Acetylcholinesterase In Serum Research Articles

The ameliorative potential of platelet-rich plasma and exosome on renal ischemia/reperfusion-induced uremic encephalopathy in rats.

Uremic Encephalopathy results from the elevation of toxins and blood-brain barrier (BBB) disruption. Renal Ischemia/Reperfusion (I/R) injury is the principal cause of acute kidney injury and brain tissue injury. The present study was crafted to estimate the restorative impact of platelet-rich plasma (PRP) and exosome injection before the reperfusion phase on the kidney following renal I/R injury and its influence on brain tissue by tracking the histopathological, biochemical, and Doppler ultrasonography alternations in both kidney and brain tissue. Forty mature male rats were divided into five groups as follows: control, I/R, PRP, exosome, and Exosome + PRP. Renal Doppler ultrasonography was traced for all rats. Serum kidney functions and acetylcholine esterase enzyme (AchE) were evaluated. Both Gamma-aminobutyric acid (GABA) and glutamate were assessed in brain tissues. The oxidative stress (malondialdehyde), anti-oxidative (glutathione and catalase), and pro-inflammatory (Tumor necrosis factor- α and interleukin-6) markers were estimated in renal tissues. Additionally, morphometric histological examination was performed in both renal and brain tissues. Both PRP and exosome-received rats exhibited a significant improvement in both serum kidney functions and AchE compared to I/R rats. There was a 3.39-fold increase in GABA and a 2.27-fold decrease in glutamate levels in the brain tissue of PRP rats compared to the I/R rats. A significant elevation (P ≤ 0.0001) of glutathione and catalase besides a significant reduction in the expression of TNF-α and IL-6 was observed in renal tissue compared to I/R rats. A significant severe reduction (P < 0.0001) in the number of Purkinje cells, pyramidal cells in the cerebellar cortex, and the CA1 region in the hippocampus was observed in I/R rats which was significantly alleviated by both PRP and exosome. Furthermore, there was a significant improvement in Doppler parameters. PRP exerted a significant superior impact on the restoration of kidney functions and repairing uremic-induced damage in brain tissue.

Reactivation by novel pyridinium oximes of rat serum and skeletal muscle acetylcholinesterase inhibited by organophosphates.

The treatment of organophosphate (OP) anticholinesterases currently lacks an effective oxime reactivator of OP-inhibited acetylcholinesterase (AChE) which can penetrate the blood-brain barrier (BBB). Our laboratories have synthesized novel substituted phenoxyalkyl pyridinium oximes and tested them for their ability to promote survival of rats challenged with lethal doses of nerve agent surrogates. These previous studies demonstrated the ability of some of these oximes to promote 24-h survival to rats challenged with a lethal level of highly relevant surrogates for sarin and VX. The reactivation of OP-inhibited AChE in peripheral tissues was likely to be a major contributor to their efficacy in survival of lethal OP challenges. In the present study, twenty of these novel oximes were screened in vitro for reactivation ability for AChE in rat skeletal muscle and serum using two nerve agent surrogates: phthalimidyl isopropyl methylphosphonate (PIMP, a sarin surrogate) and 4-nitrophenyl ethyl methylphosphonate (NEMP, a VX surrogate). The oximes demonstrated a range of 23%-102% reactivation of AChE in vitro across both tissue types. Some of the novel oximes tested in the present study demonstrated the ability to more effectively reactivate AChE in serum than the currently approved oxime, 2-PAM. Therefore, some of these novel oximes have the potential to reverse AChE inhibition in peripheral target tissues and contribute to survival efficacy.

Laxative effect of Wenyang Yiqi Decoction on loperamide-induced astriction model mice.

