In Vitro Blood-Brain Barrier Models for Neuroinfectious Diseases: A Narrative Review.

The blood-brain barrier (BBB) is a complex, dynamic, and adaptable barrier between the peripheral blood system and the central nervous system. While this barrier protects the brain and spinal cord from inflammation and infection, it prevents most drugs from reaching the brain tissue. With the expanding interest in the pathophysiology of BBB, the development of in vitro BBB models has dramatically evolved. However, due to the lack of a standard model, a range of experimental protocols, BBB-phenotype markers, and permeability flux markers was utilized to construct in vitro BBB models. Several neuroinfectious diseases are associated with BBB dysfunction. To conduct neuroinfectious disease research effectively, there stems a need to design representative in vitro human BBB models that mimic the BBB's functional and molecular properties. The highest necessity is for an in vitro standardised BBB model that accurately represents all the complexities of an intact brain barrier. Thus, this in-depth review aims to describe the optimization and validation parameters for building BBB models and to discuss previous research on neuroinfectious diseases that have utilized in vitro BBB models. The findings in this review may serve as a basis for more efficient optimisation, validation, and maintenance of a structurally- and functionally intact BBB model, particularly for future studies on neuroinfectious diseases.

Effect of aflatoxin B1 exposure on the progression of depressive-like behavior in rats.

While it is well documented that aflatoxin B1 (AFB1); one of the most toxic food contaminants is linked to the development of depression. However, the mechanism on how it affects the gut and brain health leading to depressive-like behavior remains unclear. This study was conducted to determine the effect of AFB1 on the progression of depressive-like behavior. Thirty-two (n = 32) male Sprague Dawley rats were randomly allocated into four groups: control, low-dose (5 µg AFB1/kg), high-dose (25 µg AFB1/kg) and positive control group; exposed on chronic unpredictable mild stress (CUMS). After 4 weeks of exposure, sucrose preference test (SPT) and force swim test (FST) were used to measure behavioral despair. Fecal samples were selectively cultured to profile the bacteria. Body weight and relative organs weights were compared among groups. AFB1 and CUMS caused reduction in body weight and food intake as well as increased relative weight of adrenal glands, liver, and brain. Rats in AFB1 and CUMS groups had suppressed sucrose preference and prolonged immobility time in FST, wherein this could indicate anhedonia. Besides, fecal count of Lactobacillus spp. was significantly low following AFB1 exposure, with increasing count of Bifidobacterium spp, in comparison to the control. Indeed, further biochemical analysis and metagenomic approach are warranted to explore the underlying mechanisms on the role of gut microbiota dysbiosis and dysregulation of gut-brain axis due to AFB1 neurotoxicity on the progression of depressive-like behavior.

Educating pharmacy students through a pandemic: Reflecting on our COVID-19 experience.

The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting students, educators and regulatory agencies. Pharmacy programmes have had to rapidly adapt in their delivery of education, maintaining standards while also ensuring the safety of all stakeholders. In this commentary, we describe the challenges, compromises and solutions adopted by our institution throughout the pandemic, the lessons learnt, adaptive measures taken, and strategies to develop and future-proof our curricula.

Edible Bird Nest Protects the Kidney From Gentamicin Induced Acute Tubular Necrosis.

Every year, there are about 13.3 million cases of acute kidney injury (AKI). Although AKI is a preventable and treatable disease, if left untreated, it has high risk of multiple organ failure and progression to end stage kidney disease. Acute tubular necrosis (ATN) has been recognised as one of the major causes of AKI. Till to date, there is no effective supplement or medication in treating or reversing AKI. Most of the treatment strategies involve preventative measure to minimise the occurrence of AKI or to reverse the cause of AKI. Hence one of the primary area of research interests is to explore the potential treatment for AKI. Edible bird nests (EBN) are edible food produce by the swiftlet's saliva, which is rich in sialic acids. Sialic acids are monosaccharides that play a vital role in maintaining the integrity and proper function of the human organs, including kidneys. EBN also contains epidermal growth factor, which is widely believed to have rejuvenation and tissue repairing properties. We initiate this study to study the potential reno-protective effect of edible bird's nests by studying the Wistar rat model of gentamicin-induced AKI. Besides renal profiles, renal histology was also semiquantitatively assessed. In our study, pre-treatment with EBN prevented and ameliorated the gentamicin-induced AKI. To a lesser extent, post-treatment with EBN also protected the kidney from the toxic effect of gentamicin. Our findings are highly indicative that EBN possesses reno-protective properties.

Novel polyurethane based particulate formulations of infliximab reduce inflammation in DSS induced murine model of colitis - A preliminary study.

