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Biomonitoring of pesticide exposure has become a public concern because of its potential health effects. The present study investigated the acetylcholinesterase (AChE) inhibitory levels and their associated health effects in agricultural areas in Telangana, India. This cross-sectional included 341 exposed participants and 152 control participants from agricultural areas. A structured questionnaire was completed and blood and urine samples were collected to measure pesticides, dialkyle phosphate (DAP) metabolites, and AChE activity using liquid chromatography-tandem mass spectrometry and reversed-phase high-performance liquid chromatography. twenty-eight pesticides were detected in blood samples at concentrations ranging 0.42-45.77 ng/mL. Six DAP metabolites were also measured in urine, and all DAP metabolites were significantly higher in the exposed group. AChE activity is significantly reduced in individuals exposed for >10 years, raising concerns regarding possible neurological disorders. These results emphasise the urgent need to investigate the health effects of pesticides exposure, especially in agriculture., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Sukesh Narayan Sinha reports financial support was provided by National Institute of Nutrition. Sukesh Narayan Sinha reports a relationship with National Institute of Nutrition that includes: employment. All the authors have read this paper very carefully and agree to submit it to the Environmental Research. There is no conflict of interest on our part., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aim: The rhizomes of Curcuma caesia have traditional applications for pain healing and are an imperiled species of India. A study on investigation of in vitro anti-oxidant and acetylcholinesterase (AChE) inhibitory efficacy of essential oil from the rhizome part was carried out through extraction by hydrodistillation. Materials and Methods: The phyto components present in this volatile oil were identified by gas chromatography-mass spectrometric analysis and based on Spearman's correlation, the cooccurrence network of the 21 compounds were analyzed. In vitro anti-oxidant, anti-AChE activities were assessed with different concentrations of essential oil by spectrophotometric analysis, following the standard protocols. Results: The studies revealed that major compounds identified were Androsta-1,4-dien-3-one,17-(acetyloxy)-, (17.beta.)-Santanol acetate (16.11%), Eucalyptol (12.98%), Cycloprop[e]indene-1a,2(1H)-dicarboxaldehyde,3a,4,5,6,6a,6b-hexahydro-5,5,6b-trimethyl, (1a. alpha., 3a. beta., 6a. beta., 6b. alpha) (8.96%), methyl 7,12-octadecadienoate (6.75%), and (+)-2-Bornanone (6.60%). The major interactions of terpenoidal compounds with other compounds give a picture that terpenoids have a very significant role as anti-oxidants and cholinesterase inhibitors. The essential oil showed the total phenolic content of 26.72 ± 0.38 mg/g of gallic acid equivalent and total flavonoid content of 18.92 ± 0.27 mg/g of quercetin equivalent (QE). 2, 2-diphenyl-1-picrylhydrazyl and 2, 2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid radical scavenging 50% inhibitory concentration (IC50) values of the oil were 186.33 ± 0.46 μg/mL and 109.41 ± 0.43 μg/mL. The hydrogen peroxide and nitric oxide radical scavenging IC50swere 103.45 ± 0.58 μg/mL and 190.55 ± 0.75 μg/mL, respectively. The AChE inhibitory IC50value was 156.33 ± 0.44 μg/mL. Conclusion: The study demonstrated on essential oil extracted from rhizomes of C. caesia indigenous to Arunachal Pradesh, India, has moderate anti-oxidant property and would be a valuable non-toxic source for managing neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Snakebite is one of themajor causes of morbidity and mortality in India, particularly in rural regions. Of the 57 known venomous species of snakes in India, the 4 most dangerous snakes are the cobra, the common krait, the Russell viper, and the sawscaled viper. Of these, the snakes commonly implicated with neurotoxicity are the cobra and the common krait--both elapidae. Acute neuromuscular weakness with respiratory system involvement is the most lethal neurotoxic effect. Case Report: A 24-year-old female was brought to the emergency department in an unresponsive state with a history of snakebite on the left foot. The patientwas intubated, mechanically ventilated, and promptly started on snake antivenom and anticholinesterase agents. The patient improved significantly and was extubated. On day 6, she developed blurred vision and slurred speech. She was diagnosed with bilateral optic neuropathy and treated with repeat snake antivenom and steroids. She improved significantly and was discharged on day 14. Conclusion: When a person is bitten by a venomous snake, antivenom is the mainstay of treatment, but clinicians must also consider possible reactions and complications. Optic neuritis following a snakebite is rare but does occur. The prognosis is generally good if clinical suspicion for such a complication is strong, the snake is identified, and the patient receives timely treatment with steroids. [ABSTRACT FROM AUTHOR]

