Green synthesis of 2-benzylidene-1-benzofuran-3-ones and in vitro neuraminidase study using molecular docking.

An improved and green method has been developed for the synthesis of substituted 2-benzylidene-1-benzofuran-3-ones by treating 2-hydroxychalcones with CuBr2 in DMF-water mixture (7:3; v/v) using grinding methodology. Molecular docking and in vitro studies were also carried out, and it was revealed that compound #4h binds with the active amino Glu-277, Try-406 and Arg-152 of neuraminidase against influenza virus. Compound 4h exerts best inhibition activity (13 ± 1.8%) which was found similar to oseltamivir (12 ± 0.89%).

Aflibercept in clinical practice; visual acuity, injection numbers and adherence to treatment, for diabetic macular oedema in 21 UK hospitals over 3 years.

INTRODUCTION: Randomised controlled trials provide evidence that a treatment works. Real world evidence is required to assess if proven treatments are effective in practice. METHOD: Retrospective data collection on patients given aflibercept for diabetic macular oedema over 3 years from 21 UK hospitals: visual acuity (VA); Index of multiple deprivation score (IMD); injection numbers; protocols used, compared as a cohort and between sites. RESULTS: Complete data: 1742 patients (from 2196 eligible) at 1 year, 860 (from 1270) at 2, 305 (from 506) at 3 years. The median VA improved from 65 to 71, 70, 70 (ETDRS letters) at 1, 2 and 3 years with 6, 9 and 12 injections, respectively. Loss to follow-up: 10% 1 year, 28.8% at 3. Centres varied: baseline: mean age 61-71 years (p < 0.0001); mean IMD score 15-37 (p < 0.0001); mean VA 49-68 (p < 0.0001). Only four centres provided a loading course of five injections at monthly intervals and one 6. This did not alter VA outcome at 1 year. Higher IMD was associated with younger age (p = 0.0023) and worse VA at baseline (p < 0.0001) not total number of injections or change in VA. Lower starting VA, higher IMD and older age were associated with lower adherence (p = 0.0010). CONCLUSIONS: The data showed significant variation between treatment centres for starting age, VA and IMD which influenced adherence and chances of good VA. Once treatment was started IMD did not alter likelihood of improvement. Loading dose intensity did not alter outcome at one year.

Peripapillary schisis in open-angle glaucoma.

PurposeTo report clinical features, topographic findings and outcome of 10 eyes with peripapillary schisis in open-angle glaucoma.Patients and methodsA retrospective review of patients with open-angle glaucoma who were noted to have peripapillary schisis on optical coherence tomography (OCT) were included. Serial peripapillary and macula infrared and OCT images, visual acuity, visual fields, and schisis appearance were reviewed.ResultsTen eyes of nine patients with open-angle glaucoma were detected to have the presence of peripapillary schisis. Nerve fibre layer schisis was detected in all eyes and one eye had an associated macular schisis. None of the eyes had an acquired pit of the optic nerve or pathological myopia. The mean intraocular pressures at detection was 18.3±4.3 mm Hg and the schisis resolved in four eyes after a mean follow-up of 21.2±8.8 months. Visual field worsening was noted in 4 of the 10 eyes and the resolution of schisis resulted in significant reduction in the retinal nerve fibre layer (RNFL) thickness.ConclusionsPeripapillary schisis detected during the normal course of open-angle glaucoma can resolve spontaneously and rarely involves the macula. Its resolution leads to reduction in RNFL thickness; therefore, caution is advised while interpreting serial scans.

Insights into the mechanism of natural terpenoids as NF-κB inhibitors: an overview on their anticancer potential.

The transcription factor, nuclear factor kappa B (NF-kB) is one of the principal inducible protein in mammals known to control the gene expression in many critical physiological responses such as oxidative stress, inflammation etc. and has been shown to play an important role in the pathogenesis of cancer. Terpenoids are major constituents present in nutritionally used fruits, vegetables and different spices which possess various pharmacological action including anticancer activity. Various terpenoids, viz. monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, triterpenoids, tetraterpenoids and polyterpenoids inhibit NF-kB signa-ling pathway through IkB phosphorylation, DNA binding, p65 translocation etc. Keeping in mind these facts, the present review revealed the anti-cancer potential of naturally occurring terpenoids highlighting their mechanism of NF-kB inhibition. This review also focuses on some of the naturally occurring terpenoids belonging to various chemical categories with potential inhibitory effects on NF-kB and their role in the treatment of cancer.

