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Mechanisms of ischemic stroke in young adults are poorly understood. The aim of the study was to investigate and compare the frequency of common variations in prothrombotic genes between young patients with ischemic stroke and controls. Fifty-one cases of first-ever ischemic stroke and 70 community-based controls aged below 50 years were studied. In both groups, the insertion/deletion 4G/5G variation (-675 4G/5G PAI-1) as well as the single-nucleotide polymorphism-844 G/A of the PAI-1 (-844 G/A PAI-1) gene promoter, factor V Leiden (FVL) G1691α, the prothrombin variant (allele 20210A, FIIG20210A), factor XIII-A Val34Leu polymorphism (FXIII-AVal34Leu) and C677T methylenotetrahydrofolate reductase (C677T MTHFR) polymorphism have been assessed. The -675 4G/5G PAI-1 allele distribution differed significantly between patients and controls (P=0.020), but no difference was found regarding the distribution of -844 G/A PAI-1 (P=0.493), FVL (P=0.199), FIIG20210A (P=0.410), FXIII-AVal34leu (P=0.160) and C677T MTHFR (P=0.788). A lower frequency of 5G/5G genotype and a higher frequency of the 4G/5G genotype of the PAI -675 4G/5G polymorphism was found in young ischemic stroke patients compared to healthy controls. Further epidemiological studies are needed to investigate the differences between different geographic areas, and prospective cohort studies are needed to investigate the possible protective role of 5G/5G polymorphism. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

The reaction of antimony(III) chloride with the bidentate substituted dithiooxamide ligand, N,N-dicyclohexyldithiooxamide (HDTOA), in 1:1 molar ratio, leads to the formation of the polymeric complex {[SbCl3(HDTOA)1.5]}n (1). The complex was characterized by FT-IR spectroscopy, 1H,13C NMR spectroscopy and TG-DTA analysis. Crystal and molecular structure of 1 was determined by X-ray diffraction analysis. Complex 1 ([C21H36Cl3N3S3Sb]) crystallizes in trigonal space group, with a = 13.8829(2) Γ…, b = 13.8829(2) Γ…, c = 27.3440(5) Γ…, Ξ± = 90.00Β°, Ξ² = 90.00Β°, Ξ³ = 120.00Β° and Z = 12. The complex is polymeric consisting by [SbCl3(HDTOA)1.5] building blocks. The octahedral geometric demand of the metal center is covered by three mutually cis chlorides and three sulfur atoms from three different HDTOA ligands. Each HDTOA ligand bridged two metal centers of two units through their sulfur donor atoms, acting as bidentate bridging ligand forming a 3D network. Complex 1 was also, evaluated for its in vitro cytotoxic activity against leiomyosarcoma (LMS) and human breast adenocarcinoma (MCF-7) cell lines. The ID50 values were higher than the corresponding of cisplatin against these cell lines. Partial Least Squares (PLS) regression analysis was carried out to correlate the variation of the ID50 values (Y-variables) with the variations of energetic parameters (X-variables), calculated from molecular docking calculation. Polyhedron

Four new organotin(IV) complexes of bis-(2,6-di-tert-butylphenol)tin(IV) dichloride [(tert-Bu-)(2)(HO-Ph)](2)SnCl2 (1) with the heterocyclic thioamides 2-mercapto-pyrimidine (PMTH), 2-mercapto-4-methyl-pyrimidine (MPMTH), 2-mercapto-pyridine (PYTH) and 2-mercapto-benzothiazole (MBZTH), of formulae {[(tert-Bu-)(2)(HO-Ph)](2)Sn(PMT)(2)}(2), {[(tert-Bu-)(2)(HO-Ph)](2)Sn(MPMT)(2)} (3), {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(PYT)} (4) and {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(MBZT)} (5), have been ;synthesized and characterized by elemental analysis, H-1-, C-13-, Sn-119-NMR, EPR, FT-IR, Raman and Mossbauer spectroscopic techniques. The crystal and molecular structures of compounds 1-5 have been determined by X-ray diffraction. The geometries around the metal center adopted in complexes 1-5 varied between tetrahedral in 1, trigonal bipyramidal in 3, 4, 5 and distorted octahedral in 2. Two carbon atoms from aryl groups and two chlorine atoms form a distorted tetrahedron in the case of 1. Two carbon, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin (IV) with trans-C-2, cis-N-2, cis-S-2-configurations in 2. However, in the case of 4 and 5 complexes two carbon, one sulfur, one nitrogen and one chloride atom form a distorted trigonal bipyramidal arrangement. Finally, in the case of 3 the trigonal bipyramidal geometry is achieved by two carbon, two sulfur and one nitrogen atom in a unique coordination mode of thioamides toward the tin(IV) cation. Compounds 1-5 were tested for their in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) cell line. Compound 3 exhibits strong cytotoxic activity against MCF-7 cells (IC50 = 0.58 +/- 0.1 mu M). Dalton Transactions

