Decreased Serum Cholinesterase Research Articles

Decreased Serum Cholinesterase Activity- A Reliable Diagnostic Aid for Tuberculosis

Introduction: Siderophore, the low molecular weight ferric iron chelator, is secreted extracellularly by Mycobacterium tuberculosis, an obligate aerobe. The pathogenic mycobacteria need iron as co-factor for the extracellularly secreted enzyme Superoxide Dismutase (SOD) for its pathogenicity as well as it requires iron for its metabolic functions like reduction of oxygen for synthesis of Adenosine Triphosphate (ATP), etc. The termination of impulse conduction is endorsed by the rapid hydrolysis of Acetylcholine (ACh) by Acetylcholinesterase (AChE) in the central as well as peripheral nervous system (cholinergic pathway). The inhibitors to Cholinesterase (ChE) might lead to accumulation of ACh, hyper stimulation of nicotinic and muscarinic receptors and also disruption of neurotransmission. Possibility of an inhibitor substance for AChE in Tuberculosis (TB) patients interestingly correlates with the symptom of night sweating in those subjects. Aim: To assay the level of serum ChE in normal control, lung disease control and tubercular subjects;circumvent the serum ChE level as a diagnostic potential in TB at an early stage. Materials and Methods: The study was conducted on total 124 subjects, and were divided into three groups: Group 1: normal control (n=31), Group 2: lung disease control (n=31) and Group 3: patients suffering from TB {3A: pulmonary TB (n=31) and 3B: extrapulmonary TB (n=31)}. Serum ChE activity for all the subjects were measured according to the method of Hestrin S. Serum ChE level was assayed for group 3 subjects after additional one month’s anti-TB drug treatment and also for group 2 subjects after one month with usual treatment. The level of significance was assessed using Student’s t-test. Results: There was a significant inhibition of serum ChE activity in both pulmonary and extrapulmonary TB patients in comparison to that of in normal control as well as lung disease control subjects (p<0.01). With the anti-tubercular drug therapy for one month, there was significant recovery in the serum ChE activity in pulmonary as well as extrapulmonary tubercular subjects (p<0.01). Conclusion: It appears that the high level of hydroxamate type of siderophores (secreted by Mycobacterium tuberculosis for acquiring iron) might form ACh ferric hydroxamate complex binding more strongly with serum ChE resulting in inhibition of serum ChE activity in tubercular subjects. With anti-tubercular drug therapy, there was decrease in serum ACh ferric hydroxamate complex level resulting in recovery of serum ChE activity.

Prognostic significance of nutritional and inflammatory markers in patients with unresectable pancreatic ductal adenocarcinoma treated with chemotherapy.

219 Background: Recently, several nutritional and inflammatory markers have been reported to be involved in cancer progression. The aim of this study is to evaluate whether nutritional and inflammatory biomarkers such as the modified Glasgow prognostic score (mGPS), the neutrophil‐to-lymphocyte ratio (NLR), the platelet‐to-lymphocyte ratio, the systemic-immune-inflammation index (SIII), controlling nutritional status (CONUT) score, prognostic nutritional index, and the lymphocyte‐to-monocyte ratio (LMR) could predict the prognosis in patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) who underwent chemotherapy as first-line therapy, using disease-specific survival as the primary outcome. Methods: All UR-PDAC patients were retrospectively evaluated between January 2011 and May 2017 at Toyama University Hospital. Baseline clinicopathological characteristics and pre-treatment laboratory values such as absolute neutrophil, lymphocyte and platelet counts, C-reactive protein, albumin and CA19-9 levels, were collected. Results: A total of 184 patients were diagnosed as UR-PDAC. Among them, 151 patients who underwent chemotherapy were enrolled in this study. There were significant relationships between survival and elevated mGPS, elevated NLR, elevated SIII, decreased LMR, decreased serum cholinesterase level, and low CONUT score (p < 0.001, p < 0.001, p = 0.001, p < 0.001, p = 0.026 and p < 0.001, respectively, by log-rank test). The median survival time of patients with metastatic lesions was significantly shorter than that of patients with unresectable locally advanced PDAC (9.0 vs 15.5 months, respectively; p = 0.033). There was no significant difference in survival in pre-treatment CA19-9 level and tumor location. Multivariate analysis using Cox regression model revealed that NLR and CONUT score were independent prognostic factors. Conclusions: Pre-treatment NLR and CONUT score may predict clinical outcome in patients with UR-PDAC undergoing chemotherapy as first-line therapy.

