Cholinesterase Activity Levels Research Articles

Synthesis and Structure of Novel Phenothiazine Derivatives, and Compound Prioritization via In Silico Target Search and Screening for Cytotoxic and Cholinesterase Modulatory Activities in Liver Cancer Cells and In Vivo in Zebrafish.

Phenothiazines (PTZ) are antipsychotics known to modulate a variety of neurotransmitter activities that include dopaminergic and cholinergic signaling and have been identified as potential anticancer agents in vitro. However, it is important to also test whether a highly cytotoxic, repurposed, or novel PTZ has low toxicity and neuromodulatory activity in vivo using vertebrate model organisms, such as zebrafish. In this study, we synthesized novel phenothiazines and screened them in vitro in liver cancer and in vivo in zebrafish embryos/larvae. The syntheses of several intermediate PTZ 10-yl acyl chlorides were followed by elemental analysis and determination of 1H NMR and 13C NMR mass (ESI+) spectra of a large number of novel PTZ 10-carboxamides. Cytotoxicities of 28 PTZ derivatives (1-28) screened against Hep3B and SkHep1 liver cancer cell lines revealed five intermediate and five novel leads along with trifluoperazine (TFP), prochlorperazine (PCP), and perphenazine, which are relatively more cytotoxic than the basic PTZ core. Overall, the derivatives were more cytotoxic to Hep3B than SkHep1 cells. Moreover, in silico target screening identified cholinesterases as some of the commonest targets of the screened phenothiazines. Interestingly, molecular docking studies with acetylcholinesterase (AChE) and butyrylcholinesterase proteins showed that the most cytotoxic compounds 1, 3, PCP, and TFP behaved similar to Huprin W in their amino acid interactions with the AChE protein. The highly cytotoxic intermediate PTZ derivative 1 exhibited a relatively lower toxicity profile than those of 2 and 3 during the zebrafish development. It also modulated in vivo the cholinesterase activity in a dose-dependent manner while significantly increasing the total cholinesterase activity and/or ACHE mRNA levels, independent of the liver cancer cell type. Our screen also identified novel phenothiazines, i.e., 8 and 10, with significant cytotoxic and cholinesterase modulatory effects in liver cancer cells; yet both compounds had low levels of toxicity in zebrafish. Moreover, they modulated the cholinesterase activity or expression of ACHE in a cancer cell line-specific manner, and compound 10 significantly inhibited the cholinesterase activity in zebrafish. Accordingly, using a successful combination of in silico, in vitro, and in vivo approaches, we identified several lead anticancer and cholinesterase modulatory PTZ derivatives for future research.

Evaluation of Changes in Acetylcholinesterase Activity in Workers of Mehriz Elixir Pesticide Plant in Yazd

Background and Aims: Some pesticide chemical compounds, such as organophosphates and carbamates, interfere with or inhibit cholinesterase activity. Employees working in pesticide factories are one of the groups at risk of pesticide poisoning. This study aimed to evaluate the effect of work on exposure to toxins on the serum level of erythrocyte cholinesterase activity.
 Materials and Methods: This research was conducted on Mehriz Elixir Pesticide Factory workers. Blood samples were taken from 76 employees in 2 groups as a control group, and 38 workers were exposed to organophosphorus toxins three months after starting work in a factory. Cholinesterase activity was analyzed using the Elman method, and data were analyzed using SPSS software version 22.
 Results: The mean age of the subjects was 35.07 years, which was 35.26 in the exposure group (n = 38) and 34.89 in the control group (n = 38). The activity of acetylcholinesterase enzyme in the control group at 0, 10, and 20 minutes was 12.78 ku/l, 14.24 ku/l, and 15.45 ku/l, respectively. The acetylcholinesterase enzyme activity in the exposed group was 10.77 ku/l, 10.40 ku/l, and 10.36 ku/l at 0, 10, and 20 minutes, respectively. At all stages, the mean acetylcholinesterase activity in the control group was higher than the exposed group, but significant differences were observed at 10 and 20 minutes between the 2 groups.
 Conclusion: Exposure of workers to organophosphate inhibits acetylcholinesterase, which manifests by a decrease in the activity of this enzyme.

