Relationship of E-cadherin with Cervical Lymph Node Metastasis in Laryngeal Cancer

E-cadherin, a 120 kDa transmembrane protein, plays an important role in malignant progression and tumour differentiation. The loss or reduction in E-cadherin expression has been found in several tumours including laryngeal squamous cell carcinoma. The present study aimed to investigate the prognostic implications of changes in expression of the E-cadherin in laryngeal carcinoma. E-cadherin expression was determined by immunohistochemistry in paraffin- embedded tissue specimens from 80 patients. A staining score was given based on the percentage of cells stained (0–100%). E-cadherin expression varied greatly among tissue samples from 2 to 72 (median 25). Using the median expression of E-cadherin as a cut- off, 41 (51.3%) tumours were classified in the »low E-cadherin« group and the rest, 39 (48.7%) tumours, consisted the »high E-cadherin« group. We found significant differences in the staining scores of E-cadherin between those tumours with and without nodal metastases (p=0.025) and advanced clinical stage (TNM stage III and IV) (p=0.014). The results of a stepwise logistic regression analysis showed that E-cadherin staining score and the location of primary tumour were independent predictors of nodal metastases. The immunohistochemical determination of E-cadherin expression may be useful instrument to characterise the metastatic potential of carcinomas. Larger studies are needed to confirm the role of E-cadherin expression in predicting the behavior of laryngeal squamous cell carcinomas

Side effects assessment in glicolyc acid peelings in patients with acne type I

Chemical peeling implies the application of a chemical agent to the skin, which causes controlled destruction of a part or the entire epidermis, with or without the dermis, leading to exfoliation and removal of superficial lesions, followed by regeneration of new epidermal and dermal tissues. The present study was directed toward safety concerns associated with superficial chemical peeling with glycolic acid (GA) in different concentrations at patients with acne tip I. A sample of 90 patients of either sex, aged between 17 to 21 years, were included in the study and submitted to superficial chemical peeling for acne vulgaris. The study lasted eight weeks and peeling sessions were carried out in each patient. Tolerance to the procedure and any undesirable effects noted during these sessions were recorded. For data statistical analysis and interpretation of results, software program SPSS version 13 was used. Results were expressed through the descriptive statistics, as simple frequencies and percentages, while for establishing of statistically significant differences, in use was Friedman's test of significance. Almost all the patients tolerated the procedure well. Of totally 90 patients, only six, at the end of therapy experienced hard erythema, only ten, at the end of therapy experienced hard desquamation and only eleven, at the end of therapy experienced hard sensation of pulling of facial skin. Chemical peeling with glycolic acid is a well tolerated and safe treatment modality in acne type I. © 2011 Association of Basic Medical Sciences of FBIH

Focal neuroendocrine differentiation in prostatic gland carcinoma with basaloid pattern

Introduction. Prostatic gland basal cell proliferations exhibit morphological continuum ranging from basal cell hyperplasia to basal cell carcinoma. In the following report, we described clinical features, morphological spectrum, neuroendocrine differentiation and histogenesis of prostatic gland basal cell carcinoma in our patient. Case report. Hematoxylin- eosin (HE), Alcian blu-periodic acid schiff (ABPAS) at pH 2.5 stained sections and the avidin-biotinperoxidase complex (ABC), were performed on prostate gland paraffin-embedded tissue. Monoclonal antibodies directed against cytokeratin (34βE12) which selectively stains basal cells, prostate specific antigen (PSA), chromogranine A, neuron-specific enolase (NSE), synaptophysin and CD56, were used. Basal cell proliferations exhibited a morphological continuum ranging from basal cell hyperplasia to prostatic gland carcinoma. In these prostatic lesions, positive reactivity was demonstrated for 34βE12 and CD56. These findings indicate that the basaloid cells of basal cell hyperplasia, florid basal cell hyperplasia, atypical basal cell hyperplasia and basal cell carcinoma are derived from basal cells of the normal prostate gland suggesting a continuum in the progression of hyperplasia to benign and then malignant neoplasia. The presence of CD56 protein in the discovered lesions may be related to their neuroendocrine differentiation. Conclusion. The fact, that our patient was well six years after the radical prostatectomy supports the belief of some authors that basal cell carcinoma represents a low grade carcinoma with an excellent prognosis

Neuroimunski aspekti efekata vodećih jedinjenja/lekova kandidata koji deluju preko gabaa i/ili sigma‐2 receptora na raspoloženje, anksioznost i kogniciju: in vitro/in vivo delineacija primenom nano‐ i hipsc platformi

