ABSTRACT
Background The diameter of coronary arteries serves as a potential predictor of coronary artery diseases (CADs) that can lead to sudden death. Factors such as gender, age, and coronary artery dominance play a role in influencing the size of normal coronary arteries. The outcome of coronary interventions, to a certain extent, depends on luminal size. Given the considerable variability in luminal size within the normal population, establishing the baseline size of normal coronary arteries in a specific population can aid in estimating the severity of coronary disease and predicting the outcome of interventional procedures. The current study focuses on estimating the luminal diameter of normal coronary arteries within the context of age, gender, and cardiac dominance in the South Indian population. Methods A retrospective study was conducted utilizing coronary angiograms with normal findings from 453 patients, comprising 257 males and 196 females, with a mean age of 54.66±10.66 years. These patients attended the outpatient service of the Cardiology Department at Amrita Institute of Medical Sciences, Kochi, a quaternary care center, between 2015 and 2017. The luminal diameter of coronary arteries is represented as mean±SD in millimeters. Results In the present study, we noted that the largest coronary artery was the left main coronary artery (LMCA, 3.59±0.58 mm), followed by the left anterior descending artery (LAD, 3.50±0.52 mm), the left circumflex artery (LCX, 3.31±0.57 mm), and the right coronary artery (RCA, 3.18±0.57 mm). We further broke down the statistics to evolve a gender pattern. In the raw comparison of data, the luminal size of coronary arteries in males was greater than in females, and statistical significance was noted in all except LAD. In males, the largest coronary artery was LMCA (3.70±0.60 mm), followed by LAD (3.54±0.48 mm), LCX (3.36±0.58 mm), and RCA (3.25±0.62 mm). In females, no significant size difference was observed between LMCA (3.45±0.53 mm) and LAD (3.46±0.55 mm). Females exhibited an increase in the size of LMCA with advancing age. Regardless of right or left cardiac dominance, LMCA was consistently larger than RCA in both genders. However, in cases of co-dominance, only males demonstrated significantly larger LMCA. Conclusion Precise knowledge of the size of normal coronary arteries and their influence by gender, age, and dominance can be crucial for the comprehensive evaluation of CADs and the success of interventional procedures.
ABSTRACT
We evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8-C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL). Different analogs of CA with C8 linear chain, but not higher, along with a carboxyl/ester group showed a similar anti-leishmanial effect. Ergosterol depletion was the major cause of CA-mediated cell death. Molecular docking and molecular dynamic simulation studies indicated the enzyme mevalonate kinase (MevK) of the ergosterol biosynthesis pathway as a possible target of CA. Enzyme assays with purified recombinant MevK and CA/CA analogs confirmed the target with a competitive inhibition pattern. Using biochemical and biophysical studies; strong binding interaction between MevK and CA/CA analogs was established. Further, using parasites with overexpressed MevK and proteomics studies of CA-treated parasites the direct role of MevK as the target was validated. We established the mechanism of the antileishmanial effect of CA, a natural product, against VL where toxicity and drug resistance with current chemotherapeutics demand an alternative. This is the first report on the identification of an enzymatic target with kinetic parameters and mechanistic insights against any organism for a natural medium-chain FA.
Subject(s)
Antiprotozoal Agents , Biological Products , Leishmania donovani , Leishmaniasis, Visceral , Antiprotozoal Agents/therapeutic use , Biological Products/pharmacology , Caprylates/pharmacology , Ergosterol/metabolism , Esters/pharmacology , Fatty Acids/metabolism , Humans , Leishmaniasis, Visceral/parasitology , Molecular Docking Simulation , Phosphotransferases (Alcohol Group Acceptor)ABSTRACT
OBJECTIVE: Despite the significant advancement in the understanding of the pathophysiology of systemic lupus erythematosus (SLE) variable clinical response to newer therapies remain a major concern, especially for patients with lupus nephritis and neuropsychiatric systemic lupus erythematosus (NPSLE). We performed this study with an objective to comprehensively characterize Indian SLE patients with renal and neuropsychiatric manifestation with respect to their gene signature, cytokine profile and immune cell phenotypes. METHODS: We characterized 68 Indian SLE subjects with diverse clinical profiles and disease activity and tried to identify differentially expressed genes and enriched pathways. To understand the temporal profile, same patients were followed at 6 and 12-months intervals. Additionally, auto-antibody profile, levels of various chemokines, cytokines and the proportion of different immune cells and their activation status were captured in these subjects. RESULTS: Multiple IFN-related pathways were enriched with significant increase in IFN-I gene signature in SLE patients as compared to normal healthy volunteers (NHV). We identified two transcriptionally distinct clusters within the same cohort of SLE patients with differential immune cell activation status, auto-antibody as well as plasma chemokines and cytokines profile. CONCLUSIONS: Identification of two distinct clusters of patients based on IFN-I signature provided new insights into the heterogeneity of underlying disease pathogenesis of Indian SLE cohort. Importantly, patient within those clusters retain their distinct expression dynamics of IFN-I signature over the time course of one year despite change in disease activity. This study will guide clinicians and researchers while designing future clinical trials on Indian SLE cohort.
