Revista de Bioanálise e Biomedicina

This study evaluates the antidiabetic activities of essential oil obtained by steam distillation of the leaf sheath of Cymbopogon citratus (CCEO) in poloxamer-407 induced type 2 diabetic (T2D) Wistar rats. The sample was then analyzed by gas chromatography-mass spectroscopy (GCMS) identifying 23 compounds representing 96.9% of the oil. The major compounds of essential oil were geranial (42.4%), neral (29.8%), myrcene (8.9%) and geraniol (8.5%). When compared to diabetic control rats, the CCEO treated diabetic rats presented significant amelioration of glycaemia, insulinamia and lipid dysmetabolism, accompanied by increased GLP-1 content in cecum and remarkable reduction of oxidative markers. Histopatholgical analysis of pancreas showed increase in β-cell mass, islet number and quality of insulitis. HYBRID and FRED docking were performed for 48 documented CCEO phytoconstituents for putative action mechanism concerning three proteins namely PTP-1B, PPAR-γ and DPP-IV having diabetic therapeutic properties. Phytoconstituents like myrcenol, linalool, α-elemol and β-Eudesmol showed significant interaction with PPAR-γ and DPP-IV while only pimelyl dihydrazide showed interaction with PTP-1B. The results provided a pharmacological evidence of CCEO as antidiabetic mediated by interaction of various phytoconstituents with multiple targets operating in diabetes mellitus.

In this sequel article on Amlexanox I investigate the multi-tasking potential for this drug, a recently discovered readthrough agent with immune-modulatory properties, for management of a wide range of human diseases including ageing modeled as a disease. The focus is not only on correction or disease rescue, but also on early prevention through use of Amlexanox prophylaxis. The concept of readthrough of nonsense mutations is further explored and correlation of nonsense mutation with cancer spread and stage is examined. Many other prevalent disease processes are examined in the light of nonsense-mediated causation, for example, intellectual disability and ageing. A primary aim of my current investigation is to show that both communicable diseases (related to infections from viral and bacterial agents) as well as non-communicable diseases (such as cancer, diabetes and inherited malformations/dysfunctions) may all form suited targets for Amlexanox therapy. As such, ex vivo and in vitro studies and animal models are discussed with the overall theme being to translate positive findings into the clinic. Clearly, this would have a major benefit with management in many inherited disease states and for infectious diseases. Further, a major benefit can be predicted for acquired chronic conditions too. The long understood property of Amlexanox in immune-modulation is exploited in this analysis. By acting through part-control of the NF-kappaB transcriptional factor-inflammatory axis, Amlexanox is capable of modulating the pathophysiology of such processes as cancer, vascular disease and diabetes with obesity. Moderating the response to pathogen challenge is a focus of attention in this present investigation. This is important insofar as Amlexanox mediates inflammatory-axis regulation and host-pathogen interactions, strongly suggesting that it must be explored in this context. As a result of this, interference with this arm of the innate immune system may well have consequences in terms of exposure to certain infectious agents. Detailed animal model systems as well as formal clinical trials are definitely called for to clarify the longer-term adverse reaction this may produce in the face of pathogen exposure. Amlexanox has been clinically approved for many years and, along with other drugs with similar immune-modulating capacity, appears satisfactory for long-term usage. Therefore, in practical terms, pathogen challenge in such a context may not pose significant threat. Overall, clinical trials are universally called for in order to ascertain the full potential for this old drug presenting with some exciting ‘new tricks’. I aim to be able to purposefully ‘repurpose’ Amlexanox and add this drug into the ‘Doctor’s bag’ as a highly valuable medical adjunct to manage a wide plethora of medical conditions.

Background: There has been a re-emergence of Yellow Fever (YF) disease across Africa and in South America since the 1980s. According to WHO estimate, 508 million people in 32 countries are at risk because of their location in the rainforest region, the habitat of the vector mosquito.Intense YF virus circulation occurred in West Africa in 2008 and 2009 with outbreaks reported from Burkina Faso, Cameroon, Central African Republic, Chad, Congo, Côte d’Ivoire, Guinea, Liberia and Sierra Leone. Between January 2010 and March 2011, outbreaks of YF were reported to the WHO by Cameroon, Côte d’Ivoire, Democratic Republic of Congo, Sierra Leone, Senegal and Uganda. Most recent outbreaks in Africa were reported simultaneously in Ghanaand Cameroun on the 3rd of February, 2012.This study investigates a possible correlation between vaccine manufacture, cold chain handling and vaccine potency/ stability as a risk factor in the repeated outbreak of yellow fever in the face of increased immunisation coverage in Nigeria and West Africa by extension. Methods: Samples of Stamaril®, a yellow fever vaccine collected from different open market sources were subjected to potency test by measuring their immunogenicity indicators.Their embryo infectivity dose and mice LD50 as well as their pyrogenicity were determined. Results: Results showed that 42% of the vaccines tested were not suitable for use even though the vaccine vial monitor certifies they are fit for use. Conclusion: A large proportion of YF vaccines sold in open markets in Eastern Nigeria may be compromised in terms of potency. Vaccine vial monitors only are not entirely reliable as indicators of vaccine potency or usability.

Three simple, sensitive and inexpensive spectrophotometric methods have been described for the assay of ibuprofen in bulk drugs and pharmaceutical formulations. The developed methods are based on the formation of colored charge transfer complexes of ibuprofen with p-chloranil, 7,7,8,8-tetracyanoquinodimethane, bromothymol blue, methyl orange and picric acid in acetonitrile as solvent. These newly formed complexes were found to absorb at 438, 394, 403, 418, 374 nm respectively. Optimizations of various experimental conditions are described. Beer’s law obeyed in the concentration range6-54, 2-24, 4-28, 3-21 and 4-28 μgmL-1 with correlation coefficient >0.998 in each case and lower limit of detection values were 76, 90, 234, 63 and 189 ng mL-1, respectively. The association constants and standard free energy changes were studied using Benesi-Hildebrand plots. Oscillator’s strength, ionization potential and energy of complexes in the ground state for all the complexes have been calculated. For further confirmation, solid charge transfer complexes were synthesized and characterized by IR and 1H-NMR spectroscopy. The applicability of the method was demonstrated by the determination of studied drugs in commercial tablets with satisfactory results. No interference from excipients was observed in the formulations.

Glycosylation is a critical attribute of glycoprotein products as it has been shown that the type and degree of glycosylation can have a significant impact on the product efficacy and immunogenicity. In developing generic forms of glycoprotein based therapeutic products, it is necessary to characterize the glycosylation of these products to ensure that it conforms with the original product as well as natural form of the product. In this study, we have focused on the characterization of the N-linked glycans and, in less details, on the O-linked glycans found on Etanercept (EnbrelTM). Using a series of methodologies, we mapped the N-linked glycosylation sites in Etanercept and also defined the types of glycan structures associated with each site. Separately, we also determined the extent of Etanercept O-glycosylation and the type of O-linked glycans.