesenchymal resorption starts with a smaller cavities in the the joint space and spreads to the remaining mesenchymal tissue. Once the mesenchymal tissue is completely resorbed, the knee joint cavity is formed as a single space. According to some authors pathological condition secondary to inflammation can affect the joint. There are 4 types of knee synovial plicae: infrapatellar, mediopatellar, suprapatellar and lateral (prevalence not well known, range is approximately 1 to 2%). Aim. Our aim was to present three adolescent patients, each with unusually formed residual plicae in the suprapatelo-lateral space of the knee, which were discovered by therapeutic arthroscopy treatment of recurrent luxation of the patella. Materials and Methods. Unusual intraarticular structures, which resembled to ligament, were found in three children aged from 12 to 14 yrs. Synovial plicae stretched from the medial suprapatellar to the lateral part of the articular capsule. During knee flexion the synovial plicae pulled the patella laterally and caused the obvious luxation of the patella. After these unusual structures were removed surgically, tissue samples were obtained and treated by antibodies against collagen type I and collagen type III. Results. Longitudinal histological slices were stained by HE, and on each slice central and peripheral zones were recognized. The central zone consisted of collagen fibers which were linearly arranged, with few fibroblasts between them. The blood vessels were very rare. Peripheral zone of the tissue sample is synovial sheet with a continuous layer of stratified lining epithelial cells on the surface. Beneath epithelial cells, connective tissue matrix contains blood vessels. Here, in the peripheral zone, collagen fibers were not parallel and we did not find any morphological signs of the inflammation. Immunohistochemical analyses revealed numerous type III collagen fibers, localized in the blood vessel's wall and in adjacent stroma around them. Except for those, type III collagen fibers were also located beneath epithelial layer. Only few immunopositive type I collagen fibers were detected, with overall prevalence of the type III collagen fibers. Conclusion. From above received histological findings we have presumed examined structure is probably the plica, which is relatively common occurrence and could be associated with inflammation and some other pathological conditions in orthopedics. Until now such shapes of the plicae which resembled to the ligament were not described in available literature. During adolescence lateral synovial plicae may cause lateral luxation of the patella, especially in athletes.

Kraniovertebralni venski sustav čine kranijalne i kralježnične vene. Ove vene su međusobno povezane i nemaju zalistaka, što omogućava tok krvi u oba smjera. Kranijalnim venama pripadaju vene mozga, sinus tvrde moždane ovojnice, diploične i emisarne vene, dok kralježničnim venama pripada vanjski i unutarnji vertebralni splet te bazivertebralne vene. Iz kraniovertebralnog venskog sustava krv odvode vv. vertebrales, vv. intercostales postt., vv. lumbales i v. sacralis lat. u sustave gornje i donje šuplje vene izravno ili putem sustava vene azigos. Kraniovertebralni venski sustav s ostalim sustavima tvori brojne anastomoze koje u patološkim uvjetima predstavljaju kolateralni put krvi ka srcu i omogućuju izravno širenje neoplazmi iz prsne, trbušne i zdjelične šupljine u područje kranijuma i kralježnice. Osim toga, značajna je uloga kranijalnih vena i vena gornjih dijelova dišnog sustava u selektivnom rashlađivanju mozga, što je osobito značajno u hipertermiji., The craniovertebral venous system consists of cranial veins and veins of vertebral column. These veins are interconnected with no valves, allowing blood to flow freely in both directions. The veins of brain, dural venous sinuses, diploic veins and emissary veins belong to cranial veins. The veins of vertebral column consist of external and internal vertebral venous plexus and of basivertebral veins. The vertebral veins, posterior intercostals veins, lumbar veins and lateral sacral veins drain blood directly from craniovertebral venous system in azigos vein or in superior and inferior vena cava. The craniovertebral venous system with other venous systems are forming numerous anastomosis, which in pathological conditions represent a collateral pathway for blood to the heart and allow the direct spread of neoplasms of the thoracic, abdominal and pelvic cavity in the area of the cranium and spine. In addition, the significance of cranial veins and veins of the upper part of the respiratory system are part of the selective brain cooling mechanism which is particulary important in condition of hyperthermia.

