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1.
Prostaglandins Other Lipid Mediat ; 156: 106582, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34273491

RESUMEN

Millions of people are affected by neurodegenerative diseases worldwide. They occur due to the loss of brain functions or peripheral nervous system dysfunction. If untreated, prolonged condition ultimately leads to death. Mostly they are associated with stress, altered cholesterol metabolism, inflammation and organelle dysfunction. Endogenous cholesterol and phospholipids in brain undergo auto-oxidation by enzymatic as well as non-enzymatic modes leading to the formation of by-products such as 4-hydroxynonenal and oxysterols. Among various oxysterols, 7-ketocholesterol (7KCh) is one of the major toxic components involved in altering neuronal lipid metabolism, contributing to inflammation and nerve cell damage. More evidently 7KCh is proven to induce oxidative stress and affects membrane permeability. Loss in mitochondrial membrane potential affects metabolism of cell organelles such as lysosomes and peroxisomes which are involved in lipid and protein homeostasis. This in turn could affect amyloidogenesis, tau protein phosphorylation and accumulation in pathological conditions of neurodegenerative diseases. Lipid alterations and the consequent pathogenic protein accumulation, results in the damage of cell organelles and microglial cells. This could be a reason behind disease progression and predominantly reported characteristics of neurodegenerative disorders such as Alzheimer's disease. This review focuses on the role of 7KCh mediated neurodegenerative Alzheimer's disease with emphasis on alterations in the lipid raft microdomain. In addition, current trends in the significant therapies related to 7KCh inhibition are highlighted.


Asunto(s)
Enfermedad de Alzheimer
2.
Diabetes Obes Metab ; 21(6): 1419-1428, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30768824

RESUMEN

AIMS: To study the association of body mass index (BMI) and insulin use with type 2 diabetes-related healthcare expenditures (T2D-HE). MATERIALS AND METHODS: Retrospective study using de-identified electronic health records linked to insurance claims data. Study included a prevalence-based sample of overweight or obese patients with antihyperglycaemic-treated T2D. Patients had ≥1 A1c measurement in 2014 (last observed = index A1c), ≥1 BMI measurement within ±90 days of index (average BMI = baseline BMI), and continuous enrolment for 180 days before (baseline) through 395 days after index (day 30-395 = follow-up). BMI was categorized as: 25 to 29.9 kg/m2 = overweight; 30 to 34.9 kg/m2 = obese class I (OCI); 35 to 39.9 kg/m2 = OCII; ≥40 kg/m2 = OCIII. Multivariable regressions were used to examine one-year follow-up T2D-HE as a function of BMI, insulin use, an interaction term between BMI and insulin use, and patient demographics. RESULTS: Study included 13 026 patients (mean age = 63.6 years; 48.1% female; 29.5% overweight, 31.6% OCI, 20.3% OCII, 18.6% OCIII; 25.3% insulin users). Baseline insulin use rates monotonically ranged from 19.7% in overweight patients to 33.0% in OCIII patients (P < 0.001). Together, BMI and insulin use were jointly associated with one-year follow-up T2D-HE, which monotonically ranged from $5842 in overweight patients with no insulin to $17 700 OCIII insulin users, P < 0.001. Within each BMI category, insulin users' one-year T2D-HE was at least double that of non-users. Additional analyses of all-cause healthcare expenditures yielded consistent results. CONCLUSIONS: BMI and insulin use represent simple stratifiers for identifying high-cost patients. OCIII insulin users incurred the greatest annual healthcare expenditures; these patients may be an ideal group for targeted interventions.