Plasma cholinesterase activity: A benchmark for rapid detection of pesticide poisoning in an avian scavenger

Poisoning due to exposure to organophosphate and carbamate pesticides is a common threat for many wildlife species, especially for scavengers such as vultures. The Griffon vulture population (Gyps fulvus), for instance, is deteriorating in the Eastern Mediterranean, and is considered to be critically endangered in Israel, where 48 out of 107 (45 %) known injury/mortality cases in 2010–2021 were caused by poisoning. Lack of specific clinical indications, together with levels of organophosphate or carbamate pesticides too low to detect, challenge the ability to diagnose and treat such poisoning events. The activity of cholinesterase (ChE) in plasma has the potential to serve as an effective biomarker for monitoring exposure to anticholinesterase pesticides in live vultures. Yet, the applicability of this approach has been limited by intra- and inter-species variations in ChE basal levels. The present study aims to provide a benchmark for ChE activity levels in healthy Griffons and their intra-species variation. Blood samples from free-roaming (n = 231) and captive (n = 63) Griffons were collected during routine monitoring, and ChE levels were determined using a colorimetric method. We established that the ChE in the plasma of Griffons reflects mostly acetylcholinesterase as the dominant form. ChE levels in healthy Griffons are 0.601 ± 0.011 U/ml (mean ± SE), while Griffons with suspected or confirmed pesticide poisoning display much lower levels of ChE activity (typically <0.3 U/ml). We also characterized the age dependence of ChE activity, as well as differences among groups from different locations or origins. Our study provides a rapid diagnostic tool for the detection of exposure to organophosphate and carbamate pesticides that should facilitate the lifesaving treatment and the conservation of this species. Moreover, our protocols can be adapted to other species and geographical areas, addressing pesticide poisoning worldwide and contributing to the protection of endangered species and their ecological functions (e.g. sanitation by scavengers).

Saliva and Serum Acetylcholinesterase Activity in Multiple Sclerosis.

Multiple sclerosis is mediated by the immune system that damages the myelin sheath. Most patients experience inflammation. Since one of the factors that have a role in reducing inflammation is acetylcholine, and according to the benefits of saliva, in this study, the level of salivary and serum cholinesterase activity in patients with multiple sclerosis and healthy were evaluated. Thirty women with multiple sclerosis who were hospitalized in the neurology ward of Imam Reza and Hazrat Rasoul Hospitals and 30 healthy females participated in the study. The severity of multiple sclerosis was calculated by expanded disability status scale (EDSS). Saliva and serum samples were collected in the morning. Cholinesterase activity was assessed by a photometric method. The mean cholinesterase activity in stimulated and unstimulated saliva and serum significantly reduced in the multiple sclerosis group. The cutoff for differentiation of multiple sclerosis patients from healthy individuals by assessing cholinesterase activity (IU/L) was 3577 in serum, 241 in unstimulated saliva, and 266 in stimulated saliva. It seems that cholinesterase activity decreases in patients with multiple sclerosis.

Assessment of Cholinesterase inhibition activity of birds inhabiting pesticide exposed croplands and protected area in hot semi-arid region of Pakistan.

Acetylcholinesterase (AChE) activity levels can be used as an indicator for AChE inhibition due to pesticide poisoning in bird species. We assessed the comparative brain cholinesterase (AChE) activity level of five bird species inhabiting pesticide exposed croplands and Protected Area i.e. Deva Vatala National Park (DVNP), Bhimber by using a spectrophotometric method. AChE activity levels ranged from 56.3 to 85.9 µmol/min/g of brain tissue of birds representing DVNP. However, AChE activity levels ranged from 27.6 to 79.9 µmol/min/g of brain tissue of birds representing croplands. AChE activity levels observed in Jungle babbler, Common babbler, and Red-vented bulbul showed significant differences (P < 0.05) at two sites. However, White wagtail and Black drongo demonstrated non-significant differences (P > 0.05). Maximum inhibition was recorded in Jungle babbler (53%) followed by Common babbler (35%), Red-vented bulbul (18%), White wagtail (15%), and Black drongo (7%). The brain cholinesterase inhibition levels under-protected ecosystems (DVNP, Bhimber) and agricultural landscape suggest insecticidal contamination and its impact on avifauna diversity. The study also emphasizes on the importance of pesticide-free zones to protect the biodiversity of birds.