Koštani sustav kralježnjaka vrši dvije glavne uloge: prva je biomehanička uloga koja uključuje podupiranje tijela i zaštitu unutarnjih organa i struktura te inzerciju mišićima u svrhu izvođenja pokreta, a druga uloga je metabolička koja uključuje održavanje mineralne homeostaze organizma. Zato, iako su smatrane „mrtvim” inertnim strukturama, kao što to studenti tijekom svog studija medicine doživljavaju, kosti su metabolički iznimno aktivni organi podvrgnuti kontinuiranim cjeloživotnim promjenama. Tijekom rasta i razvoja kosti se formiraju procesom oblikovanja (engl. bone modeling), što uključuje izgradnju i odlaganje koštanog matriksa na razvojno određenim i biomehanički induciranim mjestima skeleta. Čak i prije negoli se skelet u potpunosti razvije, kosti se počinju kontinuirano pregrađivati (engl. bone remodeling) u svrhu održavanja tkivnog integriteta i biomehaničke funkcije, prilagodbe koštane arhitekture prema mehaničkim zahtjevima i zbog popravaka mikrooštećenja, te ako je potrebno mobilizirati kalcij i fosfor. Proces pregradnje uključuje niz precizno reguliranih i tijesno spregnutih staničnih i molekularnih procesa koje omogućuje koordinirana aktivnost osteocita, osteoblasta i osteoklasta. Ova tri različita tipa stanica koštanog tkiva organizirana su u specifičnu morfološku i funkcionalnu višestaničnu jedinicu (engl. basic multicellular unit) koja obavlja i koordinira dva temeljna procesa u biologiji kosti: razgradnju i izgradnju kosti tijekom ciklusa nazvanog ciklus koštane pregradnje. Ovaj ciklus počinje fazom aktivacije koja uključuje mehanosenzaciju i mehanotransdukciju osteocita ili staničnim odgovorom na sistemski humoralni faktor kao što je paratireoidni hormon. Ovi startni signali potiču stvaranje specifične strukture nad koštanom površinom koju treba pregraditi i nazivamo je odjeljak koštane pregradnje (engl. bone remodeling compartment). Nadalje ovi startni signali aktiviraju osteoklastne prekursore na proliferaciju, diferencijaciju, pričvršćivanje i razgradnju određene koštane površine u sljedećoj fazi resorpcije. Nakon što se razgradi određena količina koštanog matriksa, počinje faza obrata koja uključuje oslobađanje brojnih, još uvijek nedovoljno poznatih činitelja koji povezuju razgradnju i osteoblastnu izgradnju s mineralizacijom kosti u sljedećoj fazi. Kada se stvori ista količina kosti koja se razgradila, slijedi završna faza ciklusa u kojoj se ciklus koštane pregradnje zaustavlja, a koštana površina ulazi u mirnu fazu., The bones of the vertebrate skeleton serve two main functions: the first is biomechanical function which includes support and protection of internal organs and structures, so as providing a muscle attachment for the locomotion and the second is essential metabolic function which includes mineral homeostasis maintaining. In spite skeleton is being presented as “dead”, inert structure, as often medical students learn in anatomy, it is metabolically, extremely active organ and undergoes continuous lifelong changes. Bones are initially formed by modeling processes, which include the production and deposition of bone tissue at developmental and biomechanical sites of the skeleton. Before being fully formed, bones undergo remodeling process which continues throughout life, in order to preserve the structural integrity and biomechanical function, to adjust bone architecture according to mechanical demands, to repair microdamages, and if it is needed, to mobilize stored calcium and phosphorus. The remodeling process involves a series of highly regulated and tightly coupled cellular and molecular processes, performed by coordinated activity of osteocytes, osteoblasts and osteoclasts. These different bone cells are organized into specific morphological and functional bone multicellular units which perform and coordinate two basic bone biology processes: bone resorption and bone formation, throughout a cycle of events called bone remodeling. The bone remodeling cycle starts with phase of activation, which includes mechanosensation and mechanotransduction of the osteocytes, or with cellular response to systemic humoral factors such as PTH. These are start signals which induce a formation of a specific canopy structure over the bone surfaces which need to be remodeled, called the remodeling compartment. Furthermore, these signals will activate osteoclastic precursor to proliferate, differentiate, attach and to resorb bone surface in the following resorption phase. After the certain quantity of bone was removed, the reversal phase occurres, which involves releasing of numerous, yet unknown factors that couple bone resorption and upcoming bone formation and mineralization, which are done by osteoblasts in the formation phase. After the same quantity of new bone was formed, the termination phase proceeds in which the cycle ends and bone surfaces become quiescent or “at rest”.

Građa i oblik cirkulacijskog sustava među životinjskim vrstama bitno se razlikuju, napose u pojedinim poredbeno anatomskim aspektima, čak do neprepoznatljivost. Budući da cirkulacijski sustav osigurava funkcionalnu i morfološku povezanost svih dijelova organizma, njegova konstrukcija bitno ovisi o obliku organizma i njegovim biološkim osobitostima. U ovome radu, u obliku diskusije, izneseni su neki komparativno-anatomski aspekti temeljnih načela cirkulacijskog sustava u kralježnjaka., Structure and shape of the circulatory system differ substantially among animal species, and particularly in some aspects of comparative anatomy they are unrecognizable. Since the circulatory system ensures the functional and morphological integrity of all parts of the organism, its structure depends essentially on the shape of the organism and its biological properties. This paper, in the form of a discussion, presents some aspects of comparative anatomy related to the basic principles of the vertebrate circulatory system.