CoMFA, CoMSIA, HQSAR and Molecular Docking Analysis of Ionone-based Chalcone Derivatives as Antiprostate Cancer Activity.

Androgen receptor has been proved to be effective site for treatment of prostate cancer. Molecular modeling methods performed on forty-three ionone based chalcones derivatives as anti-prostate cancer activity. The designed comparative molecular field analysis, comparative similarity indices analysis and hologram quantitative structure activity relationship models produced statistically significant results with the cross-validated correlation coefficients (q(2)) of 0.527, 0.550 and 0.670, non-cross-validated correlation coefficients (r(2)) 0.636, 0.671 and 0.746 and predicted r(2) (Pred r(2)) of 0.621, 0.563 and 0.732, respectively. Furthermore, bioactive conformation was explored and explained by docking of the potent compound 25 into the binding site of androgen receptor. Present study deals with comparative molecular field analysis, comparative similarity indices analysis and hologram quantitative structure activity relationship and molecular docking studies of the ionone-based chalcones and their derivatives, obtained from literature. The model obtained could be effectively used as a channeling tool for further structure modification and designing of some novel potent anti-prostate cancer compounds.

International challenges of self-sufficiency in blood products.

To face known and emerging threats to public health, all countries have to overcome the challenges of providing sufficient supplies of blood and blood products of the highest quality and safety. Unfortunately, self-sufficiency is not yet a reality in many countries. In 2011, experts from WHO addressed the urgent need to establish strategies and mechanisms for achieving this goal. A summary of these recommendations is further discussed.

Müller glia express rhodopsin in a mouse model of inherited retinal degeneration.

The Müller glial cells exhibit stem cell properties and express neuronal markers following experimentally induced retinal injury. However, it is not known whether Müller glia respond similarly to degenerative neuronal loss caused by genetic mutation. Here, we asked whether Müller cells dedifferentiate and express neuronal proteins in rd1 mouse, a naturally occurring mutant model of inherited retinal degeneration. Using immunohistochemistry and Western blotting, we studied expression patterns of glial fibrillary acidic protein (GFAP), nestin, rhodopsin, protein kinase C alpha (PKCα), ß-III-tubulin and recoverin in Müller glia. Reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to detect any rhodopsin mRNA in the rd1 mouse retina. We found that Müller cell processes in rd1 mouse hypertrophied and overexpressed GFAP as early as postnatal day (P)-14, features that were maintained throughout development and in the adult stage. Furthermore, Müller cells continued to express nestin, a progenitor cell marker, up to 6 months of age, raising the possibility that they remain undifferentiated for several months in rd1 mouse. We did not find nestin expression in Müller cells in 1-year-old rd1 mouse. Interestingly, Müller cell processes in rd1 mouse also expressed rhodopsin, a rod-specific protein. The rhodopsin expression in Müller cells was evident at P-21, and remained so up to at least 1 year of age. The expression of rhodopsin by Müller cells was further supported by our finding of the rhodopsin transcript in the 9-month-old rd1 mouse retina. We did not find the expression of PKCα, ß-III-tubulin or recoverin in Müller cells in adult rd1 mouse. These results suggested that Müller cells in rd1 mouse express proteins specific to retinal neurons that are the primary targets of the mutation in this mouse. Although the functional significance of rhodopsin expression by Müller cells is unclear, these results have implications for novel therapeutic strategies for retinal degeneration.

Switching biologic agents for uveitis.

PURPOSE: To observe whether switching between biological agents helps to gain or maintain uveitis remission in cases with sight-threatening refractory uveitis. METHODS: We reviewed the case notes of seven patients with refractory uveitis, who had switched between biological agents. The switch between biological agents (infliximab or adalimumab) was for gaining control of systemic symptoms, uveitis, or for the ease of administration. RESULTS: There were three adults (one each with sarcoidosis, ankylosing spondylites, and sero-negative polyarthropathy) and four children with juvenile idiopathic arthritis. The adults were switched twice between the various biological agents to gain adequate control of their systemic disease or to ease administration of the drug. All the children were switched to a second biological agent for gaining uveitis remission. Following the final switch, the concomitant immunosuppression in all the patients either reduced or remained unchanged, and only two patients remained on additional prednisolone (10 mg/day). CONCLUSIONS: Our case series provides preliminary evidence that in cases of refractory uveitis with loss of initial clinical response to one biological agent, switching to another agent can restore control of intraocular inflammation. In addition, switching helps to control systemic symptoms and allows ease of administration.

