<i>Momordica cochinchinensis</i> (Gấc) Seed Extracts Induce Apoptosis and Necrosis in Melanoma Cells

Momordica cochinchinensis is a herbal medicine used throughout Asia and this study investigated the antimelanoma potentials and molecular mechanisms of M. cochinchinensis seed with emphasis on extraction to optimise bioactivity. Overall, the aqueous extract was superior, with a wider diversity and higher concentration of proteins and peptides that was more cytotoxic to the melanoma cells than other extraction solvents. The IC50 of the aqueous extract on melanoma cells were similar to treatment with current anticancer drugs, vemurafenib and cisplatin. This cytotoxicity was cancer-specific with lower cytotoxic effects on HaCaT epidermal keratinocytes. Cytotoxicity correlated with MAPK signalling pathways leading to apoptosis and necrosis induced by triggering tumour necrosis factor receptor-1 (TNFR1), reducing the expression of nuclear factor kappa B (NF-kB), and suppression of BRAF/MEK. This efficacy of M. cochinchinensis seed extracts on melanoma cells provides a platform for future clinical trials as potent adjunctive therapy for metastatic melanoma

Recent advances in the management of diabetic retinopathy

Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the leading cause of vision loss in people with diabetes. The current treatments do not target early stages of disease or impede disease progression. Therefore, the identification of new therapeutic targets, the development of novel therapies targeting early stages of the disease and accurate models that simulate pathological characteristics of this disorder are crucial. This review provides an overview of the pathological mechanisms underlying the development of DR, highlighting the recent advances in current and emerging treatments for DR.Diabetic retinopathy is the leading cause of blindness in young adults. Current treatments target late-stage disease symptoms. This review highlights the need for new therapies that target early stages of the disease

The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma

Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC’s survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.Peer Reviewe

Quality assurance in extemporaneously compounded formulations: a titration method for ursodeoxycholic acid

OBJECTIVE — To validate an acid-base titration method, adopted from the British Pharmacopoeia, for analysis of ursodeoxycholic acid (UA) in extemporaneously compounded formulations. METHODS — Two different extemporaneously compounded formulations containing UA 15mg/ml, prepared from both pure drug and Actigall capsules were compared. A series of titrations was carried out to validate the titration method, as per International Conference on Harmonisation (ICH) guidelines. The titration method was used to analyse the stability of the UA suspensions stored for six weeks under ICH accelerated stability conditions. RESULTS —The titration method was found to be specific and accurate. Differences between the initial drug concentration of the two suspensions and the concentration after six weeks at accelerated stability conditions were statistically insignificant, indicating stability of the formulations. CONCLUSION — A simple acid-base titration method adopted from the British Pharmacopoeia has been validated to determine UA content in extemporaneously compounded suspensions, and can be recommended for quality assurance testing in hospital pharmacy

Coping mechanisms used by pharmacists to deal with stress, what is helpful and what is harmful?

Background: Australian pharmacists encountered increased stressors during the COVID-19 pandemic. This has raised questions regarding the effectiveness of the coping mechanisms used to manage this high work-related stress. Identifying useful and harmful coping mechanisms is critical for providing advice regarding addressing pharmacists' future work-related stress. Objectives: This study aimed to explore the impact of pharmacy work on stress experienced by Australian pharmacists and the coping mechanisms used during the COVID-19 pandemic. This study also aimed to evaluate the pharmacists' perceptions of the impact of these coping mechanisms on their stress. Methods: A cross-sectional study was conducted. Practising pharmacists and interns were recruited to complete an online survey that included the Perceived Stress Scale (PSS), which was used to measure pharmacists' work-related stress, and the Brief-COPE scale, used to assess the coping mechanisms used during the COVID-19 pandemic. The key outcome measure was the PSS score. A multiple regression analysis was used to evaluate the relationship between coping mechanisms and stress levels in a sample of Australian pharmacists. Results: A total of 173 pharmacists and interns were recruited. The mean PSS was 18.02 (SD = 6.7). Avoidant coping mechanisms such as social withdrawal (β = 0.31; p = 0.0001) were significantly positively associated with work-related stress. In contrast, exercise was significantly negatively associated with work-related stress (β = −0.21; p = 0.009). The most frequently reported perceived barrier to seeking help was feeling burnt out and underappreciated. Conclusions: This study highlights the association of coping mechanisms used by pharmacists during the COVID-19 pandemic with work-related stress. The study results demonstrate the importance of physical activity and spending time with pets in reducing work-related stress levels. Avoiding harmful coping mechanisms such as social withdrawal and drinking alcohol is recommended. This study also highlights the need for interventional studies to reduce work-related stress levels among pharmacists by addressing useful coping mechanisms

Properties of a formulated paediatric phenobarbitone\ud oral liquid

Aim: To formulate a stable and palatable paediatric phenobarbitone 10 mg/mL oral liquid and compare its physicochemical stability to the existing formulation compounded in some New Zealand hospitals. \ud \ud Method: Formulations were compounded from pharmaceutical standard ingredients according to good manufacturing practices and stored in glass bottles at different storage conditions. The physical stability of the formulations was determined by pH, appearance, viscosity and microbial studies; chemical stability was assessed using high performance liquid chromatography. \ud \ud Results: The new formulation and the existing hospital formulation remained physically stable for 28 days in terms of pH, appearance, viscosity and microbial stability. The phenobarbitone sodium concentration remained within an acceptable range (above 95% of the original concentration) after 28 days of storage at different conditions. The viscosity of the new formulation facilitated in masking phenobarbitone sodium's bitter taste, thus improving palatability. The palatability of the new formulation was superior to the hospital formulation. \ud \ud Conclusion: A palatable paediatric phenobarbitone oral liquid formulation with improved rheological properties was developed

IGF-1 signaling via the PI3K/Akt pathway confers neuroprotection in human retinal pigment epithelial cells exposed to sodium nitroprusside insult

The pathological increase in the levels of the second messenger nitric oxide (NO) in the vitreous cavity and retina leads to injury and cell death of the retinal pigment epithelium (RPE) cells and eventually may contribute to the occurrence and development of diabetic retinopathy. In this study, we developed a cellular model of retinopathy using D407 cells (a human RPE cell line) exposed to sodium nitroprusside (SNP) and investigated the protective effect of the insulin-like growth factor-1 (IGF-1) towards this insult. Cell death and apoptosis were examined by the methyl thiazolyl tetrazolium assay and Hoechst staining, respectively. Specific inhibitors were used and phosphorylation of relevant signaling proteins was determined by Western blotting. SNP, in a concentration-dependent fashion, increased the production of reactive oxygen species (ROS) and lipid peroxidation process causing cell death by apoptosis of D407 cells. IGF-1, in a time- and dose-dependent manner, conferred protection towards SNP-mediated insult. Both phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) were activated by IGF-1 in relation to the protective effect. Blockade of the PI3K/Akt pathway abolished the protective effect of IGF-1 whereas inhibition of the MAPK pathway was ineffective. SNP decreased the phosphorylation of Akt in the cells while IGF-1 reversed this inhibitory effect. These results indicate that the protective effect of IGF-1 on D407 exposed to SNP insult is mediated by the PI3K/Akt pathway. This proposal may be exploited in the clinic to improve the viability of insulted retinal cells for maintaining physiological vision