Mood, anxiety and cognitive symptoms in psychiatry and neurology represent a significant worldwide burden. Due to difficulties in disease modeling and drug delivering to the site of action, as well as gaps in in vitro/in vivo extrapolation, the efforts to elucidate the roles of stress and neuroimmune pathways in both, etiology and therapy of these symptoms are challenging, but may nevertheless result in novel mechanisms of action. Recent preclinical studies provided novel leads/drug candidates with promising mood, anxiety and cognitive effects, the intellectual property rights of which are co-owned by the project beneficiary. We aim to: (1) incorporate the selective ligands of GABAA and/or sigma-2 receptors, with code names GL-II-73, DK-I-56, MM-I-03 and CW-02-79, together with two reference sigma-2 receptor ligands (siramesine and RHM-1), into the optimized nanoparticles and target their delivery to the human induced pluripotent stem cell (hiPSC)- based tri-culture cell neuroinflammation model, or rat brain; (2) quantify the immunological/morphological/neurochemical markers in immunologically challenged hiPSC-derived neurons, astrocytes and glia cells, and (3) assess their effects on behavior and biological markers in immunologically challenged animals of both sexes subjected to chronic mild unpredictable stress. We assume that the targeted nanodelivery of selected compounds to the brain will improve their pharmacokinetic profile, fortify their beneficial effect on mood, anxiety and cognition, and help delineate the contributing neuroimmune effects presumably arising mainly from microglia. The familiarization with neuroimmune aspects and pharmacokinetic optimization will support the preclinical progress of these compounds and might provide a rationale for designing clinical trials.Raspoloženje, anksioznost i kognitivni simptomi u psihijatriji i neurologiji predstavljaju značajno opterećenje za zdravstvene sisteme na globalnom nivou. Usled poteškoća u modelovanju bolesti i isporuci lekova na mesto delovanja, kao i jaza u in vitro/in vivo ekstrapolaciji, potreba da se osvetle uloge stresa i neuroimunskih puteva u etiologiji i terapiji ovih simptoma je izazov, i može rezultovati u novim mehanizmima delovanja. Nedavne prekliničke studije obezbedile su nova vodeća jedinjenja/lekove kandidate sa obećavajućim efektima na raspoloženje, anksioznost i kogniciju, rezultujući prihvatanjem patentnih prava čiji je suvlasnik predlagač projekta. Cilj projekta je da: (1) inkorporiramo ligande selektivne za GABAA i/ili sigma-2 receptore, sa kodiranim imenima GL-II-73, DK-I56, MM-I-03 i CW-02-79, zajedno sa dva referentna liganda za sigma-2 receptore (siramesin i RHM-1), u optimizovane nanočestice i da omogućimo njihovu ciljnu isporuku u hiPSCbazirani trićelijski model neuroinflamacije, ili mozak pacova; (2) kvantifikujemo imunološke/morfološke/neurohemijske markere u imunološki izazvanim hiPSC-derivisanim neuronima, astrocitima i glija ćelijama, i (3) procenimo njihove efekte na ponašanje i biološke markere u imunološki izazvanim životinjama oba pola podvrgnutim blagom neočekivanom stresu. Procenjujemo da će ciljana isporuka odabranih jedinjenja pomoću nanonosača poboljšati njihove farmakokinetičke (FK) profile, ojačati njihove korisne efekte na raspoloženje, anksioznost i kogniciju i pomoći delineaciji doprinosa neuroimunskih efekata, po svemu sudeći, poreklom uglavnom od mikroglija ćelija. Upoznavanje sa neuroimunskim aspektima i FK optimizacija mogu da podrže napredak u prekliničkom razvoju ovih jedinjenja i obezbede osnov za dizajniranje prospektivnih kliničkih studija.Link to the lecture: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/4298

Neuroimmune aspects of mood, anxiety and cognitive effects of leads/drug candidates acting at GABAA and/or sigma-2 receptors: In vitro/in vivo delineation by nano- and hiPSC-based platforms

