Mycothiol (MSH), a functional analogue of glutathione (GSH) that is found exclusively in actinomycetes,reacts with electrophiles and toxins to form MSH-toxin conjugates. Mycothiol S-conjugate amidase (Mca) then catalyzes the hydrolysis of an amide bond in the S conjugates, producing a mercapturic acid of the toxin, which is excreted from the bacterium, and glucosaminyl inositol, which is recycled back to MSH. In this study, we have generated and characterized an allelic exchange mutant of the mca gene of Mycobacterium smegmatis. The mca mutant accumulates the S conjugates of the thiol-specific alkylating agent monobromobimane and the antibiotic rifamycin S. Introduction of M. tuberculosis mca epichromosomally or introduction of M. smegmatis mca integratively resulted in complementation of Mca activity and reduced levels of S conjugates. The mutation in mca renders the mutant strain more susceptible to electrophilic toxins, such as N-ethylmalemide, iodoacetamide, and chlorodinitrobenzene, and to several oxidants, such as menadione and plumbagin. Additionally we have shown that the mca mutant is also more susceptible to the antituberculous antibiotic streptomycin. Mutants disrupted in genes belonging to MSH biosynthesis are also more susceptible to streptomycin, providing further evidence that Mca detoxifies streptomycin in the mycobacterial cell in an MSH-dependent manner.After AIDS, tuberculosis (TB), caused by Mycobacterium tuberculosis, is the second leading cause of death from infectious agents worldwide (26). The resurgence of TB as a potential public health threat due to its synergy with human immunodeficiency virus and the emergence of multidrug-resistant TB strains has resulted in renewed interest in this gram-positive actinomycete. M. tuberculosis is a facultative intracellular pathogen residing in macrophages and in the granuloma, where it is faced with constant assault from toxic agents. Survival in such hostile environments is dependent on detoxification mechanisms that allow M. tuberculosis to persist in the host despite the host immune response.Detoxification processes rely on either phase I or phase II detoxification reactions, or both. In phase I reactions, cytochrome P450, a mixed-function oxidase, catalyzes the incorporation of an oxygen atom from O 2 into a xenobiotic substrate, making the toxin more hydrophilic. If the product of the cytochrome P450-mediated reaction is not sufficiently hydrophilic but is thiol reactive, a subsequent reaction where the toxin is conjugated to glutathione (GSH) occurs, an important process in the mammalian liver. In mammals, GS toxin conjugates are acted upon by a ␥-glutamyl transpeptidase that cleaves the glutamic acid group from the GSH molecule followed by hydrolysis of the glycine moiety by a peptidase resulting in a cysteine toxin conjugate in a multiorgan process. This conjugate is acetylated in the kidney by an acetyl-coenzyme A-dependent N-acetyltransferase to form a mercapturic acid that is excreted (8).Actinomycetes like M. tuberculosis do not produce ...

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INTRODUCTION: Orthodontists, for a long time have considered that occlusion and facial beauty are so interdependent that they must be equal goals of treatment.AIM: To validate the relationship between maxillary and mandibular effective lengths and dental crowding in patients with Class II malocclusions. MATERIALS AND METHOD: A sample of 40 orthodontic patients with complete bilateral Class II malocclusions in the permanent dentition (25 males, 15 females) who were divided into two groups based on severity of pre-treatment mandibular anterior dental crowding. The maxillary and mandibular effective lengths and tooth-arch size discrepancies were measured on the pre-treatment Lateral cephalograms and initial casts, respectively. Intergroup comparisons of apical base lengths were assessed with independent t-tests. Correlation between effective length and dental crowding was assessed by Pearson's correlation coefficient (P <.05).RESULTS: Subjects with Class II malocclusion and moderate to severe crowding had significantly smaller maxillary and mandibular effective lengths compared with subjects without crowding and with minimal dental crowding. A weak inverse correlation was also found between maxillary and mandibular effective lengths and the severity of dental crowding. CONCLUSION: In patients with complete Class II malocclusion, decreased maxillary and mandibular effective lengths constitute a significant factor associated with dental crowding.

The national burden of HCV has significantly mounted over the period of last few decades placing Pakistan at the worst placement of second largest burden of HCV globally. Herein for the first time from Pakistan, we examined clinical correlation of potential biomarkers with HCV. Nation-wide study was conducted on 13,348 suspected HCV patients during 2018-2022. During pre-COVID-19 era of 2018-2019, prevalence of HCV remained 30%. During 2018, among HCV positive patients, 91% of ALT, 63% of AST, 67% of GGT, 28% of Bili T, 62% of HB, 15% of HBA1C, 25% of CREAT, 15% of PT, 15% of aPTT and 64% of AFP were abnormal. During 2019, among HCV infected 74.47% of ALT, 63.54% of AST, 70.24% of GGT, 24.71% of Bili T, 8.77% of HB and 75% of AFP were raised. CT/CAT scan revealed 4.65% liver complications (mild 13.04%, moderate 30.43% and severe 56.52%). During 2020, HCV prevalence remained 25%. 65.17% of ALT, 64.20% of AST, 68.75% of GGT, 31.25% of Bili T, 20.97% of HB, 4.65% of CREAT and 73.68% of AFP levels were raised. CAT analysis revealed liver complications among 4.41% (14.81% mild, 40.74% moderate, and 44.44% sever). 85.71% of participants diabetes was out of control. During 2021, HCV prevalence remained 27.1%. ALT (73.86%), AST (50.6%), GGT (67.95%), Bili T (28.21%), HB (20%), CREAT (5.8%) and AFP (82.14%) levels were abnormal. During 2022, the levels of ALT (56.06%), AST (56.36%), GGT (56.6%), Bili T (19.23%), HB (43.48%), HBA1C (14.81), CREAT (18.92%), AFP (93.75%) were abnormal. CAT analysis revealed 7.46% liver complications (25% mild, 30.36% moderate, and 42.86% sever). During 2021-2022, 83.33% of subject’s diabetes was not controlled.