Although a common disease, astriction is difficult to treat and severely affects quality of life. Wenyang Yiqi Decoction (WYD) is a kind of traditional Chinese medicine (TCM) that is used to treat astriction; however, the mechanism remains unclear. Therefore, this work assessed the laxative effect of WYD on loperamide-induced astriction (LIA) model mice. We replicated a constipation model in mice and detected changes in fecal parameters such as feces quantity and water content, intestinal transit function, and histopathological changes in the constipated mice. After five days of WYD intervention, mouse tissues were taken out for detection. We also measured the levels of gastrin (Gas), substance P (SP), acetylcholinesterase (AChE), and vasoactive intestinal peptide (VIP) in the mice's serum. Additionally, we used quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot to detect c-Kit and stem cell factor (SCF), and examined the effects of WYD on the tight junction (TJ) proteins occludin (Ocln), zonula occludens-1 (ZO-1), and claudin-1 (Cldn-1) in the mice's intestines. Through histopathological changes, we observed less destruction of epithelial cells and greater integrity of goblet and epithelial cells in WYD-treated mice than in mice in the loperamide group. qRT-PCR and western blot analysis of c-Kit and SCF showed that WYD could boost the levels of c-Kit and SCF. The qRT-PCR and immunohistochemical (IHC) analyses of enteral tight occludin (Ocln), occludenas-1 (ZO-1), and cldin-1 (Cldn-1) showed that WYD could boost the level of ZO-1 and decrease the level of Cldn-1. The study also investigated the effect of WYD treatment on the enteral barrier function of astriction model mice and found that the TJ proteins (ZO-1, Cldn-1) in the colon of the astriction model mice had significant changes compared to the normal group, and WYD intervention was found to increase the expression of ZO-1, and decrease the expression of Cldn-1. WYD alleviates LIA by regulating enteral hormones, boosting the number of interstitial cells of Cajal (ICCs), or adjusting enteral block action.

Consumption of Dietary Fiber with Different Physicochemical Properties during Late Pregnancy Alters the Gut Microbiota and Relieves Constipation in Sow Model.

Constipation is a common problem in sows and women during late pregnancy. Dietary fiber has potential in the regulation of intestinal microbiota, thereby promoting intestinal motility and reducing constipation. However, the effects of fibers with different physicochemical properties on intestinal microbe and constipation during late pregnancy have not been fully explored. In this study, a total of 80 sows were randomly allocated to control and one of three dietary fiber treatments from day 85 of gestation to delivery: LIG (lignocellulose), PRS (resistant starch), and KON (konjaku flour). Results showed that the defecation frequency and fecal consistency scores were highest in PRS. PRS and KON significantly increased the level of gut motility regulatory factors, 5-hydroxytryptamine (5-HT), motilin (MTL), and acetylcholinesterase (AChE) in serum. Moreover, PRS and KON promoted the IL-10 level and reduced the TNF-α level in serum. Furthermore, maternal PRS and KON supplementation significantly reduced the number of stillborn piglets. Microbial sequencing analysis showed that PRS and KON increased short-chain fatty acids (SCFAs)-producing genera Bacteroides and Parabacteroides and decreased the abundance of endotoxin-producing bacteria Desulfovibrio and Oscillibacter in feces. Moreover, the relative abundance of Turicibacter and the fecal butyrate concentration in PRS were the highest. Correlation analysis further revealed that the defecation frequency and serum 5-HT were positively correlated with Turicibacter and butyrate. In conclusion, PRS is the best fiber source for promoting gut motility, which was associated with increased levels of 5-HT under specific bacteria Turicibacter and butyrate stimulation, thereby relieving constipation. Our findings provide a reference for dietary fiber selection to improve intestinal motility in late pregnant mothers.

Quercetin Abrogates Oxidative Neurotoxicity Induced by Silver Nanoparticles in Wistar Rats

This study aimed to investigate the oxidative neurotoxicity induced by silver nanoparticles (AgNPs) and assess the neuroprotective effects of quercetin against this toxicity. Forty adult male rats were divided into four equal groups: control, AgNPs (50 mg/kg intraperitoneally), quercetin (50 mg/kg orally), and quercetin + AgNPs. After 30 days, blood and brain tissue samples were collected for further studies. AgNP exposure increased lipid peroxidation and decreased glutathione peroxidase, catalase, and superoxide dismutase activities in brain tissue. AgNPs decreased serum acetylcholine esterase activity and γ-aminobutyric acid concentrations. AgNPs upregulated tumor necrosis factor-α, interleukin-1β, and Bax transcript levels. AgNPs reduced the transcripts of claudin-5, brain-derived neurotrophic factor, paraoxonase, nuclear factor-erythroid factor 2 (Nrf2), and Bcl-2. Histopathologically, AgNPs caused various degenerative changes and neuronal necrosis associated with glial cell reactions. AgNPs increased the immunohistochemical staining of glial fibrillary acidic protein (GFAP) in the cerebrum and cerebellum. Oral treatment with quercetin efficiently counteracted the opposing effects of AgNPs on brain tissue via modulation of tight junction proteins, Nrf2, and paraoxonase, and its positive mechanism in modulating pro-inflammatory cytokines and the downregulation of GFAP expression, and the apoptotic pathway. AgNPs also altered the severity of histopathological lesions and modulated GFAP immunostaining in the examined tissue.

