Isolation of an antibacterial stilbene from Combretum woodii (Combretaceae) leaves

Acetone extracts of C. woodii leaf powder was separated by solvent-solvent partition into six fractions. The highest total activity was in the chloroform fraction. This fraction contained mainly one compound active against S. aureus. This compound was isolated by bioassay-guided fractionation using silica gel open column chromatography and identified by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) as the stilbene 2’,3’,4-trihydroxyl-3,5,4’-trimethoxybibenzyl (combretastatin B5) previously isolated from the seeds of C. kraussii. It showed significant activity against S. aureus withan MIC of 16 mg/ml but with lower activity towards P. aeruginosa (125 mg/ml), E. faecalis (125 mg/ml) and slight activity against E. coli. This is the first report of the antimicrobial activity of combretastatin B5. Its concentration in the leaves was in the order of 5-10 mg/g which makes the use of non-polar leafextracts a viable proposition in treating some infections, particularly in resource-poor settings

From theory to 'measurement' in complex interventions: methodological lessons from the development of an e-health normalisation instrument

<b>Background</b> Although empirical and theoretical understanding of processes of implementation in health care is advancing, translation of theory into structured measures that capture the complex interplay between interventions, individuals and context remain limited. This paper aimed to (1) describe the process and outcome of a project to develop a theory-based instrument for measuring implementation processes relating to e-health interventions; and (2) identify key issues and methodological challenges for advancing work in this field.<p></p> <b>Methods</b> A 30-item instrument (Technology Adoption Readiness Scale (TARS)) for measuring normalisation processes in the context of e-health service interventions was developed on the basis on Normalization Process Theory (NPT). NPT focuses on how new practices become routinely embedded within social contexts. The instrument was pre-tested in two health care settings in which e-health (electronic facilitation of healthcare decision-making and practice) was used by health care professionals.<p></p> <b>Results</b> The developed instrument was pre-tested in two professional samples (N = 46; N = 231). Ratings of items representing normalisation 'processes' were significantly related to staff members' perceptions of whether or not e-health had become 'routine'. Key methodological challenges are discussed in relation to: translating multi-component theoretical constructs into simple questions; developing and choosing appropriate outcome measures; conducting multiple-stakeholder assessments; instrument and question framing; and more general issues for instrument development in practice contexts.<p></p> <b>Conclusions</b> To develop theory-derived measures of implementation process for progressing research in this field, four key recommendations are made relating to (1) greater attention to underlying theoretical assumptions and extent of translation work required; (2) the need for appropriate but flexible approaches to outcomes measurement; (3) representation of multiple perspectives and collaborative nature of work; and (4) emphasis on generic measurement approaches that can be flexibly tailored to particular contexts of study

Combretum woodii (Combretaceae) leaf extracts have high activity against Gram-negative and Gram-positive bacteria

Dried ground leaves of Combretum woodii were extracted with 10 different solvents (hexane, diisopropyl ether, diethyl ether, methylene dichloride, ethyl acetate, tetrahydrofuran, acetone, ethanol, methanol and water) to determine the best extractant for subsequent isolation and characterization of antibacterial compounds. With the exception of the water extract, which had no antibacterial activity, the other extracts were bioactive with at least one of them exhibiting minimum inhibitory concentration values of 0.04 mg/ml against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli or Enterococcus faecalis. Intermediate polarity solvents extracted c. 10% of the dry mass compared to c. 3% with the more polar or non-polar solvents. These solvents also had higher antibacterial activity than more polar or non-polar extractants. Ethyl acetate was the best extractant with an average minimum inhibitory concentration (MIC) value of 0.08 mg/ml for the four pathogens followed by acetone and methylene dichloride with values of 0.14 mg/ml. The average MIC values for the positive controls were 0.13 (ampicillin) and 0.12 mg/ml (chloramphenicol). By taking the quantity extracted from the leaf powder into consideration, the total activity, a measure of potency, was highest for methylenedichloride (1309 ml/g) followed by acetone (1279 ml/g) extracts. The antibacterial activity was high enough to consider the use of extracts for  clinical application and to isolate and characterise antibacterial compounds from the extracts. Based on the Rf values of the antibacterial compoundsdetermined by bioautography, the antibacterial compound was not a polyphenol or a tannin

