Different cytokine expression profiles in metaphyseal and diaphyseal fracture healing may provide new insights in the field of bone regeneration

Introduction Fractures are traumatic injuries that mainly occur in bone metaphysis, however most studies of bone healing have focused on diaphyseal bone. This is important because the healing process of trabecular metaphyseal bone has different healing characteristics from the diaphyseal area. Inflam- mation is thought to play an important, but different role in these two bone fracture types: diaphyseal fractures heal slowly through the formation of callus tissue, and metaphyseal trabecular bone heals faster, with no, or limited callus formation. As cytokines are key modulators of inflammation, the aim of the present study was to define the cytokine profiles at the core of these two conditions with possi- ble implications for the bone healing process. Materials and Methods This study included sixteen pa- tients with long bone metaphyseal and diaphyseal fractures and a healthy control group. Blood samples were taken at two timepoints: i) between the 1st (the day of the fracture) and the 6th day after fracture occurrence; ii) between the 7th and the 21st day after fracture occurrence. Fractures were treated either conservatively or surgically, depending on specific clinical indications. All participants with diaphyseal fractures were treated surgically. The control group provided blood samples on one occasion. The ob- tained plasma samples were pooled into 5 different experimental groups and analysed using commer- cial cytokine arrays. Results Marked differences in cytokine expression profiles were found between the fracture groups and the control group. The diaphyseal group had an “activated” pro-inflammatory cytokine profile with markedly higher levels of cytokines at both timepoints compared to the meta- physeal group, which in contrast had a “silenced” cytokine expression profile. Single cytokine analysis revealed that in both metaphyseal and diaphyseal fracture groups MCP-1 and RANTES showed the most prominent fold change at both timepoints. IL-6 and TNF-α also show similarly elevated levels in both timepoints in the diaphyseal fracture group, whereas this is not observed in the metaphyseal group. Furthermore, IL-3 expression was also elevated in the diaphyseal group, but only in the first timepoint. Conclusion This pilot study indicated chemokines which might be potential crucial driv- ers of bone healing, as well as painted distinct cytokine plasma profiles evident in metaphyseal and diaphyseal healing

Different cytokine expression profiles in metaphyseal and diaphyseal fracture healing may provide new insights in the field of bone regeneration

Introduction Fractures are traumatic injuries that mainly occur in bone metaphysis, however most studies of bone healing have focused on diaphyseal bone. This is important because the healing process of trabecular metaphyseal bone has different healing characteristics from the diaphyseal area. Inflam- mation is thought to play an important, but different role in these two bone fracture types: diaphyseal fractures heal slowly through the formation of callus tissue, and metaphyseal trabecular bone heals faster, with no, or limited callus formation. As cytokines are key modulators of inflammation, the aim of the present study was to define the cytokine profiles at the core of these two conditions with possi- ble implications for the bone healing process. Materials and Methods This study included sixteen pa- tients with long bone metaphyseal and diaphyseal fractures and a healthy control group. Blood samples were taken at two timepoints: i) between the 1st (the day of the fracture) and the 6th day after fracture occurrence; ii) between the 7th and the 21st day after fracture occurrence. Fractures were treated either conservatively or surgically, depending on specific clinical indications. All participants with diaphyseal fractures were treated surgically. The control group provided blood samples on one occasion. The ob- tained plasma samples were pooled into 5 different experimental groups and analysed using commer- cial cytokine arrays. Results Marked differences in cytokine expression profiles were found between the fracture groups and the control group. The diaphyseal group had an “activated” pro-inflammatory cytokine profile with markedly higher levels of cytokines at both timepoints compared to the meta- physeal group, which in contrast had a “silenced” cytokine expression profile. Single cytokine analysis revealed that in both metaphyseal and diaphyseal fracture groups MCP-1 and RANTES showed the most prominent fold change at both timepoints. IL-6 and TNF-α also show similarly elevated levels in both timepoints in the diaphyseal fracture group, whereas this is not observed in the metaphyseal group. Furthermore, IL-3 expression was also elevated in the diaphyseal group, but only in the first timepoint. Conclusion This pilot study indicated chemokines which might be potential crucial driv- ers of bone healing, as well as painted distinct cytokine plasma profiles evident in metaphyseal and diaphyseal healing

Current knowledge about prostatic cancer a proposal for a common therapy protocol