Subject(s)
Interferon Type I/genetics , Lupus Erythematosus, Systemic/metabolism , Lupus Nephritis/immunology , Lupus Vasculitis, Central Nervous System/immunology , Adult , Autoantibodies/immunology , Case-Control Studies , Cohort Studies , Cytokines/blood , Female , Follow-Up Studies , Gene Expression , Humans , India/epidemiology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/physiopathology , Lupus Nephritis/metabolism , Lupus Vasculitis, Central Nervous System/metabolism , Male , Microarray Analysis/methods , Severity of Illness IndexABSTRACT
Expeditious evolution of antimicrobial resistance in recent years has been identified as a growing concern by various health organizations around the world. Herein, facile and environmentally benign production of highly antibacterial carbonaceous nanomaterials from Colocasia esculenta and Nelumbo nucifera leaves is reported. After carbonization and oxidative treatment, smaller graphene domains are formed in Colocasia esculenta derivatives, whereas larger sheetlike structures are observed in the case of Nelumbo nucifera. Smaller particle size makes quantum confinement effects more prominent, as is evident in fine-tuning of the photoluminescence emission after each stage of treatment. The influence of precursor materials on the antibacterial properties of the nanosystems is also demonstrated. When microbiocidal activity was tested against model bacteria Pseudomonas aeruginosa, the nanocomposite derived from Colocasia esculenta leaves showed higher activity than the antibiotic drug clarithromycin (control) with a measured zone of inhibition of 40±0.5â mm. This is one of the highest values reported in comparison with plant-based carbon-silver nanosystems. Quantitative analysis revealed that the nanocomposite obtained from Colocasia esculenta leaves has antimicrobial efficacy equivalent to those of commercial antibiotic drugs and is able to eradicate bacteria at much lower concentrations than that obtained from Nelumbo nucifera leaves.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Colocasia/chemistry , Nelumbo/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Anti-Bacterial Agents/analysis , Graphite , Nanostructures , Oxidation-Reduction , Tin CompoundsABSTRACT
Antibacterial screening of graphene-tin oxide nanocomposites synthesized from carbonized wood and coconut shell is investigated against Pseudomonas aeruginosa for the first time. Efficient and facile one step hydrothermal process adopted in the present work for the synthesis of graphene-tin oxide nanoparticles provides an ideal method for the economic large-scale production of the same. Graphene-tin oxide nanocomposites derived from wood charcoal possess a spherical morphology whereas rod like structures are seen in the case of coconut shell derivatives. An excitation independent fluorescence response is observed in graphene-tin oxide nanohybrids while graphene oxide nanostructures exhibited an excitation dependent behavior. These hydrophilic nanostructures are highly stable and exhibited no sign of luminescence quenching or particle aggregation even after a storage of 30 months. Bactericidal effects of the nanostructures obtained from coconut shell is found to be relatively higher compared to those procured from wood. This variation in antibacterial performance of the samples is directly related to their morphological difference which in turn is heavily influenced by the precursor material used. MIC assay revealed that coconut shell derived graphene-tin oxide composite is able to inhibit the bacterial growth at a lower concentration (250 µg/mL) than the other nanostructures. Nanocomposites synthesized from agro-waste displayed significantly higher antimicrobial activity compared to the precursor and graphene oxide nanostructures thereby making them excellent candidates for various bactericidal applications such as disinfectants, sanitary agents etc.