Biomimetic modified clinical-grade POSS-PCU nanocomposite polymer for bypass graft applications: a preliminary assessment of endothelial cell adhesion and haemocompatibility.

BACKGROUND: To date, there are no small internal diameter (<5mm) vascular grafts that are FDA approved for clinical use due to high failure rates from thrombosis and unwanted cell proliferation. The ideal conditions to enhance bioengineered grafts would be the blood contacting lumen of the bypass graft fully covered by endothelial cells (ECs). As a strategy towards this aim, we hypothesized that by immobilising biomolecules on the surface of the polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU) nanocomposite polymers, which contain binding sites and ligands for cell surface receptors similar to extracellular matrix (ECM) will positively influence the attachment and proliferation of ECs. Since, the surface of POSS-PCU is inert and not directly suitable for immobilisation of biomolecules, plasma graft polymerisation is a suitable method to modify the surface properties ready for immobilisation and biofunctionalisation. METHODS: POSS-PCU was activated by plasma treatment in air/O2 to from hydroperoxides (-OH, -OOH), and then carboxylated via plasma polymerisation of a 30% acrylic acid solution (Poly-AA) using a two-step plasma treatment (TSPT) process. Collagen type I, a major component of ECM, was covalently immobilised to mimic the ECM structures to ECs (5mg/ml) using a two-step chemical reaction using EDC chemistry. Successful immobilisation of poly-AA and collagen on to the nanocomposites was confirmed using Toluidine Blue staining and the Bradford assay. Un-treated POSS-PCU served as a simple control. The impact of collagen grafting on the physical, mechanical and biological properties of POSS-PCU was evaluated via contact angle (θ) measurements, scanning electron microscopy (SEM), atomic force microscopy (AFM), dynamic mechanical thermal analysis (DMTA), ECs adhesion and proliferation followed by platelet adhesion and haemolysis ratio (HR) tests. RESULTS: Poly-AA content on each of the plasma treated nanocomposite films increased on Low, Med and High samples due to more carboxylic acid (-COOH) groups at the surface forming amide (-NH2) bonds. The amount of -COOH groups on each of the Low, Med and High nanocomposites correlated with Poly-AA grafting density at 14.7±0.9, 18.9±0.9, and 34.2±2.4 µg/cm(2). Immobilisation of collagen type I on to nanocomposite surface was also found to increase significantly on the Low, Med and High samples from 22±4, 150±15, and 219±17 µg/cm(2), respectively. The level of ECs and their adhesion efficiency were improved with increasing amounts of grafted collagen I. The maximum adhesion of ECs was found on the highest collagen type I coated nanocomposites. Platelet adhesion and activation also increased with increasing collagen density. The obtained HR values for all of the treated samples were well within the acceptable standards for biomaterials (<5% HR). CONCLUSION: Poly-AA-g-POSS-PCU surfaces offer binding sites for the covalent bonding of collagen type I and other biomolecules such as fibronectin by exposure of RGD cell binding domains and growth factors using EDC cross-linking chemistry. Collagen type I modification can yield accelerated EC growth and enhance the endothelialisation of POSS-PCU nanocomposites, and the amount of immobilised collagen can control the level of platelet adhesion on functionalized POSS-PCU via TSPT and poly acrylic acid (poly-AA) treatment. Such surface modification procedures of polymeric surfaces can improve the patency rate of POSS-PCU nanocomposites as vascular bypass grafts in the preparation of a range of medical devices ready for pre-clinical and in vivo evaluation.

Injection of colchicine intra-hippocampal cortical area 1 enhances novelty seeking behavior.

OBJECTIVE: Colchicine, a potent neurotoxin derived of plant has been recently identified as a degenerative toxin of small pyramidal cells in the hippocampal cortical area 1 (CA1). In this study, the effect of the alkaloid intra hippocampal CA1 on the novelty seeking behavior in the conditioning task was measured. MATERIALS AND METHODS: Injections of colchicine (1-75 µg/rat, intra-CA1) were performed in cannulated male Wistar rats while being settled in the stereotaxic apparatus. Control group was solely injected saline (1 µl/rat, intra-CA1). One week later, after recovery, all the animals passed the novelty seeking paradigm using an unbiased conditioning task. They were habituated with the conditioned place preference (CPP) apparatus on day 1. Then they were confined in one part of the CPP box for 3 more days. Finally, the animals were tested in the last day. To evaluate, the possible cell injury effect of the toxin on the pyramidal cells of the CA1 both the motivational staying signal in the parts of the box and the non-motivational locomotive signs of the rats were measured. RESULTS: Based on the present study, the alkaloid caused significant novelty seeking behavior at higher doses. It also affected the compartment entering behavior in the colchicine received group. However, the alkaloid did not show the significant effect on sniffing, rearing or grooming in the rats. CONCLUSION: Injection of colchicine intra-CA1 may impair the neuronal transmission of motivational information by the pyramidal cells in the dorsal hippocampus.

Effect of turbinoplasty in concha bullosa induced rhinogenic headache, a randomized clinical trial.