The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure

Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence.

Correlation of Serum Amylase, Lipase and Creatine Kinase with Severity of Organophosphate Poisoning- A Cohort Study

Introduction: Organophosphate Compounds (OP) are widely used pesticides in agriculture. It is easily available and OP poisoning is most common cause of poisoning and hospital admissions. Severe poisoning is associated with high mortality. Severity of poisoning can be assessed by Peradeniya Organophosphorus Poisoning (POP) scale, Acute Physiology and chronic Health Evaluation (APACHE) II, Glasgow Coma Scale (GCS) or serum Cholinesterase Level (ChE). Serum amylase, lipase, and creatine kinase are important biomarkers raised in OP poisoning. Aim: To correlate serum amylase, lipase, and creatine kinase with severity of OP poisoning. Materials and Methods: This was a hospital based observational cohort study conducted on 130 patients of organophosphate poisoning admitted in General Medicine wards of SCB Medical College, Cuttack, Odisha from June 2019 to December 2020. Serum Acetylcholine Esterase (AChE), amylase, lipase and creatinine kinase were estimated at admission, day 2, and at discharge. Other routine investigations were done. Acetylcholine Esterase (AChE) was used to confirm the diagnosis. The severity of poisoning was assessed using POP scale and graded as mild, moderate and severe. The severity of poisoning and the level of enzymes were correlated. The parameters were tabulated and mean values and Standard Deviation (SD) were analysed using Statistical Package For The Social Sciences (SPSS) software version 22.0. Results: Out of 130 patients 91 were males and 39 were females, mostly from rural areas, both farming and non-farming community. Age ranged from 14 years to 79 years, with majority in 19 to 39 years. AChE decreased in all cases depending on severity confirming OP poisoning. Severity as assessed by POP score were mild (52 patients), moderate (46 patients) and severe (32 patients). At admission, the Amylase (U/L), Lipase (U/L), and Creatine kinase (U/L) level (mean±SD) in mild poisoning were 83.7±41.9 U, 70.9±18.6, 72.5±34.9, in moderate poisoning 153.6±109.7, 91.9±47.4, 92.6±81.5, and in severe poisoning 243.9±113.8, 195.3±147.7, 298.8±207.4, respectively. Measurements on second day also remained elevated. Among the severe cases 24 patients developed Intermediate Syndrome (IMS), and 26 patients died. There was positive correlation between increase of enzyme levels and the severity of OP poisoning as per POP score. Conclusion: Serum amylase, lipase, and creatine kinase level correlated well with the severity of organophosphorus poisoning and scan be used additionally as an indicator to assess the severity. Serum amylase is a better indicator of severity than lipase and Creatine Kinase (CPK).

Clinical profile of patients presenting with inhalational organophosphorus poisoning in central India: a retrospective study

