Browsing by Index "PUBMED"

Now showing 1 - 20 of 7377
  • Publication
    1,3,4-thiadiazole derivatives. Synthesis, structure elucidation, and structure-antituberculosis activity relationship investigation
    (AMER CHEMICAL SOC, 2004) Oruc, EE; Rollas, S; Kandemirli, F; Shvets, N; Dimoglo, AS
    A series of 2,5-disubstituted-1,3,4-thiadiazoles were synthesized, the compounds structures were elucidated and screened for the antituberculosis activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Among the tested compounds, 2-phenylamino-5-(4-fluorophenyl)-1,3,4-thiadiazole 22 showed the highest inhibitory activity. The relationships between the structures of compounds and their antituberculosis activity were investigated by the Electronic-Topological Method (ETM) and feed forward neural networks (FFNNs) trained with the back-propagation algorithm. As a result of the approach, a system of pharmacophores and anti-pharmacophores has been found that effectively separates compounds of the examination set into groups of active and inactive compounds. The system can be applied to the screening and design of new active compounds possessing skeletons similar to those used in the present study.
  • Publication
    17 beta-estradiol increases intracellular free calcium concentrations of human vascular endothelial cells and modulates its responses to acetylcholine
    (INFORMA HEALTHCARE, 1997) Moini, H; Bilsel, S; Bekdemir, T; Emerk, K
    In this study, we have investigated the effect of (17)beta-estradiol (E2) on intracellular free calcium concentrations ([Ca2+](i)) in human umbilical vein endothelial cells (HUVEC) using fura-2 fluorescence, E2 at concentrations of 1nM-1 mu M was added subsequently to HUVEC cultures which were either deprived of estrogens or preincubated with E2 (100 nM) for 23 hours, In both groups of cultures, E2 stimulated significant increases in [Ca2+](i) in a dose-dependent manner, The effects were more prominent in E2-deprived cells, Preincubation of cells with tamoxifen or the presence of it in the buffer during the experiments did not inhibit the response of the cells to E2, Experiments performed in Ca2+ free/EGTA buffer yielded transient increases in [Ca2+](i) suggesting release of Ca2+ from intracellular stores was responsible for the initial peak, while sustained elevations were supported by Ca2+ influx from the extracellular space, Addition of La3+ abolished the sustained [Ca2+](i) elevations, Carbachol (CCh) (1nM, 100 nM) did not induce changes in [Ca2+](i) of estrogen-deprived cells but produced significant increases in [Ca2+](i) of the same cells after incubation with E2 for 30 minutes, The cultures which were preincubated with E2 for 24 hours responded to carbachol directly, The results of our study indicate that E2 may modulate the functions of endothelial cells after only a brief exposure and also may be necessary for the response to acetylcholine especially at low concentrations.
  • Publication
    17Beta-estradiol modulates endothelin-1 expression and release in human endothelial cells
    (2000) ÖZER, SIDIKA AYŞE; Bilsel, A. S.; Moini, H.; Tetik, E.; Aksungar, F.; Kaynak, B.; Ozer, A.