Concurrent Change in Serum Cholinesterase Activity and Midregional-Proadrennomedullin Level Could Predict Patient Outcome following Liver Transplantation.

Background: After liver transplantation (LTX), patients are susceptible to opportunistic infections resulting in reduced outcomes within the early post-transplantation period. The postoperative monitoring of LTX patients has gained much importance in recent years. However, reliable plasmatic markers predicting 90-day outcomes are still lacking. Methods: In the post hoc analysis of a prospective, observational study, butyrylcholinesterase (BChE), mid-regional proadrenomedullin (MR-proADM), as well as conventional inflammatory markers (procalcitonin, C-reactive protein) were evaluated in 93 patients at seven consecutive timepoints within the first 28 days following LTX. Results: Persistently reduced activity of BChE and elevated MR-proADM levels indicated reduced 90-day survival following LTX. Furthermore, reduced BChE and increased MR-proADM activity could indicate early post-transplantation bacterial infections, whereas conventional inflammatory biomarkers showed no diagnostic efficacy within the observation period. Conclusion: Concurrent assessment of BChE and MR-proADM activity might serve as a bedside diagnostic tool for early bacterial infections following liver transplantation. Thus, a combined utilization of the two biomarkers may be a useful tool in the risk evaluation of patients following liver transplantation.

Occupational risk assessment of organophosphates with an emphasis on psychological and oxidative stress factors.

Organophosphate pesticides (OPPs) are widely used all over the world in domestic and industrial settings, but these chemicals affect the nervous system, induce suicidal thoughts, depression and anxiety, and impair sleep quality. The purpose of this study was to investigate the relationship between the main toxicity mechanisms of OPPs, oxidative stress and cholinesterase inhibition, and psychological parameters in chronic exposure to OPPs. This cross-sectional study was conducted on 56 male OPPs factory workers as the worker group and 47 unexposed individuals within the same age range as the control group. Psychological factors were assessed using validated questionnaires. The activity of plasma cholinesterase and oxidative stress biomarkers, total antioxidant capacity of plasma, lipid peroxidation (LPO), and protein carbonylation were determined in blood samples by spectrophotometer. Sleep quality score in the factory workers was lower, and depression and suicidal ideation scores were higher than those in the control group. These factory workers showed 35% lower levels of plasma cholinesterase activity than did the controls. Compared to the control group, a significant impairment in oxidative stress biomarkers was also observed in the workers. Meanwhile, there was a significant relationship between the duration of employment and the level of LPO as well as a significant correlation between the quality of sleep and plasma cholinesterase in the workers. In conclusion, long-term exposure to OPPs could cause oxidative damages and neurobehavioral effects. The close monitoring of workplace exposure to organophosphates pesticides and also their respective solvents along with the reduction of working hours are of the necessities to avoid the adverse impacts of exposure to these pesticides.

Chronic oral exposure of aluminum chloride in rat modulates molecular and functional neurotoxic markers relevant to Alzheimer’s disease

Aluminum is an environmentally abundant potential neurotoxic agent that may result in oxidative damage to a range of cellular biomarkers. The potential sources of aluminum accumulation in the body include drinking water, food, medicines, vaccines, and aluminum cookware utensils, etc. The accumulation of aluminum in the brain is reported to be associated with cholinergic dysfunction, oxidative stress and neuronal damage, which may ultimately cause Alzheimer’s disease. Since chronic exposure to aluminum leads to its accumulation in the brain, so this study was done by a long-term (24 weeks) low dose (20 mg/kg) oral exposure of aluminum chloride in rats. In this chronic model, we have evaluated the major hallmarks of Alzheimer’s disease including amyloid-beta (Aβ1–42) and phosphorylated-tau (p231-tau) protein in brain tissue. Furthermore, we evaluated the level of acetyl cholinesterase activity, inflammatory cytokines such as TNF-α, IL-6 and IL-1β, and oxidative stress biomarkers in the rat brain in this model. The neurobehavioral parameters were also assessed in animals by using spontaneous locomotor activity, passive avoidance, rotarod test and novel object recognition test to evaluate alteration in learning, memory and muscle co-ordination. We found that chronic oral exposure to aluminum chloride causes a significant increase in structural hallmarks such as Aβ1–42 and p231-tau levels along with pro-inflammatory cytokines (TNF-α and IL-6), oxidative stress, and a decrease in antioxidant markers such as GSH and catalase in the brain tissue. These biomarkers significantly affected neurobehavioral parameters in animals. This study provides a mechanistic understanding of chronic aluminum-induced neuronal toxicity in the brain with relevance to Alzheimer’s disease.