Cooccurrence of Diabetes Mellitus and Alzheimer’s disease in elder people prompts scientists to develop multitarget agents that combat causes and symptoms of both diseases simultaneously. In line with this modern paradigm and as a follow-up to our previous studies, the present study is designed to investigate the crude methanolic extracts and subsequent CHCl3, n-BuOH, and H2O fractions of Acalypha alnifolia, Pavetta indica, and Ochna obtusata for their inhibitory activities towards specific targets involved in AD and DM, namely, acetylcholinesterase, butyrylcholinesterase, and α-glucosidase (α-Glc). The methanolic extract and its derived chloroform fractions exhibited remarkable inhibitory capacities with IC50 values being found at the μg/mL level. Further studies on most active chloroform fractions presented a prominent ability to scavenge DPPH and ABTS reactive species and highest neuroprotective effect against H2O2 induced cell injury. Phytochemical analysis showed a large amount of phenolics, flavonoids, and terpenoids in active fractions. In conclusion, A. alnifolia, P. indica, and O. obtusata could be promising sources for the treatment of AD and DM since these fractions induced significant anticholinesterase, antidiabetic, antioxidant, and neuroprotection effects attributable to phenolic, flavonoid, and terpenoid contents and encourage further studies for development of multifunctional therapeutic agent for AD and DM dual therapy. [ABSTRACT FROM AUTHOR]

Aim: The impact of CYP2D6 and CYP3A4 polymorphism on the steady-state plasma concentrations and therapeutic outcome of donepezil monotherapy and combination therapy in Alzheimer's disease (AD) patients. Methods: A total of 38 patients for donepezil and 17 patients for donepezil and memantine therapy, aged ≥55 years, were recruited meeting inclusion and exclusion criteria. Polymerase chain reaction-restriction fragment length polymorphism was performed. The liquid chromatography-tandem mass spectrometry method was used for estimation of drug levels of donepezil and memantine. Results: Significant allele frequency was observed for CYP2D6*3 polymorphism in patients on donepezil monotherapy and combination therapy. Significant allele frequency for CYP2D6*4 was observed in the patients on donepezil monotherapy. Conclusion: CYP2D6 polymorphism, though not significant, might partially be involved in the plasma concentration of AD drug. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cholinesterase determination indicates whether the person has been under pesticide exposure is not. It is recommended that the worker's cholinesterase level should be assessed for workers at a pesticide applied region. Hence, cholinesterase activities in blood samples of agricultural workers exposed to vegetables and grape cultivation with age matched, unexposed workers, who never had any exposure to pesticides, were estimated. Methods: The detailed occupational history and lifestyle characters were obtained by questionnaire. Cholinesterase activity was determined by the method of Ellman as modified by Chambers and Chambers. Results: AChE was ranging from 1.65 to 3.54μmoles/ min/ml in exposed subjects where as it was ranged from 2.22 to 3.51μmoles/min/ml in control subjects. BChE activity was ranging from 0.16 to 5.2μmoles/min/ml among exposed subjects, where as it was ranged from 2.19 to 5.06μmoles/min/ml in control subjects. The results showed statistically significant reduction in enzyme activities (AChE 14%; BChE 56%) among exposed subjects. Conclusion: It was concluded that the reduction in cholinesterase activity may lead to varieties of effects. Hence it is compulsory to use protective gadgets during pesticide spray. Further a continuous biomonitoring study is recommended to assess pesticide exposure. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To analyze the chemical composition and to evaluate the bioactive potential of hydroalocoholic extract of propolis. Methods: Ethanol extract of propolis was analyzed by GC-MS, HPTLC and HPLC methods and in vitro antioxidant, anticholinesterase and cytotoxicity assay were performed. Results: GC-MS analysis revealed the presence of fatty acids, alcohols, and quercetin. Quercetin was identified and quantified by HPTLC and HPLC methods. Dose dependent DPPH and hydroxyl radical scavenging activity of hydroalcoholic extract of propolis was calculated as 16.20 and 34.33 μg/mL respectively. Inhibition of lipid peroxidation was significant and the IC50 value was calculated as 55.56μg/mL. Anticholinesterase activity was less observed. The cytotoxic activity against both breast (MCF-7) and lung cancer (A543) cell lines were significant and the IC50 value was calculated as 10 and 13 μg/mL respectively. Conclusions: These findings showed that bioactive compounds present in propolis will alleviate many diseases and can be used for better human health. [Copyright &y& Elsevier]

Aim: To assess the surgical outcome of myasthenia gravis (MG) following thymectomy and to determine the outcome predictors to such therapeutic approach. Materials and Methods: This study is a retrospective review of 80 consecutive thymectomies performed for MG over a 16-year period. Results: There were 41 females and 39 males (mean age, 34.32 years) with mean disease duration of 17.45 months prior to surgery. Stagewise distribution of the patients revealed 2.5% in stage I, 48.7% in stage IIA, 33.8% in stage IIB, 8.7% in stage III, and 6.3% in stage IV. The surgical approach was either trans-sternal (n=67) or video-assisted thoracoscopic route (n=13). Follow-up was obtained in 91.2% (n=73) of patients with mean duration of 67.7 months. At their last follow-up, 26.0% were in complete remission, 35.6% were asymptomatic on decreased medications, and 17.8% had clinical improvement on decreased medications. Overall, 79.4% of patients benefited from surgery, 8.2% had unchanged disease status, and 12.3% worsened clinically. Factors influencing favorable outcome include sex, disease stage, gland weight, and preoperative medication with anti-cholinesterase (P<0.05). There was one death in the perioperative period due to septicemia. Two patients died at fourth and seventh month following thymectomy. Conclusion: Thymectomy for MG is safe and effective. Certain influencing factors may shape treatment decisions and target higher risk patients. [ABSTRACT FROM AUTHOR]