Skeletni mišić odraslog organizma je dinamično tkivo koje ima iznimnu sposobnost regeneracije nakon ozljede. Radi se o sinkroniziranim procesima koji uključuju aktivaciju populacije mišićnih prekursora koje nazivamo satelitskim stanicama. Nakon povrede skeletni mišić vrlo brzo započinje s opsežnim procesima reparacije s ciljem prevencije gubitka mišićne mase. Inicijalna faza mišićne regeneracije i reparacije karakterizirana je nekrozom oštećenog tkiva i upalom. Gotovo istodobno aktiviraju se do tada mirne satelitske stanice, proliferiraju, diferenciraju i spajaju se kako bi nastalo multinuklearno mišićno vlakno. U procesu mišićne regeneracije značajnu funkciju imaju i proteini regeneracijske (Reg) genske obitelji. Obitelj Reg gena uključena je u proces regeneracije tkiva, rast i proliferaciju različitih stanica, staničnu adheziju i otpornost na apoptozu. Reg geni očituju se u ranim fazama ozljede, što upućuje na njihovu ulogu reaktanta akutne faze upale i faktora rasta koji uzrokuje proliferaciju i rast satelitskih stanica u skeletnom mišiću, odnosno proliferaciju i rast Schwannovih stanica u ozlijeđenom perifernom živcu. Budući da se Reg 3G pojavljuje odmah nakon ozljede mišića i živca, pretpostavlja se da ima ulogu posrednika u signaliranju između ozlijeđenog živca i mišića, a moguće i makrofaga., Adult skeletal muscle is an extremely dynamic tissue which has a tremendous ability of regeneration after muscle injury. These processes are highly synchronized involving the activation of well-defined population of muscle stem cells called satellite cells. After injury skeletal muscle initiate a rapid and extensive repair process preventing the loss of muscle mass. The initial phase of muscle regeneration and repair is characterized by necrosis of the damaged tissue and inflammation. Almost simultaneously previous quiescent satellite cells are activated, proliferate, differentiate and fuse to form multinucleated myofibers. The regenerating (Reg) protein family has important role in the process of muscle regeneration. Reg proteins play important roles in tissue regeneration, cell growth and proliferation, cell adhesion and resistance to apoptosis. A Reg3G gene is upregulated in the early phase of muscle injury and acts as acute phase reactants and growth factor for muscle satellite cells and injured Schwann cells. Since the induction and release of Reg3G appeared to readily respond to muscle and nerve injury, Reg3G may function as mediators of the injury signal among the injured nerve and muscle, and possibly macrophages.

Cilj: Statini značajno smanjuju rizik od kardiovaskularnih bolesti, a s obzirom na mehanizamdjelovanja sličan bisfosfonatima, mogu povoljno djelovati i na koštani metabolizam. Ciljje bio istražiti povezanost između mineralne gustoće kosti (BMD) slabinske kralježnice i lijevogkuka s lipidnim i antropometrijskim parametrima u pacijenata liječenih zbog dislipidemije. Osimtoga, cilj je bio analizirati odnos između vremenskog perioda liječenja statinima i BMD-a. Ispitanicii metode: Ispitanici su većinom žene u postmenopauzi (N = 65), ali i muškarci (N = 15), kojise zbog dislipidemije liječe statinima. Iz ispitivane skupine isključeni su oni pacijenti koji se zbogosteoporoze liječe bisfosfonatima. U svih ispitanika su koštanom denzitometrijom izmjerenevrijednosti BMD-a slabinske kralježnice i lijevog kuka. Rezultati: BMD slabinske kralježnice pozitivnokorelira s koncentracijom triglicerida u krvi (r = 0,24, P = 0,046), ali korelira negativno sukupnim kolesterolom (r = -0,31, P = 0,008), HDL kolesterolom (r = -0,28, P = 0,020) i LDL kolesterolom(r = -0,35, P = 0,004). BMD lijevog kuka korelira pozitivno s trigliceridima (r = 0,25,P = 0,031), dok su negativne korelacije nađene s ukupnim kolesterolom (r = -0,30, P = 0,011),HDL kolesterolom (r = -0,28, P = 0,015) i LDL kolesterolom (r = -0,30, P = 0,010). Vremenski periodliječenja statinima pozitivno korelira s BMD-om slabinske kralježnice (r = 0,23, P = 0,048).Zaključak: Razvidno je da postoji povezanost između koštanog metabolizma i lipidnog statusa,kao i između koštanog metabolizma i vremenskog perioda liječenja statinima. Ipak, potrebno jeprovesti nova randomizirana klinička istraživanja kako bi se taj odnos u potpunosti razjasnio., Aim: Statins significantly reduce the risk of cardiovascular diseases, and with regardto the mechanism of action similar to bisphosphonates, may have a favorable effect on bonemetabolism. The aim was to investigate the relationship between bone mineral densities(BMD) of the lumbar spine and left hip with anthropometric and lipid parameters in patientstreated for dyslipidemia. In addition, the aim was to analyze the relationship between theperiod of treatment with statins and BMD. Patients and methods: Respondents were mostlypostmenopausal women (N = 65), and men (N = 15) who are treated with statins for dyslipidemia.Patients who are treated for osteoporosis with bisphosphonates were excluded from thestudy group. Bone densitometry was used to measure values of BMD of the lumbar spine andleft hip in all patients. Results: BMD of the lumbar spine is correlated positively with concentrationof triglycerides in the blood (r = 0.24, P = 0.046), but negatively correlated with totalcholesterol (r = -0.31, P = 0.008), HDL cholesterol (r = -0.28, P = 0.020) and LDL cholesterol(r = -0.35, P = 0.004). Left hip BMD correlated positively with triglycerides (r = 0.25, P = 0.031),whereas a negative correlation was found with total cholesterol (r = -0.30, P = 0.011), HDLcholesterol (r = -0.28, P = 0.015) and LDL cholesterol (r = -0.30, P = 0.010). Period of treatmentwith statins is positively correlated with BMD in the lumbar spine (r = 0.23, P = 0.048).Conclusion: It is obvious that there is a relationship between bone metabolism and lipid profile,as well as between bone metabolism and the period of treatment with statins. However, it is necessaryto carry out new randomized clinical researches to fully clarify these relationships.