    OBJECTIVE: In this study the role of 17beta-estradiol (E2) in the regulation of endothelin-1 (ET-1) mRNA expression and secretion was investigated in cultured human umbilical vein endothelial cells (HUVECs). METHODS: Endothelial cells were either deprived of or treated with 17beta-estradiol (10(-9), 10(-7) M) for 48 h. After the incubation, the effect of E2 on ET-1 gene expression was evaluated by Northern blot analysis. ET-1 release into the media was measured by radioimmunoassay after 6 h of incubation under basal conditions and upon stimulation with thrombin (4 U/ml). In addition, the cyclic guanosine 5'-monophosphate (cGMP) content of cells was assayed by immunoassay. In order to exclude the role of nitric oxide (NO) in E2-induced effects on endothelin-1 gene expression and secretion, nitric oxide synthase (NOS) inhibitor, N-nitro L-arginine methyl ester (1 mM) (L-NAME) was added to the media of some cultures. RESULTS: Incubation of HUVECs with 10(-9) and 10(-7) M E2 for 48 h resulted in a 30 and 47% inhibition of ET-1 mRNA expression, respectively. Incubation with E2 also decreased the basal and thrombin-stimulated ET-1 release while increasing the cGMP content of cells significantly. NOS inhibitor L-NAME increased the release of ET-1 from E2-incubated cells but did not alter the ET-1 release from hormone-deprived cells. However, ET-1 secretion of E2-treated cells were significantly less than the deprived ones. Northern blot analyses also demonstrated that inhibition of NOS only partly attenuated the effect of E2 on ET-1 gene expression. In the presence of L-NAME, treatment with 10(-7) M E2 caused a 12% decrease in ET-1 gene expression. CONCLUSION: The results demonstrate that E2 may play both direct and indirect role in regulation of ET-1 gene expression and production in human endothelial cells. E2-induced increase in NO but decrease in ET-1 production may partly explain the mechanism of the protective effects of the hormone on the cardiovascular system.
  • Publication
    2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography after breast conserving surgery: Correlation with molecular markers of breast cancer
    (MEDKNOW PUBLICATIONS & MEDIA PVT LTD, 2016) TUROĞLU, HALİL TURGUT; Ozguven, Salih; Inanir, Sabahat; Turoglu, Halil Turgut; Erdil, Tanju Yusuf; Ugurlu, Mustafa Umit; Gulluoglu, Bahadir
    Aim: To investigate the role of 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18-FDG) positron emission tomography/computed tomography (PET/CT) early after breast-conserving surgery (BCS) in patients with breast cancer (BC) and whether we can determine which molecular biomarkers of breast carcinoma put the patients at risk. Materials and Methods: This retrospective study involved 88 patients with histologically proven T1 or T2 BC, who were treated with BCS and underwent F-18-FDG PET/CT study. The correlation between biological markers (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], and Ki-67) of the primary tumor and F-18-FDG PET/CT findings was analyzed. Results: F-18-FDG PET/CT demonstrated the presence of BC disease (locoregional disease [LRD], distant metastases, or contralateral BC) in 26 of 88 patients (29.5%). Regarding immunohistochemical profiles, BC expressing high levels of Ki-67 were associated with an increased percentage of LRD, which was the major recurrence pattern on F-18-FDG PET/CT. Although the BC disease was observed more commonly in patients with HER2 positivity compared to those of HER2 negative, the difference did not reach statistical significance. The patients with T2 tumor or a higher histopathological grade had a higher percentage of BC disease. Conclusions: This study demonstrated that patients with early stage BC treated with BCS have a remarkable risk of the presence of BC even early after surgery, and there was a clinically important relationship between F-18-FDG PET/CT findings and biological markers of BC. These findings suggest that high-risk molecular biomarkers (Ki-67, HER2) can be taken into account in the decision-making the process for both preoperative imaging and planning of the surgical approach.
  • Publication
    2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2013-11) TATAR, ESRA; Kucukguzel, Ilkay; Satilmis, Gokhan; Gurukumar, K. R.; Basu, Amartya; Tatar, Esra; Nichols, Daniel B.; Talele, Tanaji T.; Kaushik-Basu, Neerja
    Hepatitis C virus (HCV) NS5B polymerase is an important and attractive target for the development of anti-HCV drugs. Here we report on the design, synthesis and evaluation of twenty-four novel allosteric inhibitors bearing the 4-thiazolidinone scaffold as inhibitors of HCV NS5B polymerase. Eleven compounds tested were found to inhibit HCV NS5B with IC50 values ranging between 19.8 and 64.9 RM. Compound 24 was the most active of this series with an IC50 of 5.6 mu M. A number of these derivatives further exhibited strong inhibition against HCV lb and 2a genotypes in cell based antiviral assays. Molecular docking analysis predicted that the thiazolidinone derivatives bind to the NS5B thumb pocketII (TP-II). Our results suggest that further optimization of the thiazolidinone scaffold may be possible to yield new derivatives with improved enzyme- and cell-based activity. (C) 2013 Elsevier Masson SAS. All rights reserved.
