School of Pharmacy
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Item AP39, A Novel Mitochondria-Targeted Hydrogen Sulfide Donor, Promotes Cutaneous Wound Healing In An In Vivo Murine Model Of Acute Frostbite Injury(Elsevier Masson SAS., 2025-01-28) Dugbartey, G.J. et alFrostbite injury refers to cold tissue injury which typically affects the peripheral areas of the body, and is associated with limb loss and high rates of morbidity. Historically, treatment options have been limited to supportive care, leading to suboptimal outcomes for affected patients. The pathophysiology of frostbite injury has been understood in recent years to share similarity with that of cold ischemia-reperfusion injury as seen in solid organ transplantation, of which mitochondria play an important contributing role. The present study investigated whether AP39, a novel mitochondria-targeted slow-releasing hydrogen sulfide donor, applied top ically in a vehicle cream at 200 nM or 1 µM could mitigate frostbite injury and promote wound healing in mice. Frostbite injury was induced continuously for 3 min on the dorsal skin of C57BL/6 mice (Mus musculus) using magnets frozen on dry ice (-80 ◦C). AP39, delivered via a vehicle cream, was used daily to treat frostbite injury until animals were euthanized on day 15 after induction of frostbite injury. Wound tissues were stained with hematoxylin and eosin along with immunofluorescence staining with cleaved caspase-3, CD31, KI-67, CD163, fibronectin and cytokeratin. While 200 nM AP39 improved granulation tissue maturation (p < 0.001), angio genesis (p < 0.01) and cell proliferation (p < 0.001) compared to vehicle control, 1 µM AP39 further increased granulation tissue formation compared to other frostbite groups (p < 0.001). Thus, AP39 promoted frostbite wound healing, and therefore could be considered as a treatment option for patients with frostbite injury.Item An exploratory study of the mandate and functions of national pharmaceutical services units: global trends and the cases of Côte d’Ivoire, Kenya, and Nepal(Journal of Pharmaceutical Policy and Practice, 2024) Koduah, A.; Kusu, N.; Ahimon, H.; et al.Background: National pharmaceutical services units (NPSUs) – organisational units within the central government usually responsible for pharmaceutical services and management – have an increasingly narrow mandate. Anecdotal evidence points to an increasing focus, almost exclusively, on logistics management, while pharmaceutical care and policy oversight have become fragmented. This study examined NPSUs’ current functions and mandates, and proposed what should be the critical functions and roles of these units going forward. Methods: Using case studies of Côte d’Ivoire, Kenya and Nepal, the study relied on a literature review and in-depth interviews. We triangulated and synthesised the findings to identify NPSUs by level in the health ministry’s hierarchy and reporting line, mandate, and function.Results: We identified medicine regulation, procurement and supply chain management, selection and rational use of medicines, and pharmacy practice regulation as four broad sets of functions that NPSUs commonly have as their mandate. A clear position in the Ministry of Health’s hierarchical structure, the legal or administrative framework that mandates an NPSU’s functions, and national pharmaceutical policies and regulations to guide the pharmaceutical sector are three critical factors for effective functioning. It is essential to have a legislative framework that at a minimum identifies one NPSU as responsible for pharmaceutical policy and governance, serving as the steward for the pharmaceutical system. This role encompasses pharmaceutical system coordination and administrative functions, formulating and implementing policies for organising, managing, financing, regulating, monitoring, and evaluating the pharmaceutical system. As such, we recommend that NPSUs should at a minimum have four broad sets of functions: pharmaceutical policy and governance, medicine regulation, pharmacy practice regulation and procurement and supply chain management. Conclusion: The study substantiates the need for a pharmaceutical policy and governance unit that stewards the pharmaceutical system and is empowered to monitor and evaluate system performance and coordinate efforts for system strengthening.Item Medicinal uses, pharmacological