Matrix Metalloproteinases and Glaucoma Treatment.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from in vivo and in vitro studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect

New connection formulae for the q-orthogonal polynomials via a series expansion of the q-exponential

Using a realization of the q-exponential function as an infinite multiplicative sereis of the ordinary exponential functions we obtain new nonlinear connection formulae of the q-orthogonal polynomials such as q-Hermite, q-Laguerre and q-Gegenbauer polynomials in terms of their respective classical analogs.Comment: 14 page

Isolation and Characterization of Bacteria Species Related to Food Contact Surfaces in Selected Cafeterias in a Tertiary Institution Campus in ABU, Zaria, Nigeria

The study was carried out to isolate and characterize bacterial species from selected cafeterias in tertiary institution campus in Ahmadu Bello University Zaria, Nigeria. A total of ten samples were selected for analysis which include; spoons, plates, forks, chopping boards, worktops, tables, hands, washing water, plate rinsing water1 and plate rinsing water2. The bacteriological analysis was carried out using the nutrient agar (NA) media, which was prepared by dissolving 28g of the NA powder in 1litre of distilled water, autoclaved and allowed to cool. The growth of the microorganisms were then observed and counted per ml. The identified species include; Staphylococcus aureus, Staphylococcus epidermis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Bacillus anthracis. The food contact surfaces analyzed revealed that Chopping board has the highest bacterial load with 28 x 105, followed by Hand 27 x 105, Worktop 20 x 105, Table 18.8 x 105, Washing water 16 x 105, Plate 13.6 x 105, Fork 12 x 105, Spoon 7.2 x 105, plate rinsing water1 6 x 105, plate rinsing water2 5 x 105. The frequency of occurrence of the isolated organisms include; Staphylococcus aureus 3(10.3), Staphylococcus epidermis 9 (31.1), Escherichia coli 4(13.8), Klebsiella pneumonia 6(20.7), Pseudomonas aeruginosa 3(10.3), Proteus mirabilis 2(6.9) and Bacillus anthracis 2(6.9). It was observed that Staphylococcus epidermis have the highest incidence of occurrence, Bacillus anthracis and Proteus mirabilis have the least incidence of occurrence

Colonic lesion characterization in inflammatory bowel disease: A systematic review and meta-analysis

Aim: To perform a systematic review and meta-analysis for the diagnostic accuracy of in vivo lesion characterization in colonic inflammatory bowel disease (IBD), using optical imaging techniques, including virtual chro-moendoscopy (VCE), dye-based chromoendoscopy (DBC), magnification endoscopy and confocal laser endomicroscopy (CLE). Methods: We searched Medline, Embase and the Cochrane library. We performed a bivariate meta-analysis to calculate the pooled estimate sensitivities, specificities, positive and negative likelihood ratios (+LHR, -LHR), diagnostic odds ratios (DOR), and area under the SROC curve (AUSROC) for each technology group. A subgroup analysis was performed to investigate differences in real-time non-magnified Kudo pit patterns (with VCE and DBC) and real-time CLE. Results: We included 22 studies [1491 patients; 4674 polyps, of which 539 (11.5%) were neoplastic]. Real-time CLE had a pooled sensitivity of 91% (95%CI: 66%-98%), specificity of 97% (95%CI: 94%-98%), and an AUSROC of 0.98 (95%CI: 0.97-0.99). Magnification endoscopy had a pooled sensitivity of 90% (95%CI: 77%-96%) and specificity of 87% (95%CI: 81%-91%). VCE had a pooled sensitivity of 86% (95%CI: 62%-95%) and specificity of 87% (95%CI: 72%-95%). DBC had a pooled sensitivity of 67% (95%CI: 44%-84%) and specificity of 86% (95%CI: 72%-94%). Conclusion: Real-time CLE is a highly accurate technology for differentiating neoplastic from non-neoplastic lesions in patients with colonic IBD. However, most CLE studies were performed by single expert users within tertiary centres, potentially confounding these results

Artificial Neural Network Controller for Reducing the Total Harmonic Distortion (THD) in HVDC

A neural network based space vector modulation (SVM) of voltage source inverter is proposed. The voltage source converter (VSC) is highly used in high voltage direct current (HVDC) transmission so that a detailed analysis and transmission of this system is carried out. In addition, a non-linear neural network controller is proposed to control the space vector pulse width modulation (SVPWM) to reduce the total harmonic distortion (THD) of the converter (inverter) output voltage. The inverter outputcurrent is analyzed with two switching frequency 1050Hz and1450Hz with and without proposed ANN controller. The results show a THD enhancement about 0.74 % for 1050Hz and 0.68 % for 1450Hz

Pharmacovigilance: a study to evaluate knowledge, attitude, and practices of and impact of educational intervention among doctors in teaching hospital, in rural area of Jalna, India