  • Publication
    2-mercaptoethane sulfonate (MESNA) protects against biliary obstruction-induced oxidative damage in rats
    (ELSEVIER IRELAND LTD, 2006) ERCAN, FERİHA; Sener, G; Kabasakal, L; Sehirli, O; Ercan, F; Gedik, N
    The aim of this study was to assess the antioxidant and antifibrotic effects of chronic administration of 2-mercaptoethane sulfonate (MESNA) on oxidative liver damage and fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). MESNA (150 mg/kg, i.p.) or saline was administered for 28 days. At the end of the experiment, rats were killed by decapitation. Serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were determined to assess liver function. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehidrogenase (LDH) were also assayed in serum samples. Liver tissues were taken for determination of the free radicals, hepatic malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker was also determined. Serum AST, ALT, LDH and TNF-alpha levels were elevated in the BDL group as compared to control group, while this increase was significantly decreased by MESNA treatment. BDL caused a significant (p < 0.05-0.001) decrease in GSH levels while MDA levels and MPO activity were increased in the liver tissue. These changes were reversed by MESNA treatment. Collagen contents of the liver tissue was increased by BDL (P < 0.001), and reversed back to the control levels with MESNA. Since MESNA administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic functions, it seems likely that MESNA with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction. (c) 2006 Published by Elsevier Ireland Ltd.
  • Publication
    2-mercaptoethane sulfonate (MESNA) protects against burn-induced renal injury in rats
    (ELSEVIER SCI LTD, 2004) YEGEN, BERRAK; Sener, G; Sehirli, O; Erkanli, G; Cetinel, S; Gedik, N; Yegen, B
    Animal models of thermal injury implicate oxygen radicals as causative agents in local wound response and distant organ injury following burn. In this study we investigated the putative protective effects of 2-mercaptoethane sulfonate (MESNA) against oxidative kidney damage in rats with thermal injury. Under ether anaesthesia, shaved dorsum of the rats was exposed to 90 degreesC bath for 10 s to induce burn injury. Rats were decapitated either 6 or 24 h after burn injury. MESNA was administered i.p. immediately after burn injury. MESNA injections were repeated once more 12 h after the first injection in the 24 h burn group. In the control group the same protocol was applied except that the dorsum was dipped in a 25 degreesC water bath for 10 s. Kidney tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, protein oxidation (PO), myeloperoxidase (MPO) activity and collagen contents. Creatinine, urea concentrations (BUN) and lactate dehydrogenase (LDH) in blood were measured for the evaluation of renal functions and tissue damage, respectively. Tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decrease in GSH level, significant increase in MDA level, protein oxidation (PO), MPO activity and collagen content of renal tissue. Serum creatinine was slightly increased at the early phase of thermal trauma but not changed in 24 h groups. On the other hand BUN and LDH were significantly elevated by thermal trauma in both 6 and 24 h of burn groups. Treatment of rats with MESNA significantly increased the GSH level and decreased the MDA level, PO, MPO activity, collagen contents, BUN and LDH. Since MESNA reversed the oxidant responses seen in burn injury, it seems likely that MESNA could protect against thermal trauma-induced renal damage. (C) 2004 Elsevier Ltd and ISBI. All rights reserved.
  • Publication
    2016 ESC and ACC/AHA/HFSA heart failure guideline updates: Changes, similarities, differences, and unresolved isssues
    (TURKISH SOC CARDIOLOGY, ) SARI, İBRAHİM; Sari, Ibrahim; Cavusoglu, Yuksel; Temizhan, Ahmet; Yilmaz, Mehmet Birhan; Eren, Mehmet
  • Publication
    2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis
    (BMJ PUBLISHING GROUP, 2018-09) DURUÖZ, MEHMET TUNCAY; Osthoff, Anne-Kathrin Rausch; Niedermann, Karin; Braun, Juergen; Adams, Jo; Brodin, Nina; Dagfinrud, Hanne; Duruoz, Tuncay; Esbensen, Bente Appel; Guenther, Klaus-Peter; Hurkmans, Emailie; Juhl, Carsten Bogh; Kennedy, Norelee; Kiltz, Uta; Knittle, Keegan; Nurmohamed, Michael; Pais, Sandra; Severijns, Guy; Swinnen, Thijs Willem; Pitsillidou, Irene A.; Warburton, Louise; Yankov, Zhivko; Vlieland, Theodora P. M. Vliet
    Regular physical activity (PA) is increasingly promoted for people with rheumatic and musculoskeletal diseases as well as the general population. We evaluated if the public health recommendations for PA are applicable for people with inflammatory arthritis (iA
  • Publication
    2021 Guideline for the Management of COPD Exacerbations: Emergency Medicine Association of Turkey (EMAT) / Turkish Thoracic Society (TTS) Clinical Practice Guideline Task Force
    (WOLTERS KLUWER MEDKNOW PUBLICATIONS, 2021) AKOĞLU, HALDUN; Dogan, Nurettin Ozgur; Varol, Yelda; Kokturk, Nurdan; Aksay, Ersin; Alpaydin, Aylin Ozgen; Corbacioglu, Seref Kerem; Aksel, Gokhan; Baha, Ayse; Akoglu, Haldun; Karahan, Sevilay; Sen, Elif; Ergan, Begum; Bayram, Basak; Yilmaz, Serkan; Gurgun, Alev; Polatli, Mehmet
    Chronic obstructive pulmonary disease (COPD) is an important public health problem that manifests with exacerbations and causes serious mortality and morbidity in both developed and developing countries. COPD exacerbations usually present to emergency departments, where these patients are diagnosed and treated. Therefore, the Emergency Medicine Association of Turkey and the Turkish Thoracic Society jointly wanted to implement a guideline that evaluates the management of COPD exacerbations according to the current literature and provides evidence-based recommendations. In the management of COPD exacerbations, we aim to support the decision-making process of clinicians dealing with these patients in the emergency setting.
  • Publication
    22q11 deletion syndrome: current perspective
    (DOVE MEDICAL PRESS LTD, 2015-05) Hacihamdioglu, Bulent; Hacihamdioglu, Duygu; Delil, Kenan
    Chromosome 22q11 is characterized by the presence of chromosome-specific low-copy repeats or segmental duplications. This region of the chromosome is very unstable and susceptible to mutations. The misalignment of low-copy repeats during nonallelic homologous recombination leads to the deletion of the 22q11.2 region, which results in 22q11 deletion syndrome ( 22q11DS). The 22q11.2 deletion is associated with a wide variety of phenotypes. The term 22q11DS is an umbrella term that is used to encompass all 22q11.2 deletion-associated phenotypes. The haploinsufficiency of genes located at 22q11.2 affects the early morphogenesis of the pharyngeal arches, heart, skeleton, and brain. TBX1 is the most important gene for 22q11DS. This syndrome can ultimately affect many organs or systems
  • Publication
    3-Pyridinylboronic acid normalizes the effects of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure in zebrafish embryos
    (TAYLOR & FRANCIS LTD, ) ALTURFAN, EBRU IŞIK; Ustundag, Fumet Duygu; Unal, Ismail; Cansiz, Derya; Ustundag, Unsal Veli; Subasat, Hulya Kara; Alturfan, A. Ata; Tiber, Pinar Mega; Emekli-Alturfan, Ebru
    1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that damages dopaminergic neurons. Zebrafish has been shown to be a suitable model organism to investigate the molecular pathways in the pathogenesis of Parkinson's disease and also for potential therapeutic agent research. Boron has been shown to play an important role in the neural activity of the brain. Boronic acids are used in combinatorial approaches in drug design and discovery. The effect of 3-pyridinylboronic acid which is an important sub-class of heterocyclic boronic acids has not been evaluated in case of MPTP exposure in zebrafish embryos. Accordingly, this study was designed to investigate the effects of 3-pyridinylboronic acid on MPTP exposed zebrafish embryos focusing on the molecular pathways related to neurodegeneration and apoptosis by RT-PCR. Zebrafish embryos were exposed to MPTP (800 mu M); MPTP + Low Dose 3-Pyridinylboronic acid (50 mu M) (MPTP + LB) and MPTP + High Dose 3-Pyridinylboronic acid (100 mu M) (MPTP + HB) in well plates for 72 hours post fertilization. Results of our study showed that MPTP induced a P53 dependent and Bax mediated apoptosis in zebrafish embryos and 3-pyridinylboronic acid restored the locomotor activity and gene expressions related to mitochondrial dysfunction and oxidative stress due to the deleterious effects of MPTP, in a dose-dependent manner.