Asunto(s)
Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Insulina , Adolescente , Adulto , Anciano , Peso Corporal , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/economía , Diabetes Mellitus Tipo 2/epidemiología , Registros Electrónicos de Salud , Femenino , Costos de la Atención en Salud/estadística & datos numéricos , Humanos , Hipoglucemiantes/economía , Hipoglucemiantes/uso terapéutico , Insulina/economía , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
3.
Int J Clin Pract ; 73(6): e13338, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30829429

RESUMEN

BACKGROUND: Moderate to severe pain is common despite the use of potent opioids during craniotomies. Non-opioid agents such as dexmedetomidine reduce undesirable opioid effects and are successfully used as primary analgesic during bariatric surgeries. This study assessed the feasibility of conducting a large randomised controlled trial comparing fentanyl with dexmedetomidine for perioperative analgesia during craniotomy. METHODS: This was a prospective single-centre randomised controlled feasibility trial. Twenty-four consenting adult patients undergoing supratentorial craniotomy at NIMHANS, Bangalore, India, were recruited after ethical approval in March and April 2018. They received either fentanyl 1 µg kg-1  h-1 (n = 12) or dexmedetomidine 0.5  µg kg-1  h-1 (n = 12) as primary intraoperative analgesic drug. Patient, anaesthesiologist, outcome assessor and data analyst were blinded to the study intervention. Our feasibility outcomes (primary) were recruitment and adherence rates. We also explored the potential efficacy of intervention and adverse events. RESULTS: We recruited 24 out of 30 eligible patients and had 100% protocol adherence, thereby demonstrating the feasibility of a larger randomised controlled trial. All 24 patients completed the study. The demographic and clinical parameters were similar between the groups. Compared between fentanyl and dexmedetomidine, there was no difference in the intraoperative fentanyl (top-up) consumption (µg), expressed as median and interquartile range: 25 (0-50) and 0 (0-50); P = 0.844; and no difference in postoperative pain at 15 and 60 minutes. Adverse events were few and similar with fentanyl and dexmedetomidine. CONCLUSIONS: A large-scale randomised controlled trial of perioperative dexmedetomidine versus fentanyl is feasible. Dexmedetomidine has the potential to be non-inferior to fentanyl for perioperative analgesia during craniotomies.


Asunto(s)
Analgésicos no Narcóticos/uso terapéutico , Craneotomía , Dexmedetomidina/uso terapéutico , Fentanilo/uso terapéutico , Cuidados Intraoperatorios/métodos , Dolor Postoperatorio/prevención & control , Adulto , Método Doble Ciego , Esquema de Medicación , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Resultado del Tratamiento
4.
Indian J Anaesth ; 68(4): 380-386, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38586253

RESUMEN

Background and Aims: The autonomic nervous system (ANS) is cardinal for systemic homeostasis. Autonomic dysfunction is prevalent in as high as 65% of patients presenting for cardiac surgery in the Indian scenario. Pre-existing cardiac autonomic dysfunction (CAD) in surgical patients can accentuate perioperative haemodynamic fluctuations during stressful intraoperative events, predispose to adverse cardiac events, and contribute to morbidity and mortality. The prevalence and predictors of CAD in the elective neurosurgical population are unknown in the Indian scenario. The current study was conducted to bridge this knowledge gap. Methods: In this single-centre prospective observational study conducted at a tertiary care neurosciences centre, among 400 consenting adult patients of either gender, between 18 and 80 years of age, undergoing elective neurosurgery, the preoperative ANS function at the bedside was assessed as the primary outcome measure. The ANS status was evaluated using ANSiscope™-derived indices of heart rate variability. The diagnosis of CAD was made when the ANS index exceeded a threshold of 13.5. Data regarding predictors of CAD were collected from patient records as the secondary outcome measure. Statistical analysis was done using the R software. A P-value of <0.05 was considered statistically significant. Results: The prevalence of preoperative CAD in our study population was 79.7% (319/400 patients). None of the demographic and baseline clinical characteristics we studied predicted CAD in our study. Conclusion: We observed a significant prevalence of preoperative CAD among elective neurosurgical patients. None of the parameters we evaluated predicted CAD in our study.

