Therapeutic Potential of Antioxidants and Hybrid TEMPOL Derivatives in Ocular Neurodegenerative Diseases: A Glimpse into the Future.

Reactive oxygen species play a significant role in the pathogenesis of various ocular neurodegenerative diseases especially glaucoma, age-related macular degeneration (AMD), and ocular ischemic stroke. Increased oxidative stress and the accumulation of ROS have been implicated in the progression of these diseases. As a result, there has been growing interest in exploring potential therapeutic and prophylactic strategies involving exogenous antioxidants. In recent years, there have been significant advancements in the development of synthetic therapeutic antioxidants for targeting reactive oxygen species (ROS) in neurodegenerative diseases. One area of focus has been the development of hybrid TEMPOL derivatives. In the context of ocular diseases, the application of next-generation hybrid TEMPOL antioxidants may offer new avenues for neuroprotection. By targeting ROS and reducing oxidative stress in the retina and optic nerve, these compounds have the potential to preserve retinal ganglion cells and trabecular meshwork and protect against optic nerve damage, mitigating irreversible blindness associated with these diseases. This review seeks to highlight the potential impact of hybrid TEMPOL antioxidants and their derivatives on ocular neurodegenerative disorders.

Long-term HIF-1α stabilization reduces respiration, promotes mitophagy, and results in retinal cell death.

Ocular hypertension during glaucoma can lead to hypoxia, activation of the HIF transcription factors, and a metabolic shift toward glycolysis. This study aims to test whether chronic HIF activation and the attendant metabolic reprogramming can initiate glaucoma-associated pathology independently of ocular hypertension. HIF-1α stabilization was induced in mice for 2 and 4 weeks by inhibiting prolyl hydroxylases using the small molecule Roxadustat. HIF-1α stabilization and the expression of its downstream bioenergetic targets were investigated in the retina by immunofluorescence, capillary electrophoresis, and biochemical enzyme activity assays. Roxadustat dosing resulted in significant stabilization of HIF-1α in the retina by 4 weeks, and upregulation in glycolysis-associated proteins (GLUT3, PDK-1) and enzyme activity in both neurons and glia. Accordingly, succinate dehydrogenase, mitochondrial marker MTCO1, and citrate synthase activity were significantly decreased at 4 weeks, while mitophagy was significantly increased. TUNEL assay showed significant apoptosis of cells in the retina, and PERG amplitude was significantly decreased with 4 weeks of HIF-1α stabilization. A significant increase in AMPK activation and glial hypertrophy, concomitant with decreases in retinal ganglion cell function and inner retina cell death suggests that chronic HIF-1α stabilization alone is detrimental to retina metabolic homeostasis and cellular survival.

Spontaneous reporting of adverse drug reaction among health professionals in Ghana.

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADR) is an effective means of ensuring postmarketing surveillance of drugs, and health professionals play a cardinal role through voluntary reporting of ADR. However, the pharmacovigilance system in Ghana is plagued with under-reporting issues, which is of public health concern. METHOD: A questionnaire-based cross-sectional study involving 268 health professionals at Kpone-Katamanso District was carried out. Data on spontaneous reporting of ADR, demographics of participants, knowledge, and attitudes of professionals towards reporting and factors that may influence ADR reporting were collected. Logistic regression models were used to examine the association of the independent variables with spontaneous reporting of ADR. RESULT: Overall, 77.6% (208) of the 268 respondents had observed ADR; however, only 17.3% of the respondents had ever reported an ADR to the Ghana FDA. Health professionals who had average knowledge on spontaneous reporting of ADR were 51.9%, while 30.3% had good knowledge of spontaneous reporting of ADR. After adjustment on potential confounding variables (Knowledge, Feedback from FDA, Uncertainty about cause of ADR, Severity of ADR), Age (AOR = 2.26, 95%CI = 1.25-4.10), Fear of Legal Consequences (AOR = 0.15, 95%CI = 0.41-0.51), Time Constraint (AOR = 0.3, 95%CI = 0.10-0.91), Pharmacovigilance training (AOR = 18.78, 95%CI = 5.46-64.59) and Unavailability of Reporting form (AOR = 0.28, 95%CI = 0.09-0.88) were found to be significantly associated spontaneous reporting of ADR. CONCLUSION: The proportion of health professionals in the Kpone- Katamanso District who spontaneously reported observed ADR was low though they had average knowledge about ADR reporting. This underscores the need for a policy to be implemented that makes spontaneous reporting of adverse drug reaction mandatory for health professionals.

Regulatory compliance among over-the-counter medicine sellers facilities within the Upper East Region of Ghana.

BACKGROUND: Easy access to medicines provided by private medicine retailing facilities including that of over-the-counter medicine retailers, have gained prominence in sub-Saharan Africa. Although over-the-counter medicine-sellers (OTCMS) facilities play an indispensable role in healthcare delivery, there is inadequate information about their regulatory environment and whether their operations conform to regulatory provisions. Hence, this study sought to investigate the characteristics and predictors of regulatory practices among over-the-counter medicine sellers in Ghana. METHODS: This was a cross-sectional study involving participants from 208 OTCMS facilities in eight (8) municipalities and districts (MDA's) of the Upper East Region of Ghana. An initial census of facilities in the region was conducted between May and August 2016 and a follow-up conducted between December 2016 and March 2017. This ensured the identification and location of all OTCMS facilities within the selected MDA's for study planning and data collection. The main outcome variable was regulatory compliance which is a composite of three indicators for regulatory practices (retention of medicine supplier's invoices and receipts on-premises), licensing and registration requirements (appropriate signage), and equipment and material requirements (availability of reference material). Regulatory compliance was assessed using bivariate and multivariate logistic regression analyses. RESULTS: In this survey, 21.5%, 38.2%, and 23.1% of the facilities surveyed had a good state of repair, had the owner of the facility available on the premises, and had received regulatory visit(s) in less than 12 months, respectively. Only 29.2% of facilities were regulatory compliant. After statistical adjustment, OTCMS facility location (compared with Rural: Urban, AOR = 4.2, 95% CI 1.74-10.17, p = 0.001) and staff trained in less than 1 year (AOR = 2.78, 95% CI 1.02-7.62, p = 0.046) were significantly associated with regulatory compliance. CONCLUSIONS: Regulatory compliance was low in the Upper East Region of Ghana, particularly across rural locations, where most of the facilities failed to meet the laid down provisions of the Pharmacy Council regarding practice, staff and premises requirements. This could be attributed to the fact that these areas are poorly resourced. Policymakers are been called on to put in place pragmatic measures in relation to OTCMS facility's location and regulatory requirements to address the inequities in compliance.