EY1920 Year Book

131 130 Master of Research in Medicine (Mres) in HKU Research Topic: Effects of lutein and candesartan co-treatment on retinal function and morphology in non-proliferative diabetic retinopathy using the InsAkita/+ mouse model. Introduction: 1. Diabetic retinopathy is one of the most common microvascular complications of diabetes 2. It is the leading cause of preventable blindness among working aged adults in developed countries 3. This study investigates the retinal protective effects of lutein and candesartan against early stages of diabetic retinopathy Methods: 1. InsAkita/+ mice were used since they lack in insulin production due to gene mutation, which mimics diabetes in human 2. InsAkita/+ mice were divided into vehicle and treatment groups with different concentrations of lutein and candesartan administered 3. Functional integrity of the retina was assessed by electroretinogram (ERG), which records the electric potential generated in the retina in response to light stimulus 4. Morphological integrity of the retina is assessed by 1) histological examination on retinal slides stained by hematoxylin and eosin, in which thickness of retinal layers was measured and number of viable neural cells was counted and 2) immunohistochemistry examination on retinal slides, in which the preservation of retinal neural cells and the extent of astrocytosis were assessed Mouse undergoing ERG H&E stained retinal section IHC stained retinal section Results: 1. Treatment shows preservation of retinal function ERG potential recorded in treatment groups was generally higher than that in vehicle groups 2. Treatment shows protective effect on retinal morphology I) Retina in treatment groups were generally thicker than that in vehicle groups, with difference in thickness mainly concentrated in nuclear layers, which represented a reduction in cell loss in the retina receiving treatments II) Retina in treatment groups generally had more viable neural cells than that in vehicle groups 3. Treatment shows astrocytosis reduction and preservation of neural cells Expression of astrocyte markers, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) was reduced while expression of neural cell markers, PKC-α, calbindin and calretinin, was increased in treatment groups. Vehicle group Treatment group GFAP expression Calbindin expression Vehicle group Treatment group Conclusion: Lutein and candesartan co- treatment exerts retinal protective effect functionally and morphologically in early non-proliferative diabetic retinopathy. MBBS Enrichment Year 2019/20 Li Long Hin Full Year < IC - M R e s( Me d) at HK U, H o ng K o ng > Li Long Hin Li Wai Tak Victor Introduction • Cannabis (a.k.a. marijuana), the most widely abused recreational drug worldwide (prevalence = 147 million), is getting legalised in various countries and regions, including Canada. • Adverse effects of cannabis include anxiety, cognitive impairment, hyperemesis syndrome, seizures and myocardial infarction. • Cerebrovascular diseases (CVD) are also reported; these include ischaemic strokes (IS), intraparenchymal haemorrhage (IPH), subarachnoid haemorrhage (SAH), transient ischaemic attack (TIA) and reversible cerebral vasoconstriction syndrome (RCVS). • Synthetic cannabinoids (SC; a.k.a. “K2”, “spice”, “bonzai”) are cannabinoid receptor agonists which may lead to severe cardio-cerebrovascular and neuropsychiatric effects. Aims • Summarise clinical characteristics of patients suffering from post-cannabinoid exposure. • Appraise epidemiological data evaluating cannabinoids as a risk factor of CVD. • Give insights to future research directions in post- cannabinoid CVD. Methodologies • Search for publication on Medline, PubMed and CINAHL. • Case reports and series of post-cannabinoid CVDs. • Inclusion criteria: (1) English reports; (2) clear exposure to cannabinoid; (3) age < 55 years old; (4) CVD – IS, IPH, SAH, TIA or RCVS as outcome; (5) CVD diagnosed by CT / CTA / MRI / MRA. • Exclusion criteria: spinal cord-related pathologies. Results • Mean age = 30.2 years old; M : F = 2.68 : 1. • By anatomical location: lacunes ( n = 12); cerebellar ( n = 9); brainstem ( n = 2); brainstem haemorrhage ( n = 3) • Causality data assessed by Bradford-Hill criteria: re- exposure ( n = 7); temporality of < 24 h ( n = 68); recent increase in use ( n = 27) • Risk factors: hypertension ( n = 31); other recreational drug use ( n = 18); past psychiatric disorder ( n = 13); past transient neurological events ( n = 13); patent foramen ovale ( n = 5) • Mortality: n = 7, all cannabis-exposed Discussion • Tetrahydrocannabinol (THC, main component of cannabis) binding to CB1 and CB2 receptors lead a spectrum of adverse events. • Post-cannabis CVD: • IS may be secondary to cardiovascular effects of THC, or through procoagulatory, negative inotropic, hyperadrenergic-inducing and oxidative stress-creating effects. • RCVS may be due to endothelial and hence cerebral blood flow dysregulation. • SAH may be from RCVS or vasculitic. • ICH may be due to cannabis-induced HT. • Post-SC CVD: • Hard to detect SC molecules from urine sample. • Mechanisms unknown. • Limitations: • Bradford Hill criteria for causality assessment is not optimal. • Lack of standardised reporting of cannabinoid use. • Multiple risk factors in patients. Epidemiological data and future aspects • Retrospective studies had shown some degree of association, but is statistically insignificant. • Prospective studies that integrates a more diverse population is required to rectify and strengthen the current evidence. • Causality between the two entities should also be delineated. • Pathogenesis and pathophysiology is to be determined, distinguished and differentiated. • Clinical awareness to post-cannabinoid stroke and aid diagnosis; a database can then be set up for future researches. MBBS Enrichment Year 2019/20 Li Wai Tak Victor Sem 1 < R A - Cannabis, synthetic cannabinoids and cerebrovascular diseases in young p atients : a systematic review on case re p orts and series at the University of B ritish Columbia, Canada >; Sem 2 < R A - Primary Angiitis of the Central Nervous System ( PACNS ) at the University of B ritish Columbia, Canada > Figure: legality of cannabis worldwide. (Taken from https://en.wikipedia.org/wiki/File :Map-of-world-cannabis-laws.svg) Key: Blue = legal Orange = illegal but decriminalised Pink = illegal but law often unenforced Red = illegal Cannabis, Synthetic Cannabinoids and Cerebrovascular Diseases in Young Patients: a Systematic Review on Case Reports and Series Wai Tak Victor LI 1 ; Hei Long LAM 1 ; Samuel YIP MD PhD 2 1 Li Ka Shing Faculty of Medicine, The University of Hong Kong 2 Vancouver Stroke Program, Division of Neurology, Department of Medicine, Faculty of Medicine, The University of British Columbia