5.
J Neurosci Rural Pract ; 15(1): 29-33, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476436

RESUMEN

Objectives: Pediatric neurosurgeries carry a considerable risk of intraoperative bleeding and, subsequently, anemia in the post-operative period. Postoperative anemia is often multifactorial with several factors contributing to its occurrence. The present study aims to quantify the incidence of postoperative anemia, identify potential risk factors, and assess the impact of post-operative anemia on clinical outcomes in the pediatric neurosurgery population. Materials and Methods: This was a single-center and retrospective cohort study which included children <18 years of age undergoing elective neurosurgery. The data were extracted from the electronic and physical patient health records. Post-operative anemia was defined for this study as a hemoglobin value below 10 g/dL at any time up to 3 days after surgery. Results: A total of 300 children were recruited during the study period. The incidence of post-operative anemia after elective pediatric neurosurgery was 21.33%. Children in the post-operative anemia group were younger (P = 0.004), had lower pre-operative hemoglobin values (P < 0.001), belonged to higher American Society of Anesthesiologists (ASA) physical status (P = 0.023), underwent predominantly supratentorial (P = 0.041) and non-tumor surgeries (0.004), and received lesser intraoperative blood transfusion (P = 0.010) compared to no post-operative anemia group. The factors that remained predictive of post-operative anemia on multivariate analysis were ASA physical status (P = 0.018, odds ratio [OR] = 1.94, 95% confidence interval [CI] of 1.12-3.36), pre-operative hemoglobin (P < 0.001, OR = 0.64, 95% CI of 0.50-0.82), and intraoperative transfusion (P = 0.028, OR = 0.45, 95% CI of 0.22-0.92). Conclusion: Optimization of modifiable risk factors is essential to reduce the occurrence of post-operative anemia and improve outcomes in pediatric neurosurgical patients.

6.
Prep Biochem Biotechnol ; 43(1): 95-107, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23215657

RESUMEN

A serine protease was purified 6.9-fold from the leaves of Thespesia populnea using ammonium sulfate fractionation followed by CM-cellulose and Sephadex G-100 chromatography. The purified enzyme was named populnein and was characterized. It was made up of a single polypeptide, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) analysis showed that the enzyme had a molecular mass of 14,518 Da. Inhibition of enzyme activity by phenyl methane sulfonyl fluoride indicates that populnein belongs to the class of serine proteases. The enzyme had appreciable pH and temperature stability. The activity of the enzyme was optimal at pH 8.0 and temperature 40°C. The enzyme was thermostable and retained 85% of its activity at 70°C after 1 hr. The enzyme was also resistant to autodigestion. The stabilization of the membrane of red blood cells exhibited by the protease populnein was found to be higher than for diclofenac. More studies are necessary to investigate the biological activity and applications of serine protease of T. populnea.


Asunto(s)
Malvaceae/química , Hojas de la Planta/química , Proteínas de Plantas/química , Serina Proteasas/química , Sulfato de Amonio , Fraccionamiento Químico , Cromatografía en Gel , Detergentes , Pruebas de Enzimas , Concentración de Iones de Hidrógeno , Cinética , Malvaceae/enzimología , Peso Molecular , Hojas de la Planta/enzimología , Proteínas de Plantas/aislamiento & purificación , Serina Proteasas/aislamiento & purificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Especificidad por Sustrato , Temperatura
7.
J Biomol Struct Dyn ; 41(23): 13595-13604, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37010992

RESUMEN

HDAC protein is associated with hepatocellular carcinoma. Different medicinal plants were selected for this study to analyze the inhibitory efficacy against the target protein, HDAC. Using virtual screening, we filtered out the best compounds, and molecular docking (XP) was carried out for the top compounds which filtered out. The molecular docking results showed that the title compound (2-methoxy-4-prop-2-enylphenyl) N-(2-methoxy-4-nitrophenyl) carbamate (MEMNC) has the highest docking score of about -7.7 kcal/mol against the targeted protein histone deacetylase (HDAC) compared with the other selected phytocompounds. From the molecular dynamics analysis, the RMSD and RMSF plots depicted the overall stability of the protein-ligand complex. Toxicity properties show the acceptable range of various kinds of toxicity that were predicted using the ProTox-II server. In addition, DFT quantum chemical and physicochemical properties of the MEMNC molecule were reported. Initially, the molecular structure of the MEMNC molecule was optimized and harmonic vibrational frequencies were calculated using DFT/B3LYP method with a cc-pVTZ basis set using Gaussian 09 program. The calculated vibrational wavenumber values were assigned based on Potential Energy Distribution calculations using the VEDA 4.0 program and correlated well with the previous literature values. The molecule has bioactivity as a result of intramolecular charge transfer interactions, as demonstrated by frontier molecular orbital analysis. Molecular electrostatic potential surface and Mulliken atomic charge distribution analyses validate the reactive sites of the molecule. Thus, the title compound can be used as a potential inhibitor of HDAC protein, which paves the way for designing novel drugs to treat Hepatocellular carcinoma.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Carcinoma Hepatocelular/tratamiento farmacológico , Carbamatos/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Neoplasias Hepáticas/tratamiento farmacológico , Teoría Cuántica , Espectrometría Raman
8.
Front Mol Biosci ; 10: 1124563, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36845553