Zbog iznimne važnosti koronarnih arterija, osobito u patogenezi srčanih bolesti, istraživanja srčanih vena desetljećima su bila zapostavljena. Napretkom moderne medicine uvođenje inovativnih dijagnostičkih i terapeutskih postupaka dovelo je do potrebe za alternativnim putovima pristupa oštećenom srcu, gdje vene srca imaju značajnu ulogu. Dok se ranije za prikaz krvnih žila srca koristila samo sekcija srca, danas su zbog primjene novih metoda prikaza krvnih žila srca prisutne različite podjele srčanih vena. Većina srčanih vena završava u desnom atriju. Istaknutu ulogu u odvođenju krvi iz srca ima koronarni sinus, sinus coronarius i njegove pritoke te prednje srčane vene, vv. cardiacae anteriores. Ove vene pripadaju velikom srčanom sustavu, dok mali srčani sustav čine Thebesijeve žile. One su predmet stalnih istraživanja jer se prilagođavaju različitim potrebama prokrvljenosti miokarda ovisno o životnoj dobi i promjenama u različitim srčanim bolestima. Varijacije srčanih vena su uobičajene. Poznavanje varijacija i anastomoza srčanih vena osobito je važno za razumijevanje i tumačenje slikovnih prikaza srčanih vena prilikom izvođenja dijagnostičkih i terapeutskih postupaka., The investigation of the cardiac veins have been neglected for decades because of the great importance of the coronary arteries in the pathogenesis of coronary heart disease. Advances in modern medicine and the introduction of innovative diagnostic and therapeutic procedures have led to the alternative routes to the access of the damaged heart, where the cardiac veins play an important role. Before the application of the new imaging methods for cardiac vessels, only dissection of the hearts were used. Now, with the help of these new diagnostic methods, the different classifications of cardiac veins was present. Most cardiac veins drain into the right atrium. The coronary sinus and its tributaries and the anterior cardiac veins have an important role in collecting and returning blood from the heart has. These veins constitute the greater cardiac venous system, while smaller cardiac venous system consists of the Thebesian vessels. They are the subject of an ongoing research in order to adapt to the different needs of myocardial drainage depending on the age and changes in various heart diseases. Variations of cardiac veins are common. The knowledge of cardiac vein variations and anastomoses have become important for understanding and interpretation of the heart vein images during performing diagnostic and therapeutic procedures.

Zdenko Križan (1915. - 2005.), liječnik, anatom i nastavnik, važna je akademska ličnost 20. stoljeća, posebno na južnoslavenskom području. Sudjelovao je u osnivanju tri anatomska zavoda i rukovodio njihovim radom. Tijekom dugogodišnje karijere bavio se nastavnim i znanstveno-istraživačkim radom. Prof. Križan je autor kompendija opće i specijalne anatomije za studente medicine i stomatologije. Rezultate svojih anatomskih istraživanja, uglavnom iz područja skeleta glave i krvnih žila, objavio je u domaćim i inozemnim znanstvenim časopisima. Ovaj rad pregledno daje biografske podatke o prof. Križanu., Zdenko Križan (1915 - 2005), physician, anatomist and teacher, is an important academic figure of the 20th century, especially in the South Slavic area. He participated in the founding of three anatomical institutes and directed their work. During the years of his career he was teaching and he did scientific research. Prof. Križan is author of three compendia of anatomy for Medicine and Dentistry students. The results of his anatomical research, mainly in the area of the head skeleton and blood vessels, were published in national and international scientific journals. This article is a rewiew of prof. Križan’s biography data.