Early SUSVIMO in Neovascular Age-Related Macular Degeneration: Real Word Case Report and Clinical Implications

Jakob Pericak,1,2 Eric K Chin,3,4 David RP Almeida2 1State University of New York at Geneseo, Geneseo, NY, USA; 2Erie Retina Research & Center for Advanced Surgical Exploration, Erie, PA, USA; 3Retina Consultants of Southern California, Redlands, CA, USA; 4Loma Linda Eye Institute; Veterans Affair Hospital, Loma Linda, CA, USACorrespondence: David RP Almeida, Erie Retina Research & Center for Advanced Surgical Exploration, 300 State Street, Suite 302, Erie, PA, 16507, USA, Tel +1 814.476.6227, Fax +1 888.422.5096, Email [email protected]: The current standard of care for neovascular age-related macular degeneration is serial vascular endothelial growth factor (VEGF) inhibitor intravitreal injections at varying treatment intervals. SUSVIMO is a port-delivery system of ranibizumab that serves as an alternative, lower-maintenance treatment.Methods: A case report from a retinal surgery clinic describing the ocular findings, diagnostic workup, and alternative treatment for an 80-year-old man presenting with new-onset neovascular age-related macular degeneration.Results: Resolved foveal thickness, macular volume, and subretinal fluid after SUSVIMO implantation OD. The patient showed a better response to SUSVIMO than to previous anti-VEGF injections. Before the first refill, the patient began to experience subretinal fluid; however, it was resolved after the refill.Conclusion: Although effective, real-world management of neovascular age-related macular degeneration is associated with an extensive treatment burden that can compromise treatment adherence. Herein, we describe how the port delivery system (PDS; SUSVIMO) - a refillable ocular implant that can continuously deliver a novel formulation of ranibizumab with refills possible at six months or longer - is a viable early therapy that mitigates the treatment burden of intravitreal injections.Keywords: neovascular age-related macular degeneration, SUSVIMO, port delivery syste

Vitamin a Deficiency in an Elderly Patient: A Diagnostic Challenge in the Age of AMD

Jakob M Pericak,1,2 Eric K Chin,3,4 David RP Almeida2 1State University of New York at Geneseo, Geneseo, NY, USA; 2Erie Retina Research & Center for Advanced Surgical Exploration, Erie, PA, USA; 3Retina Consultants of Southern California, Redlands, CA, USA; 4Loma Linda Eye Institute; Veterans Affair Hospital, Loma Linda, CA, USACorrespondence: David RP Almeida, Erie Retina Research & Center for Advanced Surgical Exploration, 300 State Street, Suite 302, Erie, PA, 16507, USA, Tel +1 814 476 6227, Fax +1 888 422 5096, Email [email protected]: The presentation of vitamin A deficiency (VAD)-induced ocular complications can be challenging to diagnose in elderly patients, particularly due to the overlap with age-related macular degeneration (AMD) symptoms. This case report details the presentation, diagnosis, and management of an 88-year-old female with vision loss, highlighting the ocular manifestations of presumed VAD. Despite vitamin A levels being at the lower end of the normal range, the patient’s symptoms and spectral domain optical coherence tomography (SD-OCT) findings suggested insufficient levels, leading to thinning of the outer nuclear layer. This case underscores the necessity of considering VAD in differential diagnoses of unexplained vision impairment, particularly in individuals with a history of intestinal malabsorption, while also emphasizing the importance of distinguishing VAD from AMD in elderly patients.Keywords: vitamin A deficiency, malabsorption syndrome, age-related macular degeneratio

Acid Glycohydrolases in Rat Spermatocytes, Spermatids and Spermatozoa: Enzyme Activities, Biosynthesis and Immunolocalization

