The new preservative-free ophthalmic formulation of bilastine 0.6% preserves the ocular surface epithelial integrity in a comparative in vitro study.

Allergic conjunctivitis (AC) is the most common form of allergic eye disease and an increasingly prevalent condition. Topical eye drop treatments are the usual approach for managing AC, although their impact on the ocular surface is not frequently investigated. The aim of this study was to perform a comparative physicochemical characterization, and in vitro biological evaluations in primary conjunctival and corneal epithelial cells of the new multidose preservative-free bilastine 0.

Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound.

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects.

Novel Concept of Micro Patterned Micro Titer Plates Fabricated via UV-NIL for Automated Neuronal Cell Assay Read-Out.

The UV-nanoimprint lithography(UV-NIL) fabrication of a novel network of micron-sized channels, forming an open channel microfluidic system is described. Details about the complete manufacturing process, from mastering to fabrication in small batches and in high throughput with up to 1200 micro titer plates per hour is presented. Deep insight into the evaluation of a suitable UV-curable material, mr-UVCur26SF is given, presenting cytotoxic evaluation, cell compatibility tests and finally a neuronal assay.

Effect of somatostatin on human retinal pigment epithelial cells permeability.

Purpose: To assess the effect of somatostatin (SST) on the permeability of human retinal pigment epithelial cells.

Methods: We conducted two experiments, exposing cells from human-fetal retinal pigment epithelium (hfRPE) cultures to vascular endothelial growth factor (VEGF), with or without SST pretreatment, in one, and to hypoxic conditions, again with or without SST pretreatment, in the other. The paracellular permeability of hfRPE was assessed by measuring transepithelial electrical resistance (TER) and fluorescein isothiocyanate-sodium (FITC-sodium) flux.

Synthesis, characterization, theoretical studies and biological (antioxidant, anticancer, toxicity and neuroprotective) determinations of a copper(II) complex with 5-hydroxytryptophan.

5-Hydroxy-L-tryptophan (5-HTP) is a serotonin pathway metabolite of L-tryptophan in the brain. In the knowledge that the biological properties of some compounds can be modified upon metal complexation, a new solid metal complex, [Cu(5-hydroxytryptophan)].HO (Cu5HTP), has been synthesized and characterized to analyze the modification of some biological properties.

Nomad Biosensors: A New Multiplexed Technology for the Screening of GPCR Ligands.

Nomad Technology (Innoprot [Innovative Technologies in Biological Systems], Derio, Spain), a novel tool for multiplexing high-throughput cell-based G protein-coupled receptor (GPCR) assays, is described in this work. This new technology comprises a family of fluorescent biosensors called Nomad Biosensors that allow for the measurement of responses mediated by G proteins through their interactions with second-messenger transduction proteins. GPCRs are one of the largest protein families of receptors in eukaryotes, and their signaling mediates important physiological processes within cells.

Inhibition of the metastatic progression of breast and colorectal cancer in vitro and in vivo in murine model by the oxidovanadium(IV) complex with luteolin.

The anticancer and antimetastatic behavior of the flavonoid luteolin and its oxidovanadium(IV) complex [VO(lut)(HO)]Na·3HO (VOlut) has been investigated. Considering that the complex displayed strong anticancer activity on MDAMB231 human breast cancer cell line we herein determined through in vitro assays that the complex would probably reduce breast cancer cell metastasis in a higher extent than the natural antioxidant. In the CT26 colon cancer cell line a stronger anticancer effect has also been determined for the complex (IC 0.

Fluorescent Parkin Cell-Based Assay Development for the Screening of Drugs against Parkinson Disease.

Parkinson disease (PD) is a prevalent neurodegenerative disease characterized by selective degeneration of dopaminergic neurons in the substantia nigra, causing tremor and motor impairment. Parkin protein, whose mutants are the cause of Parkinson disease type 2 (PARK2), has been mechanistically linked to the regulation of apoptosis and the turnover of damaged mitochondria. Several studies have implicated aberrant mitochondria as a key contributor to the development of PD.

Antioxidant, anticancer activities and mechanistic studies of the flavone glycoside diosmin and its oxidovanadium(IV) complex. Interactions with bovine serum albumin.