Mišićna masa mijenja se tijekom ljudskog vijeka. U početku se mišićna masa jako povećava, što je u vezi s rastom i razvojem. Kako starimo mišićna masa se postepeno smanjuje. U ovom radu opisane su neke promjene koje se događaju u mišićima tijekom starenja. Ostarjeli skeletni mišići, a posebno mišićna vlakna tipa II, puno su podložniji atrofiji nego mišići mlađe populacije. Mišići starijih osoba imaju i ograničenu regenerativnu sposobnost. Mnogobrojni su čimbenici koji utječu na ovo dobno uvjetovano propadanje skeletne muskulature, a navedeno stanje naziva se sarkopenija., Muscle size changes across the human lifespan, initially showing rapid increases due to grow and later gradual decreases due to aging. There are same changes in muscle mass and performance with aging. Aged skeletal muscles, particulary type II muscle fibers, are more susceptible than younger ones to muscle damage and display an impaired regenerative capacity. A number of factors have been proposed as contributing to age related loss of skeletal muscle and its contractility. This disease state termed sarcopenia.

Nrf2 transcription factor is expressed by neurons in ischemia / reperfusion injury of the spinal cord

Bone morphogenetic proteins (BMPs) are multi- functional growth factors primarily isolated from bone according to their osteoinductive capacity and exert their function by BMP pathway including BMP receptors and BMP-related Smad molecules. BMP pathway triggers various processes such as cellular migration, proliferation and differentiation, which are involved in physiological as well as in pathological conditions.As members of TGFbeta family they are also included in processes of epithelial- mesenchymal transition which is important in cancer progression. The aim of this study was to investigate the alteration of BMP pathway in colorectal cancer samples of patients who underwent the CRC surgery. This study was approved by Ethical committee of Clinical Hospital Centre and Faculty of Medicine. All samples were obtained with informed consent. The expression of BMP pathway in different stage of colorectal cancer was characterised by imunohistochemistry and western blot using Smad1/5/8 and pSmad1/5/8 antibody. The clinicopathologic data such as age, gender, Dukes’ staging and differentiation grade are also analysed. Additionally, the correlation with establish marker of cell proliferation, Ki67 was xamined. Our results showed that colorectal cancer occurred most frequently in men (75%) and in older people (more than 60 years ; 85%). The most common site of primary carcinoma was sigmoid colon and rectum (75%). According to Dukes’ staging, 55% of examined cancers were Dukes’B and 45% Dukes’C. In both stages, we have found the expression of total and active form of Smad1/5/8 which is higher in Dukes’B stage of colorectal cancer samples. We also found the positive correlation between Ki67 and Smad1/5/8 expression. These results suggested that BMP pathway has also important role in the carcinogenesis and alterations of this pathway could contribute to the cancer progression. Therefore, it could be concern that determination of the BMP pathway activity could be additional prognostic marker of colorectal cancer.

Statini značajno smanjuju rizik od kardiovaskularnih bolesti, a s obzirom na mehanizamdjelovanja sličan bisfosfonatima, mogu povoljno djelovati i na koštani metabolizam. Ciljje bio istražiti povezanost između mineralne gustoće kosti (BMD) slabinske kralježnice i lijevogkuka s lipidnim i antropometrijskim parametrima u pacijenata liječenih zbog dislipidemije. Osimtoga, cilj je bio analizirati odnos između vremenskog perioda liječenja statinima i BMD-a. Ispitanici su većinom žene u postmenopauzi (N = 65), ali i muškarci (N = 15), kojise zbog dislipidemije liječe statinima. Iz ispitivane skupine isključeni su oni pacijenti koji se zbogosteoporoze liječe bisfosfonatima. U svih ispitanika su koštanom denzitometrijom izmjerenevrijednosti BMD-a slabinske kralježnice i lijevog kuka. BMD slabinske kralježnice pozitivnokorelira s koncentracijom triglicerida u krvi (r = 0, 24, P = 0, 046), ali korelira negativno sukupnim kolesterolom (r = -0, 31, P = 0, 008), HDL kolesterolom (r = -0, 28, P = 0, 020) i LDL kolesterolom(r = -0, 35, P = 0, 004). BMD lijevog kuka korelira pozitivno s trigliceridima (r = 0, 5, P = 0, 031), dok su negativne korelacije nađene s ukupnim kolesterolom (r = -0, 30, P = 0, 011), HDL kolesterolom (r = -0, 28, P = 0, 015) i LDL kolesterolom (r = -0, 30, P = 0, 010). Vremenski periodliječenja statinima pozitivno korelira s BMD-om slabinske kralježnice (r = 0, 23, P = 0, 048). Razvidno je da postoji povezanost između koštanog metabolizma i lipidnog statusa, kao i između koštanog metabolizma i vremenskog perioda liječenja statinima. Ipak, potrebno jeprovesti nova randomizirana klinička istraživanja kako bi se taj odnos u potpunosti razjasnio.

