Intriguing physicochemical properties and impact of co-dopants on N-doped graphene oxide based ZnS nanowires for photocatalytic application.

Superparamagnetic N-doped graphene oxide (GO)- with ZnS nanowires was synthesized by a one-step hydrothermal method by doping dilute amounts of Ga, Cr, In, and Al ions for water treatment and biomedical applications. In these experiments, to enhance their properties, 2% of Ga3+, In3+, and or Al3+ were codoped along with 2% Cr ions in these ZnS nanowires. The nanocomposite with the composition, In0.02Cr0.02Zn0.96S, has better photocatalytic efficiency than other co-doped nanocomposites. The In (metalloids) and Cr (transition metal ion) are the best combinations to increase the magnetic properties which are beneficial for photocatalytic activity. Synthesized nanocomposite materials were characterized by several techniques such as X-ray diffraction, Field emission-scanning electron microscope (FESEM) with EDAX, vibrating sample magnetometer (VSM), UV-Vis, X-ray photoelectron spectroscopy (XPS), and fluorescence spectroscopy. The correlation of intriguing magnetic properties with their photocatalytic properties is also discussed. XPS was employed for the detection of surface defects, phase transformation, and the nature of chemical components present in the nanocomposites. The Frankel and substitutional defects have a direct impact on photocatalytic activity that was determined from the fluorescence (FL) spectroscopy. FL and XPS reveal that the Cr and In codoped composite has a higher percentage of defects hence its photocatalytic efficiency reaches 94.21%.

M1 and M2 mAChRs activate PDK1 and regulate PKC ßI and ε and the exocytotic apparatus at the NMJ.

Neuromuscular junctions (NMJ) regulate cholinergic exocytosis through the M1 and M2 muscarinic acetylcholine autoreceptors (mAChR), involving the crosstalk between receptors and downstream pathways. Protein kinase C (PKC) regulates neurotransmission but how it associates with the mAChRs remains unknown. Here, we investigate whether mAChRs recruit the classical PKCßI and the novel PKCε isoforms and modulate their priming by PDK1, translocation and activity on neurosecretion targets. We show that each M1 and M2 mAChR activates the master kinase PDK1 and promotes a particular priming of the presynaptic PKCßI and ε isoforms. M1 recruits both primed-PKCs to the membrane and promotes Munc18-1, SNAP-25, and MARCKS phosphorylation. In contrast, M2 downregulates PKCε through a PKA-dependent pathway, which inhibits Munc18-1 synthesis and PKC phosphorylation. In summary, our results discover a co-dependent balance between muscarinic autoreceptors which orchestrates the presynaptic PKC and their action on ACh release SNARE-SM mechanism. Altogether, this molecular signaling explains previous functional studies at the NMJ and guide toward potential therapeutic targets.

[A "fast track" to improve management of neovascular age related macular degeneration]. / Un « circuit court ¼ pour améliorer la prise en charge des patients atteints de dégénérescence maculaire liée à l'âge néovasculaire.

OBJECTIVE: To evaluate the role of a fast track for management of patients with neovascular age- related macular degeneration (nARMD) treated by intravitreal injection of anti-VEGF. PATIENTS: The records of 100 patients in the chronic maintenance phase of intravitreal anti-VEGF followed in the fast track and 63 patients followed in the standard protocol for at least 12 months were retrospectively analyzed. METHOD: Patients in the fast track underwent visual acuity (VA) testing by ETDRS, optical coherence tomography (OCT) and a physician assessment. The injection was performed the same day whenever possible. The primary endpoint to evaluate patient adherence was the time between the ideal date of visit or injection prescribed by the physician and the actual date of administration. RESULTS: The mean time between the ideal date of visit or injection prescribed by the physician and the actual date of administration was 4.1±7.5 days for the patients followed in the fast track and 5.6±18.7 days for the patients followed in the standard protocol. Mean VA remained stable for the patients followed in the fast track: 20/50 (20/800 to 20/20) at baseline vs. 20/50 (20/800 to 20/16) at the conclusion of follow-up. It dropped from 40/50 at baseline to 20/63 at the conclusion of follow-up for the patients followed in the standard protocol. CONCLUSION: In the context of a fast track, it was possible to improve the adherence of nARMD patients and maintain their VA gain or stabilization achieved after the induction phase.

Ranibizumab for exudative age-related macular degeneration: A five year study of adherence to follow-up in a real-life setting.

PURPOSE: To analyze adherence to follow-up over 5 years in patients treated with intravitreal ranibizumab for exudative age-related macular degeneration (AMD) in a tertiary health care center. To investigate factors associated with failure to continue follow-up. METHODS: Retrospective chart review of all consecutive patients with exudative AMD, who received their first intravitreal ranibizumab injection at the Créteil Intercommunal University Hospital Eye Clinic between October 1, 2006 and March 31, 2007. Patient clinical characteristics at baseline and at the last follow-up visit were recorded. Distance from home to hospital was measured for each patient. A multiple-choice telephone survey was conducted for patients lost to follow-up to determine the main reasons for failure to continue follow-up. RESULTS: Two hundred and one patients were included. The rate of loss to follow-up over the 5-year period was 57% (115/201). Fifty-eight patients lost to follow-up completed the questionnaire. The main reasons reported by patients for follow-up discontinuation were long distance from home to hospital (51.7%, 30/58), subjective dissatisfaction with the benefits of intravitreal injections (34.5%, 20/58), and the excessive burden of periodic follow-up visits (24.1%, 14/58). Three factors were significantly associated with follow-up discontinuation: high age at baseline (82.2 vs. 76.5 years, P<0.001), poor best-corrected visual acuity (BCVA) at baseline (42.5 vs. 51.0 letters, P=0.020), and long distance from home to hospital (132 vs. 17.1km, P<0.001). CONCLUSION: In this study, adherence to follow-up over 5 years was poor. Age and BCVA at baseline and distance from home to hospital were independently associated with long-term adherence.