Abstract: Illicium verum is a well known spice in traditional Indian system for its therapeutic potential. The present study was aimed to evaluate the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory (BChE) activity of standardized extracts of I. verum and its oil. Present study confirmed that anethole contributed to the anticholinesterase activity of I. verum, with more specificity towards AChE. IC50 for AChE and BChE inhibitory activity of anethole was 39.89±0.32μg/mL and 75.35±1.47μg/mL, whereas for the oil, 36.00±0.44μg/mL and 70.65±0.96μg/mL respectively. Therefore I. verum can be a good lead as anti-cholinesterase agent from natural resources. [Copyright &y& Elsevier]

Abstract: Alzheimer''s disease (AD) is the most common form of dementia, which is one of the four leading causes of death in developed nations. Until date the only symptomatic treatment for this disease is based on the “cholinergic hypothesis” where the drugs enhance acetylcholine levels in the brain by inhibiting acetylcholinesterase (AChE). In the course for screening cholinesterase inhibitors about eight seaweeds, with wide pharmaceutical applications, were collected from Hare Island, Gulf of Mannar, Marine Biosphere Reserve, Tamil Nadu, India. Inhibitory effect of methanol extract of the seaweeds was studied in vitro by incubating various concentration of the extract with AChE or butyryl cholinesterase (BuChE) and assessing their activities by Ellman''s colorimetric method. Kinetic parameters like IC50, K i and V max were also analyzed. The results showed that of the eight seaweeds screened Hypnea valentiae, Padina gymnospora, Ulva reticulata and Gracilaria edulis exhibited inhibitory activity to AChE with IC50 value of 2.6, 3.5, 10 and 3mg/ml respectively, while H. valentiae, Enteromorpha intestinalis, Dictyota dichotoma and U. reticulata showed 50% inhibition to BuChE at concentration 3.9, 7, 6.5 and 10mg/ml respectively. The inhibitory activities of the seaweed extracts were comparable to the standard drug donepezil. Enzyme kinetic analysis showed that algal extracts exhibited mixed type inhibition (partial noncompetitive inhibition). [Copyright &y& Elsevier]

• Isolation, identification and quantification of Pentylcurcumene in Geophila repens. • HPTLC method development, validation and quantification of Pentylcurcumene. • Molecular docking results support anticholinesterase activities of Pentylcurcumene. • Bioautography method for detecting anticholinesterase activities of Pentylcurcumene. • Pentylcurcumene a novel anticholinesterase drug to combat Alzheimer's disease. The aerial part of Geophila repens (L.) I.M. Johnst (Rubiaceae) has been used in India to improve intelligence and memory for a long time. As part of our ongoing efforts in discovering potential bioactive compounds from G. repens , we have studied the isolation, identification, and quantification of a new class of cholinesterase inhibitor from G. repens for Alzheimer's disease (AD). Terpene was isolated from hydroalcohol extract of G. repens (GRHA) and its structure was identified "Pentylcurcumene" by spectroscopic data. HPTLC fingerprint analysis was performed and good separation was achieved in mobile phase (benzene:methanol; 7.5:2.5, v/v, 254 and 366 nm; R f 0.51). The method was validated using ICH guidelines in terms of linearity, specificity, sensitivity, accuracy, precision, robustness and stability. In cellular antioxidant studies e.g. DPPH, oxygen-radical-absorbance-capacity (ORAC) and cell-based-antioxidant-protection-in-erythrocytes (CAP-e) assays showed that, Pentylcurcumene showed remarkably different degrees of antioxidant activities in dose-dependent manner. Pentylcurcumene demonstrated anticholinesterase activities e.g. IC 50 of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition were 73.12 ± 0.56 and 97.65 ± 0.46 μg/ml, respectively. To better understand enzyme kinetics, Lineweaver-Burk plot of Pentylcurcumene displayed the highest affinity with competitive inhibition (reversible) towards both AChE (V max 0.8) and BChE (V max 0.6). An improved and advanced HPTLC tool of bioautography detection of Pentylcurcumene has been successfully demonstrated its anticholinesterase activities. Molecular docking simulations of Pentylcurcumene (ligand) and enzymes (proteins) exhibited the binding of ligand at active sites of AChE (human/rat) and BChE (human/homology) efficiently and also predicted the hydrophobic interaction of drug towards different amino acid residue within proteins. As per the results of antioxidant study and with the support of molecular docking analysis, it is concluded that Pentylcurcumene could be a potential first-line cholinesterase-inhibitor for AD. [ABSTRACT FROM AUTHOR]