RESUMEN

Introduction: Non-Small Cell Lung Cancer is the most prevalent type of cancer in lung cancer. Chemotherapy, radiation therapy, and other conventional cancer treatments have a low success rate. Thus, creating new medications is essential to halt the spread of lung cancer. Methods: In this study bioactive nature of lochnericine against Non-Small Cell Lung Cancer (NSCLC) was analyzed using various computational approaches such as quantum chemical calculations, molecular docking, and molecular dynamic simulation. Furthermore, the MTT assay shows the anti-proliferation activity of lochnericine. Results and Discussion: Using Frontier Molecular Orbital (FMO), the calculated band gap energy value associated with bioactive compounds and the molecule's potential bioactivity is confirmed. The H38 hydrogen atom and O1 oxygen atom in the molecule are effectively electrophilic, and potential nucleophilic attack sites were confirmed through analysis of the Molecular electrostatic potential surface. Furthermore, the electrons within the molecule were delocalized, which confers bioactivity on the title molecule and was authorized through Mulliken atomic charge distribution analysis. A molecular docking study revealed that lochnericine inhibits non-small cell lung cancer-associated targeted protein. The lead molecule and targeted protein complex were stable during molecular dynamics simulation studies till the simulation period. Further, lochnericine demonstrated remarkable anti-proliferative and apoptotic features against A549 lung cancer cells. The current investigation powerfully suggests that lochnericine is a potential candidate for lung cancer.

9.
Int J Biol Macromol ; 238: 124120, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-36963549

RESUMEN

Supply of safe drinking water is a high-risk challenge faced internationally. Hybrid technologies involving nanomaterials can offer possible solutions to this research involving natural biopolymers. Porous chitosan with a high specific surface area has promising properties but its use as a membrane component in water purification is still rarely reported. Graphitic carbon nitride (g-C3N4) is a carbon nitride allotrope with a graphene-like layered structure that gifts unfamiliar physicochemical properties due to the presence of s-triazine fragments. It is a metal-free semiconductor with a band gap of ∼2.7 eV to ∼3.7 eV; which shows better visible light-activated photocatalyst properties. This work aims at synthesizing graphitic carbon nitride-biopolymer composite and exploring its properties in the field of wastewater treatment. The samples were synthesized via a soft chemical process with urea, as the source material. The flake-like morphology is displayed in the microstructural SEM image. The composition of the material was analyzed using EDS. Thermogram shows that the material is stable up to 500 °C and also confirms the formation of graphitic carbon nitride. In XRD spectra the intensity reduction shows the chitosan inclusion at the nitride site. The band gap of the prepared material was identified to be 2.3, 2.4 eV. The structural properties were analyzed using Fourier Transform Infrared Spectrometer and Raman spectroscopy. FTIR spectra and Raman spectra indicate the stretching vibration modes of CN and CN heterocycles and chitosan inclusion in the carbon nitride network. The photocatalytic activity was done in sunlight and a UV lamp with different dyes for doped and undoped g-C3N4. The doped (Porous/Non-porous chitosan) g-C3N4 showed faster dye degradation in sunlight compared to UV light. A biomolecular interaction study was done using Bovine serum albumin. It shows the material interaction with the BSA protein. The anti-microbial activity was performed on the Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli by disk diffusion method, the chitosan doped g-C3N4 showed good inhibitions against bacterial growth. The current work reveals the impact of nanoscale chitosan nanostructures doped on the optical, microstructural, catalytic, and antimicrobial properties of g-C3N4 nanosheets. This work provides new research options for nanocomposite-based photocatalytic nanomaterial g-C3N4 so that the quality of contaminated water could be improved.