Three new antimony(III) halide complexes (SbX3, X = Cl, Br and I) with the heterocyclic thione omega-thiocaprolactam (1-azacycloheptane-2-thione, (Hthcl)) of formulae {[SbCl2(mu(2)-Cl)(Hthcl)(2)](n)} (1), {[(SbBr2(mu(2)-Br)(Hthcl)(2))(2)]} (2) and {[(Sbl(2)(mu(2)-I)(Hthcl)(2))(2)]} (3) were synthesized from the reaction of antimony(III) halides with w-thiocaprolactam in 1:2 stoichiometry. The complexes were characterized by elemental analysis, FT-IR spectroscopy, H-1, C-13 NMR spectroscopy and Thermal Gravimetry-Differential Thermal Analysis (TG-DTA). Crystal structures of the ligand w-thiocaprolactam and its complexes 1-3 were determined with single crystal X-ray diffraction analysis. Complexes 1-3 and w-thiocaprolactam were evaluated for their in vitro cytotoxic activity against leiomyosarcoma (LMS) and human breast adenocarcinoma (MCF-7) tumor cell lines. Antimony complexes 1-3 exhibit strong antiproliferative activity against both cell lines tested. The higher such activity was found for 3 with IC50 values of 0.12 +/- 0.04 mu M (LMS) and 0.76 +/- 0.16 mu M (MCF-7) which are 60 and 10 times respectively, stronger than that of cisplatin. The influence of these complexes 1-3 and w-thiocaprolactam upon the catalytic peroxidation of linoleic acid to hyperoxolinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. The results were shown negligible inhibitory activity of 1-3 against LOX. (C) 2012 Elsevier Inc. All rights reserved. J Inorg Biochem

Three new antimony(III) halide complexes (SbX3, X = Cl, Br and I) with the heterocyclic thione Ο‰-thiocaprolactam (1-azacycloheptane-2-thione, (Hthcl)) of formulae {[SbCl2(ΞΌ2-Cl)(Hthcl)2]n} (1), {[(SbBr2(ΞΌ2-Br)(Hthcl)2)2]} (2) and {[(SbI2(ΞΌ2-I)(Hthcl)2)2]} (3) were synthesized from the reaction of antimony(III) halides with Ο‰-thiocaprolactam in 1:2 stoichiometry. The complexes were characterized by elemental analysis, FT-IR spectroscopy, 1H, 13C NMR spectroscopy and Thermal Gravimetry-Differential Thermal Analysis (TG-DTA). Crystal structures of the ligand Ο‰-thiocaprolactam and its complexes 1-3 were determined with single crystal X-ray diffraction analysis. Complexes 1-3 and Ο‰-thiocaprolactam were evaluated for their in vitro cytotoxic activity against leiomyosarcoma (LMS) and human breast adenocarcinoma (MCF-7) tumor cell lines. Antimony complexes 1-3 exhibit strong antiproliferative activity against both cell lines tested. The higher such activity was found for 3 with IC50 values of 0.12 Β± 0.04 ΞΌM (LMS) and 0.76 Β± 0.16 ΞΌM (MCF-7) which are 60 and 10 times respectively, stronger than that of cisplatin. The influence of these complexes 1-3 and Ο‰-thiocaprolactam upon the catalytic peroxidation of linoleic acid to hyperoxolinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. The results were shown negligible inhibitory activity of 1-3 against LOX. J. Inorg Biochem.