BACKGROUND: Rhinogenic origin is an important source for headache, which may be treated by medical or endoscopic intervention. An aim of this study was to clarify whether the surgical or medical intervention is superior. MATERIALS AND METHODS: In this randomized double blind clinical trial study, 44 patients (19 male and 25 female) with periorbital or frontal pain were enrolled. Patients were divided into 2 groups of surgical or medical intervention randomly. Medical group received 3 courses of 1.5 months 125 µg per puff, fluticason nasal spray (2 puffs Q 24 hours in each side), and oral Pseudoephedrin 30 mg Q 8 hours with 2 weeks intervals. Surgical group underwent turbinoplasty with functional endoscopic sinus surgery approach. Duration (per hour), frequency (per week) and severities of the headaches were measured by Visual Analog Scale (VAS) before treatment, and at 1.5, 3 and 6 months after institution of treatment by an examiner, who was unaware of the patients' treatment plan. RESULTS: Before treatment, chronicity (P = 0.980), severity (P = 0.742), frequency (P = 0.730), and duration (P = 0.603) of the headaches were not significantly different. The severities of the headaches in surgical group were significantly lower at 1.5, 3 and 6 months (P < 0.001), also the frequencies and the durations of the headaches were significantly lower at 6 months after an institution of treatment compared to medical group (P = 0.027, P = 0.008, respectively). CONCLUSION: Turbinoplasty in chonca bullusa patients is an acceptable and a simple procedure for relieving pain in rhinogenic headaches, compared with medical treatment.

Microinjection of l-arginine into corpus callosum cause reduction in myelin concentration and neuroinflammation.

Role of nitric oxide (NO) in inflammationary diseases such as multiple sclerosis (MS) has been proposed previously. We sought to examine if NO plays centrally a key role in MS related phenomena; demyelination or neuroinflammation. Female Wistar rats (weighing 200-250 g) were mounted in a stereotaxic apparatus and received injections of l-arginine aimed at corpus callosum (AP: 1.2, L: ±1.8, V: 3.2). The drug (50-200 µg/rat) was microinjected intra-corpus callosum repeatedly (3-5 times/each per day). Control groups solely received saline (1 µg/rat) into the corpus callosum. The animals were tested for the novelty seeking behavior using the conditioning task. Memory impairment was examined using the shuttle box and Y-maze. l-NAME was pre-injected to l-arginine to involve the NO. All animals' brains were also processed for histological evaluation. l-arginine produced significant changes in the novelty seeking behavior but not in the memory formation, evidenced by passive avoidance and alternation behaviors. Pre-injection of l-NAME reversed the response to l-arginine. Present study further revealed a prominent inflammation as well as myelin elimination in the l-arginine treated rats' brains. These data suggest that the NO infusion in the myelin rich areas such as corpus callosum may lead to MS signs centrally.

Neuroprotective effect of genistein in 6-hydroxydopamine hemi-parkinsonian rat model.

A large body of experimental evidence supports a role for oxidative stress as a mediator of nerve cell death in Parkinson's disease (PD). Phytoestrogens such as genistein have been reported to prevent neuronal degeneration caused by increased oxidative burden, therefore, this study examined whether genistein administration at a high dose would attenuate behavioral and structural abnormalities in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5 microg/5 microL of saline-ascorbate)-lesioned rats were intraperitoneally pretreated with a single and high dose of genistein (10 mg/kg) 1 h before surgery. Apomorphine-induced rotations and the number of Nissl-stained neurons in the substantia nigra pars compacta (SNC) were counted after 2 weeks. Genistein administration could attenuate the rotational behavior in lesioned rats and protect the neurons of SNC against 6-OHDA toxicity. Genistein administration has a protective effect against 6-OHDA toxicity.

Long-term ocular complications of sulfur mustard in the civilian victims of Sardasht, Iran.

Eyes are very sensitive to sulfur mustard (SM) gas because they have wet surfaces. The severity of ocular damage is related to the dose and duration of exposure to SM, and recovery may take up to several years after the exposure. We conducted a large cohort study to evaluate the ocular signs and symptoms of 367 chemical war victims in Sardasht City, Iran, 20 years after their exposure to mustard gas. The results of these chemical war victims (i.e., the cases) were compared with the results for 128 unaffected civilians (i.e., the controls). Photophobia was the most significant symptom in the cases (36.8%) (compared with 20.3% in the controls) (p < or = .001). Ocular surface discomfort (burning, itching, and redness) was the second most significant symptom in the cases (29.2%) (compared with 19.5% in the controls) (p = .034). Other symptoms such as foreign-body sensation, tearing, pain, blurring of vision, and dry eye sensation were not significantly different between the 2 groups. In the slit-lamp findings, bulbar conjunctival abnormality was the most significant sign in the cases (9.3%) (compared with 1.6% in the controls) (p = .004). Limbal tissue changes were the second most significant sign in the cases (3.0%) (compared with 0.0% in the controls) (p = .048). Other slit-lamp findings related to tearing and abnormalities in the lids and cornea were not significantly different between the 2 groups. Our findings in the present study showed that photophobia and ocular surface discomfort (burning, itching, and redness) were the most significant symptoms. In addition, bulbar conjunctival abnormalities and limbal tissue changes were the most significant signs among the sulfur mustard chemical war victims.