Mood, anxiety and cognitive symptoms in psychiatry and neurology represent a significant worldwide burden. Due to difficulties in disease modeling and drug delivering to the site of action, as well as gaps in in vitro/in vivo extrapolation, the efforts to elucidate the roles of stress and neuroimmune pathways in both, etiology and therapy of these symptoms are challenging, but may nevertheless result in novel mechanisms of action. Recent preclinical studies provided novel leads/drug candidates with promising mood, anxiety and cognitive effects, the intellectual property rights of which are co-owned by the project beneficiary. We aim to: (1) incorporate the selective ligands of GABAA and/or sigma-2 receptors, with code names GL-II-73, DK-I-56, MM-I-03 and CW-02-79, together with two reference sigma-2 receptor ligands (siramesine and RHM-1), into the optimized nanoparticles and target their delivery to the human induced pluripotent stem cell (hiPSC)- based tri-culture cell neuroinflammation model, or rat brain; (2) quantify the immunological/morphological/neurochemical markers in immunologically challenged hiPSC-derived neurons, astrocytes and glia cells, and (3) assess their effects on behavior and biological markers in immunologically challenged animals of both sexes subjected to chronic mild unpredictable stress. We assume that the targeted nanodelivery of selected compounds to the brain will improve their pharmacokinetic profile, fortify their beneficial effect on mood, anxiety and cognition, and help delineate the contributing neuroimmune effects presumably arising mainly from microglia. The familiarization with neuroimmune aspects and pharmacokinetic optimization will support the preclinical progress of these compounds and might provide a rationale for designing clinical trials.Link to the conference object: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/4297

Kernel modifications and tryptophan content in QPM segregating generations

Maize has poor nutritional value due to deficiency of two essential amino acids - tryptophan and lysine. Although recessive opaque2 (o2) mutation significantly increases their content in the endosperm, incorporation of opaque2 into high yielding cultivars was not commercially successful, because of its numerous agronomic and processing problems due to soft endosperm. Quality protein maize - QPM has lately been introduced as opaque2 maize with improved endosperm hardness and improved agronomic traits, but mostly within tropical and subtropical germplasm. The ongoing breeding project at MRI includes improvement of MRI opaque2 lines and conversion of standard lines to QPM germplasm. The main selection steps in QPM breeding involve assessing kernel modifications and tryptophan level in each generation. Herein, we present the results of the analysis for these traits on F3 and BC1F1 generations of QPM x opaque2, opaque2 x QPM and standard lines x QPM crosses. The results showed that the majority the genotypes had kernel types 2 and 3 (good modifications). The whole grain tryptophan content in F3 and BC1F1 genotypes of crosses between QPM and opaque2 germplasm was at the quality protein level, with a few exceptions. All BC1F1 genotypes of standard lines x QPM had tryptophan content in the range of normal maize, while majority of F3 genotypes had tryptophan content at level of QPM. The progeny (with increased tryptophan levels) of QPM and opaque2 crosses had significantly higher tryptophan content compared to the progeny of crosses between standard and QPM lines - 0.098 to 0.114 and 0.080, respectively. All genotypes that had poorly modified kernels and/or low tryptophan content will be discarded from further breeding

Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration

Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration Jelena Mitrović1, Tanja Ilić1, Ivan Jančić2, Biljana Bufan2, Miroslav Savić3, Snežana Savić1 1 Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia 2 Department of Microbiology and Immunology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia 3 Department of Pharmacology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia Estimation of endotoxin level in parenteral formulations is a prerequisite for numerous in vitro tests in preclinical studies and for future clinical development. However, the Limulus amoebocyte lysate (LAL) test in formulations containing nanoparticles could often lead to misinterpretation of results. Therefore, we tested if endotoxins could be detected in nanocrystal dispersions by the commercial gel clot assay kit. Nanocrystals of DK-I-56-1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one) were prepared by wet-ball milling, lyophilized and reconstituted with water for injection prior experiment. Different dilutions of nanocrystal dispersion in LAL reagent water were prepared as well as positive and negative control. Despite difficulties to detect gel clots, they were visible in the sample at dilutions 1:75 and below. According to the protocol, the endotoxin limit was estimated to be 25.00 EU/ml, which corresponds to <12.50 EU/mg of DK-I-56-1. This value relates to the endotoxin limit for diazepam, with the similar dosing regimen as proposed for DK-I-56-1

Modifikacija zrna i sadržaj triptofana u segregirajućim generacijama kukuruza visokog kvaliteta proteina