Cilj: Utvrditi primjenjivost anatomskog modela nosne šupljine i pripadajućih parana- zalnih sinusa „3D fess slices®” u nastavi anatomije i otorinolaringologije. Metode: U istraživa- nje u školskoj godini 2012./2013. bile su uključene dvije grupe studenata, studenti Sveučilišta u Zürichu na kolegiju Klinička anatomija (N = 94) i studenti Medicinskog fakulteta Sveučilišta u Rijeci (N = 116). U Rijeci su to bili studenti Dentalne medicine, prve (N = 29), treće godine (N = 23) i pete godine Opće medicine na kolegiju Otorinolaringologija (N = 64). Nakon proučavanja anatomskih modela nosne šupljine i paranazalnih sinusa, studenti su ispunili anketu koju je oblikovala jedna od autorica (T. Š. V.). Rezultati: Svi studenti izrazito su pozitivnim od- govorom na posljednje pitanje ankete pokazali veliku motiviranost u učenju anatomije kroz primjenu anatomskog modela „3D fess slices®”, kao i olakšano razumijevanje u učenju pojedinih dijelova nosne šupljine i paranazalnih sinusa. Zaključak: Anatomski model „3D fess slices®” pokazao se kao pozitivna nadopuna u učenju anatomije nosne šupljine i paranazalnih sinusa. Ova studija pridonosi medicinskoj edukaciji u svrhu uključivanja ovog, kao i drugih sličnih anatomskih modela., Aim: To determine the applicability of an anatomical model of the nasal cavity and paranasal sinuses, named the ”3D fess slices®”, in teaching anatomy. Methods: This study was conducted during the academic year 2012/2013 and included two groups of students: students of the Clinical Anatomy course of the University of Zürich (N = 94) and students of the Faculty of Medicine, University of Rijeka (N = 116). The students from Rijeka were in their first (N = 29) and the third year (N = 23) of the School of Dental Medicine, and fifth year of Otorhinolaryngology course of the School of Medicine (N = 64). After studying the anatomical model of the nasal cavity and paranasal sinuses, the students filled out a survey formed by one of the authors (TŠV). Results: All students answered highly positive to the last question of the survey and in that way demonstrated outstanding motivation to learn anatomy using the “3D fess slices®” anatomical models, which facilitated the understanding of certain parts of the nasal cavity and paranasal sinuses. Conclusion: The “3D fess slices®” anatomical model proved to be a useful supplement in teaching the anatomy of the nasal cavity and paranasal sinuses. Our results demonstrated that including this or similar anatomical models in teaching will contribute to medical education.

Colorectal cancer is common cancer of the digestive tract with increasing incidence in the last decade. The higher incidence was observed in developed countries and connection with typical Western lifestyle and diet was emphasized. Colorectal cancer is the third most common cancer and is the second leading cause of death because of cancer. Extensive research was conducted to explore the genes and factors that may trigger the initiation and the progression of colorectal cancer (1). Among the genes which are known that affect the cancer development, BMPs and their signaling pathway have been under intensive research (2, 3). BMP signaling is required for the maintenance of intestinal epithelia stem cell, maturation of secretory cell lineage and apoptosis of mature colonic epithelial cells (4). Previously, we have shown the expression profile of BMPs and BMP pathway components in experimentally induced colitis (5). BMP pathway is preserved in the colon of diseased animals and its expression during experimentally colitis is recovered by the BMP7 therapy. To further characterize the role of BMPs in the intestine pathophysiology, we have studied the alteration of BMP signaling pathway in colon cancer samples of patients who underwent CRC surgery. The normal colon tissues samples were used as control. The patient and tumor characteristics such as age, gender, tumor location, Duke’s stage and grade differentiation are analyzed. The BMP signaling pathway expression was investigated using immunohistochemistry and Western blott. Also, we explored the expression of Ki-67, a typical marker of cell proliferation and the presence of neutrophils. Our results showed that adenocarcinoma represent the most common pathology and the sigmoid colon and rectum are the most common sites of primary carcinoma localization (75%). According to gender and age, colon cancer occurred more frequently in men (75%) and in the elderly (more than 60 years ; 80%). Smad1/5/8 cytoplasmatic and pSmad1/5/8 nuclear staining was present in all colon cancer samples and difference was found in intensity of staining which is also confirmed by Western blot. The nuclear staining of Ki-67 was observed in all colon cancer samples with the common presence of 50% of positive cells. The neutrophils are present in 50% of colon cancer samples. They are found at the border between the tumor cells and surrounding normal tissue and in areas of tumor necrosis. These results suggested that the BMP pathway is preserved and active in colon cancer but alteration of this pathway is occurred in the different stages of colon cancer.