activities, and bioactive compounds of Nauclea latifolia and implications in the treatment of tropical diseases(HSI Journal, 2024) Bekoe, E.O.; Lartey M.; Gordon, A.; Asante, B.Nauclea latifolia Sm. is a medicinal plant from the family Rubiaceae which is widely distributed in the tropical regions of Africa and Asia. Different parts of the plant are known to have many ethnomedicinal uses. The aim of this review is to compile knowledge available on the ethnomedicinal uses, pharmacological activities, and bioactive compounds present in different parts of the plant and identify their relevance in the treatment of tropical diseases. This review will preserve traditional knowledge, promote responsible use, and advance scientific and medical research on this plant. N. latifolia is used for the treatment of malaria, skin conditions, pain, hypertension, diabetes, fever, stomach problems, female infertility, gastric ulcer, jaundice, respiratory tract ailments, eye conditions, menstrual disorders, yellow fever, gonorrhoea, haemorrhoids, urine retention, male sexual dysfunction, dysentery, diarrhoea, HIV/ AIDS, measles, typhoid fever, leprosy, oral diseases, hernia, cancer, filariasis (helminthiasis) and central nervous system injuries. This plant has been investigated for its antidepressant, anticonvulsant, antimicrobial, antiplasmodial, antioxidant, antidiabetic, anti-ulcer, antipyretic, antinociceptive, hepatoprotective, larvicidal, ovicidal, antidiarrheal, antihypertensive, hypocholesterolemic, hypoglycaemic, anti-inflammatory, anxiolytic, myorelaxant and sedative activities. Scientific justification for its usage in the treatment of viral infections, hypertension, helminthiasis, stomachache, diabetes, backache, fever, cancer, malaria, diarrhoea, measles, conjunctivitis, and gastric ulcer has been established. However, further studies are needed to justify its use in the treatment of urine retention, male sexual dysfunction, HIV/ AIDS, hernia, female infertility, as well as Parkinson’s and Alzheimer’s disease. The phytoconstituents documented include proanthocyanins, alkaloids, tannins, flavonoids, glycosides, phenols, steroids, saponins, and terpenoids, with many compounds having been isolated.Item Cellular and molecular mechanisms of cell damage and cell death in ischemia–reperfusion injury in organ transplantation(Molecular Biology Reports, 2024) Dugbartey, G.J.Ischemia–reperfusion injury (IRI) is a critical pathological condition in which cell death plays a major contributory role, and negatively impacts post-transplant outcomes. At the cellular level, hypoxia due to ischemia disturbs cellular metabo lism and decreases cellular bioenergetics through dysfunction of mitochondrial electron transport chain, causing a switch from cellular respiration to anaerobic metabolism, and subsequent cascades of events that lead to increased intracellular concentrations of Na+, H+ and Ca2+ and consequently cellular edema. Restoration of blood supply after ischemia provides oxygen to the ischemic tissue in excess of its requirement, resulting in over-production of reactive oxygen species (ROS), which overwhelms the cells’ antioxidant defence system, and thereby causing oxidative damage in addition to activating pro-infammatory pathways to cause cell death. Moderate ischemia and reperfusion may result in cell dysfunction, which may not lead to cell death due to activation of recovery systems to control ROS production and to ensure cell survival. However, prolonged and severe ischemia and reperfusion induce cell death by apoptosis, mitoptosis, necrosis, necroptosis, autophagy, mitophagy, mitochondrial permeability transition (MPT)-driven necrosis, ferroptosis, pyroptosis, cuproptosis and parthanoptosis. This review discusses cellular and molecular mechanisms of these various forms of cell death in the context of organ transplantation, and their inhibition, which holds clinical promise in the quest to prevent IRI and improve allograft quality and function for a long-term success of organ transplantation.Item Redox System and Oxidative Stress-Targeted Therapeutic Approaches in Bladder Cancer(Antioxidants, 2024) Dugbartey, G.J.; Relouw, S.; McFarlane, L.; Sener, A.Bladder cancer (BCa) is the most common genitourinary malignancy, with a high global incidence and recurrence rate that is paired with an increasing caregiver burden and higher financial