Fish Oil Ameliorates Doxorubicin Induced Memory Impairment in Wistar Rats

According to the World Health Organization, cancer is the leading cause of death in 112 countries under the age of 70 in 2019. Cognitive impairment is a common chemotherapeutic drug side effect that affects 15-80 % of cancer patients. These cognitive changes persist for one or two years following chemotherapy and sometimes persist for life time. Due to impaired cognitive function, survivors find utmost difficulty to perform day to day activities and lose their independency which has a negative impact on standard of living (SOL). The Antineoplastic drug doxorubicin has been associated with severe neurotoxicity, which manifests as a loss of cognitive abilities, most likely due to oxidative stress in the brain. Naturally occurring Omega-3 fatty acids have potential health benefits. They are abundant in fish oil. Fish oil is used as dietary supplement and is well known for anti-inflammatory, anti-hyperlipidaemia, cardio protective, and antioxidant and neuro protective functions. The current study explored to investigate Fish oil potential neuro protection and memory-improving advantages against Doxorubicin-induced cognitive and neurobiological impairments. The preventive effect of Fish oil against doxorubicin-induced memory impairments in rats was evaluated by using a novel object recognition task and the Morris water maze test. Doxorubicin-induced memory impairment was considerably prevented by fish oil treatment (50 mg/kg and 100 mg/kg). The levels of tumour necrosis factor (TNF-α) and acetyl cholinesterase activity were dramatically reduced with both dosages of Fish oil. Furthermore, Fish oil protected the frontal cortex and hippocampus parts of the brain from doxorubicin-induced oxidative and inflammatory damages. These findings suggest that Fish oil may be a promising adjuvant therapeutic option for decreasing doxorubicin-related side effects

Ipidacrine (Axamon), A Reversible Cholinesterase Inhibitor, Improves Erectile Function in Male Rats With Diabetes Mellitus-Induced Erectile Dysfunction.

ABSTRACTSBackgroundManagement of diabetes mellitus-induced erectile dysfunction (DMED) is challenging because of its insufficient responses to phosphodiesterase type 5 inhibitors.AimTo compare the effects of ipidacrine, a reversible cholinesterase inhibitor, and sildenafil on DMED in a rat model of streptozotocin (STZ)-induced diabetes.MethodsErectile dysfunction (ED) caused by STZ-induced diabetes mellitus was modeled in adult male Wistar rats, which were randomized to 4 groups: untreated diabetic rats, sildenafil (5 mg/kg), ipidacrine (3.6 mg/kg) and ipidacrine (6.7 mg/kg). The test drug (ipidacrine), comparator (sildenafil) or control substance (1% starch solution) were administered orally for 5 days or 14 days. Erectile function was assessed by the change in the maximum intracavernous pressure (ICPmax) following cavernous nerve electrical stimulation. The mean arterial pressure (MAP) was recorded, and the ICPmax/MAP ratio was calculated. Sexual behavior, cholinesterase activity and blood testosterone level tests assessed.Main Outcome MeasureThe quantitative value of ICPmax/MAP 14 days after the start of administration of the test drug and the comparison drug.ResultsAnimals with STZ-induced diabetes mellitus showed a significant decrease in ICPmax and ICPmax/MAP ratio compared to the intact control group. When ipidacrine was administered to rats with DMED for 14 days, an increase in these indicators was noted. It was proved that ipidacrine at a dose of 6.7 mg/kg has noninferiority compared to sildenafil on the DMED model. Significant increase in ICPmax compared to STZ-control after electrostimulation of the cavernous nerve was recorded following administration of ipidacrine at a dose of 6.7 mg/kg (P < .05) and sildenafil at a dose 5 mg/kg (P < .05). Neither the test drug, nor the comparator were associated with increase in testosterone levels in blood; as well both drugs did not promote activation of sexual behavior.Clinical ImplicationsIpidacrine may be considered as an effective therapy for DMED but needs to be verified in human investigations.Strengths & LimitationsThe role of ipidacrine, was firstly demonstrated in rats with DMED. However, the results were obtained in animal experiments, and will be further tested in the study of receptor interactions and the determination of cellular targets.ConclusionThis is the first study to show that administration of ipidacrine, the reversible cholinesterase inhibitor, improved erectile function in diabetic rats and these results may be beneficial in further studies using ipidacrine for treatment of DMED, particularly in non-responders to PDE5 inhibitors.Bykov V, Gushchina E, Morozov S, et al. Ipidacrine (Axamon), A Reversible Cholinesterase Inhibitor, Improves Erectile Function in Male Rats With Diabetes Mellitus-Induced Erectile Dysfunction. Sex Med 2022;10:100477.