Background: World Health Organisation (WHO) report through International Programme on Chemical Safety (IPCS), poisoning is a significant global public health problem. According to WHO data, in 2012 an estimated 193,460 people died worldwide from unintentional poisoning. Intentional and unintentional pesticide poisoning has been acknowledged as a serious problem in many countries, including India, Limited literature available on clinical profile of organophosphorus poisoning cases, with this background present study was attempted. Objective of the study was to know the clinical presentation of OP poisoning cases admitted in tertiary care hospital.Methods: A retrospective record based observational study was conducted.Results: A total of 535 patients presented in the emergency department with the clinical features of OP poisoning. Mean age of the persons presenting in the emergency was 33.3±10.1 years. Nausea and vomiting is the most commoner symptom reported by 60.7% of patients followed by giddinesss (41.3%), loose motion (28.2%) and secretions (9.5%). Signs like abnormal pupil size, fasciculations and inability to neck holding were common with 23.55% 19.3% and 21.1% respectively. Statistical significance was found between Serum acetylcholine esterase level and outcome of patients (p&lt;0.01). 96.1% received treatment less than half an hours. 18 patients required ventilator and among these 13 were died.Conclusions: Majority of the patients were of young age with males outnumbering females. Nausea and vomiting was the most common symptom reported by the patients while abnormal pupil size was the most common sign observed at the emergency department.

Synthesis, Structural and Biological Studies of Some Metal Complexes derived from Tridentate Pyrazole-based Ligand

The new derivatives of heterocyclic resulting, studying spectral Cobalt(II), Nickel(II), Copper(II), and Cadmium (II) with new tridentate ligand namely [3-(1-acetyl-4-[4- (dimethylamino)phenyl]-1H-pyrazol-3-yl)-4-hydroxy-6-methyl-5,6-dihydro-2H-pyran-2-one] which was formed by the (E)-3-(3-(4-(dimethylamino) phenyl)acryloyl)-4-hydroxy-6-methyl- 2H-pyran-2-one with excess of hydrazine monohydrate in glacial acetic acid. NMR, FTIR, MS spectra as well as the elemental analyses, identified the new ligand and TLC was carried out to confirm their structures. The Cobalt (II), Nickel (II), Copper (II) and Cadmium (II) were precipitated by direct reactions of their chlorides with the solution of the ligand in 2:1 molar ratios. All complexes have been identified on the basis of the preliminary analysis, infrared, ultraviolet spectra of the visible moments of magnetic conductivity measurements were conducted for radiation conclude the octahedral geometry around Cobalt (II), Copper (II), and Nickel (II). The Cadmium (II) complex was investigated as tetrahedral in 1:1 ratio. The biological activity of the ligand and its metal complexes in DMSO against some bacterial strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and P. aeruginosa). Effected of the syntheses of HL ligand, [Co(L)2] and [Cu(L)2] complexes were studied on Acetylcholinesterase (AChE) in healthy human serum. Results indicated that all of the compounds displayed moderate and selective AChE inhibitory activity. The complexes of [Cu(L)2] and [Co(L)2] showed inhibition constant in the range (Ki: 8.333×10-4, 3.159×10–12, 2.5×10-6, 3.333×10-4 M respectively) higher than HL ligand (1.1×10-4, 1.964×10–12 respectively) M for AChE.

Effects of Guilingji on Aging Rats and Its Underlying Mechanisms.

Guilingji (GLJ), a traditional Chinese medicine, is of wide concern because of its remarkable antiaging effect with a long application history. It mainly consists of traditional Chinese herbs, that is, Ginseng radix et rhizoma rubra. This study focused on the anti-aging effects of GLJ on natural aging rats and its underlying mechanisms. Morris water maze was used to determine the learning and memory ability of rats. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), acetylcholine (ACh), and acetylcholinesterase (AChE) in serum were determined. Furthermore, a 1H-NMR-based serum metabolomics coupled with multivariate data analysis was used to identify potential biomarkers and corresponding metabolic pathways. The results showed that GLJ significantly improved the learning and memorial dysfunctions of natural aging rats. The mechanisms of the anti-aging and memory ameliorative effects of GLJ related to balancing oxidative stress, improving cholinergic system. Its specific mechanism of action may be through regulating pyruvate metabolism and arginine and proline metabolism.

Quercetin plays protective role in oxidative induced apoptotic events during chronic chlorpyrifos exposure to rats.