Our recent study showed that novel infliximab (INF) loaded polyesterurethane (INF-PU) and INF-PU-PEG particulate formulations reduced inflammation in an in-vitro epithelial inflammation model. In this study we investigated therapeutic potential of novel INF-PU and INF-PU-PEG particulate formulations to reduce inflammation in a dextran sodium sulfate (DSS) induced murine model of colitis. Severity of colitis was assessed by measurement of disease activity index (DAI) score, inflammatory markers (neutrophil infiltration, TNFα) and histological score. Treatment groups orally administered with INF-PU and INF-PU-PEG particulate formulations showed improvement in the clinical signs of colitis, similar to that observed with intraperitoneally administered INF, in both, moderate and severe DSS induced colitis model. This was related to a significant reduction in inflammatory cytokines, resulting in a significant reduction in histological score (ANOVA; p < 0.05), indicative of mucosal healing, a key goal of IBD therapy. This could be attributed to its targeted delivery to the inflamed colon and higher permeation of these particulate formulations across the inflamed colonic mucosa, as observed by the confocal images, resulting in local inhibition of TNFα at its site of production. These promising preliminary results warrant further investigation of orally administered INF and its novel particulate formulations in a wider preclinical study.

p53 upregulated mediator of apoptosis (Puma) deficiency increases survival of adult neural stem cells generated physiologically in the hippocampus, but does not protect stem cells generated in surplus after an excitotoxic lesion.

OBJECTIVES: Neurogenesis occurs in the mammalian brain throughout adulthood and increases in response to metabolic, toxic or traumatic insults. To remove potentially superfluous or unwanted neural stem cells/neuronal progenitors, their rate of proliferation and differentiation is fine-tuned against their rate of apoptosis. Apoptosis requires the transcriptional and posttranslational activation of Bcl-2-homolgy domain 3 (BH3)-only proteins. Previously, we demonstrated that the BH3-only protein p53-upregulated mediator of apoptosis (Puma) controls the physiological rate of apoptosis of neural precursor cells in the adult mouse hippocampus. Puma's role in controlling a lesion-induced increase in neural stem cells is currently not known. METHODS: We employed a model of local, N-methyl-D-asparte (NMDA)-induced excitotoxic injury to the CA1 hippocampal subfield and immunofluorescence labelling to produce increased neural stem cell proliferation/ neurogenesis in the dentate gyrus at two survival times following the excitotoxic lesion. RESULTS: Deletion of puma failed to rescue any NMDA-induced increase in adult born cells as assessed by BrdU or Doublecortin labelling in the long-term. No difference in the proportion of BrdU/NeuN-positive cells comparing the different genotypes and treatments suggested that the phenotypic fate of the cells was preserved regardless of the genotype and the treatment. CONCLUSIONS: While neurogenesis is up-regulated in puma-deficient animals following NMDA-induced excitotoxicity to the hippocampal CA1 subfield, puma deficiency could not protect this surplus of newly generated cells from apoptotic cell death.

Evaluation of the effect of insulin sensitivity-enhancing lifestyle- and dietary-related adjuncts on antidepressant treatment response: A systematic review and meta-analysis.

BACKGROUND: Depression is associated with insulin resistance (IR). However, the potential beneficial effect, on antidepressant treatment response, of adjunctive therapy with insulin sensitivity-enhancing lifestyle and dietary interventions (exercise; supplementation with: vitamin D, magnesium, zinc, probiotics or omega-3 fatty acids) has not been systematically explored. AIMS: To determine the effect of the above stated adjuncts on antidepressant treatment response in clinically depressed patients via a systematic review and meta-analysis. METHODS: RCTs which assessed the effect, on antidepressant treatment response of adjunctive therapy with any of the interventions in comparison with treatment as usual were included. RESULTS: The interventions had a significant antidepressant effect, with SMD for follow-up (end of study) scores and change (from baseline) scores being -0.88, [95% CI: -1.19 to -0.57; P < 0.001] and -1.98 [95% CI -2.86 to -1.10; P < 0.001], respectively. The odds ratio (OR) for remission was 2.28 (95% CI 1.42 to 3.66; P < 0.001). The number-needed-to-treat (NNT) for remission was 6. Subgroup analysis of the follow-up scores revealed age effect: SMD significant in those with mean age ≤50 (-1.02 SMD; 95% CI: -1.40 to -0.64; p < 0.001) and insignificant in those with mean age >50 (-0.38 SMD (95% CI: -0.82 to 0.05; P = 0.08)). Also, the interventions were more beneficial among outpatients- SMD: -0.97 (95% CI: -1.32 to -0.62; P < 0.001) compared to inpatients- SMD: -0.34 (95% CI: -0.88 to 0.20; P = 0.22). Sensitivity analysis did not change the results. CONCLUSION: The finding that antidepressant treatment response may be improved using insulin sensitivity-enhancing lifestyle and dietary adjuncts is worthy of further exploration.

