ABSTRACT
Cryptosporidiosis is a neglected tropical disease caused by the protozoan parasite Cryptosporidium parvum. Limited therapeutic options, limitation in in vitro parasite culture, and lack of a reliable animal model of parasite for replication of in vivo life cycle and drug testing demand alternative methods for drug development. The in silico methods of drug discovery prove a crucial process in such conditions.Recent research reported a limited number of small molecules for drug development. Purine nucleotide biosynthesis in Cryptosporidium species is dependent on the IMPDH (CpIMPDH) enzyme, so distortion of parasite IMPDH has been pursued as a compelling strategy for curbing Cryptosporidium infection due to its different kinetics from the host enzyme. Our study's primary aim was to discover novel ligand molecules with noticeable activity against Cryptosporidium parvum IMPDH. For this purpose, we selected 18 previously discovered ligands to understand the interaction feature between ligand and receptor, and their shape and electronic features are employed as a template for shape-based virtual screening of the ZINC database (drug-like subset) search approach via Schrodinger-2019 (Maestro 11.9). The obtained hits were subsequently subjected to structure-based screening, quantum polarized ligand docking (QPLD), and molecular dynamics simulations to fetch potential small molecules with the highest binding affinity for CpIMPDH protein. Further ligand binding energy and pharmacokinetic analysis were also taken into consideration as filtering criteria for selecting the most promising drug-like compounds. On this experimentation analysis, three top-ranked (ZINC24855054, ZINC58171263, and ZINC08000072) molecules were found to have appropriate pharmacokinetic properties along with surpassing in silico inhibitory potential towards the CpIMPDH compared to known inhibitors. The molecular docking and molecular dynamics simulation analysis results satisfactorily confirmed the inhibitory action. Therefore, these new scaffolds deduced by the presented computational methodology could recommend lead molecules for designing promising anti-cryptosporidial drugs targeting CpIMPDH protein.
ABSTRACT
Retinoblastoma is the most common intraocular neoplasm of children. Retinoblastomas can present at birth but are usually diagnosed between 1 and 2 years of age, with heritable cases arising in younger infants. This is a retrospective study conducted at a Tertiary care centre, RAJENDRA INSTITUTE OF MEDICAL SCIENCES, RANCHI from May, 2018 to April 2019. 4 cases with histopathological diagnosis of retinoblastoma were included in the study. The age of the patients of these 4 cases were 20months, 24months, 31months and 68months. The mean age being 35.75months and median age being 22months. 3 out of 4 cases were male patients. Optic nerve as involved in 2 of the cases. It is important that attention be given to the details of the histopathological report in Retinoblastoma, particularly optic nerve invasion, corneal involvement, anterior and posterior chamber involvement to determine post-enucleation therapy and prognosis.
ABSTRACT
Epidermal cysts are common skin lesions, but they occur rarely in the oral cavity. Very few cases have been reported in the literature, and, here we present one such rare case of epidermal cyst of the base of the tongue in a 24 year male patient. The patient presented with the complain of swelling below the tongue which was gradually increasing in size for the past one and half year with difficulty in speech, mastication and closure of mouth. Intraoral examination revealed presence of large solitary swelling in the sublingual region more towards the right side. It was non-tender, fluctuant soft and fixed to the underlying mucosa having no secondary changes. Aspiration cytology was performed which was consistent with the diagnosis of Epidermal cyst.
ABSTRACT
Background: We conducted a tuberculin survey to estimate the annual risk of tuberculous infection (ARTI) among children in a sub-division of rural Bangalore district. A TB disease survey was conducted in the same area around the same time and has already been published. DOTS strategy is being implemented in the study area since 2002. Methods: The tuberculin survey was conducted during 2010-2011 among 3838, 5-9-year-old children attending 147 schools selected by simple random sampling. Children were tuberculin tested with 2TU PPD RT23 with Tween 80 and maximum diameter of induration was measured between 48-96 hours. ARTI was computed from prevalence of infection estimated by mirror-image technique. Prevalence of smear positive pulmonary TB estimated during the disease prevalence survey in 2008-10 was used to find out its relationship with ARTI. Results: Using the observed mode of tuberculin reaction sizes at 19 mm, among surveyed children, prevalence of infection was estimated at 7.3% (CI: 6.5-8.1); ARTI was computed at 1.05%. Considering the mean age of children, estimated ARTI most closely approximated to the year 2008. Every one per cent ARTI was found to correspond to a prevalence of 103 sputum smear positive patients of PTB, which was similar to the ratio of 106 found in the same study area during 1960s. Conclusion: There has been no change in the relationship between ARTI and prevalence of smear positive pulmonary TB from the pre-DOTS era and thus in the number of children infected by each adult point prevalent case of smear positive pulmonary TB each year suggesting the need for early case detection and treatment.