Pneumatosis Cystoides Intestinales and Portomesenteric Venous Gas following Anticholinesterase Pesticide Poisoning

Pneumatosis cystoides intestinalis and portomesenteric venous gas are uncommon radiological findings, but are found commonly in cases of bowel ischemia, or as a result of various non-ischemic conditions. A 72-year-old man visited an emergency center with altered mental status 2 hours after ingestion of an unknown pesticide. On physical examination, he showed the characteristic hydrocarbon or garlic-like odor, miotic pupils with no response to light, rhinorrhea, shallow respiration, bronchorrhea, and sweating over his face, chest and abdomen. Laboratory results revealed decreased serum cholinesterase, as well as elevated amylase and lipase level. We made the clinical diagnosis of organophosphate poisoning in this patient based on the clinical features, duration of symptoms and signs, and level of serum cholinesterase. Activated charcoal, fluid, and antidotes were administered after gastric lavage. A computerized tomography scan of the abdomen with intravenous contrast showed acute pancreatitis, poor enhancement of the small bowel, pneumatosis cystoides intestinalis, portomesenteric venous gas and ascites. Emergent laparotomy could not be performed because of his poor physical condition and refusal of treatment by his family. The possible mechanisms were believed to be direct intestinal mucosal damage by pancreatic enzymes and secondary mucosal disruption due to bowel ischemia caused by shock and the use of inotropics. Physicians should be warned about the possibility of pneumatosis cystoides intestinalis and portomesenteric venous gas as a complication of pancreatitis following anticholinesterase poisoning.

Analysis of risk factors for acute kidney injury in patients with decompensated cirrhosis

To investigate the risk factors for and the prognosis of acute kidney injury (AKI) in decompensated cirrhotic patients. A total of 126 patients with decompensated cirrhosis and with (n =60) or without (n =66, control group) AKI were enrolled in this retrospective analysis. Follow-up was carried out on all patients, with durations ranging from less than 1 year to up to 4 years. Blood biochemistry, liver and renal functional parameters and prognosis of these patients were recorded. Logistic regression analysis was used to evaluate possible risk factors for decompensated cirrhotic patients developing AKI. The patients with AKI had a significantly lower survival rate than the patients without AKI (55.0% vs.83.3%, x2 =13.270, p =0.001). Unconditional multivariate logistic regression analysis identified risk factors of AKI development in decompensated cirrhotic patients as increased serum creatinine (odds ratio (OR):1034), increased total bilirubin (OR:1.005), increased international normalized ratio (INR; OR:2.471), decreased plasma sodium concentration (OR:0.910), decreased serum cholinesterase (OR:0.999), and decreased glomerular filtration rate (GFR; OR:0.972) (all P less than 0.05). The development of acute kidney injury represents an adverse prognosis in decompensated cirrhotic patients. An increase in serum creatinine, total bilirubin or INR or a decrease in plasma sodium concentration, serum cholinesterase or GFR may be early-warning factors of development of AKI in decompensated cirrhotic patients.