Statewide Evaluation of the California Medical Supervision Program Using Cholinesterase Electronic Laboratory Reporting Data: An Update

The California Medical Supervision Program is designed to protect agricultural workers from overexposure to Toxicity Category I and II organophosphate (OP) and carbamate (CB) pesticides by routinely monitoring their blood cholinesterase (ChE) activity levels. ChE testing is conducted at State-approved laboratories and electronically reported to the Department of Pesticide Regulation (DPR) and the Office of Environmental Health Hazard Assessment (OEHHA) for review. In 2015, OEHHA and DPR evaluated the effectiveness of the Program by analyzing ChE data from pesticide handlers performed between 2011 and 2013, which revealed issues with the data quality that hindered the evaluation process. Several interventions have been implemented since then to improve data quality and the overall function of the Program. A new evaluation was conducted in 2020 to 2021 using data from 2014 to 2019 to determine the effectiveness of the Program, Program compliance, and efficacy of the interventions. The analysis revealed similar data quality issues identified in the last evaluation, however, an improvement in data quality was observed. The number of individuals with ChE depression below the action level threshold have decreased in recent years, corresponding to the implementation of certain interventions, indicating that the effectiveness of the Program has improved. Spatial and temporal analysis showed the proportion of pre-exposure baseline tests inversely correlated with pesticide use data while routine follow-up ChE test results showed a positive correlation, indicating a high degree of Program compliance across the state. Major improvements in the data cleaning and analysis since the last evaluation have also improved the evaluation: pesticide handlers under the Program were able to be identified with more certainty and ChE depressions were able to be calculated with increased accuracy. However, further improvements to the data collection process could enhance future evaluations of the Program.

Hydrolase-Treated Royal Jelly Attenuates H2O2- and Glutamate-Induced SH-SY5Y Cell Damage and Promotes Cognitive Enhancement in a Rat Model of Vascular Dementia.

Vascular dementia (VaD) is the second most common type of dementia following Alzheimer's disease, but the therapeutic efficacy is still not effective. This makes the searching for novel neuroprotective agents important. Therefore, we hypothesized that royal jelly, a well-known traditional medicine, could attenuate memory impairment and brain damage in vascular dementia. This study determined the effects of royal jelly hydrolysate (RJH) and possible mechanism of cell damage and cognitive-enhancing effect in animal study. An in vitro study assessed the effects of RJH on acetylcholinesterase inhibitor, cell viability, and cell damage in SH-SY5Y neuroblastoma cells. Then, an in vivo study examined vascular dementia by the occlusion of the right middle cerebral artery (Rt.MCAO); adult male Wistar rats had been orally given RJH at doses ranging from 10, 50, to 100 mg/kg for 14 days before and 14 days after the occlusion of Rt.MCAO to mimic the VaD condition. Rats' spatial memory was evaluated using Morris water maze and radial arm maze every 7 days after Rt.MCAO throughout a 14-day experimental period, and then, they were sacrificed and the acetylcholinesterase (AChE) activity in the hippocampus was determined. The results showed that RJH has no cytotoxic effect with the final concentration up to 500 μg protein/ml and reduces cell death from the H2O2- and glutamate-induced cell damage in in vitro neuroblastoma cells. Importantly, RJH significantly improved memory performance in Morris water maze test and radial arm maze and decreased the level of acetyl cholinesterase activity. In conclusion, RJH is the potential neuroprotective agent and cognitive enhancer for VaD.

