Serum glutamine synthetase activity as biomarker for tuberculosis diagnosis and monitoring anti-tubercular drug therapy success

Tuberculosis is a major public health problem in developing countries. It is one of the most widely spread human diseases globally. While the new diagnostics for tuberculosis (TB) have created greater interest, their full impact on global propaganda against tuberculosis is yet to be evaluated. Most of the TB cases are prevalent in the underdeveloped and developing regions of the world where the means to diagnose and to treat TB cases are limited. As a result, the infectious TB cases might remain undiagnosed or diagnosed late. So, the need of the hour is to launch a rapid but simple, inexpensive, sensitive and specific test to diagnose TB cases at the earliest. The abundant presence of glutamine synthetase (GS) in the culture filtrate of pathogenic mycobacteria has correlation with the occurrence of poly L-glutamate/glutamine component in the cell wall of these pathogenic mycobacteria but not in non-pathogenic mycobacteria. The GS seems to be stable in the infected host and also is present in host tissues and fluid. GS is demonstrated to be present in the serum of subjects suffering from pulmonary or extra-pulmonary tuberculosis; but not detectable at all in normal control and disease control (lung disease control) subjects. With anti-tubercular (A-TB) drug therapy in pulmonary and extra-pulmonary tubercular subjects, the serum GS levels fall significantly. To confirm that only the Mycobacterium tuberculosis (M. tuberculosis) GS is being assayed, the serum GS activity may be assayed in the presence of L-methionine-S, R-sulfoximine (MSO), a selective inhibitor of M. tuberculosis GS. The concentration of this inhibitor is so selected that it is sufficient to inhibit mycobacterial GS activity but not the human (mammalian) GS activity. It increases the specificity of the test. Thus, an ELISA or latex agglutination test might be inducted to assay the serum GS activity for the rapid and reliable detection of active or latent tubercular subjects and also detecting the presence of drug sensitivity or the emergence of resistance against A-TB drugs. Nevertheless, for rapid field study, the card assay technique might be implemented; where when a drop of serum from a suspected subject be placed on the substrate for GS; a definite colour change would mark the test positive. The assay for serum GS requires only a sample of serum from the patient and takes only few minutes to perform. Therefore, the results will be available nstantaneously when the patient is at the medical facility centre or even at home and this will curtail the number of visits to the medical facility centre. This is really advantageous in developing and underdeveloped countries where in many cases the patients do not have the capability of making multiple visits to the medical facility centre. The test procedure can also be used as an assay to monitor the response and success of anti-tubercular drug therapy. The procedure can very well indicate whether the treatment is successful or a change in the antibiotic drug therapy would be needed.

A Study of the Congenital Anomalies of the Ear with Special Reference to Microtia.

Congenital abnormalities of the ear is rare. It has been estimated that it occurs once in 2,00,000 births. Children with this malformation are usually sent to plastic surgery Dept. In bilateral cases they are often referred to E N T Dept. because of the hearing loss and the treatment becomes a combined problem. The outstanding role of radiological revaluation of the external, middle and internal ear apparatus is of paramount importance. Methods & Materials : The patients attending E.N.T., Out Patient Department was utilized as case materials. Besides clinical study, Plain X-Ray and C.T. plays an important role. C.T and plain X-Rays including lateral oblique mastoid views, Submentovertical view, Stenver’s views, Towne’s view, would be taken for assessment of external, middle and internal ear development. Whenever necessary, views for Mandible shall be recorded also. Aims and Objectivies : Objective of the present study is to classify congenital anomalies and to record the type of disabilities with the help of radiological investigations. Systemic study of incidence of such cases shall be recorded.

Rh Blood Grouping of the Individuals Born of Rh Negative Mother and Rh Positive Biological Father.

Unlike ABO antigens, Rh antigens are present only on Red Blood Cells (RBC), RhO(D) antigen is clinically the most important in the Rh system because it is highly antigenic. In India, as reported, 95% population is Rh positive whereas 05% is Rh Negative(approximately). Rh antibodies are the major cause3 of haemolytic disease of newborn (HDN) and lead to destruction of transfused Rh Positive red cells. A total number of 799 pregnant mothers having RhD Negative Blood Group (and also their husband possessing RhD Positive Blood Group) were surveyed. Out of the 799 babies born, 662 possessed RhD Positive and 137 possessed RhD Negative Blood Group. Besides this, twin babies born of RhD Negative mother and RhD Positive Biological Father were computed separately (Total No.of such mothers being 12). In case of twin delivery, the twins babies all possessed RhD Positive Blood Group. Calculation shows that about 17% of babies were RhD Negative and 83% were RhD Positive.

Efficacy of Zinc Supplementation as an Adjunct to Anti Tubercular Drug Therapy.

Zinc being a stronger electron acceptor than iron might replace iron from the critical thiol groups. So, Zinc supplementation in Tubercular Subjects might help the decompartmentalised state of iron in the body to revert back to normal compartmentalized state of iron. Again, Zinc inhibits the formation of superoxide radicals. Thus, Zinc supplementation might decrease the excess superoxide with simultaneous decrease in the formation of soluble oxygen made by dismutation reaction by the iron cofactored superoxide dismutase secreted extracellularly by the pathogenic M. tuberculosis. The study shows early and effective recovery with Zinc supplementation (50mgm. of elemental zinc orally / day for one month) along with anti - Tubercular drug therapy. This gets support by the significant changes in the serum level of three enzymes – Glutamine Synthetase, Superoxide Dismutase and Cholienesterase. Again, the dose of zinc supplementation instituted with a great benefit and without any toxic symptoms and signs, is below the Lowest Observed Adverse Effect Level (LOAEL) based on the superoxide dismutase activity in erythrocytes with zinc intake.