Maize has poor nutritional value due to deficiency of two essential amino acids - tryptophan and lysine. Although recessive opaque2 (o2) mutation significantly increases their content in the endosperm, incorporation of opaque2 into high yielding cultivars was not commercially successful, because of its numerous agronomic and processing problems due to soft endosperm. Quality protein maize - QPM has lately been introduced as opaque2 maize with improved endosperm hardness and improved agronomic traits, but mostly within tropical and subtropical germplasm. The ongoing breeding project at MRI includes improvement of MRI opaque2 lines and conversion of standard lines to QPM germplasm. The main selection steps in QPM breeding involve assessing kernel modifications and tryptophan level in each generation. Herein, we present the results of the analysis for these traits on F3 and BC1F1 generations of QPM x opaque2, opaque2 x QPM and standard lines x QPM crosses. The results showed that the majority the genotypes had kernel types 2 and 3 (good modifications). The whole grain tryptophan content in F3 and BC1F1 genotypes of crosses between QPM and opaque2 germplasm was at the quality protein level, with a few exceptions. All BC1F1 genotypes of standard lines x QPM had tryptophan content in the range of normal maize, while majority of F3 genotypes had tryptophan content at level of QPM. The progeny (with increased tryptophan levels) of QPM and opaque2 crosses had significantly higher tryptophan content compared to the progeny of crosses between standard and QPM lines - 0.098 to 0.114 and 0.080, respectively. All genotypes that had poorly modified kernels and/or low tryptophan content will be discarded from further breeding.Iako recesivna opaque2 (o2) mutacija značajno povećava sadržaj lizina i triptofana u zrnu kukuruza, inkorporacija opaque2 u visoko prinosne genotipove nije uspela, zbog brojnih problema koji su se javili kao posledica mekog endosperma. Kukuruz visokog kvaliteta proteina (QPM) je opaque2 kukuruz sa poboljšanom tvrdoćom zrna i dobrim agronomskim performansama, stvoren prvenstveno od tropske i subtropske germplazme. U Institutu za kukuruz je u toku projekat koji za cilj ima poboljšanje sopstvenih opaque2 linija i prevođenje standardnih linija u QPM kukuruz. U ovom radu predstavljamo rezultate analiza modifikacije zrna i sadržaja triptofana u F3 i BC1F1 generacijama ukrštanja QPM x opaque2, opaque2 x QPM i standardne linije x QPM. Većina genotipova je imala zrno tipa 2 i tipa3 (dobre modifikacije). Sadržaj triptofana u celom zrnu genotipova ukrštanja QPM i opaque2 linija je bio na nivou karakterističnom za QPM, sa nekoliko izuzetaka. Sadržaj triptofana u potomstvu ukrštanja standardne linije x QPM je bio povećan kod većine F3 genotipova. Potomstvo (sa povećanim sadržajem triptofana) ukrštanja QPM i opaque2 linija je imalo znatno veći sadržaj ove aminokiseline u odnosu na potostvo ukrštanja standardne linije x QPM - - od 0.098 do 0.114 prema 0.080. Genotipovi sa lošim modifikacija zrna i/ili niskim sadržajem triptofana ce biti eleminisani iz daljeg procesa selekcije

Uticaj resorptivne membrane humanog porekla na regeneraciju koštanog tkiva - patohistološka studija

Background/Aim. Filling a bone defect with bone substitution materials is a therapy of choice, but the infiltration of connective tissue from the mucoperiostal flap may compromise a healing of bone substitutions with bony wall defects. Application of membrane as a barrier is indicated as a solution to this problem. The aim of this study was to show a pathohistological view of bone regeneration and the significance of human resorbable demineralized membrane (HRDM), 200 μ thick in bone regeneration regarding mandibular defects in an experiment on dogs. Methods. The experiment was performed on six dogs. Bone defects were created in all six dogs on the right side of the mandible after the elevation of the mucoperiostal flap. One defect was filled with human deproteinised bone (HDB), and in between HDB and soft tissue RHDM of 200 μ thick was placed. In the second defect, used as a control one, only HDB without RHDM was placed. Two dogs were sacrificed two months after the surgery, another two dogs four months after the surgery and the last two dogs six months after the surgery. After that, samples of bone tissue were taken for histopathological analysis. Results. In all the six dogs with defects treated with HDB and RHDM the level of bone regeneration was much higher in comparison with the control defects without RHDM. Conclusion. Membrane, as a cover of bony defect, is useful and benefits bone regeneration. Bony defects covered with RHDM show better bony healing despite the fact that bone regeneration was not fully complete for as long as six months after the RHDM implantation.Uvod/Cilj. Popunjavanje koštanih defekata zamenicima kosti je terapija izbora, ali prorastanje vezivnog tkiva iz mukoperiostalnog režnja može kompromitovati sam proces zarastanja zamenika kosti sa zidovima koštanih defekata. U cilju rešavanja ovog problema indikovana je primena membrane kao barijere. Cilj ove studije bio je da se prikaže patohistološki izgled koštane regeneracije i značaj resorptivne demineralizovane membrane humanog porekla (RHDM), debljine 200 mikrona, u regeneraciji kosti kod mandibularnih defekata u eksperimentu rađenom na psima. Metode. Eksperiment je vršen na šest pasa kojima je sa desne strane donje vilice, po podizanju mukoperiostalnog režnja, pravljen koštani defekt. U jedan defekt stavljana je humana deproteinizovana kost (HDK), a između nje i mekotkivnog dela stavljana je RHDM debljine 200 mikrona. U drugi defekt, koji je služio kao kontrola, stavljena je samo HDK, bez RHDM. Dva psa žrtvovana su dva meseca nakon hirurške intervencije, dva posle četiri meseca, a preostala dva šest meseci nakon hirurške intervencije. Nakon žrtvovanja uzimani su isečci za patohistološku analizu. Rezultati. Kod svih šest pasa kod kojih je u koštani defekt ugrađena HDK i RHDM stepen koštane regeneracije bio je daleko veći u odnosu na kontrolne defekte bez RHDM. Zaključak. Membrana, kao pokrivač koštanog defekta, podesna je i poboljšava koštanu regeneraciju. Koštani defekti prekriveni RHDM pokazali su značajno bolje koštano zarastanje, mada koštana regeneracija nije bila potpuna ni šest meseci nakon njene ugradnje