Asunto(s)
Antiinfecciosos , Quitosano , Grafito , Grafito/química , Catálisis
10.
J Family Med Prim Care ; 11(1): 113-117, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35309653

RESUMEN

Introduction: Diabetic neuropathy is a complication affecting almost 50% of the diabetic patients. Diabetic Peripheral Neuropathy (DPN) predominantly affects the hands and lower limbs. It leads to loss of protective sensation resulting in continuous injury to insensitive feet. The early detection of DPN using an objective screening test followed by its appropriate management is important as up to 50% of the patients may be asymptomatic. Objectives: To screen Diabetic patients attending an Urban Health and Training Centre of a medical college in Tamilnadu for Diabetic Peripheral Neuropathy. To assess the association between DPN and selected variables such as socio-demographic factors, glycaemic control, duration of diabetes, physical activity, body mass index, smoking and consumption of alcohol. Methods: The study was conducted among 204 diabetic patients attending an Urban Health and Training Centre. Participants were assessed using Michigan Neuropathy Screening Instrument (MNSI), which involves using a questionnaire followed by a physical examination. Results: Of the 204 patients, 58.8% were male. The mean age was 54.8 years (SD = 8.8 years). About 79.9% were employed of which 29.4% were skilled labourers. Mean duration of diabetes was 6.2 years (SD = 5.3 years). The proportion of diabetics who screened positive for Peripheral Neuropathy was 23% and 45.6% using MNSI questionnaire and examination, respectively. An age of 60 years and above was significantly associated with DPN (OR = 2.505, P value = 0.003). A duration of more than 4 years of diabetes was also significantly associated with DPN (OR = 1.872, P value = 0.02820). Conclusion: A high proportion of diabetics with peripheral neuropathy did not express symptoms specific for diabetics. Thus, a simple tool like MNSI would be useful in primary care settings to screen for peripheral neuropathy, and hence prevent disability".

11.
Asian J Anesthesiol ; 60(3)2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35791454

RESUMEN

Synchrony between basic neuroscience investigations and clinical research has been deficient for quite some time. Translational research includes several dimensions such as laboratory research, clinical demands, government policies, and availability of funds. Through translational research, techniques of neuroanesthesia have become precise and secure over time. Perioperative translational science and contemporary translational research are the two major dimensions of translational research in perioperative neurosciences. The knowledge gap in perioperative neuroscience can be filled with scientific and technological advances with a multidisciplinary approach. In this review, we will discuss various domains of translational research in perioperative neurosciences and have a glance into the translated clinical applications.


Asunto(s)
Neurociencias , Investigación Biomédica Traslacional , Humanos , Estudios Interdisciplinarios , Conocimiento , Neurociencias/métodos
12.
J Biomol Struct Dyn ; 40(24): 13997-14012, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34738880