Chlorpyrifos (CPF), an organophosphate insecticide has a wider application throughout the world to protect agricultural crops and vegetables from insects. Polyphenolic compounds are considered as beneficial against toxicities induced by organophosphates. The present study was conducted to understand the neuroprotective role of quercetin in chlorpyrifos-induced apoptotic events in rats. Twenty-four male Sprague Dawley rats weighing 170 to 200 g were divided into four groups viz: Control, chlorpyrifos treated (13.5 mg/kg body wt. alternate day), quercetin treated (50 mg/kg body wt. every day) and combined chlorpyrifos + quercetin treated. All the treatments were carried out for a total duration of 60 days. Protein carbonyl content and acetylcholinesterase activity were estimated in serum along with cerebrum and cerebellum to ascertain neurotoxicity. Further, for appraisal of neurodegeneration as a consequence of apoptosis, protein expressions of Bcl-2, Bax, cytochrome c, caspase-8, and caspase-9 were assessed. The results showed that protein carbonyl contents were markedly increased in both serum and brain tissues (cerebrum and cerebellum) of chlorpyrifos-treated rats when compared with control group and were appreciably improved upon simultaneous supplementation with quercetin. Further, chlorpyrifos treatment revealed a significant decrease in the enzyme activity of acetylcholinesterase in serum as well as in cerebrum and cerebellum, which however was increased upon concomitant treatment with quercetin. In chlorpyrifos-treated animals, we have observed a significant decrease in the protein expression level of Bcl-2, but a remarkable increase in the expression levels of Bax, cytochrome c, caspase-8, and caspase-9 in both cerebrum and cerebellum. Interestingly, when chlorpyrifos-treated animals were supplemented with quercetin, a significant increase in the expression of Bcl-2 and an appreciable decline in the expression levels of Bax, cytochrome c, caspase-8, and caspase-9 was observed. In conclusion, the present study advocates that quercetin may prove to be a useful candidate in containing the oxidative-induced apoptotic events during chlorpyrifos exposure.

Potential role of α-lipoic acid and Ginkgo biloba against silver nanoparticles-induced neuronal apoptosis and blood-brain barrier impairments in rats

AimsThis study explored whether silver nanoparticles (AgNPs) can disrupt tight-junctions integrity resulted in blood-brain barrier dysfunction along with oxidative stress, pro-inflammation, and apoptosis induction. Additionally, neuroprotective activities of α-lipoic acid (LA) and Ginkgo biloba (GB) were investigated. Main methodsForty adults rats were enrolled into; Control, AgNPs (50 mg/kg), LA (100 mg/kg) + AgNPs, and GB (120 mg/kg) + AgNPs. After 30 days, neuronal changes were assessed biochemically and histopathologically. Brain tissues oxidative indices, mRNA expression of proinflammatory cytokines and tight-junction proteins and pro-apoptotic biomarker, caspase-3 were investigated. Key findingsAgNPs exposure enhanced lipid peroxidation (+195%) along with declines in glutathione (−43%), glutathione peroxidase (−34%), glutathione S-transferase (−31%), catalase (−43%), and superoxide dismutase (−38%) activities in brain tissues. The apparent brain oxidative damage was associated with obvious neuronal dysfunction that was ascertained by neuropathological lesions. AgNPs lowered serum acetylcholine esterase, iron and copper levels, and increased creatine phosphokinase and creatine phosphokinase–brain type activities. Following AgNPs exposure, brain silver and iron contents were increased, but the copper level was decreased. AgNPs up-regulated TNF-α (6.5-fold) and IL-1β (8.9-fold) transcript levels, and simultaneously over-expressed the caspase-3 protein in cerebrum and cerebellum inducing cell apoptosis. Moreover, AgNPs down-regulated the transcript levels of tight-junction proteins; JP-1 (0.65-fold) and JAM-3(0.81-fold). SignificanceLA and relatively GB improved the serious effects of AgNPs on the blood-brain barrier function and tight-junction proteins through their antioxidants, anti-inflammatory, and anti-apoptotic efficacies. Co-treatment with LA or GB may be favorable in ameliorating the neurotoxic side effects of AgNPs.

