Perceptions of health professionals using the Umbiflow portable continuous wave doppler in two (2) urban hospitals in South Africa

Master of Public Health - MPHSouth Africa had a stillbirth rate of 16.4/1000 in 2019. Umbiflow is a sophisticated portable continuous wave Doppler device with bidirectional indication of blood flow velocity in the umbilical cord. Umbiflow clinical trial results have indicated that several stillbirths were avoided by screening pregnant women classed as low risk. The study aimed to describe the perceptions of health professionals on the Umbiflow screening tool. The objectives were to explore the health professionals’ perceptions on the usability, acceptability and the perceived challenges with implementation of Umbiflo

An investigation of the binding capacities of recombinant domain mutants of the human Polymeric Immunoglobulin Receptor (pIgR)

The membrane bound glycoprotein, polymeric immunoglobulin receptor (pIgR) is the primary transport molecule of the polymeric immunoglobulins, dimeric IgA and pentameric IgM, across epithelial cells. This process, known as transcytosis, is essential in order to establish immunity at mucosal surfaces. Typically, pIgR binds to the polymeric immunoglobulin at the basolateral surface of the epithelial cell, via five homologous immunoglobulin-like domains of the ectodomain. Binding is covalent to IgA and non-covalent to IgM; the IgM binding varying among species. The pIgR-bound complex is released at the apical surface of the cell after cleavage of pIgR at Arg585, thereafter referred to as secretory component (SC). SC confers protective and immunologic functions to the polymeric immunoglobulin. Free SC, i.e. not complexed with polymeric immunoglobulins, is also known to be released into mucosal secretions; and binds to pathogenic bacteria and bacterial products. It is known that domain I of the ectodomain is the primary domain in the interaction with polymeric immunoglobulins, while domain V is involved in a covalent linkage with IgA. However, little is known of domains II-IV and their role in immunoglobulin binding, particularly to IgM. This study aimed to characterize the binding of recombinant human pIgR domain mutants to polymeric IgM using immunological, biophysical and cell based techniques; thereby allowing greater insight into the contribution of each of the five domains. The unique domain structure allowed for selective amplification of single and multiple domain mutants from cloned human PIGR ectodomain cDNA. Mutants were cloned and expressed in Esherichia coli BL21 (DE3) as inclusion bodies. Recombinant mutant proteins were refolded in vitro by equilibrium gradient dialysis and purified to homogeneity. Equilibrium binding data show significant contributions to specific binding as a factor of domain presence. Binding kinetics determined by biophysical surface plasmon resonance measurements show the interplay between association and dissociation rates as defined by individual domains. In vitro competitive binding studies using the human intestinal carcinoma, HT29, known to constitutively express pIgR, show that the constructed recombinant domain mutants outcompete native pIgR. The level of competition is shown to be dependant on the domains downstream of domain I. The data also confirm the biological activity of the first in vitro refolded recombinant human SC

Photophysical behavior and photodynamic therapy activity of conjugates of zinc monocarboxyphenoxy phthalocyanine with human serum albumin and chitosan

Zincmonocarboxyphenoxy phthalocyanine (ZnMCPPc) was linked to human serum albumin (HSA) and chitosan via amide bond formation. The photophysical behavior and photodynamic therapy (PDT) activity (against human breast adenocarcinoma cell line (MCF-7 cells) of ZnMCPPc alone and its conjugates were investigated. The conjugates showed improved fluorescence, triplet and singlet oxygen quantum yields when compared to ZnMCPPc alone. The in vitro dark cytotoxicity and PDT studies were carried out at a dose of 3.6 μg/mL to 57.1 μg/mL. The in vitro dark cytotoxicity studies of ZnMCPPc showed cell viability more than 50% at 28.6 μg/mL and 57.1 μg/mL, while the conjugates showed > 50% in all their tested concentrations (3.6 to 57.1) μg/mL. Thus, conjugation of ZnMCPPc to HSA and chitosan improves its dark cytotoxicity, an important criteria for molecules meant for photodynamic therapy. Complex 1 showed the most efficacious PDT activity with cell viability more than 50% at concentration range of (14.3 to 57.1) μg/mL in comparison to the conjugates which only showed more than 50% cell viability at 28.6 μg/mL and 57.1 μg/mL for 1-HSA and 57.1 μg/mL for 1-Chitosan

Photophysicochemical properties of nanoconjugates of zinc (II) 2 (3)-mono-2-(4-oxy) phenoxy) acetic acid phthalocyanine with cysteamine capped silver and silver–gold nanoparticles

