CURRENT GOOD MANUFACTURING GUIDELINES FOR MEDICINAL PRODUCT

The holder of a manufacturing  authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorisation and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company’s suppliers and by the distributors. To achieve the quality objective reliably there must be a comprehensively designed and correctly implemented system of Quality Assurance Incorporating Good Manufacturing Practice, and thus Quality Control and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Quality Assurance systems should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the holder of the manufacturing  authorisation and for the  authorised person Keywords: Good Manufacturing Practice, Quality control, Quality assurance, authorise

Report of four novel variants in ASNS causing asparagine synthetase deficiency and review of literature

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145519/1/cga12275.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145519/2/cga12275_am.pd

Dohra- a mixture of potent carcinogens

Background & objectives: Dohra is a areca nut preparation used with or without tobacco in a few of the areas of Uttar Pradesh (UP), India. There is evidence that it causes potentially malignant disorders and oral cancer. This study was undertaken to provide information on dohra by searching through literature and also through a survey in three areas of Uttar Pradesh (UP), India. Methods: The information on dohra was collected through literature search, study tour to different areas of UP, where group discussions with dohra vendors and with community members of different age group were done to obtain information. Results: Dohra was prepared by the users for their personal use or prepared by small-scale industry for sale. It was available mostly in betel shops or any other store/kiosks and was also available in special dohra shops. Dohra was available in both dry and wet form. Its common constituents were areca nut, catechu (Acacia catechu), edible lime, peppermint (Mentha piperita), cardamom (Elettaria cardamomum) and some flavoring agents. Dohra was consumed as such or with tobacco. Interpretation & conclusions: Different varieties of Dohra were available such as sukha dohra, sukha mulethi dohra and geela dohra. Different processing methods for producing dohra existed. As dohra increases the risk of cancer, it needs to be banned or it should be sold in packets with the details of its constituents and also statutory warning about its adverse health effects

Piscidin-1-analogs with double L- and D-lysine residues exhibited different conformations in lipopolysaccharide but comparable anti-endotoxin activities

To become clinically effective, antimicrobial peptides (AMPs) should be non-cytotoxic to host cells. Piscidins are a group of fish-derived AMPs with potent antimicrobial and antiendotoxin activities but limited by extreme cytotoxicity. We conjectured that introduction of cationic residue(s) at the interface of polar and non-polar faces of piscidins may control their insertion into hydrophobic mammalian cell membrane and thereby reducing cytotoxicity. We have designed several novel analogs of piscidin-1 by substituting threonine residue(s) with L and D-lysine residue(s). L/D-lysine-substituted analogs showed significantly reduced cytotoxicity but exhibited either higher or comparable antibacterial activity akin to piscidin-1. Piscidin-1-analogs demonstrated higher efficacy than piscidin-1 in inhibiting lipopolysaccharide (LPS)-induced pro-inflammatory responses in THP-1 cells. T15,21K-piscidin-1 (0.5 mg/Kg) and T15,21dK-piscidin-1 (1.0 mg/Kg) demonstrated 100% survival of LPS (12.0 mg/Kg)-administered mice. High resolution NMR studies revealed that both piscidin-1 and T15,21K-piscidin-1 adopted helical structures, with latter showing a shorter helix, higher amphipathicity and cationic residues placed at optimal distances to form ionic/hydrogen bond with lipid A of LPS. Remarkably, T15,21dK-piscidin-1 showed a helix-loop-helix structure in LPS and its interactions with LPS could be sustained by the distance of separation of side chains of R7 and D-Lys-15 which is close to the inter-phosphate distance of lipid A.MOE (Min. of Education, S’pore)Published versio

TREX tetramer disruption alters RNA processing necessary for corticogenesis in THOC6 Intellectual Disability Syndrome

Abstract THOC6 variants are the genetic basis of autosomal recessive THOC6 Intellectual Disability Syndrome (TIDS). THOC6 is critical for mammalian Transcription Export complex (TREX) tetramer formation, which is composed of four six-subunit THO monomers. The TREX tetramer facilitates mammalian RNA processing, in addition to the nuclear mRNA export functions of the TREX dimer conserved through yeast. Human and mouse TIDS model systems revealed novel THOC6-dependent, species-specific TREX tetramer functions. Germline biallelic Thoc6 loss-of-function (LOF) variants result in mouse embryonic lethality. Biallelic THOC6 LOF variants reduce the binding affinity of ALYREF to THOC5 without affecting the protein expression of TREX members, implicating impaired TREX tetramer formation. Defects in RNA nuclear export functions were not detected in biallelic THOC6 LOF human neural cells. Instead, mis-splicing was detected in human and mouse neural tissue, revealing novel THOC6-mediated TREX coordination of mRNA processing. We demonstrate that THOC6 is required for key signaling pathways known to regulate the transition from proliferative to neurogenic divisions during human corticogenesis. Together, these findings implicate altered RNA processing in the developmental biology of TIDS neuropathology

Proceedings of the International Conference on Frontiers in Desalination, Energy, Environment and Material Sciences for Sustainable Development

This proceeding contains articles on the various ideas of the academic community presented at the International Conference on Frontiers in Desalination, Energy, Environment and Material Sciences for Sustainable Development (FEEMSSD-2023) & Annual Congress of InDA (InDACON-2023) jointly organized by the Madan Mohan Malaviya University of Technology Gorakhpur, KIPM-College of Engineering and Technology Gida Gorakhpur, and Indian Desalination Association, India on 16th-17th March 2023.  FEEMSSD-2023 & InDACON-2023 focuses on addressing issues and concerns related to sustainability in all domains of Energy, Environment, Desalination, and Material Science and attempts to present the research and innovative outputs in a global platform. The conference aims to bring together leading academicians, researchers, technocrats, practitioners, and students to exchange and share their experiences and research outputs in Energy, Environment, Desalination, and Material Science.  Conference Title: International Conference on Frontiers in Desalination, Energy, Environment and Material Sciences for Sustainable Development & Annual Congress of InDAConference Acronyms: FEEMSSD-2023 & InDACON-2023Conference Date: 16th-17th March 2023Conference Location: Madan Mohan Malaviya University of Technology, GorakhpurConference Organizers: Madan Mohan Malaviya University of Technology Gorakhpur, KIPM-College of Engineering and Technology Gida Gorakhpur, and Indian Desalination Association, Indi