A case of decreased serum cholinesterase caused by distigmine bromide for patient of carcinoma of the lower gingiva

A case of decreased serum cholinesterase caused by distigmine bromide for patient of carcinoma of the lower gingiva

Do patients with liver cirrhosis undergoing cardiac surgery have acceptable outcomes?☆

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether patients with liver cirrhosis have acceptable outcomes after undergoing cardiac surgery. Altogether 97 papers were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, year, journal, country of study, study type, patient group studied, relevant outcomes, results and study weaknesses were tabulated. One prospective and another eight retrospective studies involving adult population of patients with liver cirrhosis undergoing various cardiac surgical procedures were selected. In these studies, the overall mortality was 17.1% and combined mean mortality for Child-Pugh class A, B and C was 5.2%, 35.4% and 70%, respectively. The major morbidity ranged from 20 to 60% in group A and 50 to 100% in the patients with more advanced hepatic disease. Some studies have demonstrated that thrombocytopenia, decreased serum cholinesterase and high preoperative total bilirubin levels are significantly associated with worse clinical outcomes. These studies, although with small samples, collectively demonstrate that patients with Child-Pugh class A cirrhosis tolerated cardiac surgical procedures with a mild increase in mortality and morbidity. However, the risk of mortality in patients with Child-Pugh class B and C or MELD score>13 is extremely high. Nevertheless, even if these patients underwent successful surgery, their long-term survival was significantly poorer and their health status remains compromised even well after cardiac surgery because of persistent liver dysfunction.

Common null variant, Arg192Stop, in a G‐protein coupled receptor, olfactory receptor 1B1, associated with decreased serum cholinesterase activity

Non-functioning single nucleotide polymorphisms (nSNPs) that result in premature termination codons, that is null-alleles of the respective genes, may have phenotypic effects on clinical parameters. We conducted association studies involving several G-protein coupled receptors (GPCRs) that harbor nSNPs, using clinical parameters of liver function in a general population consisting of 2969 Japanese adults. SNP typings were performed with TaqMan and Invader assays. Quantitative associations between genotypes and clinical parameters were analyzed by analysis of variance. Linkage disequilibrium (LD) was tested by Haploview Version 3.3. Haplotype-based association was performed using the haplo.stats program. A significant correlation (P = 0.0057) was identified between serum cholinesterase activity (CHE) and an nSNP (Arg192Stop) in the olfactory receptor (OR) 1B1 gene, a member of the GPCR gene family. This nSNP was associated with decreased serum CHE (P = 0.0013). LD analysis based on eight selected SNPs at the locus revealed three LD blocks. The Arg192Stop nSNP was located on the second LD block, which covered one-third of the 3'-portion of the gene. These results suggested that the null-allele of OR1B1 might affect metabolism of serum cholinesterase in carriers of this nSNP.

Human brain structural change related to acute single exposure to sarin

This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to sarin. Thirty-eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated. The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05). Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals.

The Effects of Acute and Repeated Pyridostigmine Bromide Administration on Response Acquisition with Immediate and Delayed Reinforcement

VAN HAAREN, F., R. DE JONGH, J. B. HOY, J. L. KARLIX, C. J. SCHMIDT, I. R. TEBBETT AND D.WIELBO. The effects of acute and repeated pyridostigmine bromide administration on response acquisition with immediate and delayed reinforcement. PHARMACOL BIOCHEM BEHAV 62(2) 389–394, 1999.—This experiment was designed to assess the effects of acute and repeated administration of pyridostigmine bromide (a carbamate with prophylactic and therapeutic uses) on response acquisition. Experimentally naı̈ve, male Sprague–Dawley rats were exposed to a situation in which lever presses were either immediately followed by food-pellet presentation or after a 16-s resetting delay. Different groups of rats received either one acute administration of pyridostigmine bromide (10 mg/kg, by gavage) or repeated pyridostigmine administration for 7 days (1.5 mg/kg/day, by gavage). Other groups were treated with distilled water for the same period of time. Both acute and repeated pyridostigmine bromide administration decreased serum cholinesterase levels by approximately 50%, but neither treatment affected brain cholinesterase levels in our assay. Acute and repeated drug administration produced the same behavioral effects. Subjects exposed to the 0-s delay conditions obtained many more food pellets than those exposed to the 16-s delay conditions. Administration of pyridostigmine bromide delayed the onset of responding in some, but not all, of the subjects in the treated groups, independent of the delay condition to which they were exposed. Many more responses were observed on an inoperative lever during the 16-s delay conditions than during the 0-s delay conditions, especially during the 16-s delay condition in which subjects had received acute vehicle administration. Whether or not these effects of small doses of pyridostigmine bromide on response acquisition are of central or peripheral origin will need to be determined in future studies, as response acquisition in the present experiment may have been affected by pyridostigmine’s effects on gastrointestinal functioning and/or motor activity.

Elevated frequency of sister chromatid exchanges in lymphocytes of victims of the Tokyo sarin disaster and in experiments exposing lymphocytes to by-products of sarin synthesis

More than 5000 passengers of Tokyo subway trains were injured with toxic chemicals including the nerve gas sarin. Most of the victims examined had marked miosis and decreased serum cholinesterase activity. To monitor the genetic aftereffects of sarin exposure, we measured sister chromatid exchanges (SCEs) of the victims using peripheral blood lymphocytes. The frequency of SCEs was significantly higher in the victims than in the control group. Analyzing results using samples of urine from the victims suggested that the victims were exposed to not only sarin per se, but by-products of sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and ethyl isopropyl methylphosphonate (EIMP). Thus, the in vitro SCE-inducing effect of DIMP, DEMP and EIMP was examined using human lymphocytes and we obtained positive results.

Biological monitoring of metabolites of sarin and its by-products in human urine samples.

More than 20,000 passengers of Tokyo underground trains were intoxicated with warfare toxic chemicals. Most of the patients examined had marked miosis and decreased serum cholinesterase activity. Transient increase of serum CPK activity after 3 days of the exposure was the another sign. We intensively analyzed the metabolites in the urine of 4 patients. The following analytic results indicated the exposure to sarin as well as contaminated compounds such as diisopropyl methylphosphonate (DIMP), ethyl methylphosphonate fluoridate (EMPF, or ethylsarin), diethyl methylphosphonate (DEMP), and ethyl isopropyl methylphosphonate (EIMP). (1) Isopropanol (IPA) and ethanol (EtOH) were detected of large quantities in the urine samples, and were thought to be derived from sarin and the sarin counterpart, EMPF, DIMP, DEMP and EIMP. (2) Monoalkyl methylphosphonic acids (isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) also were excreted in large amounts with taking the similar excretion pattern of IPA and EtOH. (3) The metabolite only derived from sarin and ethylsarin is F anions whose integral output in the urine was less than the equimolar level of the excreted (IMPA + EMPA + IPA + EtOH). (4) Other corroborative findings were low lethality: of more than 5,510 patients treated, 11 were acutely dead. (5) Nine exposed males had higher sister chromatid exchange (SCE) rate (5.00 +/- 1.48/cell) than the control (3.81 +/- 0.697/cell), because dialkyl methylphosphonates seemed to have alkylating activity and producing DNA adducts. The SCE rate also increased after the in vitro exposure of lymphocytes to dialkyl methylphosphonates.

Prevalence of congenital deficiency in serum cholinesterase.

The most economical blood test for the monitoring of workers who are exposed to organophosphate pesticides is serum cholinesterase; however, serum cholinesterase can be affected by conditions other than pesticide exposure. The results of studies in Europe indicate a 4% prevalence of congenital serum cholinesterase deficiency. Prevalence rates in the United States have not been reported. In this study, 127 workers who were part of an employee health program were evaluated. Workers who had decreased serum cholinesterase levels on baseline testing before pesticide exposure were evaluated for a congenital deficit in serum cholinesterase. Five (3.9%) individuals had baseline measurements below the laboratory normal reference value: 4 (3.1 %) were heterozygote for the deficiency, and the remaining individual did not return to test for the genetic deficiency. No one was found to have the homozygote deficiency. The prevalence of congenital deficiency in serum cholinesterase in a midwestern population was 3.1-3.9%. We found it useful to incorporate the knowledge of who has a congenital deficiency into our employee health program, the purpose of which is to monitor workers who spray organophosphates.

