Preclinical challenges for developing long acting intravitreal medicines

The majority of blinding conditions arise due to chronic pathologies in the retina. During the last two decades, antibody-based medicines administered by intravitreal injection directly into the back of the eye have revolutionised the treatment of chronic retinal diseases characterised by uncontrolled blood vessel growth, e.g. wet age-related macular degeneration (wAMD), diabetic retinopathy (DR) and choroidal neovascularisation. Although intravitreal injections have become a commonly performed ophthalmic procedure that provides a reproducible dose to maximise drug exposure in the back of the eye, there is a need to minimise the frequency and cumulative number of intravitreal injections. Developing longer-acting intraocular therapies is one key strategy that is being pursued. Pharmaceutical preclinical development of intraocular medicines is heavily reliant on the use of animal models to determine ocular tolerability, pharmacokinetics, biodistribution and drug stability. Animal eyes are different from human eyes, such as the anatomy, organisation of vitreous macromolecular structure, aqueous outflow and immune response; all which impacts the ability to translate preclinical data into a clinical product. The development of longer acting protein formulations using animals is also limited because animals reject human proteins. Preclinical strategies also do not account for differences in the vitreous due to ageing and whether a vitrectomy has been performed. Intraocular formulations must reside and clear from the vitreous body, so there is a need for the formulation scientist to have knowledge about vitreous structure and physiology to facilitate preclinical development strategies. Preclinical pharmaceutical development paradigms used to create therapies for other routes of administration (e.g. oral and intravenous) are grounded on the use of preclinical in vitro models. Analogous pharmaceutical strategies with appropriately designed in vitro models that can account for intraocular mass transfer to estimate pharmacokinetic profiles can be used to develop in vitro-in vivo correlations (IVIVCs) to accelerate the preclinical optimisation of long acting intraocular formulations. Data can then inform preclinical in vivo and clinical studies. With the now widespread use of intravitreal injections, it has also important early in preclinical studies to ensure there is a viable regulatory pathway for new therapies. Knowledge of these factors will help in the development of long acting intravitreal medicines, which is rapidly evolving into a distinct pharmaceutical discipline

Dietary Pattern, Anthropometric Indices and Developmental Milestone of Children Aged 6-60 Months in Peri-Urban Communities East of Nigeria

Background: Good nutritional status is of paramount importance for a child’s physical, mental and social development after inter-uterine life. Objective: Dietary pattern, anthropometric indices and developmental milestone of children aged 6-60 months in peri-urban communities were investigated. Design: The children (236) were randomly selected from health centers and nursery schools in three selected communities. Data were collected with structured questionnaire and anthropometry. The questionnaire administered to the mothers of the children elicited information on their socioeconomic characteristics, dietary pattern and developmental milestones of the children. Anthropometric parameters of the children were measured using standard instruments and procedures. The mean length/height and weight of the children in relation to their ages were compared with WHO child growth standard. Data collected were statistically analyzed using SPSS version 16. Results: Less than 6% of the mothers introduced complementary food at 6 months, 31.4% introduced before 6 months and 63.2% after 7 months. Majority (97.5%) of the mothers enriched complementary foods with fish (73.7%), infant formular (72.9%), soybean powder (66.5%) and egg (64.0%). A total of 10.6% and 1.7% of the children were moderately and severely stunted, respectively while 4.7% of them had moderate wasting. Underweight was observed more among children within 6 – 24 months. The mean ages for sitting, crawling, standing with support and standing without support reported in this study were 6, 7, 8 and 10 months, respectively. Conclusion: Scaling up actions on optimal complementary feeding of children would go a long way in improving their nutritional status and physical development

Dual acting therapeutic proteins for intraocular use

Antibody-based medicines that target vascular endothelial growth factor (VEGF) are administered by intravitreal injection to treat chronic neovascular retinal diseases. Much ongoing effort is focused on enhancing therapeutic outcome of these medicines. One strategy is the use of dual acting drugs (e.g. bispecific antibodies) to simultaneously bind to more than one intraocular biological target. A dual acting molecule targeting components within the vitreal cavity could also potentially extend vitreous residence time. In this review, the applications of bispecific antibodies within the eye are described with consideration to potential targets, applications and suitable bispecific formats

Nutrient composition of freeze-dried and oven-dried soursop (annona muricata) pulp powders and sensory evaluation of their drinks compared to fresh one

