Zinc (Ii)-Vanillic Acid Complex: Synthesis, Characterisation And Evaluation Of Antidiabetic And Antioxidative Properties

DissertationBackground: Diabetes is a major non-communicable disease that contributes to morbidity and mortality outcomes, globally. The morbidity and mortality outcomes of diabetes has been attributed to several vascular complications associated with the disease. Oxidative stress has been implicated in several mechanisms underlying the development and progression of diabetic complication. Blood glucose-lowering drugs are commonly used to manage diabetes and mitigate the development of vascular complication. However, many of these antidiabetic drugs have been associated with several unpleasant side effects, which have, somehow, discouraged their use. Moreover, some of these antidiabetic drugs are not affordable to most people in under-developed or developing countries, especially those in the middle- and low-income communities. Supplements and medicinal plants are, however, gaining attention in the prevention and management of many diseases, including diabetes and oxidative stress, perhaps due to their perceived holistic medicinal profile and minimal safety concern. In fact, studies have given credence to the antidiabetic and antioxidative pharmacological potentials of plant-derived phenolics. Vanillic acid is a natural phenolic acid with documented oxidative stress and diabetes related pharmacological properties. Also, zinc mineral has been reported to have insulin mimetic potentials. Data from clinical trials suggest that zinc may be useful in glycaemic control, as well as in diabetes prevention and management. Zn(II) has been complexed with many ligands, to develop potent antidiabetic agents. However, it has been mostly complexed with synthetic organic ligands that has potential toxic effects and little or no reported pharmacological property. In fact, antioxidant ligands such as natural phenolic acids have been scarcely studies as possible ligands of bioactive Zn(II) complexes, despite the minimal toxicity concerns of natural phenolic acids. Specifically, vanillic acid has not been studied as possible ligand to develop a bioactive Zn(II) complex. Therefore, the aim of this study was to synthesize and evaluate the antioxidative and antihyperglycaemic effects of a novel Zn(II)-vanillic acid complex. Materials and methods: Zn(II)-vanillic acid complex was synthesised from zinc sulphate heptahydrate and vanillic acid precursors. After synthesis, the complex was characterised using Fourier-transform infrared (FT-IR) and proton nuclear magnetic resonance (1H NMR) spectroscopic techniques. The effect of the complex on the viability of Chang liver cells and L-6 myotubes was evaluated. Then, different in vitro, cellular and ex vivo experimental models were used to measure the antihyperglycaemic and antioxidative activity of the complex, which was compared to the activity of the complex’s precursors. The in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals scavenging and ferric reducing antioxidant activities of the complex and precursors were measured. Also, the inhibitory activity of the test samples on ⍺-glucosidase, ⍺-amylase and glycation activities was measured in vitro. The effect of the test samples on glucose uptake was measured in L-6 myotubes and isolated rat psoas muscle tissue. Finally, the anti-lipid peroxidative effect of the test samples was measured in isolated rat liver tissues induced with oxidative stress. Results and discussion: FT-IR and NMR data suggest that vanillic acid complexed with Zn(II) through a Zn(O6) coordination mode by using its carboxylic functional group. Thus, it is proposed that the complex has three moieties of vanillic acid. This structural property of the complex appears to influence its activity relative to vanillic acid. The DPPH (IC50 = 95.9 μM) and ABTS (IC50 = 12.2 μM) radicals scavenging and Fe3+ reducing (251 mmol/mol AAE at 40 μM) activities of the complex were, respectively, 2.3 (p ˂ 0.05), 1.8 and 1.5 (p ˂ 0.05) folds stronger than those of vanillic acid. Also, the anti-lipid peroxidative activity of the complex (IC50 = 667 μM) in rat liver tissue was 9.7 folds more potent (p ˂ 0.05) than that of vanillic acid (IC50 = 6470 μM) and statistically comparable to that of ascorbic acid standard. Complexing Zn(II) with vanillic acid resulted in a complex with stronger α-glucosidase (IC50 = 48.3 μM; p ˂ 0.05), amylase (IC50 = 5.86) and glycation (IC50 = 19.8 μM) inhibitory activities relative to those of vanillic acid. The potent activity of the complex may be partly attributed to its three vanillic acid moiety, which can collectively potentiate stronger activities compared to vanillic acid alone. Zn(II) conferred potent L-6 myotube (EC50 = 20.4 μM) and muscle tissue (EC50 = 612 μM) glucose uptake effects on vanillic acid. Cytotoxicity data showed that the complex did not reduced the viability of L-6 myotubes and Chang liver cells, suggesting it may not pose hepatotoxicity concerns. Conclusion: Data of this study showed that complexing Zn(II) with vanillic acid resulted in a complex with improved antioxidant and antihyperglycaemic activity relative to vanillic acid. Zn(II) may be further studied as potential adjuvant for vanillic acid in developing bioactive antidiabetic and antioxidative nutraceutical for prevention and management of diabetes and oxidative complications