cost, in addition to increasing morbidity and mortality worldwide. Histologically, BCa is categorized into non-muscle invasive, muscle invasive, and metastatic BCa, on the basis of which the therapeutic strategy is determined. Despite all innovations and recent advances in BCa research, conventional therapies such as chemotherapy, immunotherapy, radiotherapy, and surgery fall short in the complete management of this important malignancy. Besides this worrying trend, the molecular basis of BCa development also remains poorly understood. Burgeoning evidence from experimental and clinical studies suggests that oxidative stress resulting from an imbalance between reactive oxygen species (ROS) generation and the body’s antioxidant production plays an integral role in BCa development and progression. Hence, ROS-induced oxidative stress-related pathways are currently under inves tigation as potential therapeutic targets of BCa. This review focuses on our current understanding regarding ROS-associated pathways in BCa pathogenesis and progression, as well as on antioxidants as potential adjuvants to conventional BCa therapyItem Evaluating the Effects of Kidney Preservation at 10 ◦C with Hemopure and Sodium Thiosulfate in a Rat Model of Syngeneic Orthotopic Kidney Transplantation(International Journal of Molecular Sciences, 2024) Taka, M.A.; Dugbartey, G.J.; Richard-Mohamed, M.; et al.Kidney transplantation is preferred for end-stage renal disease. The current gold standard for kidney preservation is static cold storage (SCS) at 4 ◦C. However, SCS contributes to renal graft damage through ischemia–reperfusion injury (IRI). We previously reported renal graft protection after SCS with a hydrogen sulfide donor, sodium thiosulfate (STS), at 4 ◦C. Therefore, this study aims to investigate whether SCS at 10 ◦C with STS and Hemopure (blood substitute), will provide similar protection. Using in vitro model of IRI, we subjected rat renal proximal tubular epithelial cells to hypoxia–reoxygenation for 24 h at 10 ◦C with or without STS and measured cell viability. In vivo, we preserved 36 donor kidneys of Lewis rats for 24 h in a preservation solution at 10 ◦C supplemented with STS, Hemopure, or both followed by transplantation. Tissue damage and recipient graft function parameters, including serum creatinine, blood urea nitrogen, urine osmolality, and glomerular filtration rate (GFR), were evaluated. STS-treated proximal tubular epithelial cells exhibited enhanced viability at 10 ◦C compared with untreated control cells (p < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts (p < 0.05) in the early time period after the transplant, but long-term function did not reach significance. Overall, renal graft preservation at 10 ◦C with STS and Hemopure supplementation has the potential to enhance graft function and reduce kidney damage, suggesting a novel approach to reducing IRI and post-transplant complications.Item Transforming Supply Logistics for Health Commodity Security in Africa(Global Health: Science and Practice, 2024) Tetteh, E.K.To resolve the problem of ensuring secure supplies of all health commodities, health planners in African countries must first identify arrangements that best serve the public interests of promoting choice and competition in ensuring health commodity security. Investments in inventory management should not be viewed as a one-off exercise but rather as a continuous search for the optimal scale and scope of operations that ensure the availability of essential health commodities most of the time. Without competing alternatives to manage inventory, public-sector logistics monopolies lack adequate incentives to devise ways of reducing costs and improving output. Further, these monopolies make it more difficult to minimize the impact and duration of catastrophic supply disruptions. Current efforts to improve public-sector supply logistics must be extended to include the transformation of existing public and private logistics infrastructure for inventory management into a state of prudent multiplicity—one in which there are at least 2 full-line national logistics institutions competing to serve all government, nongovernmental, and private health facilities. Health planners should consider creating a state of prudent multiplicity in their roadmaps, master plans, and health system strengthening initiatives.Item In-vitro and in-vivo