Analiza varijabilnosti normalnih i opaque2 inbred linija kukuruza

Nutritional value of maize is poor due to deficiency of two essential amino acids - tryptophan and lysine. It was shown than opaque2 (o2) mutations can nearly double the lysine and tryptophan content of the endosperm compared with the normal type. Maize Research Institute Gene bank maintains a collection of opaque2 inbred lines developed in the seventies, primarily based on kernel hardness and analytical methods. In order to describe these lines in more detail they were analyzed for tryptophan content and subjected to SSR analysis with opaque2 markers, a marker for endosperm hardness modifier gene and the most significant amino acid modifier markers. Also, a pathogenicity test for inbred lines tolerance to Fusarium spp., which is one of the most important maize pathogens in our region and a causer of maize stalk, root and ear rot, was performed. Differences in tryptophan content between normal and opaque2 lines were significant. All primers used for distinguishing alleles between normal and opaqu2 inbred lines gave positive results. Each genotype gave a specific allelic pattern with amino acid modifier gene primers, without any obvious correspondence to the tryptophan content. Phythopathogenicity test showed on average higher susceptibility to Fusarium graminearum of opaque2 genotypes. These results gave an insight into the applicability of the methods in describing opaque2 lines to be converted into quality protein maize QPM - genotype in which opaque2 has been incorporated along with associated modifiers.Kukuruz ima nisku hranjivu vrednost zbog nedostatka dve esencijalne amino kiseline - triptofana i lizina. Utvrđeno je da opaque2 (o2) mutacija može skoro udvostručiti sadržaj lizina i triptofana u endospermu kukuruza. Banka gena instituta za kukuruz 'Zemun Polje' poseduje kolekciju opaque2 inbred linija razvijenih tokom sedamdesetih godina, prvenstveno na osnovu tvrdoće zrna. Sa ciljem detaljnijeg opisa ovih linija urađena je analiza sadržaja triptofana i SSR analiza sa opaque2 markerima, markerom za gen modifikator tvrdoće endosperma i najsignifikantnijim markerima za gene modifikatore amino kiselina. Takođe je urađen test fitopatogenosti radi utvrđivanja osetljivosti opaque2 genotipova na Fusarium gramaenarum, jednog od najvažnijih prouzrokovača truleži stabla, korena i klipa kukuruza u našem regionu. Utvrđene su značajne razlike u sadržaju triptofana između normalnih i opaque2 linija kukuruza. Svi SSR prajmeri korišćeni za razlikovanje normalnih i opaque2 linija su dali pozitivne rezultate. Svaki od analiziranih genotipova je dao specifičnu alelnu sliku sa markerima za gene modifikatore amino kiselina, bez očigledne saglasnosti sa sadržajem triptofana. Test fitopatogenosti je, u proseku, pokazao veću osetljivost opaque2 linija na Fusarium graminearum. Ovi rezultati su dali uvid u primenjivost navedenih metoda za opisivanje opaque2 linija radi njihovog konvertovanja u kukuruz visokog kvaliteta proteina (QPM) - genotipa u koji se opaque2 inkorporira zajedno sa odgovarajućim genima modifikatorima