Granulomatous meningo-encephalitis caused by Toxoplasma gondii in three bulls, a possible explanation for unexplained sporadic bovine meningo-encephalitis

peer reviewe

Nicotinamide-functionalized multiwalled carbon nanotubes increase insulin production in pancreatic beta cells via MIF pathway

Ioana Ilie,1 Razvan Ilie,2 Teodora Mocan,3 Flaviu Tabaran,4 Cornel Iancu,4 Lucian Mocan4 1Department of Endocrinology, 2Department of Microbiology, 3Department of Physiology, 4Third Surgery Clinic, Department of Nanomedicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania Abstract: Recent data in the literature support the role of nicotinamide (NA) as a pharmacologic agent that stimulates pancreatic beta-cells to produce insulin in vitro. There are data showing that carbon nanotubes may be useful in initiating and maintaining cellular metabolic responses. This study shows that administration of multiwalled carbon nanotubes (MWCNTs) functionalized with nicotinamide (NA-MWCNTs) leads to significant insulin production compared with individual administration of NA, MWCNTs, and a control solution. Treatment of 1.4E7 cells for 30 minutes with NA-MWCNTs at concentrations ranging from 1 mg/L to 20 mg/L resulted in significantly increased insulin release (0.18 ± 0.026 ng/mL for 1 mg/L, 0.21 ± 0.024 ng/mL for 5 mg/L, and 0.27 ± 0.028 ng/mL for 20 mg/L). Thus, compared with cells treated with NA only (0.1 ± 0.01 ng/mL for 1 mg/L, 0.12 ± 0.017 ng/mL for 5 mg/L, and 0.17 ± 0.01 ng/mL for 20 mg/L) we observed a significant positive effect on insulin release in cells treated with NA-MWCNTs. The results were confirmed using flow cytometry, epifluorescence microscopy combined with immunochemistry staining, and enzyme-linked immunosorbent assay techniques. In addition, using immunofluorescence microscopy techniques, we were able to demonstrate that MWCNTs enhance insulin production via the macrophage migration inhibitory factor pathway. The application and potential of NA combined with MWCNTs as an antidiabetic agent may represent the beginning of a new chapter in the nanomediated treatment of diabetes mellitus. Keywords: carbon nanotubes, NA, insulin-producing cells, insulin, macrophage migration inhibitory factor, diabetes mellitu

Surface plasmon resonance-induced photoactivation of gold nanoparticles as bactericidal agents against methicillin-resistant Staphylococcus aureus

Lucian Mocan,1 Ioana Ilie,2 Cristian Matea,1 Flaviu Tabaran,1 Ersjebet Kalman,1 Cornel Iancu,1 Teodora Mocan3 13rd Surgery Clinic, Department of Nanomedicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Department of Endocrinology, Department of Nanomedicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3Department of Physiology, Department of Nanomedicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania Abstract: Systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other bacteria are responsible for millions of deaths worldwide, and much of this mortality is due to the rise of antibiotic-resistant organisms as a result of natural selection. Gold nanoparticles synthesized using the standard wet chemical procedure were photoexcited using an 808 nm 2 W laser diode and further administered to MRSA bacteria. Flow cytometry, transmission electron microscopy, contrast phase microscopy, and fluorescence microscopy combined with immunochemical staining were used to examine the interaction of the photoexcited gold nanoparticles with MRSA bacteria. We show here that phonon–phonon interactions following laser photoexcitation of gold nanoparticles exhibit increased MRSA necrotic rates at low concentrations and short incubation times compared with MRSA treated with gold nanoparticles alone. These unique data may represent a step forward in the study of bactericidal effects of various nanomaterials, with applications in biology and medicine. Keywords: MRSA, SPR, multi-drug resistant bacteria, infection, gold nanoparticles, lase