A novel asymmetrical zinc(II) 2(3)-mono-2-(4-oxy)phenoxy)acetic acid phthalocyanine (complex 1) was synthesized and subsequently linked to cysteamine capped silver (AgNPs) and silver–gold (AgAuNPs) nanoparticles (NPs) via amide bonds. The photophysicochemical properties and in vitro photodynamic therapy activity of complex 1 and its nanoconjugates were investigated. The nanoconjugates showed improved photophysical properties compared to complex 1 alone. The fluorescence, triplet and singlet quantum yields of complex 1 were found to be 20%, 48%, and 43% respectively. Complex 1 showed in vitro dark cytotoxicity, but the dark toxicity was reduced for the combination of complex 1 with AgAuNPs, this combination also gave the best photodynamic therapy activity when compared to complex 1 and its conjugate with AgNPs without AuNPs

The photophysicochemical properties and photodynamic therapy activity of In and Zn phthalocyanines when incorporated into individual or mixed Pluronic® micelles

The synthesis, photophysicochemical properties and photodynamic activity (PDT) of tetra-pyridyloxy (1,2) and benzothiazole (3, 4) substituted indium (III) (1,3) and zinc (2, 4) phthalocyanines (Pcs) and their incorporation into Pluronic® F127 and Pluronic L121/F127 mixed micelles (the latter for 3 and 4 only) are presented in this study. The InPcs exhibited higher singlet oxygen (ΦΔ) at 0.76 and 0.68 compared to the ZnPc’s at 0.47 and 0.44 in dimethyl sulfoxide. The ΦΔ values in the presence of Pluronic® F127 and in water, were 0.39 and 0.42 for InPcs and 0.23 and 0.37 for ZnPc. The ΦΔ values in the presence of Pluronic F127/L121 mixed micelles for complex 3 and 4 were 0.51 and 0.29 in water. The Kp was determined using the water and octanol system. InPcs had larger Kp values suggesting that they are more likely to be taken up by the cancer cells hence they showed better PDT activit

The effects of silica based nanoparticles on the photophysicochemical properties, in vitro dark viability and photodynamic therapy study of zinc monocarboxyphenoxy phthalocyanine

Aminopropyl triethoxysilane functionalized core SiO2 and core/shell ZnO/SiO2 nanoparticles (NP) were covalently linked to zinc monocarboxyphenoxy phthalocyanine (ZnMCPPc, complex 1) via amide bond formation. The photophysicochemical behavior, in vitro dark viability and photodynamic therapy (PDT) activity against human breast adenocarcinoma cell line (MCF-7 cells) of the conjugates were studied. The nanoconjugates showed enhanced photophysicochemical behavior as compared to complex 1 alone. Complex 1 showed higher dark toxicity against MCF-7 cells when compared to the conjugates. In the dark, complex 1 accounted for less than 50% viable cells at 28.6 μg/mL and 57.1 μg/mL compared to the conjugates which accounted for more than 50% cell viability at these concentrations. The in vitro dark viability and PDT activity of complex 1 was reduced in the presence of these nanoparticles

A gold–chitosan composite with low symmetry zinc phthalocyanine for enhanced singlet oxygen generation and improved photodynamic therapy activity

Novel zinc(II) 3-(4-((3,17,23-tris(4-(benzo[d]thiazol-2-yl)phenoxy)phthalocyanine-9-yl)oxy)phenyl)propanoic acid (complex 3) was synthesised. Complex 3 was subsequently reacted with gold nanoparticles (AuNPs), chitosan (CT) and a gold–chitosan (AuCT) hybrid to form 3-AuNPs, 3-CT and 3-AuCT, respectively. The conjugates afforded a decrease in fluorescence quantum yield with a corresponding increase in the triplet and singlet quantum yields compared to complex 3. The in vitro dark cytotoxicity and photodynamic therapy activity (PDT) of complex 3 and 3-AuCT composites were investigated against epithelial breast cancer cells (MCF-7) with both the samples showing minimum dark cytotoxicity. They both accounted for a cell viability of ≥90% at a concentration of ≤59.2 μg mL−1. 3-AuCT showed better PDT activity (compared to 3 alone) with less than 50% viable cells at a concentration of ≥29.6 μg mL−1 making it potentially applicable for PDT. On the other hand, AuCT displayed some activity against cancer cells, probably due to photothermal activity since gold is a light absorber, however it had more than 50% viable cells at a concentration of ≤59.2 μg mL−1