Ukupna učestalost karcinoma prostate znatno premašuje učestalost klinički dokazanog karcinoma, iako je to najčešći rak u muškaraca. Dijagnoza kliničkog raka prostate postavlja se danas na osnovi sigurnih i neizbježnih pokazatelja. To su: rektalni pregled, UZV pregled transrektalnom sondom, povišene vrijednosti prostatičnog specifičnog antigena (PSA) u serumu i transrektalna punkcijska biopsija. Suvremena klasifikacija mora odvojiti lokaliziranu bolest od uznapredovale i diseminirane bolesti. Kako veliki dio karcinoma prostate predstavlja stacionarnu bolest, potrebno je utvrditi prediktore malignog potencijala s pomoću kojih će se odvojiti slučajevi agresivnog karcinoma koji zahtijevaju terapiju. To su: povećanje limfnih čvorova zdjelice, povišeni PAP, veličina primarnog tumora, niskodiferencirani epitel primarnog tumora i stanična aneuploidija. Lokalizirani agresivni karcinom prostate, uz ispunjene opće uvjete operacije, zahtijeva radikalnu prostatektomiju. Uznapredovali karcinom ili diseminirana bolest diktiraju kombiniranu terapiju kojoj je osnova potpuna androgena blokada. To se u prvoj fazi terapije postiže orhidektomijom + analozi GnLH + antiandrogeni. Druga se faza terapije osniva na fosforiliziranim esterima stilbena (Honvan i Estracyt), treća na citostaticima i posljednja na suzbijanju boli.General frequency of prostatic cancer (including incidental and undetected) outnumbers clinical prostatic cancer, although this one is by far the most frequent cancer of man. Current diagnosis of clinical prostatic cancer is based on digital examination, rectal ultrasound, serum prostatic specific antigen level and transrectal biopsy. Modern classification has to separate localized from advanced and disseminated disease. A high percent age of prostatic cancer is inactive disease whose mortality does not outnumber the man lethality without cancer. Today, we have some concrete factors indicating the disease aggressive potential, e.g. regional lymph node growth, high PSA and PAP levels, primary tumor size, high grading and nuclear aneuploidy. With them, the cases requiring therapy can be differentiated from those with inactive cancer. Localized aggressive prostatic cancer with general conditions for operation fulfilled indicates radical prostatectomy. The advanced and disseminated disease is an indication for paliative therapy, which is based on complete androgen deprivation. This is achieved in the first phase of therapy with orchydectomy + GnLH analogues + antiandrogens. The next therapeutic phase (after new disease progression ) consists of phosphorilized stilbens, such as Estracyt and Honvan. The final, exclusively symptomatic therapy should be preceded by chemotherapy

First Characterization of ADAMTS-4 in Kidney Tissue and Plasma of Patients with Chronic Kidney Disease—A Potential Novel Diagnostic Indicator

Background: We have previously shown that metzincin protease ADAMTS-4 accompanies renal fibrogenesis, as it appears in the blood of hemodialysis patients. Methods: Native kidney (NKB) and kidney transplant (TXCI) biopsy samples as well as plasma from patients with various stages of CKD were compared to controls. In paired analysis, 15 TXCI samples were compared with their zero-time biopsies (TX0). Tissues were evaluated and scored (interstitial fibrosis and tubular atrophy (IFTA) for NKB and Banff ci for TXCI). Immunohistochemical (IHC) staining for ADAMTS-4 and BMP-1 was performed. Plasma ADAMTS-4 was detected using ELISA. Results: ADAMTS-4 IHC expression was significantly higher in interstitial compartment (INT) of NKB and TXCI group in peritubular capillaries (PTC) and interstitial stroma (INT). Patients with higher stages of interstitial fibrosis (ci > 1 and IFTA > 1) expressed ADAMTS-4 in INT more frequently in both groups (p = 0.005; p = 0.013; respectively). In paired comparison, TXCI samples expressed ADAMTS-4 in INT and PTC more often than TX0. ADAMTS-4 plasma concentration varied significantly across CKD stages, being highest in CKD 2 and 3 compared to other groups (p = 0.0064). Hemodialysis patients had higher concentrations of ADAMTS-4 compared to peritoneal dialysis (p < 0.00001). Conclusion: ADAMTS-4 might have a significant role in CKD as a potential novel diagnostic indicator

VLA-COSMOS 3 GHz Large Project

VizieR online Data Catalogue associated with article published in journal Astronomy &amp; Astrophysics with title 'The VLA-COSMOS 3 GHz Large Project: Continuum data and source catalog release.' (bibcode: 2017A&amp;A...602A...1S