A new mixed ligand-silver(I) complex of formula [Ag(tpp)2(p-Hbza)] (1) (p-HbzaH = 4-hydroxybenzoic acid and tpp = triphenylphosphine) has been synthesized and characterized by elemental analysis, mp, vibrational spectroscopy (mid- and far-FT-IR), 1H-NMR, UV-vis, ESI-MS spectroscopic techniques and X-ray crystallography. Complex 1 and the already known mixed ligand-silver(I) complexes of formulae [Ag(tpp)2(salH)] (2) (salH2 = salicylic acid or 2-hydroxy-benzoic acid) and {[Ag(tpp)3(asp)](dmf)} (3) (aspH = o-acetylsalicylic acid) were used for the clarification of the cytostatic activity mechanism. Thus, 1-3 were tested for their in vitro cytotoxic activity against leiomyosarcoma (LMS) and human breast adenocarcinoma (MCF-7) cells with trypan blue and Thiazolyl Blue Tetrazolium Bromide (MTT) assays. For both cell lines, complexes 1-3 were found to be more active than cisplatin. Due to the morphology of the LMS cells after incubation with 1-3, the type of cell death was evaluated by flow cytometry assay and DNA fragmentation. The results show that LMS cells undergo programmed cell death (apoptosis). DNA binding tests indicate the ability of complexes 1-3 to modify the activity of the cells. The binding constants of 1-3 towards calf-thymus DNA (CT-DNA) ((27.7 ± 7.9) × 104 (1), (13.3 ± 6.5) × 104 (2) and (11 ± 2.8) × 104 (3) M�1) indicate strong interaction. Moreover, the influence of complexes 1-3 on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically studied. Finally, docking studies on DNA binding interactions were performed. Metallomics

Four new organotin(IV) complexes of bis-(2,6-di-tert-butylphenol)tin(IV) dichloride [(tert-Bu-)2(HO-Ph)]2SnCl2 (1) with the heterocyclic thioamides 2-mercapto-pyrimidine (PMTH), 2-mercapto-4-methyl-pyrimidine (MPMTH), 2-mercapto-pyridine (PYTH) and 2-mercapto-benzothiazole (MBZTH), of formulae {[(tert-Bu-)2(HO-Ph)]2Sn(PMT)2} (2), {[(tert-Bu-)2(HO-Ph)]2Sn(MPMT)2} (3), {[(tert-Bu-)2(HO-Ph)]2SnCl(PYT)} (4) and {[(tert-Bu-)2(HO-Ph)]2SnCl(MBZT)} (5), have been synthesized and characterized by elemental analysis, 1H-, 13C-, 119Sn-NMR, EPR, FT-IR, Raman and Mössbauer spectroscopic techniques. The crystal and molecular structures of compounds 1-5 have been determined by X-ray diffraction. The geometries around the metal center adopted in complexes 1-5 varied between tetrahedral in 1, trigonal bipyramidal in 3, 4, 5 and distorted octahedral in 2. Two carbon atoms from aryl groups and two chlorine atoms form a distorted tetrahedron in the case of 1. Two carbon, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin(IV) with trans-C2, cis-N2, cis-S2-configurations in 2. However, in the case of 4 and 5 complexes two carbon, one sulfur, one nitrogen and one chloride atom form a distorted trigonal bipyramidal arrangement. Finally, in the case of 3 the trigonal bipyramidal geometry is achieved by two carbon, two sulfur and one nitrogen atom in a unique coordination mode of thioamides toward the tin(IV) cation. Compounds 1-5 were tested for their in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) cell line. Compound 3 exhibits strong cytotoxic activity against MCF-7 cells (IC50 = 0.58 ± 0.1 μM). Dalton Transactions

The reaction between 2-thiobarbituric acid (H(2)TBA), which was treated with an equimolar amount of potassium hydroxide, in a water with triphenytin chloride in methanol, results in the formation of the {[Ph3Sn(O-HTBA)]}(n) (1) complex. Crystals of the hydrated 1 with formula {[Ph3Sn(O-HTBA)]center dot 0.7(H2O)}(n) were growth from methanol/acetonitrile solution, of the white precipitation, filtered off, from the reaction. The crystal structure of complex 1 has been determined by X-ray diffraction at 120K. Complex 1 is polymeric. The geometry around the tin(IV) ions is trigonal bi-pyramidal with coordination to three C atoms from phenyl groups and one O atom from a de-protonated HTBA ligand. Complex 1 and the already known [(n-Bu)(3)Sn(O-HTBA)center dot H2O] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (cervical), OAW-42 (ovarian), MCF-7 (breast, ER positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (renal) and additionally, the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) and normal immortalized human mammary gland epithelial cell line MTSV17 with a Trypan Blue assay. Moreover complex I was evaluated for its in vitro cell growth proliferation activity against leiomyosarcoma cells (LMS), MCF-7 and MRC-5 cells with a Thiazolyl Blue Tetrazolium Bromide (MU) assay. The type of cell death caused by complexes 1 and 2 was also evaluated by use of flow cytometry assay. The results showed that these compounds mediate a strong cytotoxic response to normal and cancer cell lines tested through apoptosis and induce cell cycle arrest in S phase of the cell cycle, suggesting DNA intercalation (direct or indirect) with the complexes. Finally, the influence of these complexes 1 and 2 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. (C) 2011 Elsevier Masson SAS. All rights reserved. Eur J Med Chem

