Peptide Based Tuberculosis Treatment: A Million Dollar Question | Chapter 08 | Emerging Research in Medical Sciences Vol. 3

Tuberculosis (TB) is a deadly tropical disease that is mainly caused by Mycobacterium tuberculosis. The pathogen is known to invade and replicate inside the host’s macrophage. Due to the emerging dilemma of multi-drug resistant TB and extensively-drug resistant TB, the exigency for finding new TB drugs is an obligation now. Among the propitious anti-tubercular agents studied in the past few decades, peptides from diversified sources have been substantiated to be persuasive with multiple advantages such as low immunogenicity, selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action. This chapter highlights the role of prime peptides exploited from several other unplumbed sources as anti-tubercular agents.

Author(s) Details

Ameer Khusro
Department of Plant Biology and Biotechnology, Loyola College, Nungambakkam, Chennai-34, India.

Chirom Aarti
Department of Plant Biology and Biotechnology, Loyola College, Nungambakkam, Chennai-34, India.

View Books:

Adjunctive Therapeutic Effects of Zinc Supplementation in Tuberculosis Treatment among Adults in Calabar, Nigeria | Chapter 01 | Emerging Research in Medical Sciences Vol. 3

Tuberculosis (TB) is a contagious bacterial disease caused by Mycobacterium tuberculosis, which most commonly affects the lungs. It is the leading killer from a single infectious agent worldwide, especially in Asia and Africa. Each year globally, about 1.3 million people die of TB. Majority of the cases are pulmonary TB (PTB) with approximately 15% being extra pulmonary (ETB). The infection is an insidious; chronic process which may take several weeks or months to become clinically patent. The symptoms of PTB include cough, chest pain and hemoptysis.  Systemic symptoms of TB include fevers, chills, night sweats, easy fatigability, loss of appetite and weight loss. Tuberculosis has long been associated with malnutrition. Micronutrients including Zinc; deficiency is considered to be the most frequent cause of secondary immunodeficiency and infection related to morbidity such as tuberculosis. Zinc deficiency affects the host defences in a variety of ways. It results in decreased phagocytosis and leads to a reduced number of circulating T-cells and reduced tuberculin reactivity, at least in animals. In vitro cellular killing by macrophages was found to be reduced during zinc deficiency and rapidly restored after zinc supplementation. This article aimed to describe the convalescence of patients with tuberculosis who received Zinc supplementation in comparison to those that did not during the course of tuberculosis treatment in Calabar, Cross River State, Nigeria.

Eligible patients (81) out of the 182 assessed were randomized to receive anti-TB drug regimen plus oral administration of individual zinc, 25 mg daily for 60 days (intervention group), while the control group received anti-tuberculosis drug regimen only for 60 days. Both qualitative and quantitative data were collected. Clinical examination, Karnofsky performance scale index, direct sputum examination, anthropometric measurements and blood collection for haematological and zinc assessment were carried out before and 2 months after anti-TB treatment began. The mean serum zinc levels at 2 months of TB treatment were significantly higher in the intervention group (14.4 ± 0.37 µmol/L) in comparison with the control (12.9 ± 0.37 µmol/L); (p = 0.004). A significant difference (p = 0.010) in the serum concentrations of zinc was observed between the two groups when adjustments were made for TB-HIV co-infection. Risk reduction of about 41% for acid fast bacilli (AFB) positivity (RR: 0.59; 95% CI 0.23 to 1.46) was observed after 2 months of anti-TB treatment in favour of the intervention group. There was a significant improvement in the haematological parameters as evidenced by significant higher proportion of patients in the intervention group than the control group with values above the lower ranges for these parameters. Therefore, irrespective of HIV status in individuals with TB, zinc supplementation significantly increases clinical outcomes, haematological parameters, improves nutritional status as proxied by anthropometric indices and leads to faster sputum smear conversion. The article adds to the growing body of evidence in support of the beneficial role of zinc in TB control.

Author(s) Details

Regina I. Ejemot-Nwadiaro
Department of Public Health, Faculty of Allied Medical Sciences, University of Calabar, Nigeria

Edisua H. Itam
Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, Nigeria.

Prof. Emmanuel N. Ezedinachi [MD, DTMH]
Calabar Institute of Tropical Diseases Research and Prevention, University of Calabar Teaching Hospital, Calabar, Nigeria.

View Books:

Effectiveness and Properties of Hydrazide Drugs that Inhibit Growth of Mycobacterium tuberculosis | Chapter 12 | Modern Advances in Pharmaceutical Research Vol. 2

Aims: To examine the properties of hydrazide compounds shown to inhibit Mycobacterium tuberculosis. To identify properties that affect efficiency of bacterial inhibition.

Study Design: Utilizing data from previous studies of compounds that inhibit Mycobacterium tuberculosis, then statistical and pattern recognition methods are applied to identify interrelationships.

Place and Duration of Study: Department of Chemistry, Durham Science Center, University of Nebraska at Omaha, from January 2016 to July 2016.

Methodology: Interrelationships of pharmacological properties were identified by use of various pattern recognition techniques, such as hierarchical cluster analysis and path analysis. Molecular properties and descriptors for all compounds were determined, with additional characteristics such as structure scaffolding and functional group position was accomplished. Statistical analysis, including Pearson r correlation, Mann-Whitney test, one-way ANOVA, Kruskal-Wallis, and descriptive statistics were determined. Multiple regression analysis of molecular property values allows prediction of similar compounds. Determination of any numerical outliers was accomplished by applying Grubb’s test.                                                                                                    

Results: Compounds inhibiting the growth of Mycobacterium tuberculosis contained an aromatic ring or were non-aromatic structures (no ring). There was weak negative correlation of MIC to formula weight. The average formula weight, polar surface area, and Log P, is 183.55 grams/mole, 63.70 A2, and 0.768, respectively. Values of MIC ranged from 14.7 µg/mL to 100 µg/mL. Extent of bacterial inhibition was similar between aromatics to non-aromatics. No outliers were identified by Grubb’s test for all values of MIC taken together. Path analysis showed polar surface area to have most effect on MIC.

Conclusion: The measured level of growth inhibition MIC, showed strong positive relationship to polar surface area, number of hydroxyl and amine groups, oxygen and nitrogen atoms. Two aromatic compounds having a pyridine ring were found to be most similar to isoniazid. Aromatic and non-aromatic compounds showed similar levels of bacterial inhibition overall.

Author(s) Details

Dr. Ronald Bartzatt
Durham Science Center, University of Nebraska, 6001 Dodge Street, Omaha, Nebraska 68182, USA.

Read full article:
View Volume: