Determinants of Poison-related Mortality in Tertiary Care Hospital, South India.

Aims and background: Acute poisoning is one of the most common emergencies in India and around the world. Understanding the factors associated with mortality can aid us in devising appropriate preventive strategies to curtail deaths due to poisoning. Purpose of this study is to find various factors that determine the mortality among acute poisoning cases admitted in a tertiary care center. Materials and methods: A retrospective hospital records-based study was conducted at Chengalpattu Medical College Hospital. The study included 2,123 cases of various poisoning cases admitted for a year from January to December 2022. Cases of bites, stings, drowning, and hanging were excluded. Information on sociodemographic profile, type of poison, time since ingestion and admission, and treatment outcome were collected using a structured pro forma. Results: The mean age of the study population was 29.90 ± 14.98 years. Poisoning was found to be predominantly among males (56.42%) and residents of rural areas (58%). Insecticide consumption (27.0%) was the most common modality, followed by oleander poisoning (20%), corrosive poison (17%), rat poison (15%), tablet poison (13%), and other poisons. The overall case fatality rate (CFR) was 5.2%, with the highest CFR of 12.25% with insecticide poisoning. In multivariate analysis, Glasgow coma scale (GCS) score at admission is the only parameter showing a statistically significant association with mortality (adjusted odds-ratio 0.271(0.2-0.38, p-value < 0.01). Conclusion: Acute poisoning primarily affects the young and economically productive population. In the south Indian population, pesticides are still the major contributor though corrosives are a major contributor among children. Mortality is still significant, and GCS status admission is the only predictor of mortality. How to cite this article: Krishnasamy N, Narmadhalakshmi R, Parameshwari P, Jayalakshmi R, Lokesh R, Jayanthi R, et al. Determinants of Poison-related Mortality in Tertiary Care Hospital, South India. Indian J Crit Care Med 2024;28(4):329-335.

Synergistic effect of metformin and vemurufenib (PLX4032) as a molecular targeted therapy in anaplastic thyroid cancer: an in vitro study.

BACKGROUND: Survival rate of patients affected with anaplastic thyroid carcinoma (ATC) is less than 5% with current treatment. In ATC, BRAFV600E mutation is the major mutation that results in the transformation of normal cells in to an undifferentiated cancer cells via aberrant molecular signaling mechanisms. Although vemurufenib is a selective oral drug for the BRAFV600E mutant kinase with a response rate of nearly 50% in metastatic melanoma, our study has showed resistance to this drug in ATC. Hence the rationale of the study is to explore combinational therapeutic effect to improve the efficacy of vemurafenib along with metformin. Metformin, a diabetic drug is an AMPK activator and has recently proved to be involved in preventing or treating several types of cancer. METHODS AND RESULTS: Using iGEMDock software, a protein-ligand interaction was successful between Metformin and TSHR (receptor present in the thyroid follicular cells). Our study demonstrates that combination of vemurufenib with metformin has synergistic anti-cancer effects which was evaluated through MTT assay (cytotoxicity), colony formation assay (antiproliferation evaluation) and suppressed the progression of ATC cells growth by inducing significant apoptosis, proven by Annexin V-FITC assay (Early Apoptosis Detection). Downregulation of ERK signaling, upregulation of AMPK pathway and precision in epithelial-mesenchymal transition (EMT) pathway which were assessed by RT-PCR and Western blot provide the evidence that the combination of drugs involved in the precision of altered molecular signaling Further our results suggest that Metformin act as a demethylating agent in anaplastic thyroid cancer cells by inducing the expression of NIS and TSHR. Our study for the first time explored cAMP signaling in ATC wherein cAMP signaling is downregulated due to decrease in intracellular cAMP level upon metformin treatment. CONCLUSION: To conclude, our findings demonstrate novel therapeutic targets and treatment strategies for undifferentiated ATC.

Functional characterization of intracellular Dictyostelium discoideum P2X receptors.

Indicative of cell surface P2X ion channel activation, extracellular ATP evokes a rapid and transient calcium influx in the model eukaryote Dictyostelium discoideum. Five P2X-like proteins (dP2XA-E) are present in this organism. However, their roles in purinergic signaling are unclear, because dP2XA proved to have an intracellular localization on the contractile vacuole where it is thought to be required for osmoregulation. To determine functional properties of the remaining four dP2X-like proteins and to assess their cellular roles, we recorded membrane currents from expressed cloned receptors and generated a quintuple knock-out Dictyostelium strain devoid of dP2X receptors. ATP evoked inward currents at dP2XB and dP2XE receptors but not at dP2XC or dP2XD. beta,gamma-Imido-ATP was more potent than ATP at dP2XB but a weak partial agonist at dP2XE. Currents in dP2XB and dP2XE were strongly inhibited by Na(+) but insensitive to copper and the P2 receptor antagonists pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid and suramin. Unusual for P2X channels, dP2XA and dP2XB were also Cl(-)-permeable. The extracellular purinergic response to ATP persisted in p2xA/B/C/D/E quintuple knock-out Dictyostelium demonstrating that dP2X channels are not responsible. dP2XB, -C, -D, and -E were found to be intracellularly localized to the contractile vacuole with the ligand binding domain facing the lumen. However, quintuple p2xA/B/C/D/E null cells were still capable of regulating cell volume in water demonstrating that, contrary to previous findings, dP2X receptors are not required for osmoregulation. Responses to the calmodulin antagonist calmidazolium, however, were reduced in p2xA/B/C/D/E null cells suggesting that dP2X receptors play a role in intracellular calcium signaling.

Preparation of Celery Essential Oil-Based Nanoemulsion by Ultrasonication and Evaluation of Its Potential Anticancer and Antibacterial Activity.

INTRODUCTION: Plants have always been a significant source of natural active components with biological properties. Celery seed oil (extracted from Apium graveolens) has several potential applications, but its therapeutic uses in the form of nanoemulsion formulation need to be investigated further in order to meet the demand in cancer treatment, and to alleviate the prevailing crisis arising from increased antimicrobial resistance. METHODS: The therapeutic potential of celery seed oil was investigated through the formulation and testing of a nanoemulsion developed with Tween 80 (a non-ionic surfactant) and the utilization of an ultrasonication technique. Anticancer and apoptotic properties of the formulation were evaluated through MTT and Annexin V-FITC assays. The clonogenic assay aided in the identification of the antiproliferative properties of the formulation on oral squamous cell carcinoma. The antimicrobial study was supported by agar well diffusion assay, membrane integrity test and scanning electron microscopy. RESULTS: Experiments identified relevant parameters, including optimal surfactant concentration and emulsification time. GC-MS analysis identified various components in the celery oil, but not their biological activities. A sonication time of 20 min resulted in a droplet diameter of 23.4 ± 1.80 nm. The IC50 concentration of the optimal nanoemulsion formulation against SAS cells was 1.4 µL/mL. At this concentration, cell proliferation was significantly reduced through inhibition of the anchorage-independent cell growth by disrupting colony formation and inducing cell death (apoptosis) of cancer cells. The nanoemulsion was also treated with a microbial suspension of S. aureus, and displayed antibacterial properties through lipid membrane fusion, causing cytoplasmic leakage as verified through agar well diffusion and membrane permeability assays. Scanning electron microscopy revealed complete distortion of the bacterial pathogen. CONCLUSION: The results in this study present celery as a possible constituent for cancer therapeutics and as a candidate for aggressive, yet safe cancer treatment. The celery-based nanoemulsion has the potential to act as a key alternative to standard antibiotic therapy.

Ultrasonic Nanoemulsification of Cuminum cyminum Essential Oil and Its Applications in Medicine.