Understanding the role of quercetin during neurotoxicity induced by Chlorpyrifos

Organophosphate Chlorpyrifos (CPF), a pesticide, is widely used across the world to control worms and insects. It is highly toxic and causes neurobehavioral disorders. Naturally occurring compounds having polyphenols as their structural units are considered beneficial against toxicities inflicted by organophosphates. The present study reports that quercetin, a polyphenol, provides neuroprotection following neurotoxicity induced by chlorpyrifos. To carry out the study, male Sprague Dawley rats weighing 170-200g were segregated into four groups viz: normal control, CPF treated (13.5mg/kg b. wt. alternate day), Quercetin treated (50mg/kg b. wt. every day) and combined CPF +Quercetin treated. All the treatments were carried out for a total duration 60 day. Rota-rod performance test and Actophotometer test were undertaken to evaluate the locomotor activity and muscular strength of animals. Further, experiments were also conducted to assess neurotoxicity and structural alterations of cerebrum and cerebellum of brain, if any, inflicted by chlorpyrifos. The results revealed a significant decrease in locomotor activity as well as muscular strength of animals following chlorpyrifos treatment which however were appreciably improved upon simultaneous supplementation with quercetin. Further, treatment with chlorpyrifos resulted in a significant decrease in the activity of acetyl cholinesterase in serum as well as in cerebrum and cerebellum which however was increased upon co-treatment with quercetin. On the contrary, we noticed a significant increase in the levels of acetylcholine both in cerebrum and cerebellum which were modulated upon supplementation of quercetin. Light micrographs of both cerebrum and cerebellum showed histoarchitectural alterations which were improved upon co-treatment with quercetin. This study therefore concludes that quercetin when used as a prophylactic intervention would provide protection against CPF induced neurotoxicity.

Neuroprotective potential of crocin against malathion-induced motor deficit and neurochemical alterations in rats.

In several epidemiological studies, an association between pesticide exposure and the incidence of Parkinson's disease (PD) has been reported. Increasing evidence showed that oxidative stress plays an important role in the pathogenesis of PD. The present study investigated the preventive effect of crocin, saffron active components, on malathion (an organophosphate pesticide (OP))-induced Parkinson-like behaviors in rat. Rats were divided into eight groups: control (normal saline), malathion (100mg/kg/day, i.p), crocin (10, 20, or 40mg/kg/day, i.p) plus malathion, levodopa (10mg/kg/day, i.p) plus malathion, crocin (40mg/kg/day, i.p), and PEG (vehicle of levodopa) groups. Treatments were continued for 28days. The neurobehavioral tests which include open field, rotarod and catalepsy were performed on day 28. The activity of acetylcholinesterase (AChE) in serum, the levels of malondialdehyde (MDA), reduced glutathione (GSH), TNF-α, and IL-6 in striatum at the end of treatments were evaluated. Results showed that malathion induced neurobehavioral impairments together with elevation of MDA, TNF-α and IL-6 levels, reduction of GSH, and AChE activity. Crocin (10, 20, and 40mg/kg) improved neurobehavioral impairments induced by malathion but not AChE activity. Crocin (10, 20, and 40mg/kg) or levodopa plus malathion decreased MDA and increased GSH. Also crocin (10mg/kg) decreased TNF-α and IL-6 levels in striatum. In summary, subchronic malathion exposure induced Parkinson-like behavior in rat. Crocin exhibited protective effects against malathion-induced Parkinson-like behavior through reducing lipid peroxidation, improvement of motor deficit and anti-inflammatory effects.

Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation.

Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.

English

This study aimed to assess the correlation of serum lactate and creatine phosphokinase (CPK) levels, and their association with severity of organophosphrus poisoning in order to use one of them or both as tools in predicting prognosis. This study was conducted over one year and 68 organophosphate (OP)-poisoned patients were enrolled. Clinical severity of cases was categorized according to Peradeniya organophosphorus poisoning (POP) scale. Levels of serum acetyl choline esterase (AChE), serum CPK and serum lactate were measured on admission (0 h), 6 and 24 h post-ingestion. The results showed a high statistically significant difference between cases and control regarding AChE, CPK and lactate on admission. Also, there was high statistically significant difference regarding AChE, CPK and lactate among different categories of cases on admission, 6 and 24 h post admission. In addition, there was a statistically significant increase among different categories of POP scale regarding the quantity of atropine used in management of cases. Regarding oximes and stay in ICU, there was a statistically significant increase in severe poisoned patients when compared with moderate poisoned ones. A significant negative correlation was observed between AChE and severity of poisoning as well as significant positive correlation between CPK and lactate. It is concluded that serum CPK and serum lactate can be used as predictor of outcomes in OP poisoning and helps in determining cases that need follow up. Serum CPK and serum lactate can be used as predictors of outcomes in OP poisoning and helping in determining the cases that need follow up. Key words: Organophosphrus poisoning, serum lactate, predicting prognosis, serum, admission.