Transiliac bone biopsy is necessary tool in diagnostic procedures, and frequently used method in therapeutic follow-up of the resistant osteoporosis. On the other hand, bone densitometry is the most frequently used technique in estimation of the bone status. The aim was to analyze the extent to which: anthropometry, age, bone densitometry and ash density affect bone changes of the iliac crest, assessed by bone histomorphometry. Iliac crest's bone samples were obtained out of 88 autopsy cases. Prior to bone histomorphometry, two consecutive 5 µm sections were stained and photographed at 40X. Bone samples of the third lumbar vertebra underwent bone densitometry and atomic absorption spectrometry. Results revealed that bone volume (BV/TV) was significantly predicted by age (β = -0, 7), ash density (AD) (β = -0, 23) and BMD (β = 0, 23). Bone surface (BS/TV), trabecular number (Tb.N), trabecular separation (Tb.Sp) and cortical bone volume (CV), were significantly predicted by age, with beta ponder values of: β = -0, 36, β = -0, 75, β = 0, 8 and β = -0, 41, respectively. Trabecular thickness was significantly predicted by age (β = -0, 3) and BMD (β = 0, 44). Cortical thickness was significantly predicted by age (β = 0, 1), body height (β = -2, 4), body weight (β = 3, 8), BMI (β = -2, 5) and BMD (β = 0, 5). Bone mineral density is the strongest and also positive predictor of the iliac crest's trabecular thickness and cortical thickness. This suggests that total amount of the inorganic matter of the scanned vertebral bone surface is strongly related, and therefore, could predict changes that affect the iliac crest's trabecular and cortical thickness.

BMP-9 is transforming growth factor beta (TGF-β) member. BMP-9 mRNA is isolated out of the different populations of the liver cells, but mostly in hepatocytes and intrahepatic billiary epithelial cells. BMP-9 role in the human liver is little known. Similarly to BMP-7 in intestines, BMP-9 could prevent epithelial to mesenchymal transition in the liver. After the immunoassaying was done, the aim was to measure the intensity of the immunohistochemical staining by use ImageJ software for: BMP-9, Phospho-Smad 1/5/8, TGF-β1, Phospho-Smad 2/3, Glial Fibrillary Acidic Protein (GFAP) and Alpha Smooth Muscle Actin (α-SMA). Acute inflammation was established by blood concentrations of the enzymes Alanine- Aminotransferase (U/L) and Aspartate-Aminotransferase (U/L). The animal model of acute liver injury was established with one single carbon-tetrachloride injection. Mice were sacrificed on 6th hours, 12th hours, day 1, day 2, day 3 and day 7. BMP-9 showed the highest expression after 12 hours with maximum on the day 1 of the toxic injury, which corresponded to expression of the Phospho-Smad 1/5/8, expressed after 6 hours with maximum at the day 1, which was followed by decrease in Phospho-Smad 1/5/8 and BMP-9 expression. Early increase in GFAP expression which was after 12 hours of liver injury, implies to early activation of the hepatic stellate cells. The expression of the TGF-β1 and Phospho-Smad 2/3 was the highest at day, but persisted during days 2 and 3, implying that TGF-β1 supports pro fibrotic response, confirmed by α-SMA expression, which was the highest at the day 3 of the liver injury. BMP-9, TGF-β1 and their intracellular messengers had the highest expression after 24 hours, which implies fine balance between inflammatory and protective cytokines, and therefore supports the hypotheses of the protective role of the BMP-9 in chemically induced acute hepatitis.

Introduction: Lateral intercondylar ridge (LIR) is recognized as anterior border of the anterior cruciate ligament’s (ACL) femoral footprint. It is the main landmark to determine the placement of the femoral tunnel during anatomic reconstructions of the anterior cruciate ligament. Aim: The purpose of this investigation was to establish the incidence of presence of the LIR in femoral specimens, and to determine the length and position of the LIR on the roof of the intercondylar fossa. Materials and methods: We analyzed 19 femoral specimens of unknown age and gender at the Department of Anatomy, Faculty of Medicine, University of Rijeka. The LIR has been divided into the part that belongs to the condyle and the part that belongs to the roof of intercondylar fossa. The border is presented by the sagittal axis which is extending in the spatial angle between the lateral condyle and the roof of intercondylar fossa. The length of LIR was measured from the sagittal axis to the LIR end on the roof of intercondylar fossa. Results: The condylar part of the RR was in standard linear position in all examined specimens. The length of the LIR at the roof of intercondylar fossa was 0, 631 cm expressed as mean value (SD ± 0, 065). In only one case the LIR at the roof of intercondylar fossa was double–curved, "S" form. In some cases, the LIR at the roof of intercondylar fossa exceeds from linear form to irregularly shaped rough area. Conclusion: Our result showed that LIR is represented rather by straight line than curved. Its part which belongs to lateral femoral condyle is mostly linear. In majority of samples LIR part which belongs to the roof of the intercondylar fossa is also linear. These findings are important in performing anatomic ACL reconstructions, especially if personalized double bundle technique is used.