RESUMEN

Hepatocellular carcinoma (HCC) is a pervasive type of liver malignant growth and the third-driving reason for disease-related overall mortality with an expanding pervasiveness worldwide. Besides, no successful treatment can be utilized on patients with the cutting-edge or metastatic illness. Some of the natural therapeutics are paved the way for developing potential inhibitors for many types of cancer. Ocimum basilicum is one of the most well-known herbs, which contains numerous therapeutic properties and is widely used for various health issues. This study focused on its valuable medicinal property against HCC via in silico approach. Bioactive constituents from O. basilicum is subjected to molecular docking and dynamics study for 100 ns against the HCC targets (FGFR1, FGFR2, FGFR3, and FGFR4), and the selected lead compounds showed better interactions, docking score, obeys Lipinski's rule of five, highest occupied molecular orbital, lowest unoccupied molecular orbital hypothesis, protein-complex stability throughout the simulation period and the pharmacophoric features were analysed. Out of selected seven compounds, Campesterol revealed its potential therapeutic activity (Docking score - FGFR1 - 8.59 Kcal/Mol, FGFR2 - 7.11 Kcal/Mol, FGFR3 - 10.53 Kcal/Mol and FGFR4 - 9.17 Kcal/Mol, respectively. And also, it maintains good stability with the targets without any fluctuations. So, we concluded our findings that Campesterol is considered as, such a promising and potential inhibitor for HCC.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ocimum basilicum , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Neoplasias Hepáticas/tratamiento farmacológico , Simulación de Dinámica Molecular
13.
SN Comput Sci ; 3(5): 399, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35911436

RESUMEN

At the point when the global pandemic hit, we saw one of the greatest monetary accidents in late history. With crashes in the securities exchange and irregularities in all business sectors and ventures, one thing that never appears to change is the increment in worth of homes. This pandemic had made the land area take a significant misfortune. The sentiment scores of the real estate partners had arrived at an unequalled low score of 31. The crash of the real estate put many companies and brokers into bankruptcy. People stopped investing in real estate while others withdrew any sort of the ongoing investments. The conditions worsened with the second wave. The second wave, unlike the first, had a significantly higher death rate and spread very quickly instilling fear in the minds of the people. This became a factor in the huge economic crash that this pandemic has provided. The government has been desperately looking for measures to come back stronger but have failed. This called for research into this domain and start predictions with various models to help prepare for any foreseeing losses/crashes. Within the past 10 years, the housing market has gotten more and more modest with houses that used to be affordable being valued at absurdly high amounts. This increase in value has seen a reduction in home proprietorship percentage in proportion to populace of the country. Our project aims to project values for real estate in the absence of covid. The difference in values are analyzed and generalized. Furthermore, solutions to improve the current condition will also be given.

14.
Comput Intell Neurosci ; 2022: 2213273, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35242176

RESUMEN

The emergence of powerful deep learning architectures has resulted in breakthrough innovations in several fields such as healthcare, precision farming, banking, education, and much more. Despite the advantages, there are limitations in deploying deep learning models in resource-constrained devices due to their huge memory size. This research work reports an innovative hybrid compression pipeline for compressing neural networks exploiting the untapped potential of z-score in weight pruning, followed by quantization using DBSCAN clustering and Huffman encoding. The proposed model has been experimented with state-of-the-art LeNet Deep Neural Network architectures using the standard MNIST and CIFAR datasets. Experimental results prove the compression performance of DeepCompNet by 26x without compromising the accuracy. The synergistic blend of the compression algorithms in the proposed model will ensure effortless deployment of neural networks leveraging DL applications in memory-constrained devices.


Asunto(s)
Compresión de Datos , Algoritmos , Análisis por Conglomerados , Compresión de Datos/métodos , Redes Neurales de la Computación
15.
J Genet Eng Biotechnol ; 20(1): 35, 2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35195803