Early remodeling in an inducible animal model of retinal degeneration.

Photoreceptor degeneration is followed by significant morphological changes in the second-order retinal neurons in humans and in several genetic animal models. However, it is not clear whether similar changes occur when photoreceptor degeneration is induced nongenetically, raising the question whether these changes are a general effect of deafferentation independent of the cause of degeneration. We addressed this by inducing selective photoreceptor degeneration with N-methyl-N-nitrosourea (MNU) and studying its effects on inner retinal neurons in a mouse for up to 3 months, using immunocytochemistry and iontophoretic labeling. To develop objective measures of photoreceptor degeneration and of retinal remodeling, we measured several retinal proteins using immunoblot analysis, and quantified gross visual ability of the animal in a visual cliff test. The MNU-induced progressive degeneration of rods and cones was associated with declining levels of postsynaptic density 95 protein in the retina, and with deteriorating visual performance of the animal. Müller glial cells showed enhanced reactivity for glial fibrillary acidic protein as demonstrated by immunocytochemistry, which also reflected in increased levels of the protein as demonstrated by immunoblotting. Horizontal cells and rod bipolar cells progressively lost their dendritic processes, which correlated with a slight decline in the levels of calbindin and protein kinase C alpha respectively. Horizontal cell axons, immunoreactive for nonphosphorylated neurofilaments, showed sprouting into the inner nuclear layer. Ganglion cells and their synaptic inputs, probed by immunolocalizing beta-III-tubulin, neurofilaments, bassoon and synaptophysin, appeared to be unaffected. These results demonstrate that MNU-induced photoreceptor degeneration leads to retinal remodeling similar to that observed in genetic models, suggesting that the remodeling does not depend on the etiopathology that underlies photoreceptor degeneration.

[Safety of blood transfusion at the international level. The role of WHO]. / La sécurité transfusionnelle à l'échelle internationale: le rôle de l'OMS.

Blood safety is an international public health challenge, particularly since the emergence of HIV AIDS. Recognizing the gross disparities between countries in the adequacy of national blood supplies and the risks arising from poorly organized services, particularly in developing countries, the World Health Organization has developed a global strategy for blood safety and availability. Dr N. Dhingra, coordinator, blood transfusion safety, WHO Headquarters, and Dr V. Hafner, focal point for blood safety in the WHO regional office for Europe, present the main features of this strategy: well-organized, nationally coordinated blood transfusion services with quality systems in all areas; the collection of blood only from voluntary non-remunerated blood donors from low-risk populations; the quality-assured testing of all donated blood; the safe and appropriate use of blood and blood products; and global collaboration for blood safety. WHO's programs, some difficulties encountered and outcomes are also described in this article.

Synaptic development in semi-dissociated cultures of rat retina.

Cultured neurons provide a simpler and more accessible environment to study the synaptic physiology. However, it is not clear if development of synapses in culture is similar to that in the in vivo condition. We studied the developmental sequence and morphological differentiation of chemical synapses in semi-dissociated rat retinal cultures that consisted of dissociated neurons as well as undissociated retinal aggregates. Synapses were quantified by synaptophysin immunoreactive puncta. During second week of in vitro development the average number of chemical synapses on the cell body decreased while that on the neurites increased significantly. Conventional synapses appeared both in aggregate and in dissociated neurons, with the developmental profile similar to that reported for in vivo retina. In contrast, the development of ribbon synapses was adversely affected by the in vitro microenvironment as suggested by following observations. The ribbon synapses were more frequently found in aggregate than in dissociated neurons, and were not associated with dyadic or triadic synaptic arrangement. The photoreceptor ribbons did not contact a postsynaptic process while bipolar ribbons made single (monadic) synapses. Further, photoreceptor ribbons in dissociated neurons were late to form and took more time to mature as compared to those in the aggregate cultures. Most of the rod bipolar cells, identified by their immunoreactivity to protein kinase C (PKC), had three or more neurites. Unlike in the in vivo retina, the dissociated rod bipolar cells did not show any PKC immunoreactive varicosities, suggesting that they failed to develop a well-differentiated synaptic terminal. Interestingly, we did not find any parvalbumin positive AII amacrine cells that are normally postsynaptic to rod bipolar cells. These results show that the conventional synapses of retina, which are similar to chemical synapses in other parts of the brain, develop normally both in aggregate and dissociated neurons. However, the highly specialized ribbon synapses have more stringent developmental requirements, and their normal development may require the presence of postsynaptic neurons in their close vicinity.