Experimental, epidemiologic, and clinical trial data indicate the antineoplastic effects of calcium and vitamin D in large-bowel neoplasia. The aim of this study was to determine serum levels of vitamin D metabolites and parathormone (PTH) in patients with colorectal cancer (CRC) and to extract conclusions comparing their different levels in serum with healthy individuals. Group 1 (cancer patients) was consisted of 140 patients with CRC with clinical stages Duke's A: 12, B: 52, C: 62, and D: 14. Serum levels of 25(OH)D 3, 1,25(OH)2D3, and PTH were determined in all patients. The findings are: (a) No significant difference was found in the serum levels of 25(OH)D3 in each Duke's clinical stage in cancer patients, (b) serum 1,25(OH)2D3 levels decreased with advanced cancer stages, and (c) serum levels of PTH showed a corresponding increase. Low serum levels of 1,25(OH)2D3 on one hand and increased levels of PTH in patients with CRC on the other might be strongly related to the carcinogenetic process. © 2009 Springer-Verlag.

Administration of imunno-enhanced nutritional support may decrease postoperative morbidity, mortality, and infectious complications in cancer patients. The aim of this study was to verify that perioperative enteral diet, enriched with the nutrients arginine, ribonucleic acid (RNA), and ω-3 fatty acids improves outcomes of head and neck cancer patients undergoing major surgery. Forty patients with squamous cell carcinoma of the head and neck were studied. Group 1 received no preoperative nutritional support, whereas Group 2 received an oral formula with nutrients arginine, RNA, and ω-3 fatty acids. After surgery, Group 1 received a standard enteral formula, whereas Group 2 received an enriched enteral formula. Albumin (g/dl), prealbumin, fibrinogen, CRP, Il-6, and TNFa were measured 5 days before and 8 days after surgery. No statistically significant difference was observed for all the evaluated markers between postoperative and preoperative levels for both groups. The rate of complications was significantly reduced in the total number of patients receiving immunonutrition and in the particular subgroup of well-nourished patients receiving an immuno-enhanced diet. Perioperative enteral immuno-enhanced feeding in head and neck cancer patients undergoing major surgery may influence the postoperative outcomes by reducing the frequency rate of infections and wound complications. Copyright © 2010, Taylor & Francis Group, LLC.

Direct reaction of copper(I) chloride with triphenylphosphine (tpp) in molar ratio 2: 3 and 1: 3, results in the formation of the [(tpp)Cu(mu(2)-Cl)(2)Cu(tpp)(2)] (1) and {[CuCl(tpp)(3)]center dot(CH(3)CN)} (2) complexes. The complexes have been characterized by melting point, FT-IR, UV-Vis spectroscopic data and X-ray crystallography. Complex 1 is di-nuclear. Two mu(2)-Cl atoms bridge two copper(I) ions with tetrahedral and trigonal geometry respectively. The short copper-copper bond distance of 2.9039(6) angstrom in case of 1 indicates d(10)-d(10) interaction between metal centers. Thus, our studies were extended here in the determination of the quasi-aromaticity, which results in strong Cu-Cu interactions, using the computational method of nucleus-independent chemical shifts (NICS). The NICS calculated at the inner region of the Cu(2)Cl(2)P(3) core in complex 1 is shielded up to -6.05 ppm. Complex 2 is mono-nuclear where three phosphorus and one chloride atoms form a tetrahedron around the copper(I) ion. Photolysis of both complexes 1 and 2, results in the formation of triphenylphosphine oxide. The complexes 1 and 2, were tested for their in vitro cytotoxic activity against leiomyosarcoma cells (LMS) and human breast adenocarcinoma cells (MCF-7). The type of LMS cell death caused by the complexes was also evaluated by use of a flow cytometry assay. The results show that at concentration of 5 mu M of complexes 1 and 2, 34.1% (1) and 19.6 (2)% of LMS cells undergo programmed cell death (apoptosis), while at 10 mu M, 80.4% (1) and 65.2% (2) of LMS cells undergo apoptosis. The light sensitivity of the complex is discussed in relation with the biological activity. (C) 2009 Elsevier B. V. All rights reserved. Inorganica Chimica Acta