Allelophatic effect of prosopis africana (guill and per) taub pod powder on the germination indices of three varieties of abelmoschus esculentus (l.) Moench

The release of certain chemicals by plants has been found to significantly affect different facets of other plant life cycles, from germination through to reproduction. The study was carried out to investigate the allelopathic effect of Prosopis Africana pod powder on the germination, growth and yield attributes of three varieties of Abelmoschus esculentum. Germination indices such as germination percentage, germination rate and germination index were evaluated. Growth parameters namely; number of leaves, plant height, stem girth and leaf area were also assessed. The data collected were subjected to analysis of variance using Statistical Package for Social Science (SPSS) 16.0 version. Duncan Multiple Range Test was used to separate mean differences (P<0.05). Results revealed that the highest germination percentage, index and rate values were recorded for variety Yellen (100%, 3.447 and 0.5), respectively when treated with Prosopis Africana pod powder extract. Highest germination index values were recorded in okra varieties Yellen, Clemson spineless and NHAe when treated with 40, 60 and 40 g of the pod extract (3.447, 3.057 and 3.39) respectively. Least germination percentage, and germination index recorded in okra variety Clemson spineless and NHAe (7.22% and 0.39) respectively. Administration of 80 and 100 g of the Prosopis Africana pod powder extract resulted in a detrimental effect on the three okra varieties, thus concluded allelopathic at these concentrations

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

The extent to which political and economic risks have affected the tourism industry in Nigeria

Objective: The study aims to determine the extent to which political and economic risks have affected the tourism industry and the economy in Nigeria. Prior Work: In recent times, there has been a clamour for the development of t The study aims to determine the extent to which political and economic risks have affected the tourism industry and the economy in Nigeria. Prior Work: In recent times, there has been a clamour for the development of the Nigerian tourism industry but such has been beset by a spate of religious intolerance, insurgency, and changes in government, among others. There seems to be dearth of literature and empirical evidence to show the extent to which political risk has influenced tourism in Nigeria. Approach: Time series secondary data from the World Travel and Tourism Council, 2017 were used in the regression analysis. Regression statistical technique was used to examine the relationship between political and economic risk and tourism in Nigeria specifically between 2006 and 2017. Results: The study adopted a regression approach and found out that causality exists and there is a positive significant relationship between political and economic risk in Nigeria. Implication: The result of the relationship shows that political and economic risk have effects on tourism, and tourism has a significant impact on the economy. The significant effect of political and economic risk on tourism calls for adequate security in the country, and better legal and institutional frameworks. This will enhance the economic impact of tourism on the Nigerian economy

Evaluation of the coverage and effective use rate of long-lasting insecticidal nets after nation-wide scale up of their distribution in Benin