anti-inflammatory properties of extracts and isolates of Pangdahai(Phytomedicine Plus, 2024) Oppong, M. B.; Lartey, M.; Adutwum, L. A.; et alBackground: : Pangdahai (matured, ripened, and dried seeds of Scaphium affine (Mast.) Pierre) is widely used in managing several diseases in countries like China, Vietnam, Japan, and India. This study evaluated the anti-inflammatory effects of the crude extracts (ethanol and aqueous) and isolated compounds of Pangdahai. Methods:: Xylene-induced ear edema in mice, carrageenan-induced paw edema in rats, and nitric oxide (NO) assay were used to evaluate and screen the crude extracts and isolated compounds from the ethanolic extracts of Pangdahai. TNF-α and IL-1β levels in the tissues of rat foot and ear were determined by ELISA. The cytotoxicity of the isolated compounds was also determined by MTT assay. Molecular docking studies using targets involved in the inflammatory process were also used to further evaluate the compounds. Results: : Both aqueous and ethanol extracts demonstrated significant anti-inflammatory effect and markedly attenuated vascular permeability in mice induced by acetic acid in a dose-independent manner. The ethanol extract also significantly inhibited levels of IL-1β and TNF-α. Four (4) compounds exhibited significant inhibitory effects on NO release without cytotoxicity on RAW 264.7 macrophage. These compounds also showed good binding affinities for COX-2, PLA2, IRAK-4 and NIK. Conclusions: This study validates, provides scientific evidence and justification for the use of the aqueous de coctions of Pangdahai in pharyngitis traditionally. (+) – Pinoresinol, tiliroside, Z-caffeic acid, and 3,4-dihydrox ybenzoic acid (protocatechuic acid) isolated from Pangdahai showed anti-inflammatory activities, which might be responsible for the actions of Pangdahai. Tiliroside showed a high binding affinity comparable to the native ligands of inflammatory mediators.Item Phytochemical Analysis and Elemental Contents of Varieties of Polyalthia longifolia (Sonn.) Thwaites(Journal of Natural Remedies, 2024) Bekoe, E. O.; Lartey, M.; Orman, E.; et alPolyalthia longifolia (Sonn.) is a medicinal plant that belongs to the family Annonaceae, and it is distributed in the tropics. This plant is widely grown in West Africa for its ornamental and medicinal purposes. There are two varieties of P. longifolia which are commonly distinguishable by the direction of their branches. One has spreading perpendicular branches, and the other has drooping pendulous branches. Traditional herbal practitioners believe that one variety (P. longifolia cv. pendula) is more medicinal than the other. This study, therefore, sought to investigate the phytochemical components of the two varieties of P. longifolia by HPTLC, UPLC, and elemental analysis by ICP-EOS. No observable differences were found in the phytochemical and elemental profiles of these varieties that could help distinguish one from the other or could account for its supposed differences in medicinal properties. A total of 22 elements were detected in the samples of the two varieties of the plant. Qualitatively, the elemental content of both varieties was similar. Only Iridium was not detected in all samples. Heavy metals including As, Pb, Cd, and Hg had their levels above the recommended limits.Item Undescribed sesquiterpenoids with NO production inhibitory activity from oleo-gum resin of Commiphora myrrha(Phytochemistry, 2024) Zhang, B.; Chao, W.; Donkor, P.O.; et al.Six undescribed cadinane sesquiterpenoids (1− 6), two undescribed guaiane sesquiterpenoids (7− 8), and an undescribed germacrane sesquiterpenoid (9) were isolated from the oleo-gum resin of Commiphora myrrha. Their structures were determined by the analysis of 1D/2D NMR and HRESIMS data, as well as quantum chemical ECD and NMR calculations. All the sesquiterpenoids were evaluated for their NO production inhibitory activity in LPS-stimulated RAW 264.7 mouse monocyte-macrophages. The results revealed that commiphone A (1) and commipholide D (7) exhibited significant inhibitory effect on NO generation with IC50 values of 18.6 ± 2.0 and 37.5 ± 1.5 μM, respectively. Furthermore, 1 and 7 dose-dependently inhibited the mRNA expression of in flammatory cytokines IL-1β, IL-6 and TNF-α induced by LPS in the RAW264.7 cells, indicating that 1 and 7 possess potent anti-inflammatory activity in vitro.