Mammalian sperm acrosome contains several glycohydrolases thought to aid in the dispersion and digestion of vestments surrounding the egg. In this study, we have used multiple approaches to examine the origin of acrosome-associated glycohdyrdolases. Mixed spermatogenic cells, prepared from rat testis, were separated by unit gravity sedimentation. The purified germ cells (spermatocytes [SP], round spermatids [RS], and elongated/condensed spermatids [E/CS]) contained several glycohydrolase activities. Metabolic labeling in the cell culture, immunoprecipitation, and autoradiographic approaches revealed that β-D-galactosidase was synthesized in SP and RS in 88/90 kDa forms which undergo processing in a cell-specific manner. Immunohistochemical approaches demonstrated that the enzyme was localized in Golgi membranes/vesicles, and lysosome-like structures in SP and RS, and forming/formed acrosome of E/CS

Gas phase conformational basicity of carvedilol fragment B, 2(S)-1-(ethylamonium)propane-2-ol: An ab initio study on a protonophoretic of oxidative phosphorylation uncoupling

Carvedilol is cardiovascular drug of proven efficacy. It is believed that carvedilol exerts cardio-protective effects by acting as a mild uncoupler of mitochondrial oxidative phosphorylation, thereby protecting mitochondria from oxidative stress and preserving proper bioenergetics and cardiac function. This uncoupling occurs via a proton-shuttling mechanism involving the amino group of carvedilol's side-chain. However, the molecular details of carvedilol's proton affinity have not yet been completely worked out, especially with regards to the attributes of molecular conformation. In the present study, the full conformational basicity of a fragment of carvedilol, 2(S)-1-(ethylamonium)propane-2-ol (Fragment B), is presented to illustrate the protonophoretic character of carvedilol. Full gas phase geometry optimizations were performed at the ab initio, RHF/3-21G, level of theory for the entire potential energy hypersurface (PEHS) of Fragment B. Subsequently, since deprotonation can occur via two different protons, a two-prong methodology was applied to calculate vertical and adiabatic energies of deprotonation. A total of 18 out of a possible 81 minima converged and the dominant characteristic in all protonated and deprotonated conformers was a gauche plus effect in the rotation about the C-OH bond at the Fragment B stereocentre. Optimized energies of deprotonation ranged from 245 to 262 kcal mol-1 while protons involved in internal hydrogen bonding required an extra 6-8 kcal mol-1 for deprotonation compared to protons that were oriented away from the backbone structure. The overall trend indicates that conformers devoid of significant stabilization interactions possessed lower energies of deprotonation; in other words, as the relative conformer energy increased, vertical and adiabatic energies of deprotonation tended to decrease. Thus, extrapolating to carvedilol and the proton transfer mechanism involved in oxidative phosphorylation uncoupling, events of deprotonation will favour molecular conformations with minimal intramolecular stabilization and with higher relative energies

A finite strain fibre-reinforced viscoelasto-viscoplastic model of plant cell wall growth

A finite strain fibre-reinforced viscoelasto-viscoplastic model implemented in a finite element (FE) analysis is presented to study the expansive growth of plant cell walls. Three components of the deformation of growing cell wall, i.e. elasticity, viscoelasticity and viscoplasticity-like growth, are modelled within a consistent framework aiming to present an integrative growth model. The two aspects of growth—turgor-driven creep and new material deposition—and the interplay between them are considered by presenting a yield function, flow rule and hardening law. A fibre-reinforcement formulation is used to account for the role of cellulose microfibrils in the anisotropic growth. Mechanisms in in vivo growth are taken into account to represent the corresponding biologycontrolled behaviour of a cell wall. A viscoelastic formulation is proposed to capture the viscoelastic response in the cell wall. The proposed constitutive model provides a unique framework for modelling both the in vivo growth of cell wall dominated by viscoplasticity-like behaviour and in vitro deformation dominated by elastic or viscoelastic responses. A numerical scheme is devised, and FE case studies are reported and compared with experimental data