Background: Soursop is underutilized and highly perishable, tropical fruit rich in several nutrients. Objective: This study determined the nutrient composition of freeze-dried and oven-dried soursop (Annona muricata) pulp powders and sensory evaluation of drinks made from them compared with the fresh one. Materials and Methods: Mature soursop fruits were purchased at a local market in Nsukka, Enugu State, Nigeria.The fruits were allowed to ripen for 5 days at room temperature (37°C). The ripe fruits were washed, peeled, seeds handpicked and the pulp dried. Freeze-drying was done at -40°C for 72 hours, oven-drying at 70° C for 48 hours. Nutrient content was determined using standard methods. Each of the freeze-dried and oven-dried soursop powders (100g) was liquefied with 500mls of water to formulate unsweetened drinks. A hundred grammes each of the dried powders were liquefied with 500mls of water and flavoured with four tablespoons (60g) of honey to formulate sweetened drinks. Fresh soursop pulp (200g) was liquefied with 400mls of water and flavoured with four tablespoons (60g) of honey to formulate sweetened fresh drink. Sensory evaluation of all the drinks was conducted using a 9-point hedonic scale. Data obtained from the study were analyzed using the Statistical Product for Service Solution (SPSS) for Windows version 21. Results were presented as means and standard deviations. The researcher used Analysis of Variance (ANOVA) and Duncan's new multiple range tests to separate and compare means at p <0.05. Results: The freeze-dried powder had higher moisture (12.86±0.01%), fat (6.66±0.01%) and carbohydrate (43.70±0.01%) contents while the oven-dried sample had higher protein (20.37±0.01%), ash (12.26±0.01%) and crude fibre (16.36±0.01%) contents. Vitamin C content was 2.76mg/100g (Freeze-dried soursop, FrDS) and 1.69mg/100g (Oven-dried soursop, ODS), vitamin B was 0.05mg/100g (FrDS) and 0.04mg/100g (ODS) and 1vitamin B was 0.09mg/100g (FrDS) and 0.05mg/100g (ODS). Ca was 1.18mg/100g and 1.46mg/100g; Fe was 22 4.26mg/100g and 33.35mg/100g; Mg was 42.26mg/100g and 55.58mg/100g; Na was 20.15mg/100g and 25.58mg/100g; K was 23.35mg/100g and 36.67mg/100g; Zn was 0.87mg/100g and 1.56mg/100g while P was 29.36mg/100g and 66.57mg/100g for the FrDS and ODS soursop powders respectively. The drink from fresh soursop (FSD) had the best score for overall acceptability (7.75±0.85) at p < 0.05 compared to the other drinks. Conclusion: Dried soursop pulp, especially oven-dried, can be a good source of protein, fibre and minerals including K, Fe, P, Mg and Na while the freeze-dried soursop is a better source of carbohydrate, fat and vitamins than the oven-dried. Dried soursop pulp has potential in the prevention of micronutrient deficiencies as well as PEM

FOOD PRESERVATION AND SECURITY AT HOUSEHOLD LEVEL IN RURAL NSUKKA, ENUGU STATE, NIGERIA

ABSTRACT Household food security exists when members at all times have physical and economic access to adequate, safe, acceptable and nutritious foods to meet their daily requirements and food preferences for an active and healthy life. Preservation of post-harvest surpluses makes local staples available and affordable during off season. In Nigeria, food insecurity at the household level can partly be attributed to poor preservation of post-harvest surpluses. This study sought to demonstrate a relationship (if any) between preservation of post harvest surpluses and food security at rural household level. Eha-Alumona and Opi-Uno, in Nsukka, Enugu State were the two rural communities selected because they have farming as their major occupation. Interviews and questionnaires were used to elicit information on socio-economic characteristics, foods preserved and methods, problems encountered and effect of preservation on food security of two hundred households. Data collected were analyzed using descriptive statistics and results presented as frequencies and percentages. About 42% of households partly produced and partly purchased foods, while 17% depended solely on family food production. Most households (90%) preserved foods mainly by sun-drying cereal, legumes, vegetables and roots/tubers. All the households (100%) stored palm oil in bottles or jars while 87.5% smoked meat/fish. Sun-dried foods were perceived wholesome until used by 61.5% households. About 62% households consumed their preserved foods, 19% sold, while 19.4% consumed part and sold part. Sixty-four percent (64%) were food-secure which they attributed to preservation of post-harvest surpluses. However, 36% did not have enough because of spoilage and rodent/ insect attack. Hunger at rural household level can be reduced if post harvest surpluses are properly preserved. The Nigerian local government should encourage community food preservation through cooperative societies, provision of necessary infrastructure, funding and education