BACKGROUND AND STUDY: Cumin seed oil (extracted from Cuminum cyminum) has many applications but conclusive evidence of its therapeutic uses has not been presented. This study has explored the anticancer and antibacterial properties of the seed oil. METHODS: The cumin nanoemulsion was prepared with Tween 80 non-ionic surfactant employing ultra-sonication technology. The anticancer activity of the nanoscale-based emulsion was evaluated through cell viability (MTT), antiproliferation evaluation through clonogenic assay, and apoptosis through Annexin V-FITC assay. Agar well diffusion was used to study the antimicrobial activity, and this was supported by membrane integrity analysis. RESULTS: A thorough study of process parameters, aimed at obtaining the optimal surface concentration and emulsification time, was completed. GC-MS data indicated cumaldehyde as a major component. The resultant droplet diameter after a sonication time of 5 min was 10.4 ± 0.5 nm. MTT assay revealed the IC50 value at 1.5 µL/mL and the early induction of apoptosis was evident. Tongue carcinoma cell line treated with cumin nanoemulsion presented a diminished colony formation. The nanoemulsion exhibited significant antibacterial activity against S. aureus. A significant cytoplasmic leakage was observed on treatment with cumin nanoemulsion. The consequences of the analysis projected cumin as a potential component for cancer therapy. CONCLUSION: This study provides definitive evidence for cumin essential oil nanoemulsion as a legitimate plant-based medicine that can bypass the drawbacks of the present aggressive treatment of cancer, can overcome the antimicrobial resistance, and can also meet all prerequisites.

A novel reporter system for cyclic AMP mediated gene expression in mammalian cells based on synthetic transgene expression system.

Cyclic AMP (cAMP) is an important second messenger that mediates various biological functions in both prokaryotes and eukaryotes. Due to the ever increasing significance in studying the function and modulation of cAMP-based signaling, it is important to develop a protein-based biosensor that reports the cAMP mediated gene expression. Based on a synthetic transgene approach, an artificial mammalian transactivator was developed by fusing a transcriptional regulatory element cAMP receptor protein (CRP) of Escherichia coli to the VP16 transactivation domain of Herpes simplex virus in a mammalian expression vector (pLA1) that activates CRP specific operator site present in a chimeric promoter (OCRP- PhCMVmin- Luciferase) in a concentration dependent manner in mammalian cells. Our results reveal that the engineered transactivator report the gene expression mediated by cAMP directly in mammalian cells and this cAMP reporter system works irrespective of Protein kinase A (PKA) - cyclic AMP response element binding protein (CREB) - cyclic AMP response element (CRE) signaling since the luciferase activity mediated by synthetic gene construct is seen even in the presence of PKA inhibitor H-89 (derived from H-8 (N-[2-(methylamino) ethyl]-5-isoquinoline-sulfonamide). Furthermore this synthetic transcription factor plays a significant role in reporting and mediating cAMP signaling in tumorigenic cells which possess an aberrant cAMP signaling due to PKA and CREB mutations.

Anticancer and antibacterial effects of a clove bud essential oil-based nanoscale emulsion system.

BACKGROUND AND PURPOSE: The essential oil derived from clove buds (Syzygium aromaticum) has been used as a chemopreventive agent in Ayurvedic medicine. The antiviral, antibacterial, and anticancer properties of its chemo-skeleton have motivated this study to explore its efficacy in pharmaceutics. METHODS: Nanoscale-based emulsions were prepared by employing a spontaneous emulsification technique through self-assembly using varying concentrations of Tween 20 and Tween 80 surfactants. Their physicochemical properties and stability were studied in order to choose an optimum formulation which was clear and stable. The cytotoxicity of the stable oil-based emulsion system was evaluated using MTT assay, colony formation assay, and Annexin V-FITC assay against the thyroid cancer cell line (HTh-7). RESULTS: All three methods verified apoptosis and reduction in cancer cell proliferation, making the formulation a promising candidate as an alternative cancer drug. The oil-based emulsion system was also tested for its antibacterial properties against Staphylococcus aureus. Membrane permeability studies proved its efficacy to permeate through cell membrane, thereby increasing the leakage of cytoplasmic contents. CONCLUSION: Many current treatments for cancers are aggressive yet ineffective. This study positions the clove bud-based nanoscale emulsion as a suitable candidate for further in vivo studies and trials as a cancer drug.