RESUMEN

AIM: The aim of this investigation is to detect potential inhibitor for visceral leishmaniasis through computational analysis. BACKGROUND: Leishmaniasis is categorized as a vector born pathogenic infection prevalent in tropical, subtropical, and in Mediterranean zones spread by intra-macrophage protozoa. The clinical syndrome of leishmaniasis is divided into the following type's namely cutaneous leishmaniasis, mucocutaneous leishmaniasis, visceral leishmaniasis, and dermal leishmaniasis. Trypanothione synthetase is a key enzyme involving in glutathione biosynthesis as well as hydrolysis. Trypanothione is one of the promising drug targets for parasites. Parasites are inimitable with concern to their dependence on trypanothione to regulate intracellular thiol-redox balance in fighting against oxidative stress and biochemical anxiety. However, trypanothione synthetase was presumed as the target therapeutic alternate in VL therapy. OBJECTIVE: The important objective of this current investigation is to identify or analyze the potential inhibitor for V. leishmaniasis through computational approaches which include virtual screening, molecular docking, ADME prediction, and molecular dynamic simulation. METHODS: An investigation was performed to develop a 3D protein structure, using computational screening among associated similar structured proteins from popular compound database banks such as Specs, Maybridge, and Enamine, to detect novel staging with a series of validation for emerging innovative drugs molecules. Modeled protein ligand complex was further analyzed to know the binding ability of the complex. Molecular dynamics were performed to ascertain its stability at 50 ns. RESULTS: Trypanothione synthetase overall ability in the outcome of series of analysis. Among three database compounds screened, the compound from the Specs database exhibited the better protein-ligand docking scores and fulfilled the drug-like properties through ADMET analysis, and the docked complexes had better stability throughout the simulation. Besides, the other two database leads fulfilled the pharmacological properties, and the complexes were stable in the simulation. CONCLUSION: By analyzing the various compounds from different databases, we concluded that the Specs database compound exhibits potential activity against the target protein and is considered a promising inhibitor for trypanothione synthetase.

16.
J Clin Neurosci ; 98: 78-82, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35134661

RESUMEN

Remote ischemic preconditioning (RIPC) can ameliorate cerebral vasospasm and delayed cerebral ischemia and improve neurological outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Monitoring of regional cerebral oxygen saturation (rScO2) during the critical phase after aSAH can help detect ischemia and assess the effect of RIPC intervention. We investigated the effect of RIPC on rScO2 in patients with aSAH. Our study was a single-center, prospective, parallel-group, randomized pilot trial. After approval by institutional ethics committee, consenting patients (n = 25) with aSAH presenting within 72 h of ictus and scheduled for surgical clipping of cerebral aneurysm were randomized 1:1 to true RIPC (inflation of upper extremity blood pressure cuff thrice to 30 mmHg above systolic blood pressure for 5 min) or sham RIPC (inflation of blood pressure cuff thrice to 30 mmHg for 5 min). In this secondary analysis, our outcome measures assessed by a blinded observer were incidence of cerebral oxygen desaturation (COD) during 7-10 days after ictus and Glasgow outcome scale extended (GOSE) at discharge. The incidence of COD (decrease in rScO2 > 20% from baseline) was lower in the RIPC group (15.4% versus 33.3%); p = 0.378. The absence of ipsilateral COD resulted in a higher mean GOSE (estimate 1.15, p = 0.015). The RIPC group had a higher mean GOSE compared to sham group (estimate 0.8, p = 0.027). This pilot trial demonstrated that RIPC has the potential to prevent COD in patients with aSAH. Larger trials with cerebral oxygenation as the primary outcome are needed to confirm our findings.


Asunto(s)
Precondicionamiento Isquémico , Accidente Cerebrovascular , Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Humanos , Precondicionamiento Isquémico/efectos adversos , Precondicionamiento Isquémico/métodos , Saturación de Oxígeno , Estudios Prospectivos , Accidente Cerebrovascular/etiología , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Vasoespasmo Intracraneal/etiología
17.
J Clin Neurosci ; 99: 169-189, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35286970

RESUMEN

Autism spectrum disorder (ASD) is a serious multifactorial neurodevelopmental disorder often accompanied by strained social communication, repetitive behaviour, immune dysregulation, and gastrointestinal (GI) issues. Recent studies have recorded a link between dysbiosis in the gut microbiota (gm) and the primary stages of ASD. A bidirectional connection (also called microbiota-gut-brain-axis) exchanges information between the gut bacteria and central nervous system. When the homeostasis of the microenvironment of the gut is dysregulated, it causes oxidative stress, affecting neuronal cells and neurotransmitters, thereby causing neurodevelopmental disorders. Studies have confirmed a difference in the constitution of gut bacteria among ASD cases and their controls. Numerous studies on animal models of ASD have shown altered gm and its association with abnormal metabolite profile and altered behaviour phenotype. This process happens due to an abnormal metabolite production in gm, leading to changes in the immune system, especially in ASD. Hence, this review aims to question the current knowledge on gm dysbiosis and its related GI discomforts and ASD behavioural symptoms and shed light on the possible therapeutic approaches available to deal with this situation. Thereby, though it is understood that more research might be needed to prove an association or causal relationship between gm and ASD, therapy with the microbiome may also be considered as an effective strategy to combat this issue.