Background: In Benin, around four million Long-Lasting Insecticide-treated Nets were freely distributed to household to prevent malaria in 2011. In contrast to a previous campaign that targeted only children under 5 years and pregnant women, this distribution campaign was conducted in order to achieve universal coverage. This study presents the results of LLIN coverage and utilization after the distribution campaign. Methods: The study was a cross-sectional household survey which utilized a stratified two-stage cluster sampling design. The strata represented the twelve departments covered by the national distribution campaign in 2011 and included a total of 4,800 households randomly selected in the country. A questionnaire adapted from the standard Malaria Indicator Survey (MIS) Household Questionnaire was used. Data were entered using QPS software and analyzed with R 2.14.1. Results: LLIN ownership was 86.4% (74 - 94). On average, each household received 3 LLINs (2-4). The proportion of households that met the ratio one net for two persons was 77%. The proportions of individuals sleeping under LLINs were high (84.8%). LLIN use among urban residents was 10% lower than in effective users from rural areas (P = 0.00224). Conclusions: The universal distribution campaign conducted in Benin has increased LLIN ownership and use in the community. But additional efforts are need to improve and maintain LLIN coverage

Comparative study of the effectiveness of combination therapies based on atemisinine in Dassa Zounme and Parakou: case of Artemether lumefantrine and Artesunate amodiaquine

The National Malaria Control Program recommended in 1993, the use of Chloroquina (CQ) as first line drug for malaria treatment, and sulfadoxin pyrimethamin as second drug. After years, Benin knows resistance about these antimalarials. Quinina was to treat gravities. In 2004, the strategy of treatment changed. Treatment of malaria cases is based on use of arteminisinia therapeutic combination. The goal of this study is to be sure that these drugs are efficace before general use in the country and in some regions as Dassa Zounmè where the resistance is up (61. 3% for Chloroquina CQ and 45.9% for SP in 2002).The study is based on: comparison of therapeutic efficacy of artemether Lumefantrine and Artesunate Amodiaquine. Results show that all of the tested drugs have good therapeutic efficacy. Most important rate failure is in Dassa Zounmè (33, 86%) than Parakou (23, 44%). They are parasitologic failure and are probably due to the reinfestation of children. Two drugs have a good parasitological clearance and eliminate fever after 2 days of treatment. Published by the International journal of Microbiology and Mycology (IJMM

Open Access

Impact of long-lasting, insecticidal nets on anaemia and prevalence of Plasmodium falciparum among children under five years in areas with highly resistant malaria vector

Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: evidence from health facility data from Benin

Abstract Background Insecticide-based interventions have averted more than 500 million malaria cases since 2000, but insecticide resistance in mosquitoes could bring about a rebound in disease and mortality. This study investigated whether insecticide resistance was associated with increased incidence of clinical malaria. Methods In an area of southern Benin with insecticide resistance and high use of insecticide-treated nets (ITNs), malaria morbidity and insecticide resistance were measured simultaneously in 30 clusters (villages or collections of villages) multiple times over the course of 2 years. Insecticide resistance frequencies were measured using the standard World Health Organization bioassay test. Malaria morbidity was measured by cases recorded at health facilities both in the whole population using routinely collected data and in a passively followed cohort of children under 5 years old. Results There was no evidence that incidence of malaria from routinely collected data was higher in clusters with resistance frequencies above the median, either in children aged under 5 (RR = 1.27 (95% CI 0.81–2.00) p = 0.276) or in individuals aged 5 or over (RR = 1.74 (95% CI 0.91–3.34) p = 0.093). There was also no evidence that incidence was higher in clusters with resistance frequencies above the median in the passively followed cohort (RR = 1.11 (0.52–2.35) p = 0.777). Conclusions This study found no association between frequency of resistance and incidence of clinical malaria in an area where ITNs are the principal form of vector control. This may be because, as other studies have shown, ITNs continue to offer some protection from malaria even in the presence of insecticide resistance. Irrespective of resistance, nets provide only partial protection so the development of improved or supplementary vector control tools is required to reduce Africa’s unacceptably high malaria burden