The aim of this study was to establish a 14-day time course study on innervated and denervated rat soleus and tibialis anterior muscles after treatment with salbutamol, a 2 adrenoceptor agonist to assess fiber type selectivity in their type composition. Soleus, as a slow-twitch muscle, is composed of 90% type I fibers and 10% type II fibers. On the other hand, tibialis anterior muscle is fast-twitch with 91, 6% type II fibers and 8, 4% type I fibers. We observed that during the period of denervation occurs the conversion from type I to type II muscle fibers. However, in soleus muscle of the animals which were treated with salbutamol this conversion was less expressed and an increased number of type I fibres were observed. In tibialis anterior muscle, fibres conversion was higher what caused the significant increase in number of type II fibres. Groups of healthy muscles that were treated with salbutamol, showed an increase in number in both muscles of fibres type II until 9th day of experiment. While in soleus the number of fibres type II was increasing towards the end of experiment, in tibialis anterior muscle showed a conversion in second part of experiment from type II fibers to type I. In this study, we have shown how muscles of different properties reacted differently to various stimuli.

During the anatomical dissection of the pelvic blood vessels we found a very rare variation of the obturator vessels. The obturator artery arises from the femoral artery and the obturator vein ends in the femoral vein. Knowledge of this possibility in clinical medicine, especially in surgery is very important because the injury of the obturator artery during the surgery can cause a life- threatening consequences for the patient.

The human coronary sinus is a major component of the cardiac venous system that serves as an anatomic landmark as well as a conduit for many diagnostic and therapeutic procedures in cardiology. The objective of this study is to explore the anatomical variations of the coronary sinus and its tributaries. Morphological features of the veins have been studied on the 20 adult human cadaveric hearts, both sexes, 25 to 70 years of age. The hearts had been fixed in formalin solution and studied by manual dissection and the ink-gelatine methods. The length of the human sinus varied from 20 to 44 mm (average 29, 6±4.6 mm). The diameter of the coronary sinus at its opening into right atrium was 7 to 13 mm (average 8.5±1.5 mm). Two most frequent pattern of venous drainage into the coronary sinus are: the great cardiac vein, the middle cardiac vein, posterior veins of ventricle and oblique vein of left atrium in 40% specimens and the great cardiac vein, the middle cardiac vein, the minor posterior veins of ventricle, the posterior vein of left ventricle and oblique vein of left atrium in 30% specimens. The small cardiac vein was present only in 5% specimens. Myocardial bridges of the cardiac veins were found in 3 specimens over great cardiac vein during its course in anterior interventicular sulcus. The knowledge of cardiac veins variation will contribute to the better understanding and interventions in heart vascular disease.

INTRODUCTION: RANKL/RANK/OPG system has key role in bone metabolism. Beyond its role in bone loss, it was also documented their importance during inflammation which is occurred in inflammatory bowel disease (IBD). The aim of this study was to investigate the expression of receptor activator of NF-B ligand (RANKL) and its receptors RANK as well its decoy receptor osteoprotegerin (OPG) in colon during experimantal IBD and following BMP7 or corticosteroid therapy. METHODS/DESIGN: IBD was induced by intrarectal administration of trinitrobenzenesulfonic acid (TNBS). After the IBD induction, the rats were treated with BMP-7 (100 g/ml) and sacrificed on the 2nd, 5th, 14th, and 30th day after the TNBS induction. The presence of RANKL, RANK and OPG in inflammatory bowel disease was determined by the continuous monitoring of the expression level of in rat colons during different phases of experimental IBD as well as after BMP7 treatment. An expression level of OPG was determined by RT-PCR and immunohistochemical analyses. Additionally, to investigate the influence of corticosteroid therapy on RANKL/RANK/OPG expression, we treated the diseased animals by 2 mg/kg of dexamethasone during 5 days. RESULTS: During IBD the expression of RANKL/RANK/OPG system was found in all colon samples. The expression level of OPG increased with disease duration and showed the largest expression on 30th day of colitis which is opposite to expression level of RANK which expression decreased according to disease duration. BMP7 therapy as well as ethanol control showed no significant difference in their expression levels compared with diseased animals. Immunohistocemical analysis revealed the presence of OPG in epithelial cells and in limphoid infilration. RANKL expression was also detected in colon samples with increased expression after corticosteroid therapy. CONCLUSION: The expression pattern of all components of RANKL/RANK/OPG system during IBD suggests on their important role in inflammation and probably on bone loss associated with IBD.

Ekspresija receptora aktivatora nuklearnog faktora kappa B i njegovog liganda u leukocita tijekom akutnog bubrežnog odbacivanja nakon transplantacije bubrega u štakora