Background and Aim: Medical humanities is a multidisciplinary field, consisting of humanities (theory of literature and arts, philosophy, ethics, history and theology), social sciences (anthropology, psychology and sociology) and arts (literature, theater, cinema, music and visual arts), integrated in the undergraduate curriculum of Medical schools. The aim of the present study is to discuss medical humanities and support the necessity of introduction of a medical humanities course in the curriculum of Greek medical schools.Materials, Methods and Results: Through the relevant Pub-Med search as well as taking into account various curricula of medical schools, it is evident that medical education today is characterized by acquisition of knowledge and skills and development of medical values and attitudes. Clinical observation with the recognition of key data and patterns in the collected information, is crucial in the final medical decision, i.e. in the complex process, through which doctors accumulate data, reach conclusions and decide on therapy. All sciences included in medical humanities are important for the high quality education of future doctors. The practice of Medicine is in large an image-related science. The history of anatomy and art are closely related, already from the Renaissance time. Studies have shown that attendance of courses on art critics improves the observational skills of medical students. Literature is the source of information about the nature and source of human emotions and behavior and of narratives of illness, and increases imagination. Philosophy aids in the development of analytical and synthetical thinking. Teaching of history of medicine develops humility and aids in avoiding the repetition of mistakes of the past, and quite often raises research and therapeutic skepticism. The comprehension of medical ethics and professional deontology guides the patient-doctor relationship, as well as the relations between physicians and their colleagues. The Medical Humanities course, which is already integrated in the undergraduate curriculum of many medical schools of Europe, USA and Australia, includes lectures by experts and students presentations on the above-mentioned areas and could be offered, for a semester, during the first years.Conclusion: The aim of Medical Humanities course is the development of imagination and interpretation of data through analytical complex procedures, the development of skills of close observation and careful interpretation of the patient "language" and the enhancement of empathy for the patients, as well as the development of the physician-patient relationship and finally the conceptualization/construction of personal and professional values. Hippokratia

The present review article regarding the kinin system-bradykinin is dealing with the biological effects of the abovementioned entity mediated by specific B1 and B2 receptors as well as with its clinical implications known nowadays. The activation of the kinin system-bradykinin is particularly important in blood pressure regulation and in inflammatory reactions, through bradykinin ability to elevate vascular permeability and to cause vasodilatation in some arteries and veins. Recent data on bradykinin formation and release, synergy with ligands, receptors for bradykinin as well as on bradykinin participation in the mitogenesis process, are given in detail. Therapeutic potentials and future applications in many clinical situations including respiratory allergic reactions, septic shock, hypertension and its treatment, hypotensive transfusion reactions, heart diseases, pancreatitis, hereditary and acquired angioedema, Alzheimer disease and liver cirrhosis with ascites, are discussed in brief. Its role as a neuromediator, regulator of several vascular and renal functions, and its participation in signaling pathways, is also discussed in some detail. Hippokratia

N Engl J Med

Introduction. Primary localized laryngeal amyloidosis is an extremely rare condition. It usually presents with hoarseness, pain and/or difficulty in breathing. Case presentation. We present the case of a 23-year-old woman with primary localized laryngeal amyloidosis who presented with hoarseness and dysphagia. Conclusion. A search of PubMed shows that dysphagia in patients with laryngeal amyloidosis has been reported only once, although this symptom is relatively common in other conditions presenting with laryngeal mass. There were no signs of any systemic disease in our patient and diagnosis was established histopathologically. She was treated surgically by microlaryngoscopy under general anesthesia and the mass was excised using a CO2 laser technology method. © 2009 Yiotakis et al.; licensee Cases Network Ltd.