Background: According to WHO Pharmacovigilance is “The science and activities which are related to the detection, assessment, understanding, and the prevention of adverse effects or any other drug-related problems.” A majority of India’s population prefers government hospitals when they are in need of health care facilities. The patients also prefer other available free health care facilities. Hence, these hospitals can be a good source for generating an adverse drug reactions database. However, the Herculean task is to foster a culture of reporting among the doctors, especially among the junior doctors, as they are more closely associated with the patient care, hence the present study to assess awareness of pharmacovigilance among the doctors and to evaluate the impact of an educational intervention for improving awareness of pharmacovigilance among doctors in an Indian tertiary care teaching hospital.Methods: A suitable self-administered knowledge, attitude, practice (KAP) survey questionnaire was designed, based on previous studies. An interventional educational activity was organized and the impact of the educational Intervention was evaluated by again administering the similar questionnaire. The statistical analysis was carried for comparing the pre- and post-intervention.Results: It was seen that the KAP of pharmacovigilance among doctors is low. The results also showed that there was an improvement after the educational intervention.Conclusions: The KAP of pharmacovigilance is low among doctors and educational intervention can improve it

The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells

BACKGROUND: The control of breast cell survival is of critical importance for preventing breast cancer initiation and progression. The activity of many proteins which regulate cell survival is controlled by reversible phosphorylation, so that the relevant kinases and phosphatases play crucial roles in determining cell fate. Several protein kinases act as oncoproteins in breast cancer and changes in their activities contribute to the process of transformation. Through counteracting the activity of oncogenic kinases, the protein phosphatases are also likely to be important players in breast cancer development, but this class of molecules is relatively poorly understood. Here we have investigated the role of the serine/threonine protein phosphatase 4 in the control of cell survival of breast cancer cells. METHODS: The breast cancer cell lines, MCF7 and MDA-MB-231, were transfected with expression vectors encoding the catalytic subunit of protein phosphatase 4 (PP4c) or with PP4c siRNAs. Culture viability, apoptosis, cell migration and cell cycle were assessed. The involvement of phosphoprotein enriched in astrocytes 15kDa (PEA15) in PP4c action was investigated by immunoblotting approaches and by siRNA-mediated silencing of PEA15. RESULTS: In this study we showed that PP4c over-expression inhibited cell proliferation, enhanced spontaneous apoptosis and decreased the migratory and colony forming abilities of breast cancer cells. Moreover, PP4c down-regulation produced complementary effects. PP4c is demonstrated to regulate the phosphorylation of PEA15, and PEA15 itself regulates the apoptosis of breast cancer cells. The inhibitory effects of PP4c on breast cancer cell survival and growth were lost in PEA15 knockdown cells, confirming that PP4c action is mediated, at least in part, through the de-phosphorylation of apoptosis regulator PEA15. CONCLUSION: Our work shows that PP4 regulates breast cancer cell survival and identifies a novel PP4c-PEA15 signalling axis in the control of breast cancer cell survival. The dysfunction of this axis may be important in the development and progression of breast cancer

Interactions between PP4 and PEA-15 in the regulation of cell proliferation and apoptosis of breast cancer cells

Background The serine/threonine protein phosphatase 4 (PP4) is recognised to regulate a variety of cellular functions. Our previous work has shown that the catalytic subunit of PP4 (PP4c) promotes cell death and inhibits proliferation in breast cancer cells, suggestive of a role of PP4c as tumour suppressor gene. Phosphoprotein enriched in astrocytes 15 (PEA-15), a member of the death effector domain protein family known to control cell survival, is reported to be regulated by PP4c. The aims of this study were to investigate the involvement of PEA-15 in mediating the effects of PP4c on breast cancer cells. Method PEA-15 phosphorylation was examined by western blot analysis on proteins extracted from MCF7 and MDA-MB-231 cells over-expressing PP4 and PP4 knock down cells. To investigate the role of PEA-15 in mediating the effects of PP4c, MCF7 and MDA-MB-231 were transfected with control (-) siRNA or with three different PEA-15 specific siRNAs. 48 h post-transfection, control cells (transfected with negative control siRNA) and cells transfected with PEA-15 siRNAs were transiently transfected with pcDNA3.1-PP4c expression construct or pcDNA3.1. Cell viability and apoptosis level were assessed post transfection. Results In MCF7 and MDA-MB-231 cells, the phosphorylation state of PEA-15 increased when PP4c expression was suppressed and decreased when PP4c was over-expressed. Over-expression of PP4c in cells transfected with (-) siRNA caused 50% reduction in viability compared to cells transfected with empty vector. Cells transfected with PEA-15 siRNAs showed a decrease in viable cell number and long term survival. However, over-expression of PP4c in these cells did not have any additional effect on the decrease in cell viability. Conclusion These observations suggest that the induction of apoptosis by over-expression of PP4c is mediated, at least in part, by the dephosphorylation of PEA-15. The interactions between PEA-15 and PP4c may therefore be critical in breast cancer tumorigenesis