Ethologically based behavioural and neurochemical characterisation of mice with isoform-specific loss of dysbindin-1A in the context of schizophrenia.

Dysbindin-1 is implicated in several aspects of schizophrenia, including cognition and both glutamatergic and dopaminergic neurotransmission. Targeted knockout of dysbindin-1A (Dys-1A KO), the most abundant and widely expressed isoform in the brain, is associated with deficits in delay/interference-dependent working memory. Using an ethologically based approach, the following behavioural phenotypes were examined in Dys-1A KO mice: exploratory activity, social interaction, anxiety and problem-solving ability. Levels of monoamines and their metabolites were measured in striatum, hippocampus and prefrontal cortex using high-performance liquid chromatography with electrochemical detection. The ethogram of initial exploration in Dys-1A KO mice was characterised by increased rearing from a seated position; over subsequent habituation, stillness was decreased relative to wildtype. In a test of dyadic social interaction with an unfamiliar conspecific in a novel environment, female KO mice showed an increase in investigative social behaviours. Marble burying behaviour was unchanged. Using the puzzle-box test to measure general problem-solving performance, no effect of genotype was observed across nine trials of increasing complexity. Dys-1A KO demonstrated lower levels of 5-HT in ratio to its metabolite 5-HIAA in the prefrontal cortex. These studies elaborate the behavioural and neurochemical phenotype of Dys-1A KO mice, revealing subtle genotype-related differences in non-social and social exploratory behaviours and habituation of exploration in a novel environment, as well as changes in 5-HT activity in brain areas related to schizophrenia.

The complexities of behavioural assessment in neurodegenerative disorders: A focus on Alzheimer's disease.

Rodent models of human diseases that accurately and reproducibly capture their pathology are key tools in furthering our understanding of the mechanisms behind these diseases and in the development of novel treatment approaches. However, pre-clinical studies in rodents are often criticised for the relative lack of replication and success upon translation to humans. Animal models of neurodegenerative diseases (and other CNS conditions) are very complex, often with multifactorial inputs into their development and progression. This complexity is a significant challenge. In addition to this, there are often concerns raised about the conduct, analysis and interpretation of the model results. This review focuses on Alzheimer's disease as a representative neurodegenerative disorder and will examine disease model end-points, in particular, behavioural phenotyping which, while appearing relatively straightforward, has the potential to be poorly conducted and the results misconstrued. This review uses a sample of the literature to illustrate the breadth of techniques used in behavioural assessment of Alzheimer's disease models, highlight the complexity, illustrate some procedural, interpretational and translational issues and provide recommendations to improve conduct of pre-clinical testing with the hope that this may lead to more consistency and translational success.

A standardised Andrographis paniculata Burm. Nees aqueous extract prevents Lipopolysaccharide-induced cognitive deficits through suppression of inflammatory cytokines and oxidative stress mediators.

Substantial evidence has shown that most cases of memory impairment are associated with increased neuroinflammation and oxidative stress. In this study, the potential of a standardised Andrographis paniculata aqueous extract (APAE) to reverse neuroinflammation and cognitive impairment induced by lipopolysaccharide (LPS) was examined in vivo. Rats were treated with APAE (50, 100, 200, and 400 mg·kg-1, p.o.) for 7 consecutive days prior to LPS (1 mg·kg-1, i.p.)-induced neuroinflammation and cognitive impairment. Spatial learning and memory were evaluated using the Morris water maze (MWM) test, while neuroinflammation and oxidative stress were assessed through the measurement of specific mediators, namely, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, superoxide dismutase (SOD), catalase (CAT), antioxidant glutathione (GSH), reactive oxygen species (ROS), and thiobarbituric acid reactive substance (TBARS). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were also evaluated. LPS caused significant memory deficits in the 2-day MWM protocol, whereas pretreatment with standardised APAE dose-dependently improved performance in the MWM test. APAE treatment also blocked the LPS-induced hippocampal increase in the concentration and expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and production of ROS and TBARS and enhanced the activities of AChE and BChE. Furthermore, APAE enhanced the decrease in the levels and expression of hippocampal antioxidant enzymes (SOD and CAT) following LPS-induced neuroinflammation and cognitive deficit. The findings from these studies suggested that standardised APAE improved memory and had potent neuroprotective effects against LPS-induced neurotoxicity.