Hydrodynamics of Intravitreal Injections into Liquid Vitreous Substitutes

Intravitreal injections have become the cornerstone of retinal care and one of the most commonly performed procedures across all medical specialties. The impact of hydrodynamic forces of intravitreal solutions when injected into vitreous or vitreous substitutes has not been well described. While computational models do exist, they tend to underestimate the starting surface area of an injected bolus of a drug. Here, we report the dispersion profile of a dye bolus (50 µL) injected into different vitreous substitutes of varying viscosities, surface tensions, and volumetric densities. A novel 3D printed in vitro model of the vitreous cavity of the eye was designed to visualize the dispersion profile of solutions when injected into the following vitreous substitutes-balanced salt solution (BSS), sodium hyaluronate (HA), and silicone oils (SO)-using a 30G needle with a Reynolds number (Re) for injection ranging from approximately 189 to 677. Larger bolus surface areas were associated with faster injection speeds, lower viscosity of vitreous substitutes, and smaller difference in interfacial surface tensions. Boluses exhibited buoyancy when injected into standard S1000. The hydrodynamic properties of liquid vitreous substitutes influence the initial injected bolus dispersion profile and should be taken into account when simulating drug dispersion following intravitreal injection at a preclinical stage of development, to better inform formulations and performance

How Nigeria’s 2015 presidential election outcome was forecasted with geodemographics and public sentiment analytics

In 2015, Nigeria held one of the most fiercely contested presidential elections in the nation’s recent democratic history. The outcome of the election was expected to exert significant influence on democratic practices on the African continent. The stiffness of the contest also meant that it was difficult to predict the likely winner of the election. This paper summarizes how an empirical approach was used to forecast the outcome of the election by modeling public sentiment data-set using a geodemographic framework. Results indicate that the main electorates that determined the outcome of the election were situated in thirteen battleground states. Additionally, results showed that two years before the presidential election, Goodluck Jonathan’s public approval ratings on corruption, insecurity, and the economy (the main drivers of the 2015 election) had nose-dived across many of the battleground states. This eventually contributed toward his loss

Genomic analysis of microRNA time-course expression in liver of mice treated with genotoxic carcinogen N-ethyl-N-nitrosourea

<p>Abstract</p> <p>Background</p> <p>Dysregulated expression of microRNAs (miRNAs) has been previously observed in human cancer tissues and shown promise in defining tumor status. However, there is little information as to if or when expression changes of miRNAs occur in normal tissues after carcinogen exposure.</p> <p>Results</p> <p>To explore the possible time-course changes of miRNA expression induced by a carcinogen, we treated mice with one dose of 120 mg/kg <it>N</it>-ethyl-<it>N</it>-nitrosourea (ENU), a model genotoxic carcinogen, and vehicle control. The miRNA expression profiles were assessed in the mouse livers in a time-course design. miRNAs were isolated from the livers at days 1, 3, 7, 15, 30 and 120 after the treatment and their expression was determined using a miRNA PCR Array. Principal component analysis of the miRNA expression profiles showed that miRNA expression at post-treatment days (PTDs) 7 and 15 were different from those at the other time points and the control. The number of differentially expressed miRNAs (DEMs) changed over time (3, 5, 14, 32, 5 and 5 at PTDs 1, 3, 7, 15, 30 and 120, respectively). The magnitude of the expression change varied with time with the highest changes at PTDs 7 or 15 for most of the DEMs. In silico functional analysis of the DEMs at PTDs 7 and 15 indicated that the major functions of these ENU-induced DEMs were associated with DNA damage, DNA repair, apoptosis and other processes related to carcinogenesis.</p> <p>Conclusion</p> <p>Our results showed that many miRNAs changed their expression to respond the exposure of the genotoxic carcinogen ENU and the number and magnitude of the changes were highest at PTDs 7 to 15. Thus, one to two weeks after the exposure is the best time for miRNA expression sampling.</p

Nutrient intake of children (36 months) fed fermented foods in urban and rural communities in Anambra and Enugu states, Nigeria

A 3-day weighed food intake study was conducted with 200 children aged 36 months in two urban and rural communities in Anambra and Enugu states. Means, standard error of the mean and Duncan's multiple range test were the statistical tools used to analyze the data. The daily mean energy intake, protein, thiamin, niacin, vitamin A and ascorbate were higher than 90% of the FAO/WHO/UNU (1985) and WHO (1974) requirements in the eight communities. The rural children consumed more than the urban children. The iron intake, calcium and riboflavin were generally low