Search

TB is a deadly infectious disease, in existence since time immemorial. This article traces the journey of TB developments in the last few decades and the path breaking moments that have accelerated the efforts towards Ending TB from National Tuberculosis Control Program (NTCP 1962-1992) to Revised National Tuberculosis Control Program (RNTCP - 1992-2019) and to National Tuberculosis Elimination Program (NTEP) as per the vision of Honorable Prime Minister of India. From increased funding for TB, the discovery of newer drugs and diagnostics, increased access to health facilities, greater investment in research and expanded reach of public health education, seasoned with TB activism and media's proactive role, private sector participation to political advocacy and community engagement, coupled with vaccine trials has renewed the hope of finding the elusive and miraculous breakthrough to END TB and it seems the goal is within the realms of the possibility. The recent paradigm shift in the policy and the drive of several states & UTs to move towards TB free status through rigorous population-based vulnerability mapping and screening coupled with active case finding is expected to act as the driving force to lead the country towards Ending TB by 2025. Continued investments in research, innovations and availability of more effective drugs and the vaccines will add to existing armamentarium towards Ending TB.

The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility.

Objective This review presents current literature on desmopressin acetate as mono- and adjuvant therapy and its ability to stabilize platelet function in patients presenting with intracranial hemorrhage on pre-injury antiplatelet agents of aspirin, clopidogrel, prasugrel and/or ticagrelor. Design PubMed, MEDLINE and International Pharmaceutical Abstracts were searched through to 1st March 2016. Inclusion criteria were case reports, reviews, short communications and brief reports on reported patients with any type of intracranial hemorrhage while on oral antiplatelet agents. Reports on desmopressin acetate in surgical candidates were excluded due to the nature of the bleed. Results A scoping search was performed in three databases with 89 articles identified based on the search criteria. All returned articles were evaluated by the authors with four articles suitable for inclusion. Conclusion While desmopressin acetate has a promising mechanism of action for enhancing primary hemostasis, the articles reported conflicting results possibly due to limited study sample sizes, lack of standards on measuring platelet function, data on weight-based dosing and guidelines. Further research is needed to evaluate desmopressin acetate as monotherapy. If used, it should be considered adjunct therapy to platelet transfusions for patients on oral antiplatelet agents requiring emergent hemostasis.

Background Drug-resistant TB is a serious public health problem in India. Pre-existing resistance to fluoroquinolones (FQs) and second-line injectable drugs (SLIDs) in strains of Mycobacterium tuberculosis (MTB) resistant to rifampicin (RIF) and/or isoniazid (INH) contributes to treatment failures and consequent transmission of drug-resistant TB. A baseline assessment of resistance of MTB to FQs and SLIDs may help guide policies to further improve management of drug-resistant TB in India. This study aims to determine the prevalence of resistance to FQs and SLIDs among MTB strains having RIF and/or INH resistance in central India. Method A total of 1032 smear positive sputum samples were subjected to line probe assay (GenoType MTBDRsl version 2) to test for resistance to FQs and SLIDs, according to the integrated diagnostic algorithm of the revised national TB control programme. Results Of 1032 samples, 92 (8.91%) were not interpretable and hence excluded, 295 (31.38%) were resistant to FQs alone, 13 (1.38%) were resistant to SLIDs alone, 15 (1.59%) were resistant to both FQs as well as SLIDs and 617 (65.63%) were sensitive to both FQs and SLIDs. The most common mutations in gyrA and gyrB genes were observed at codons D94G and E540V, respectively. Mutations at codon A1401G in rrs genes and in the C-14 T region of eis genes were most frequently observed. Conclusion High levels of FQ resistance points towards indiscriminate use of this class of drugs. Regulation for judicial use of FQs is an urgent requirement.

In May 2018, the US Food and Drug Administration approved pegvaliase-pqpz (Palynziq*), the first enzyme substitution therapy for the treatment of phenylketonuria (PKU). This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, and the safety and tolerability profile of pegvaliase.Relevant information was identified through a comprehensive literature search of several databases using the keywords pegvaliase, rAvPAL-PEG, and phenylketonuria. Additional information was gathered from the pegvaliase package insert, posters presented at scientific meetings, and materials provided from the manufacturer, BioMarin.Pegvaliase is effective in decreasing blood phenylalanine levels, and is associated with a manageable side-effect profile. Phase III clinical trial data demonstrated that 60.7% of patients were able to achieve blood phenylalanine levels less than the guideline recommended 360 µmol/L at 24 months. Brief sub-studies also showed the improvement in inattention symptoms in patients treated with pegvaliase, compared to placebo.Pegvaliase is a promising new treatment option for adults living with PKU. Further studies are warranted to determine long-term safety and clinical efficacy in sub-populations.

Cyclodextrins are a group of water-insoluble, donut-shaped, naturally occurring cyclic oligosaccharides that are produced as a result of the bacterial breakdown of α-d-glucose polymers, such as cellulose. They are inactive molecules that do not display any innate biological activity. The ocular delivery of certain drugs is affected not only by the drug’s physicochemical properties but also by the anatomical barriers of the eye. Drug-cyclodextrin complexes, formed by the physical occlusion of the torus cavity by the drug molecule, redress this issue. Thus, the ocular delivery of glaucoma drugs (e.g., carbonic anhydrase inhibitors, prostaglandin derivatives, pilocarpine), nonsteroidal anti-inflammatory drugs (e.g., indomethacin), and antifungal drugs (e.g., voriconazole) is enhanced by such inclusion complexes. Additionally, specific drug delivery systems (e.g., hydrogels, mucoadhesives, ocular gels) are harnessed to deliver the drug payload from the drug-cyclodextrin complex in a tunable fashion. This chapter seeks to elaborate on the chemical, biological, and pharmaceutical aspects governing cyclodextrins in the context of ocular drug delivery.