Purpose: To examine the acoustic results over a long period of time, in patients who underwent ossiculoplasty with Plastipore, and to report the percentage of prosthesis extrusion and factors related to the prognosis. Procedures: Forty-two patients, who underwent ossiculoplasty with Plastipore, were studied. Patients were followed up for the next 14 years. The surgical procedures were classified as: tympanoplasty, tympanoplasty with mastoidectomy with canal wall up, and tympanoplasty with mastoidectomy with canal wall down. A successful hearing result was defined as a postoperative air-bone gap (ABG) of 20 dB or less. Results: Successful results were seen in 65% of our patients, 68.8% with a partial ossicular replacement prosthesis (PORP) and a 62.5% success rate with a total ossicular replacement prosthesis (TORP). The mean value for ABG improvement was 25.5 dB. Prosthesis extrusion occurred in 4.7%. Conclusions: The ossiculoplasty-Plastipore technique leads to good hearing results and a low percentage of prosthesis extrusion in long-term follow-ups. Copyright © 2009 S. Karger AG, Basel.

Virchows Archiv

New organotin(IV) complexes with heterocyclic thioamides 2-mercapto-benzothiazole (Hmbzt), 5-chloro-2-mercapto-benzottliazole (Hcmbzt) and 2-mercapto-benzoxazole (Hmbzo) of formulae [(C(6)H(5))(3)Sn(mbzt)] (1), [(C(6)H(5))(3)Sn(cmbzt)] (3) and [(C(6)H(5))(2)Sn(cmbzt)(2)] (4), together with the already known [(C(6)H(5))(3)Sn(mbzo)] (2), [(n-C(4)H(9))(2)Sn(cmbZt)(2)] (5) and [(CH(3))(2)Sn(cmbzt)(2)] (6) were used to study their influence on the peroxidation of oleic acid. The influence of complexes (3)-(6) upon peroxidation of oleic acid showed that the formation of reactive radicals caused the initiation of the chain radical oxidation of the substrate. The influence of complexes (1)-(6) upon the catalytic peroxidation of linoleic acid by the enzyme lipoxygenase (LOX) was also studied and compared to those of cisplatin. Compounds (1)-(6) were finally tested for in vitro cytotoxicity against leiomyosarcoma cells. (c) 2007 Elsevier Masson SAS. All rights reserved. Eur J Med Chem

In the present review article a global approach regarding the usefulness of genomic microarrays in prostate cancer management, is attempted. Cancer is a multistep process of mutations in key regulatory genes and epigenetic alterations that result in loss of balanced gene expression. A complete knowledge of the interaction between the genetic variability of the neoformation (tumor profiling) and the genetic variability of the host (inherited genome profiling), will be able to determine the better strategy against the cancer and the less toxicity for the patient. Alterations in the sequence of the hormone binding domain of the androgen receptor as well as mutations in some genes, determine radioresistance and resistance or sensitivity to some chemotherapeutic drugs. New therapies using monoclonal antibodies directed against specific extracellular binding domains of some receptors are based on molecular alterations observed in tumors. В обзоре обсуждается целесообразность применения геномных микрочипов для выявления рака предстательной железы. Рак является многоэтапным процессом мутаций в ключевых регуляторных генах и эпигенетических изменений, приводящих к утрате сбалансированной экспрессии генов. Фундаментальные знания о взаимосвязи между генетической вариабельностью опухолевых клеток (молекулярном профиле опухоли) и генетической вариабельностью хозяина (наследуемый геномный профиль) позволит выбрать наилучшую стратегию противоопухолевой терапии при низкой токсичности таковой. Изменения последовательности гормонсвязывающего домена рецептора андрогена наряду с мутациями некоторых генов определяют устойчивость к лучевой терапии и устойчивость или чувствительность к ряду химиопрепаратов. Новые виды терапии с использованием моноклональных антител против специфичных внеклеточных связывающих доменов ряда рецепторов основаны на данных о молекулярных особенностях новообразований.