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  • Publication
    3D bioprinting applications in neural tissue engineering for spinal cord injury repair
    (ELSEVIER, 2020) GÜNDÜZ, OĞUZHAN; Bedir, Tuba; Ulag, Songul; Ustundag, Cem Bulent; Gunduz, Oguzhan
    Spinal cord injury (SCI) is a disease of the central nervous system (CNS) that has not yet been treated successfully. In the United States, almost 450,000 people suffer from SCI. Despite the development of many clinical treatments, therapeutics are still at an early stage for a successful bridging of damaged nerve spaces and complete recovery of nerve functions. Biomimetic 3D scaffolds have been an effective option in repairing the damaged nervous system. 3D scaffolds allow improved host tissue engraftment and new tissue development by supplying physical support to ease cell function. Recently, 3D bioprinting techniques that may easily regulate the dimension and shape of the 3D tissue scaffold and are capable of producing scaffolds with cells have attracted attention. Production of biologically more complex microstructures can be achieved by using 3D bioprinting technology. Particularly in vitro modeling of CNS tissues for in vivo transplantation is critical in the treatment of SCI. Considering the potential impact of 3D bioprinting technology on neural studies, this review focus on 3D bioprinting methods, bio-inks, and cells widely used in neural tissue engineering and the latest technological applications of bioprinting of nerve tissues for the repair of SCI are discussed.
  • Publication
    3D Printed Polycaprolactone/Gelatin/Bacterial Cellulose/Hydroxyapatite Composite Scaffold for Bone Tissue Engineering
    (MDPI, 2020-08-29) ŞAHİN, ALİ; Cakmak, Abdullah M.; Unal, Semra; Sahin, Ali; Oktar, Faik N.; Sengor, Mustafa; Ekren, Nazmi; Gunduz, Oguzhan; Kalaskar, Deepak M.
    Three-dimensional (3D) printing application is a promising method for bone tissue engineering. For enhanced bone tissue regeneration, it is essential to have printable composite materials with appealing properties such as construct porous, mechanical strength, thermal properties, controlled degradation rates, and the presence of bioactive materials. In this study, polycaprolactone (PCL), gelatin (GEL), bacterial cellulose (BC), and different hydroxyapatite (HA) concentrations were used to fabricate a novel PCL/GEL/BC/HA composite scaffold using 3D printing method for bone tissue engineering applications. Pore structure, mechanical, thermal, and chemical analyses were evaluated. 3D scaffolds with an ideal pore size (similar to 300 mu m) for use in bone tissue engineering were generated. The addition of both bacterial cellulose (BC) and hydroxyapatite (HA) into PCL/GEL scaffold increased cell proliferation and attachment. PCL/GEL/BC/HA composite scaffolds provide a potential for bone tissue engineering applications.