A Case of Acute Respiratory Failure with a Decrease of Serum Cholinesterase Caused by Distigmine Bromide

We presented a case of acute respiratory failure with decreased serum cholinesterase caused by an anticholinesterase agent (distigmine bromide).A 70-year-old man had been taking distigmine bromide for prostatic hypertrophy. He underwent coronary artery bypass grafting for unstable angina. Dyspnea, diarrhea and bradycardia were noticed on the 5th postoperative day. Blood gas analysis showed marked respiratory acidosis (facemask; O2 5l·min-1, pH7.186, PaCO2 86.4mmHg, PaO2 97.6mmHg and BE 12.6mml·l-1). The clinical features were similar to acute organophosphate poisoning. We diagnosed these symptoms as a cholinergic crisis from distigmine bromide poisoning as serum cholinesterase decreased to 91 (normal range: 3000-6500) IU·l-1. The clinical symptoms improved after stopping the administration of distigmine bromide.This case shows us that we should be aware of the possibility of acute respiratory failure due to cholinergic crisis in patients taking distigmine bromide.

Methicillin‐resistant staphylococcus aureus: colonization and development of infection in patients with haematological disorders

A retrospective study of 53 patients with haematological disorders whose bacterial cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA), was performed to analyse the risk factors for MRSA infection, and the prognostic factors. Sixteen patients showed colonization by MRSA but never developed infection(C), 16 showed colonization and subsequent infection(C-I), while 21 had MRSA infection at the time of first culture (I). Poor performance status, thrombocytopenia, increased serum urea nitrogen and decreased serum cholinesterase were more prominent in (I) than (C) + (C-I). The risk factors associated with the development of infection from colonization were age and serum cholinesterase. In addition, lower respiratory tract infection as a type of infection, non-remission status of the haematological malignancy and an inappropriate antibiotic therapy were associated with a poor prognosis for MRSA infection.

Succinylcholine Pharmacodynamics in Peripartum Patients

Leighton, B. L.; Cheek, T. G.; Gross, J. B.; Apfelbaum, J. L.; Shantz, B. B.; Gutsche, B. B.; Rosenberg, H. Author Information

Growth hormone modulates serum cholinesterase.

Adult male rats have lower serum cholinesterase activity levels than adult female rats and hypophysectomized male rats have higher activity levels than sham-operated males (similar to control females). GH administered to hypophysectomized male rats abolishes the effect of hypophysectomy on serum cholinesterase. Adult male rats treated neonatally with monosodium L-glutamate to induce arcuate nucleus lesions of the hypothalamus have higher serum cholinesterase activities and decreased serum GH concentrations. GH administered to these male rats results in decreased serum cholinesterase activities. These experiments demonstrate that GH is a negative modulator of serum cholinesterase in the male rat.

Succinylcholine pharmacodynamics in peripartum patients.

Serum cholinesterase activity decreases 30% during pregnancy and remains depressed during the postpartum period. However, succinylcholine recovery is not prolonged in term-pregnant patients. This contrasts with results obtained in other patients with decreased serum cholinesterase activity. To better understand this paradox, the authors compared serum cholinesterase activity and recovery from succinylcholine, 1 mg/kg, in nonpregnant (with and without oral contraceptive use), in term-pregnant, and in postpartum patients. Serum cholinesterase activity was lower in both term-pregnant (3.66 +/- 0.39 U/ml, means +/- SE) and postpartum (2.84 +/- 0.35 U/ml) patients than in nonpregnant patients not taking oral contraceptives (5.01 +/- 0.33 U/ml, P less than 0.05). Cholinesterase activity in postpartum patients also was significantly lower than in nonpregnant patients taking oral contraceptives (4.81 +/- 0.63, P less than 0.05). In contrast, the time to 25% twitch-height recovery did not differ between term-pregnant (470 +/- 56 s) and nonpregnant patients taking (499 +/- 29 s) or not taking (501 +/- 21 s) oral contraceptives, but was significantly increased in postpartum patients (685 +/- 22 s, P less than 0.001). The similar duration of action of succinylcholine in term-pregnant patients (with decreased serum cholinesterase activities) and nonpregnant patients may be related to the increased volume of distribution of succinylcholine at term.