Association between Exposure to Pesticides and Cognitive Function in Greenhouse Workers (Case Study: Ahmadabad Village of Yazd Province)

Introduction: Exposure to pesticides in greenhouse workers is associated with several health outcomes, such as cognitive impairment. This study aimed to investigate the association between exposure to pesticides and cognitive function in Yazd city greenhouse workers and those living in the proximity of the greenhouses.&#x0D; Materials and Methods: In this study, three groups of participants were selected, including the greenhouse workers, the residents in the proximity of the greenhouses, and the control group. A semi-quantitative assessment of pesticide exposure was used to calculate the subjects’ cumulative pesticide exposure as a proxy for long-term exposure to pesticides. Blood level of acetylcholinesterase (AChE) activity was measured as a biomarker of effect. Frontal Assessment Battery (FAB), and Mini–mental State Examination (MMSE) were used to assess cognitive functions (including memory, executive functions, attention, visual, and verbal functions).&#x0D; Results: Mean cholinesterase activity in the greenhouse workers (average = 7009.3 U/L) was lower than the two other groups. The results of the cognitive function score for both FAB and MMSE tests did not show a significant difference between the direct exposure and indirect exposure groups, although the cognitive function score in the pesticide applicators was lower than the two other study groups (e.g. for FAB score: 13.89, 14.55, and 15.4 for the greenhouse workers, the residents in the proximity of greenhouses, and the control group). The results also showed that in the direct exposure group, those with lower levels of cholinesterase activity also had a lower cognitive function.&#x0D; Conclusion: The findings indicated that there is a potential link between impaired cognitive function and exposure to pesticides in the greenhouse workers.

Occupational use of agrochemicals results in inhibited cholinesterase activity and altered reproductive hormone levels in male farmers from Buea, Cameroon.

The efficiency of agro pesticides and fertilizers in eliminating pests and scaling up crop yield has motivated farmers to increase their use. Unfortunately, health hazards caused on farmers by these agrochemicals are of growing concern, though not well elucidated. In order to evaluate the effects of occupational exposure to agrochemicals on some key parameters of male farmers' health in Buea Subdivision, Cameroon, a total of 101 men, including 62 farmers using the agrochemicals and a reference population of 39 men not involved in occupational utilization of the agrochemicals, were interviewed on use of protective equipment, exposure symptoms and reproductive health status. Thereafter, serum cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] activities, total antioxidant capacity and reproductive hormones [follicle-stimulating hormone (FSH), luteinizing hormone and testosterone] were assessed. Results revealed that farmers mainly used insecticides followed by fungicides, herbicides and fertilizers, but with inadequate protective measures. The use of agrochemicals resulted in several exposure symptoms including weakness, itches, burning sensation, headache, sneezing, coughing and vomiting, as well as decrease in serum AChE activity when compared to the reference population. The agrochemicals impacted negatively on the farmers' reproductive health as evidenced by increased FSH levels. Taken altogether, these results suggested that exposure to agrochemicals adversely affects farmers' health. Therefore, there is a need to further sensitize the farmers on the use of protective equipment to mitigate the exposure and resulting health hazards.