The natural antioxidant flavonoid diosmin, found in citric fruits, showed low antioxidant properties among other flavonoids due to its structural characteristics and low cytotoxicity against lung (A549) and breast (T47D, SKBR3 and MDAMB231) cancer cell lines. The anticancer behavior has been improved by the metal complex generated with the flavonoid and the oxidovanadium(IV) ion. This new complex, [VO(dios)(OH)3]Na5·6H2O (VOdios), has been synthesized and characterized both in solid and solution states.

Bovine serum albumin binding, antioxidant and anticancer properties of an oxidovanadium(IV) complex with luteolin.

Chemotherapy using metal coordination compounds for cancer treatment is the work of the ongoing research. Continuing our research on the improvement of the anticancer activity of natural flavonoids by metal complexation, a coordination compound of the natural antioxidant flavone luteolin (lut) and the oxidovanadium(IV) cation has been synthesized and characterized. Using different physicochemical measurements some structural aspects of [VO(lut)(H2O)2]Na·3H2O (VOlut) were determined.

Solid lipid nanoparticles for delivery of Calendula officinalis extract.

Solid lipid nanoparticles (SLN) composed of long-chain fatty acids (palmitic acid, stearic acid or arachidic acid), Epikuron 200 (purified phosphatidylcholine), and bile salts (cholate, taurocholate or taurodeoxycholate) have been prepared by dilution of a microemulsion. A total of five different systems were prepared, and characterized by photon correlation spectroscopy, transmission electron microscopy, differential scanning calorimetry, and infrared spectroscopy. The SLN formulation showing optimal properties (lowest size and polydispersity index and highest zeta potential) was obtained with stearic acid and taurodeoxycholate as cosurfactant.

Insights into the mechanisms underlying the antitumor activity of an oxidovanadium(IV) compound with the antioxidant naringenin. Albumin binding studies.

Naringenin, a natural antioxidant present in grapefruit, oranges and the skin of tomatoes showed low antioxidant properties among other flavonoids due to its structural characteristics. Since many flavonoids were shown to have cell-killing and antioxidant activities, naringenin was investigated herein. In parallel with its antioxidant activities the flavonoid showed very low cytotoxicity at concentrations up to 100 μM against lung (A549) and breast (SKBr3 and MDAMB231) cancer cell lines.

Promising antioxidant and anticancer (human breast cancer) oxidovanadium(IV) complex of chlorogenic acid. Synthesis, characterization and spectroscopic examination on the transport mechanism with bovine serum albumin.

A new chlorogenate oxidovanadium complex (Na[VO(chlorog)(H2O)3].4H2O) was synthesized by using Schlenk methodology in the course of a reaction at inert atmosphere in which deprotonated chlorogenic acid ligand binds to oxidovanadium(IV) in a reaction experiment controlled via EPR technique and based in a species distribution diagram. The compound was characterized by FTIR, EPR, UV-visible and diffuse reflectance spectroscopies and thermogravimetric, differential thermal and elemental analyses.

Biological evaluation of morin and its new oxovanadium(IV) complex as antioxidant and specific anti-cancer agents.

It is known that flavonoids possess, among others, antioxidant and antitumoral properties that depend on their molecular structure. The central objective if this study was to investigate the potential antioxidant and antiproliferative properties of the flavonol morin and its new oxovanadium(IV) complex (VOmor) that was synthesized in order to modify the morin chemical structure. Two osteoblast (UMR106 and MC3T3E1), two breast tumor (T47D and SKBR3) and breast epithelial cell lines in culture were used for the antitumoral determinations.

2009 H1N1: risk factors for hospitalization in a matched case-control study.

In order to compare sociodemographical data and preexisting risk medical conditions in patients requiring hospital admission for 2009 pandemic influenza A (H1N1) virus infection and those managed on an outpatient basis, a prospective observational, matched case-control study in 36 hospitals of the Spanish National Health Service was conducted from July 2009 to February 2010. Cases were patients aged 6 months to 18 years hospitalized for influenza syndrome, in whom 2009 influenza A (H1N1) virus infection was confirmed using real-time reverse-transcription polymerase chain reaction. Controls were patients aged 6 months to 18 years with confirmed 2009 influenza A (H1N1) infection managed on an outpatient basis.

Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2.

Background: Human melanoma frequently colonizes bone marrow (BM) since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC) microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2) in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown.

Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18.

Background: Implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanisms. A hepatic melanoma metastasis model where a majority of metastases are generated via interleukin-18-dependent mechanisms was used to test whether anti-inflammatory properties of resveratrol can interfere with mechanisms of metastasis.

Methods: Two experimental treatment schedules were used: 1) Mice received one daily oral dose of 1 mg/kg resveratrol after cancer cell injection and the metastasis number and volume were determined on day 12.

[Utility of infliximab therapy in severe enterorrhagia associated with Crohn's disease. Report of three cases].

Severe lower gastrointestinal (GI) bleeding is an infrequent complication in Crohn's disease. We report the cases of three patients with Crohn's disease, localized in distinct areas, who developed severe enterorrhagia requiring multiple transfusions. All three patients responded favorably to infliximab administration, which resolved the life-threatening hemorrhages and avoided emergency surgical resection, which had seemed inevitable.

[Generalized epileptic seizures in an infant due to passive exposure to cocaine].

Background: The differential diagnosis of afebrile seizures in the first year of life is extensive.

Case Report: A 7-month old infant presented two afebrile generalized tonic-clonic seizures in 23 hours; her psychomotor and growth development followed a normal course. Laboratory analysis, cerebral echography and electroencephalogram were normal.

Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis.

Background: The recruitment of vascular stromal and endothelial cells is an early event occurring during cancer cell growth at premetastatic niches, but how the microenvironment created by the initial three-dimensional (3D) growth of cancer cells affects their angiogenesis-stimulating potential is unclear.

Methods: The proangiogenic profile of CT26 murine colorectal carcinoma cells was studied in seven-day cultured 3D-spheroids of <300 mum in diameter, produced by the hanging-drop method to mimic the microenvironment of avascular micrometastases prior to hypoxia occurrence.

Results: Spheroid-derived CT26 cells increased vascular endothelial growth factor (VEGF) secretion by 70%, which in turn increased the in vitro migration of primary cultured hepatic sinusoidal endothelium (HSE) cells by 2-fold.

[Paraneoplastic opsoclonus myoclonus ataxia syndrome].

Opsoclonus myoclonus ataxia syndrome (OMAS) is a very infrequent paraneoplastic or postinfectious movement disorder, which may occur at any age, most commonly between 6 and 36 months of age. In four days, a previously healthy 30-month-old girl progressively developed gait instability, intention tremor, dysarthric speech, irritability and altered sleep. Physical and neurological examination did not reveal additional deficits.

Clinical and experimental approaches to the pathophysiology of interleukin-18 in cancer progression.

Interleukin-18 (IL-18, interferon [IFN]-gamma-inducing factor) is a proinflammatory cytokine converted to a biologically active molecule by interleukin (IL)-1beta converting enzyme (caspase-1). A wide range of normal and cancer cell types can produce and respond to IL-18 through a specific receptor (IL-18R) belonging to the toll-like receptor family. The activity of IL-18 is regulated by IL-18-binding protein (IL-18bp), a secreted protein possessing the ability to neutralize IL-18 and whose blood level is affected by renal function and is induced by IFNgamma.

Inhibition of cytokine-induced microvascular arrest of tumor cells by recombinant endostatin prevents experimental hepatic melanoma metastasis.

We investigated effects of endostatin (ES) in the prometastatic microenvironment of inflammation occurring during the microvascular phase of cancer cell infiltration in the liver. We used a model of intrasplenic injection of B16 melanoma (B16M) cells leading to hepatic metastasis through vascular cell adhesion molecule-(VCAM-1)-mediated capillary arrest of cancer cells via interleukin-18 (IL-18)-dependent mechanism. We show that administration of 50 mg/kg recombinant human (rh) ES 30 min before B16M, plus repetition of same dose for 3 additional days decreased metastasis number by 60%.