Evaluation of the effect of insulin sensitivity-enhancing lifestyle- and dietary-related adjuncts on antidepressant treatment response: protocol for a systematic review and meta-analysis.

BACKGROUND: Depression is the leading cause of disability worldwide and is known to be associated with insulin resistance (IR). Insulin resistance worsens the symptoms of depression and reduces the effectiveness of antidepressant medications in some depressed patients. Many studies have assessed the effect of adjunctive exercise, vitamin D supplementation, zinc supplementation, magnesium, probiotics, unsaturated fatty acids, and hygienic-dietary recommendations (sleep hygiene, healthy diet, physical activity, and sunlight exposure, combined or singly used), individually, on antidepressant treatment response. However, despite the reported insulin sensitivity-enhancing potential of these adjuncts, no systematic review has collectively analysed their antidepressant effect with regards to insulin sensitivity. METHODS/DESIGN: In this systematic review, we will analyse the effect of the above-stated adjuncts on antidepressant treatment response (primary outcome) in comparison with treatment as usual with or without adjunctive placebo after identifying the relevant trials from a systematic literature search. Randomised controlled trials involving clinically depressed patients with diagnosis of major depressive, dysthymic or bipolar disorder will be considered. Changes in insulin sensitivity parameters, following treatment, will also be analysed as the secondary outcome. Effect estimates of the included trials will be combined using random-effects meta-analysis, while addressing risk of bias issues. Any significant heterogeneity between studies will be explored using sensitivity and subgroup analyses. DISCUSSION: The findings of this review will contribute to the evidence base regarding the utility of non-pharmacological insulin-sensitising treatments in enhancing conventional antidepressant treatment response.

Pharmacology through Play: using Lego® to revise core concepts for undergraduates.

This article was migrated. The article was marked as recommended. Background: Pharmacology, while critical knowledge for healthcare professionals, is often viewed by students as dry and difficult to understand. We sought to examine the student acceptability of a Lego®-based learning session, in an attempt to improve pharmacology learning. Methods: In line with constructivist theories, students were facilitated to build, in small groups, their own Lego® shape to represent an area of core pharmacology and to use this to explain the concept to other students (e.g. agonist-receptor interactions). The validated Course Experience Questionnaire (CEQ) was used to gauge students' ideas on the session. Multiple choice questions were used before and after the session to evaluate knowledge. Results: Most students were positive regarding the session, finding it enjoyable, relevant for their learning and even recommending it be used to explore more complex areas of pharmacology. In addition, there was a significant increase in the MCQ scores following the session. Conclusions: This study used constructivist theory to develop a novel teaching intervention to create a more student-centred, active learning environment. This effective low-cost method could be applied to other teaching programmes to enhance student learning.

Effect of Edible Bird's Nest Extract on Lipopolysaccharide-Induced Impairment of Learning and Memory in Wistar Rats.

Cognitive disability is a common feature associated with a variety of neurological conditions including Alzheimer's Disease (AD), Parkinson's Disease (PD), brain injury, and stroke. Emerging evidence has demonstrated that neuroinflammation plays an important role in the development of cognitive impairment. Current available therapies are relatively ineffective in treating or preventing cognitive disabilities, thus representing an important, unfulfilled medical need. Hence, developing potential treatment is one of the major areas of research interest. Edible bird's nests (EBN) are nests formed by swiftlet's saliva containing sialic acid, which is believed to improve brain function. This present study was embarked upon to evaluate the learning and memory enhancing potential effect of EBN by using Morris water maze test in a Wistar rat model of LPS-induced neuroinflammation. LPS elicited cognitive impairment in the rats by significantly increasing the escape latency while decreasing the number of entries in the probe trial, which are coupled with increased production of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and oxidative markers (ROS and TBARS) in the hippocampus. Treatment with EBN (125 mg/kg, 250 mg/kg, and 500 mg/kg; p.o.) effectively reversed the effect of LPS on escape latency and probe trial and, in addition, inhibited the LPS-induced upregulation of proinflammatory cytokines and oxidative markers. These findings are suggestive that there is existence of neuroprotective effect contained inside the edible bird's nest.

Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammation.