Neurotrophins are proteins that regulate neuronal survival, axonal growth, synaptic plasticity and neurotransmission. They are members of the neurotrophic factors family and include factors such as the nerve growth factor (NGF), the brain derived neurotrophic factor (BDNF), the neurotrophin-3 (NT-3), and the neurotrophin-4/5 (NT-4/5). These molecules bind to two types of receptors: i) tyrosine kinase receptors (TrkA, TrkB, TrkC) and ii) a common neurotrophin receptor (p75NTR). The two receptor types can either suppress or enhance each other's actions. Neurotrophins have a multifunctional role both in the central and peripheral nervous system. They have been suggested as axonal guidance molecules during the growth and regeneration of nerves. It has also been proven that they stimulate axonal growth by mediating the polymerization and accumulation of F-actin in growth cones and axon shafts. Neurotrophins, as other neurotrophic factors, have been shown that they reduce neuronal injury by exposure to excitotoxins, glucose deprivation, or ischemia. Furthermore, the nerve regeneration promoting effect of these growth factors is well documented for many different models of central or peripheral nervous system injury. Several studies have shown that exogenous administration of these factors has protective properties for injured neurons and stimulates axonal regeneration. Based on these properties, these molecules may be used as therapeutic agents for treating degenerative diseases and traumatic injuries of both the central and peripheral nervous system. Curr Neurovasc Res

Int J Surg Pathol

BACKGROUND AND STUDY AIMS: Primary carcinoma of the gallbladder may present as acute lithiasic cholecystitis that leads to severe septic complications. The correlation between severe sepsis of the gallbladder and primary carcinoma is unclear. The goal of the present study is to examine the relation between severe septic complications of lithiasic cholecystitis and primary carcinoma of the gallbladder. PATIENTS AND METHODS: A group of 72 patients (22 males, 50 females, age range: 45-99, mean age: 68.6 years), with severe septic cholelithiasic cholecystitis was treated with emergency surgery after failure of conservative treatment, and patients found with primary carcinoma of the gallbladder were registered. The resectability and operability of the tumor were studied, as well as tumor staging and overall patient survival. RESULTS: During urgent surgery for severe septic lithiasic cholecystitis, 12 patients (12/72, 16.6%) were found with gallbladder carcinoma. Patients with septic acute lithiasic cholecystitis and carcinoma had a higher mean age compared to those without carcinoma (74.8 vs. 67.4 yrs). Eleven of 12 (91.6%) carcinomas were inoperable, despite resectability of 8 out of 12 (66.6%), and overall patient survival was limited to a few months after surgery. CONCLUSIONS: Severe septic complications in elderly patients with a long-standing history of gallbladder stones may co-exist with primary carcinoma of the gallbladder. The percentage of a gallbladder carcinoma detected in septic patients reaches up to 16.6%. Even if these patients have a poor general health, surgical intervention is a solution when they appear with severe septic clinical symptoms caused by gallstones or carcinoma, in order to avoid lethal sepsis. The possibility of a carcinoma hidden in the gallbladder must be in mind during surgery. Imaging studies before surgery may detect the carcinoma; in most cases carcinomas are inoperable, although colecystectomy may be performed during surgery. Acta Gastroenterol Belg

In multicellular organisms the development of adhesion bonds, either among cells or among cells and components of the extracellular matrix, is a crucial process. These interactions are mediated by molecules which are named adhesion molecules and play a main role both at the early stages of the development of tissue integrity and later. Cell adhesion molecules (CAMs) have a key role in several pathologies such as cancer and inflammatory diseases. Selectins, integrins and immunoglobulin gene superfamily of adhesion receptors mediate different steps of leukocyte migration from the bloodstream towards the inflammatory foci. Leukocyte interactions with the vascular endothelium are highly orchestrated processes that include the capture of free-flowing leukocytes from the blood with subsequent leukocyte rolling, arrest, firm adhesion and ensuing diapedesis. These interactions occur under high shear stresses within venules and depend on multiple families of adhesion molecules. As a response to infection mediators, leukocyte gathering is considered to be crucial for the adequate defence of the organism to any kind of injury or infection. Endothelial activation contributes significantly to the systemic inflammatory response to bacteraemia and increased expression. Release of soluble endothelial markers into the circulation has been demonstrated together with elevated plasma levels of CAMs and has been reported in bacteraemic patients. It has been proposed that infection of endothelial cells with Staphylococcus aureus, Streptococcus sanguis, or Staphylococcus epidermidis induces surface expression of ICAM-1 and VCAM-1 and monocyte adhesion. In general, leukocyte/endothelial cell interactions such as capture, rolling, and firm adhesion can no longer be viewed as occurring in discrete steps mediated by individual families of adhesion molecules but rather as a series of overlapping synergistic interactions among adhesion molecules resulting in an adhesion cascade. These cascades thereby direct leukocyte migration, which is essential for the generation of effective inflammatory responses and the development of rapid immune responses. In Vivo