Evaluating Diagnostic Value of Electrophysiological Testing (EMG-NCV) Compared to the Activity Level of Acetylcholinesterase in Serum and Red Blood Cells of Patients with Moderate to Severe Organophosphate Poisoning

Abstract Background: Organophosphate compounds cause poisoning and death more than any other insecticide. These toxins can cause peripheral neuropathy which is delayed for about 3 - 6 weeks and no method has been known for predicting the incidence. It has been claimed that electrophysiological tests (EMG - NCV) can help in predicting the disorder. Objectives: The main purpose of this research was to study EMG - NCV tests in patients with moderate to severe organophosphate poisoning. Methods: This was a cross-sectional study conducted on patients with moderate to severe organophosphate poisoning from 2014 to 2016 in Imam Reza hospital of Mashhad. The minimum sample size was calculated as 68 patients and then all data was collected on the basis of inclusion and exclusion criteria using data collection form designed by the researcher, and finally data were analyzed using SPSS V.21 software, descriptive tests (including mean, median, mode) and analytical tests (K square, ANOVA). Results: Of all 78 patients with the mean age of 27.5010.0, 45 were female and the rest were male. Totally 29.5% of the patients had abnormal EMG - NCV. Although no significant differences were observed between electro diagnostic tests (EMG - NCV) and age, gender, clinical symptoms and levels of acetylcholinesterase serum activity, the relationship between EMG - NCV and RBC levels of acetylcholinesterase activity was significant. Conclusions: Electrophysiological tests are not associated with clinical symptoms (muscle weakness) and they cannot be considered as a determining factor to discharge the patients; therefore, careful examination of the patients or evaluating the level of AChE activity in red blood cells is needed.

The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer's disease

To analyze the activity of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and neprilysin (NEP) in the blood serum in elderly people with different types of cognitive impairment and evaluate the effect of ceraxon on the biochemical parameters. Three groups of patients: without cognitive disorders (controls--CG), with amnestic mild cognitive impairment (а-MCI) and with Alzheimer's disease (AD were studied). The activity of AChE, BChE and NEP was reduced in the blood serum of patients with a-MCI and, to the greater extent, in patients with AD compared to CG and correlated with the level of cognitive dysfunction evaluated by MMSE, ADAS-cog, and other tests. For the first time, it has been shown that treatment of a-MCI patients with ceraxon (citicolin) results in an increase of the activity of blood serum AChE, BChE and NEP to the values observed in the CG. Thus, the activities of blood serum AChE, BChE and NEP reflect the level of cognitive dysfunction and can be used as prognostic biomarkers of the level of dementia progression in patients with impaired memory.

Preventive Effect of Lactobacillus fermentum Zhao on Activated Carbon-Induced Constipation in Mice.

The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1×10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1×10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB.

Preventive effect of Dendrobium candidum Wall. ex Lindl. on activated carbon-induced constipation in mice.

The aim of this study was to investigate the effects of Dendrobium candidum Wall. ex Lindl. (D. candidum) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered D. candidum for 9 days. Body weight, defecation status, gastrointestinal (GI) transit and defecation times, in addition to the levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were used to evaluate the preventive effects of D. candidum on constipation. The laxative drug bisacodyl acted as a positive control. The time to the first defecation of a black stool for the normal, control, bisacodyl-treated (100 mg/kg), 200 and 400 mg/kg D. candidum-treated mice was 84, 202, 126, 161 and 142 min, respectively. Following the consumption of 200 and 400 mg/kg D. candidum or bisacodyl (100 mg/kg), the GI transit was reduced to 57.7, 74.6 and 90.2%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with D. candidum compared with those in the untreated control mice (P<0.05). These results demonstrate that D. candidum has preventive effects on constipation in mice, and a greater functional activity was observed when a higher concentration was administered.