The role of oximes in the management of acute poisoning with cholinesterase inhibitors pesticides: Case reports

Acute pesticides poisonings is a serious public health problem in Algeria. The indication of oximes in the treatment of poisoning by cholinesterase inhibitors pesticides is still controversial in practice, although it seems theoretically interesting because of the reversibility of the toxic-cholinesterase binding and the atropine-like effect. The interest of oximes in the management of cholinesterase inhibitors pesticides poisoning will be discussed through the study of the observation of 4 patients received at University Hospital Center of Oran (Algeria). Observations and discussion The study of the 4 observations enabled us to highlight the following points. For collapsed cholinesterase activity levels, it is better to administrate the highest recommended doses of Pralidoxime immediately, this will allow a rapid regeneration of an important fraction of inhibited cholinesterase activity, process which is concentration-dependent. Early intake of Pralidoxime with continuous injections appeared to have resulted in a rapid and favourable evolution. The use of oximes in carbamate poisoning is still debatable and needs further research. In view of the data presented, oximes retain their place in the treatment of acute intoxication with cholinesterase inhibitors. Their indication should be discussed for each case taking into account the anamnesis, clinical presentation and level of cholinesterase activity.

Hubungan Paparan Pestisida Kadar Enzim Kolinesterase dengan Kadar Trigliserida pada Pekerja yang Terpapar Pestisida Golongan Organofosfat

Alzaimer degerative diseases that attack the brain that occur due to several things including cholesterol and poisoning due to organopathic pesticides, cholinesterase. Triglycerides are a part of kolesterol which consists of about 20% of total cholesterol. Pesticide buildup in the body often occurs due to work risks. This study aims to determine how much cholinesterase activity and triglyceride levels are in workers exposed to organophosphate pesticides, and to determine the relationship of pesticide exposure to cholinesterase enzyme levels with triglyceride levels in workers who are exposed to workers exposed to pesticides. This research is an observational research with an experimental approach. The study was conducted at PT.X, which was exposed to 15 pesticides. This study uses a correlation test that will be shown if p 0.05 so it was concluded that there was no relationship between cholinesterase activity with triglyceride levels.

Cholinergic signalling mechanisms and early implant healing phases in healthy versus generalized aggressive periodontitis patients: A prospective, case-control study.

Periodontal diseases negatively affect implant osseointegration. Perturbations in non-neuronal cholinergic signalling mechanisms are associated with periodontitis; however, their role in generalized aggressive periodontitis (GAgP) is unknown. The aim of this prospective case-control study was to determine the relationship between non-neuronal cholinergic signalling mechanisms, secreted Ly-6/uPAR-related protein-1 (SLURP-1), interleukin-17 (IL-17) family cytokines and healing of dental implants in health and GAgP. Thirteen GAgP patients and seven periodontally healthy individuals (PH) were recruited. Peri-implant crevicular fluid (PICF) was obtained at baseline and 1month post-placement. Acetylcholine (ACh) levels and cholinesterase activity were determined biochemically. SLURP-1, IL-17A and IL-17E levels were determined by ELISA. Marginal bone loss (MBL) at 1 and 6months post-placement was determined radiographically. The concentration of ACh, cholinesterase activity and IL-17A levels was elevated in PICF of patients with GAgP compared to PH individuals at baseline and 1month post-placement. The concentration of ACh and cholinesterase activity levels in PICF correlated with levels of IL-17A and MBL around implants 1month post-placement in patients with GAgP. Non-neuronal cholinergic mechanisms may play a role in the aetiopathogenesis of GAgP and may directly or indirectly, through modulation of IL-17A, influence early implant osseointegration and potential long-term implant survival.

Peripheral vascular responses to acetylcholine as a predictive tool for response to cholinesterase inhibitors in Alzheimer\u2019s disease