  • Publication
    3D printing in the battle against COVID-19
    (SPRINGERNATURE, 2021-02) GÜNDÜZ, OĞUZHAN; Aydin, Ayca; Demirtas, Zeynep; Ok, Merve; Erkus, Huseyin; Cebi, Gizem; Uysal, Ebru; Gunduz, Oguzhan; Ustundag, Cem Bulent
    Coronavirus disease 2019 (COVID-19) that is SARS-CoV-2, previously called 2019-nCoV, is a kind of human infectious disease caused by severe acute respiratory syndrome coronavirus. Based on the prompt increase of human infection rate, COVID-19 outbreak was distinguished as a pandemic by the World Health Organization (WHO). By 2020, COVID-19 becomes a major health problem all around the world. Due to the battle against COVID-19, there are some adversities that are encountered with. The most significant difficulty is the lack of equipment for the COVID-19 battle. Lately, there is not sufficient personal protective equipment (PPE) for hospital workers on the front lines in this terrifying time. All around the world, hospitals are overwhelmed by the volume of patients and the lack of personal protective equipment including face masks, gloves, eye protection and clothing. In addition, the lack of nasal swabs, which are necessary components, that are used for testing is another issue that is being faced. There are a small number of respirators, which are emergency devices that help patients breathe for a short period of time. To overcome the limited number of equipment available, the foremost solution can be 3D printing that allows three-dimensional renderings to be realized as physical objects with the use of a printer and that revolutionized prototyping. Low-cost desktop 3D printers allow economical 3D models and guides but have less quality approvals. 3D printing is already well integrated into the process of COVID-19 battle by manufacturing the equipment that are convenient. The goals of this review are to explore the techniques of 3D printing for the equipment that are used for COVID-19 battle and evaluate the materials that are used for manufacturing and the manufactured equipment. Lastly, the advantages and disadvantages of 3D printing are figured out.
  • Publication
    3D Propolis-Sodium Alginate Scaffolds: Influence on Structural Parameters, Release Mechanisms, Cell Cytotoxicity and Antibacterial Activity
    (MDPI, 2020-11-02) AKSU, MEHMET BURAK; Aranci, Kubra; Uzun, Muhammet; Su, Sena; Cesur, Sumeyye; Ulag, Songul; Amin, Al; Guncu, Mehmet Mucahit; Aksu, Burak; Kolayli, Sevgi; Ustundag, Cem Bulent; Silva, Jorge Carvalho; Ficai, Denisa; Ficai, Anton; Gunduz, Oguzhan
    In this study, the main aim was to fabricate propolis (Ps)-containing wound dressing patches using 3D printing technology. Different combinations and structures of propolis (Ps)-incorporated sodium alginate (SA) scaffolds were developed. The morphological studies showed that the porosity of developed scaffolds was optimized when 20% (v/v) of Ps was added to the solution. The pore sizes decreased by increasing Ps concentration up to a certain level due to its adhesive properties. The mechanical, swelling-degradation (weight loss) behaviors, and Ps release kinetics were highlighted for the scaffold stability. An antimicrobial assay was employed to test and screen antimicrobial behavior of Ps against Escherichia coli and Staphylococcus aureus strains. The results show that the Ps-added scaffolds have an excellent antibacterial activity because of Ps compounds. An in vitro cytotoxicity test was also applied on the scaffold by using the extract method on the human dermal fibroblasts (HFFF2) cell line. The 3D-printed SA-Ps scaffolds are very useful structures for wound dressing applications.
  • Publication
    40 Hz auditory steady-state response in eleven subjects with false hearing loss
    (WILEY, 2020) ATILGAN, ATILIM; Yuksel, Mustafa; Atilgan, Atilim; Derinsu, Ufuk
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  • Publication
    5-fluorouracil-loaded chitosan microspheres: Preparation and release characteristics
    (TAYLOR & FRANCIS LTD, 1996) Akbuga, J; Bergisadi, N
    Cross-linked chitosan microspheres containing 5-Fluorouracil (5-FU) were prepared. Variables believed to be important for microsphere properties were examined; these included: drug and chitosan concentrations, cross-linking process, the type of oil, stirring rate and also additives. Initial 5-FU concentration, the type and concentration of chitosan, the viscosity of oil phase and glutaraldehyde concentration affected drug release from chitosan microspheres. 5-FU release from cross-linked chitosan microspheres is characterized by an initial rapid release of drug. Addition of substances such as alginic acid, chitin, agar, sodium caprylate and stearic acid changed the release properties of 5-FU microspheres.