Antigen-specific tolerance of human alpha1-antitrypsin induced by helper-dependent adenovirus.

As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body. Some studies suggest that immunity to serum proteins can be avoided in some mouse strains by using tissue-specific promoters. Here we show that expression of human alpha1-antitrypsin (AAT) was nonimmunogenic in the immune-responsive strain C3H/HeJ, when expressed from helper-dependent (HD) vectors using ubiquitous as well as tissue-specific promoters. Coadministration of less immunogenic HD vectors with an immunogenic first-generation vector failed to immunize, suggesting immune suppression rather than immune stealth. Indeed, mice primed with HD vectors were tolerant to immune challenge with hAAT emulsified in complete Freund's adjuvant. Such animals developed high-titer antibodies to coemulsified human serum albumin, showing that tolerance was antigen specific. AAT-specific T cell responses were depressed in tolerized animals, suggesting that tolerance affects both T and B cells. These results are consistent with models of high-dose tolerance of B cells and certain other suppressive mechanisms, and suggest that a high level of expression from HD vectors can be sufficient to induce specific immune tolerance to serum proteins.

Modulation of TNFalpha, a determinant of acute toxicity associated with systemic delivery of first-generation and helper-dependent adenoviral vectors.

Understanding the determinants of the host innate immune response to systemic administration of adenoviral (Ad) vectors is critical for clinical gene therapy. Acute toxicity occurs within minutes to hours after vector administration and is characterized by activation of innate immune responses. Our data indicate that in mice, indicators of vector toxicity include elevations of cytokine levels, liver transaminase levels and thrombocytopenia. To discern potential targets for blunting this host response, we evaluated genetic factors in the host response to systemically administered first-generation Ad vectors (FGV) and helper-dependent Ad vectors (HDV) containing beta-galactosidase expression cassettes. A preliminary screen for modulation of vector-induced thrombocytopenia revealed no role for interferon-gamma, mast cells or perforin. However, vector-induced thrombocytopenia and interleukin 6 (IL-6) expression are less evident in tumor necrosis factor alpha (TNFalpha)-deficient mice. Moreover, we also demonstrated that TNFalpha blockade via antibody or huTNFR:Fc pretreatment attenuates both thrombocytopenia (>40% increase in platelet count) and IL-6 expression (>80% reduction) without affecting interleukin 12 , liver enzymes, hematological indices or vector transduction in a murine model. Our data indicate that the use of HDV, in combination with clinically approved TNFalpha immunomodulation, may represent an approach for improving the therapeutic index of Ad gene therapy for human clinical trials.

Utilization of banana agricultural waste: production of cellulases by soil fungi.

Banana a major cash crop of Maharashtra is cultivated over 46900 hectares generating large amount of agro waste after the harvest. Attempts were made to utilize these agro wastes for production of cellulases. Of the 127 fungi isolated from the soil of banana field, 12 fungi were found to utilize cellulose as source of carbon. Trichoderma lignorum showed appreciable cellulolytic activity. It produced Cl, Cx and beta glucosidase in Carboxymethyl Cellulose Peptone medium as well as on agro waste based medium containing leaves, stem and rhizome powders. T. lignorum (0. 45 U/ml) produced maximum enzymes on leaf based medium.

Experimental evaluation of the antidepressant and neuroleptic activity of maprotiline.

Maprotiline, a tetracyclic antidepressant drug, was evaluated for antidepressant and neuroleptic activity. In antidepressant tests, maprotiline antagonized reserpine-induced ptosis in rats but, unlike the tricyclic antidepressants, was found to antagonize methamphetamine stereotypy in rats, to decrease the intensity of L-dopa induced behavioural syndrome in pargyline-pretreated mice and to be ineffective in intensifying the 5-HTP induced behavioural syndrome. In neuroleptic tests, maprotiline was found to, antagonize apomorphine-induced cage climbing behaviour, induce catalepsy, inhibit the CAR and traction response, decrease the spontaneous motor activity and exploratory behaviour, and to potentiate the hypnotic effect of pentobarbitone. Our results indicate that maprotiline exhibits a profile of activity which resembles the neuroleptics and most probably exerts post-synaptic striatal DA receptor blocking activity.

Blockade of the dopamine depressor response by molindone, a newly introduced neuroleptic.

Pretreatment with the neuroleptics, haloperidol and molindone, significantly antagonized the dopamine-induced depressor response in the anaesthetized dogs. The depressor response to dopamine was however, not significantly affected by propranolol, atropine or antazoline pretreatment. The results suggest that molindone like haloperidol, is capable of blocking the vascular dopamine receptors responsible for mediating dopamine-induced vasodilatation in the coeliac, mesenteric and renal vascular bed and fall in blood pressure.