Quantum dots in imaging, drug delivery and sensor applications

Cristian T Matea,1,* Teodora Mocan,1,2,* Flaviu Tabaran,1,3,* Teodora Pop,1,4,* Ofelia Mosteanu,1,4,* Cosmin Puia,1,5,* Cornel Iancu,1,5,* Lucian Mocan1,5,* 1Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 2Department of Physiology, University of Medicine and Pharmacy, “Iuliu Hatieganu”, 3Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, 4Department of Gastroenterology, 5Department of Surgery, University of Medicine and Pharmacy, “Iuliu Hatieganu”, Cluj-Napoca, Romania *These authors contributed equally to this work Abstract: Quantum dots (QDs), also known as nanoscale semiconductor crystals, are nanoparticles with unique optical and electronic properties such as bright and intensive fluorescence. Since most conventional organic label dyes do not offer the near-infrared (>650 nm) emission possibility, QDs, with their tunable optical properties, have gained a lot of interest. They possess characteristics such as good chemical and photo-stability, high quantum yield and size-tunable light emission. Different types of QDs can be excited with the same light wavelength, and their narrow emission bands can be detected simultaneously for multiple assays. There is an increasing interest in the development of nano-theranostics platforms for simultaneous sensing, imaging and therapy. QDs have great potential for such applications, with notable results already published in the fields of sensors, drug delivery and biomedical imaging. This review summarizes the latest developments available in literature regarding the use of QDs for medical applications. Keywords: quantum dots, biomedical applications, nanoprobes, theranostic platform

The effects of chitosan and low dose dexamethasone on extrahepatic cholestasis after bile duct ligation in Wistar rats

Inflammation and oxidative stress are important pathways in the development of liver fibrosis following biliary obstruction.Aim: To evaluate the effects of low dose dexamethasone and chitosan, a natural compound with no side-effects, on liver damage caused by bile duct ligation in rats.Materials and methods: Fifty female Wistar rats, randomly and equally divided in 5 groups: I (SHAM) underwent only laparotomy, II (BDL) with bile duct ligation, III (DEX) 0.125 mg/kg dexamethasone i.m. daily, IV (CS) 1 mg/kg chitosan by gavage and group V (DEX+CS), both substances. After six days, the following parameters were assessed from liver homogenates: malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), total SH groupings, nitric oxide (NO), and from plasma: MDA, γ-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB). A histopathological examination was performed using some of the elements of the Knodell Histological Activity Index.Results: BDL significantly increases the levels of MDA, liver enzymes, and the necro-inflammatory score compared to the sham group and it decreases the antioxidant capacity. DEX protects against lipid peroxidation and improves the antioxidant capacity, but it is not able to protect the hepatocytes. Chitosan significantly decreases (p<0.05) the levels of MDA (0.07±0.01 vs 0.10±0.01 nmoles/mg protein BDL group, p=0.027) and also ALT, TB, GGT and reduces liver necrosis and inflammation (2.75±0.95 vs 1±0, p<0.05). Both CS and DEX reduce the level of NO significantly.Conclusion: BDL induces severe oxidative stress damage after six days already. Chitosan proved very efficient in protecting the hepatocytes against oxidative stress, a fact supported by the histological findings

IN vitro toxicology : from INtestine to braIN

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Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes

Lucian Mocan1, Flaviu A Tabaran2, Teodora Mocan1, Constantin Bele3, Anamaria Ioana Orza1, Ciprian Lucan4, Rares Stiufiuc1, Ioana Manaila1, Ferencz Iulia1, Iancu Dana1, Florin Zaharie1, Gelu Osian1, Liviu Vlad1, Cornel Iancu11Department of Nanomedicine, &amp;ldquo;Iuliu Hatieganu&amp;rdquo; University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Department of Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania; 3Department of Biochemistry, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania; 4Clinical Institute of Urology and Renal Transplantation, Cluj-Napoca, RomaniaAbstract: The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called &amp;ldquo;nanophotothermolysis&amp;rdquo;. We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum albumin (HSA). With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra-arterial perfusion.Keywords: noncovalent functionalization, irradiation, tumor, malignant, MWCNT