BackgroundCholinesterase inhibitors remain the first line therapy for people with mild to moderate Alzheimer’s disease (AD). Response is modest and difficult to predict from pre-treatment characteristics. We hypothesise that skin vascular response to iontophoresis of acetylcholine, which is partly determined by the level of cholinesterase activity, may be a pre-treatment measure that could predict response to therapy.MethodsTwenty-four people with probable AD underwent iontophoresis of acetylcholine to the volar surface of the forearm skin prior to treatment with a cholinesterase inhibitor. The peak skin vascular response and the resolution to baseline levels were measured using laser Doppler perfusion imaging. Response to treatment was assessed after 6 months using criteria from the National Institute for Health and Care Excellence (NICE) and iontophoresis with acetylcholine was repeated. Blindness between clinical and laboratory assessments was maintained.ResultsFourteen out of twenty-four people responded to treatment using NICE criteria. By comparison to non-responders, responders to treatment had a faster resolution to baseline from acetylcholine-induced vasodilation prior to treatment, which slowed with treatment. In this pilot study there was a high level of accuracy in the classification of response using this variable. No baseline cognitive or functional measures discriminated end-point responders from non-responders.ConclusionCholinesterase inhibitors are well tolerated but the number of people with adverse effects would be reduced if it was possible to predict response. The role of vasodilator response to acetylcholine and recovery as a potential biomarker for efficacy of treatment should now be evaluated and may possibly be of relevance in stratifying samples for interventional studies in AD and other forms of dementia. We feel that a more definitive study is now justified.

Isorhamnetin enhanced cortico-hippocampal learning and memory capability in mice with scopolamine-induced amnesia: Role of antioxidant defense, cholinergic and BDNF signaling

Isorhamnetin (IRN), a 3′-O-methylated metabolite of quercetin has antioxidant, anti-inflammatory and neuroprotective properties. In this study, we investigated the learning and memory enhancing effects of IRN on spatial and non-spatial learning and memory deficits induced by scopolamine (3 mg/kg, i.p; muscarinic antagonist) using the novel object recognition test (NORT) and Morris water maze (MWM) task. IRN (1, 5 or 50 mg/kg, p.o.) or vehicle was administered to male albino for 3 consecutive days, scopolamine was given 1 h after last administration on day 3. Five minutes post scopolamine administration the behavioural test of cognitive function was carried out. One hour after probe test (MWM task) on day 7, the brains were isolated to assay for oxidative stress, cholinesterase activity and brain derived neurotrophic factor (BDNF) levels in the prefrontal cortex (PFC) and hippocampus (HIPPO). IRN treatment significantly improved scopolamine-induced learning and memory impairment in behavioural tests. IRN reduced malondialdehyde and nitrite generation induced by scopolamine through increase in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities in the prefrontal cortex and hippocampus. In addition, IRN attenuates scopolamine induced cholinesterase activity and BDNF level in the prefrontal cortex and hippocampus of mice. Findings from this study showed that IRN possesses cognition and memory enhancing properties possibly through enhancement of antioxidant defense system, cholinergic signaling and synaptic plasticity.

Efficacy of atropine sulfate/obidoxime chloride co-formulation against sarin exposure in guinea pigs

The efficacy and pharmacokinetics of the aqueous co-formulation contents of the Trobigard™ (atropine sulfate, obidoxime chloride) auto-injector were evaluated in a sarin exposed guinea pig model. Two subcutaneous (sc) sarin challenge doses were evaluated in guinea pigs instrumented with brain and heart electrodes for electroencephalogram (EEG) and electrocardiogram (ECG). Sarin challenge doses were chosen to reflect exposure subclasses with sublethal (moderate to severe clinical signs) and lethal consequences. The level of protection of intramuscular human equivalent doses of the co-formulation was defined by (1) the mitigation of signs and symptoms at a sublethal level and (2) the increase of survival time at the supralethal sarin dose levels.Pharmacokinetics of both atropine sulfate and obidoxime were proportional at 1 and 3 human equivalent doses, and only a small increase in heart rate was observed briefly as a side effect.At both sarin challenge doses, 54 μg/kg and 84 μg/kg, the co-formulation treatment was effective against sarin-induced effects. Survival rates were improved at both sarin challenge levels, whereas clinical signs and changes in EEG activity could not in all cases be effectively mitigated, in particular at the supralethal sarin challenge dose level. Reactivation of sarin inhibited cholinesterase was observed in blood, and higher brain cholinesterase activity levels were associated with a better clinical condition of the co-formulation treated animals.Although the results cannot be directly extrapolated to the human situation, pharmacokinetics and the effects over time related to plasma levels of therapeutics in a freely moving guinea pig could aid translational models and possibly improve prediction of efficacy in humans.