RATIONALE: Major depressive disorder (MDD) is a highly prevalent illness that affects large populations across the world, and increasing evidence suggests that neuroinflammation and levels of brain-derived neurotrophic factor (BDNF) are closely related to depression. Dihydromyricetin (DHM) is a kind of flavonoid natural product that has been reported to display multiple pharmacological effects, including anti-inflammatory and anti-oxidative properties, and these may contribute to ameliorate MDD. OBJECTIVE: This study investigated the effect of DHM on depression-related phenotypes in various experimental animal models. METHODS: The antidepressant-like effect of DHM was validated via depression-related behavioral tests in naïve male C57BL/6 mice, as well as in the acute lipopolysaccharide-induced mouse model of depression. The chronic unpredicted mild stress (CUMS) mouse model of depression was also used to assess the rapid antidepressant-like effect of DHM by tail suspension test (TST), forced swimming test (FST), locomotor activity, and sucrose preference test (SPT). The expression of BDNF and inflammatory factors were determined through Western blotting and enzyme-linked immunosorbent assay, respectively. RESULTS: DHM reduced immobility time in the TST and FST both in mice and the acute LPS-induced mouse model of depression. Seven days of DHM treatment ameliorated depression-related behaviors induced by CUMS, whereas similar treatment with the typical antidepressant venlafaxine did not. DHM activated the ERK1/2-CREB pathway and increased glycogen synthase kinase-3 beta (GSK-3ß) phosphorylation at ser-9, with upregulation of BDNF expression, in both hippocampal tissues and cultured hippocampal cells. CONCLUSION: The present data indicate that DHM exerts a more rapid antidepressant-like effect than does a typical antidepressant, in association with enhancement of BDNF expression and inhibition of neuroinflammation.

Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability.

OBJECTIVE: This study was aimed to investigate the potential of formulated valproic acid-encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA). METHODS: Valproic acid-encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in-vitro blood-brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain. KEY FINDINGS: Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In-vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE-treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half-life and reduction in clearance compared to VPA. Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half-life of VPA by encapsulating it within the nanoemulsion-T80. CONCLUSIONS: Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA.

Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes.

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A-/-, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A-/- showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A-/- provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects.

Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability.

Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21±0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood-brain barrier in the treatment of epilepsy.

Nanoemulsion-based Parenteral Drug Delivery System of Carbamazepine: Preparation, Characterization, Stability Evaluation and Blood-Brain Pharmacokinetics.

Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchi's equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.

Hydroxycinnamic acid amide derivatives of polyamines reverse spermine-induced CNS excitation.

The aim of this study was to examine the acute effect of a range of novel hydroxycinnamic acid derivatives of spermine on the development of spermine-induced CNS excitation and convulsions in female Laca mice, and to assess the chronic adverse behavioural effect profile of these compounds over a 5day period. Four of the six novel polyamine analogues dose-dependently inhibited body tremor and tonic convulsions caused by spermine, when administered centrally (icv) or peripherally (ip). BU43b was the most potent analogue tested, but BU31b, 33b, and 36b were also effective (p<0.01, Mann-Whitney U test). A similar profile of effectiveness was seen with peripheral and central administration, indicating that the analogues may cross the blood brain barrier. More chronic investigation of the adverse effects of the compounds administered alone over 5days of observation indicated that the drugs were well tolerated, only causing reduced locomotor activity on the first day of the study and mild changes in behaviours linked to CNS and ANS function. It is likely that NMDA receptor NR2B subunit inhibition is involved in the anticonvulsant effect of these novel analogues, but other mechanisms may also be involved. These novel polyamine derivatives warrant further investigation of their therapeutic potential in treating epilepsy and CNS disorders where excitotoxicity is implicated.

Relationship between performance barriers and pharmacist competency towards the implementation of an expanded public health pharmacy role.

OBJECTIVE: The objective of this study was to examine the relationship between performance barriers and competency, and implementation of an expanded public health role for community pharmacists. METHODS: A validated questionnaire was utilised for this study whereby three variables of the study (performance barriers, competency and public health role) were measured using a 5-point Likert scale. Three hundred questionnaires were distributed to target respondents of registered community pharmacies in five states (Johor, Negeri Sembilan, Selangor, Perak and Penang) in Malaysia. The data were analysed utilising the principles of structural equation modelling. KEY FINDINGS: There were 191 completed and usable responses received, which represented a 66.7% response rate. This study showed perceived competency had a direct relationship with delivering a general public health role. A perceived lack of competency was shown to be a barrier to fulfilling a public health role. However, other factors, such as design of premises, IT infrastructure and pay, were not viewed as barriers to carrying out a public health role. CONCLUSION: Perceived competency is an obstacle for community pharmacists to undertake a public health role in Malaysia. Adequate training programmes in pharmaceutical public health have to be put in place to address this concern and this should therefore be a priority.