Asunto(s)
Trastorno del Espectro Autista , Microbioma Gastrointestinal , Animales , Ansiedad , Trastorno del Espectro Autista/terapia , Eje Cerebro-Intestino , Disbiosis/complicaciones , Humanos
18.
Indian J Biochem Biophys ; 48(6): 435-9, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22329247

RESUMEN

The production of a protease and a lipase from Bacillus pumilus SG2 on solid-state fermentation using Pongamia pinnata seed cake as substrate was studied. The seed cake was proved to be a promising substrate for the bacterial growth and the enzyme production. The initial pH, incubation time and moisture content were optimized to achieve maximal enzyme production. Maximum protease production was observed at 72 h and that of the lipase at 96 h of incubation. The production of protease (9840 U/g DM) and lipase (1974 U/g DM) were maximum at pH 7.0 and at 60% moisture content. Triton X-100 (1%) was proved to be an effective extractant for the enzymes and their optimal activity was observed at alkaline pH and at 60 C. The molecular mass of the protease and lipase was 24 and 40 kDa, respectively. Both the enzymes were found to be stable detergent additives. The study demonstrated that inexpensive and easily available Pongamia seed cake could be used for production of industrially important enzymes, such as protease and lipase.


Asunto(s)
Bacillus/enzimología , Fermentación , Lipasa/metabolismo , Millettia/embriología , Péptido Hidrolasas/metabolismo , Semillas/metabolismo , Millettia/metabolismo
19.
Neurol India ; 69(1): 187-189, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33642299

RESUMEN

BACKGROUND: The anaesthetic mandate for a combination of electrocorticography (ECoG) and subcortical motor evoked potential mapping (SCMEPM) substantially differs from that required for each of these monitors in isolation. There is no current consensus defining the anaesthetic management for intraoperative multimodal monitoring combining these two modalities. CASE DESCRIPTION: We report our experience of anaesthetising a drug resistant epileptic patient for craniotomy and resection of his frontal gliotic lesion. We propose a novel anaesthetic technique to cater to the multiple goals of this surgery like optimal neuromonitoring under adequate depth of anaesthesia. We used balanced anaesthesia technique. Continuous intravenous (IV) infusions of Inj. Dexmedetomidine of 1.5 mcg/kg/hour and Inj. Ketamine at 0.5mg/kg/hour were used to supplement inhalational anaesthetic titrated to a MAC up to 0.5. Neuromuscular blockade was avoided after the initial tracheal intubation dose. CONCLUSION: To the best of our knowledge, this is the first case reporting the safety and efficacy of balanced anaesthetic technique for concurrent ECoG and SCMEPM. Successful intraoperative ECoG and SCMEPM monitoring with absent intraoperative awareness confirmed the safety of our anaesthetic technique. Through this, a composite of patient safety, surgeon satisfaction and adequate intraoperative monitoring could be achieved.


Asunto(s)
Anestésicos , Monitorización Neurofisiológica Intraoperatoria , Neurocirugia , Craneotomía , Humanos , Procedimientos Neuroquirúrgicos
20.
J Supercomput ; 77(2): 1517-1536, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32836793

RESUMEN

Reliability analysis is one of the crucial issues for any scalable optical interconnection network. Torus is a highly scalable optical interconnect for data centre networks. The traditional torus network has XY routing algorithm. We have proposed a novel optimised routing algorithm. This paper focuses on the time-dependent and time-independent analysis for both terminal and broadcast reliabilities of the torus network using XY and optimised routing algorithm under various network sizes ( N × N where N = 8 , 16 , 32 , 64 ). The results are evaluated and compared considering nodes failures in MATLAB.

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