Atividade basal de acetilcolinesterase e níveis plasmáticos de serotonina não se associam ao delirium em pacientes gravemente enfermos / Baseline acetylcholinesterase activity and serotonin plasma levels are not associated with delirium in critically ill patients

RESUMO Objetivo: Investigar se os níveis plasmáticos de serotonina e atividade de acetilcolinesterase determinados por ocasião da admissão à unidade de terapia intensiva preveem a ocorrência de disfunção cerebral aguda em pacientes internados em unidade de terapia intensiva. Métodos: Foi conduzido no período entre maio de 2009 e setembro de 2010 um estudo prospectivo de coorte em uma amostra com 77 pacientes não consecutivos. A ocorrência de delirium foi determinada utilizando a ferramenta Confusion Assessment Method for the Intensive Care Unit, tendo sido determinadas as avaliações de acetilcolinesterase e serotonina em amostras de sangue coletadas até um máximo de 24 horas após admissão do paciente à unidade de terapia intensiva. Resultados: No presente estudo, 38 pacientes (49,6%) desenvolveram delirium durante sua permanência na unidade de terapia intensiva. Nem os níveis de atividade de acetilcolinesterase nem os de serotonina tiveram associação independente com delirium. Não se observaram correlações significantes entre atividade de acetilcolinesterase e níveis de serotonina com o número de dias livres de delirium/coma, porém, em pacientes que desenvolveram delirium, ocorreu uma forte correlação negativa entre níveis de acetilcolinesterase e número de dias livres de delirium/coma, demonstrando que níveis mais elevados de acetilcolinesterase se associaram com menos dias de vida sem delirium e coma. Nenhuma associação foi identificada entre os biomarcadores e mortalidade. Conclusão: Nem a atividade de acetilcolinesterase nem os níveis séricos de serotonina se associaram com delirium ou disfunção cerebral aguda em pacientes gravemente enfermos. A ocorrência de sepse não modificou esse relacionamento. .

ABSTRACT Objective: The aim of this study was to investigate whether plasma serotonin levels or acetylcholinesterase activities determined upon intensive care unit admission could predict the occurrence of acute brain dysfunction in intensive care unit patients. Methods: A prospective cohort study was conducted with a sample of 77 non-consecutive patients observed between May 2009 and September 2010. Delirium was determined using the Confusion Assessment Method for the Intensive Care Unit tool, and the acetylcholinesterase and serotonin measurements were determined from blood samples collected up to a maximum of 24 h after the admission of the patient to the intensive care unit. Results: In the present study, 38 (49.6%) patients developed delirium during their intensive care unit stays. Neither serum acetylcholinesterase activity nor serotonin level was independently associated with delirium. No significant correlations of acetylcholinesterase activity or serotonin level with delirium/coma-free days were observed, but in the patients who developed delirium, there was a strong negative correlation between the acetylcholinesterase level and the number of delirium/coma-free days, indicating that higher acetylcholinesterase levels are associated with fewer days alive without delirium or coma. No associations were found between the biomarkers and mortality. Conclusions: Neither serum acetylcholinesterase activity nor serotonin level was associated with delirium or acute brain dysfunction in critically ill patients. Sepsis did not modify these relationships. .

Influence of Toxoplasma gondii Acute Infection on Cholinesterase Activities of Wistar Rats

Several studies have shown the mechanisms and importance of immune responses against Toxoplasma gondii infection and the notable role of cholinesterases in inflammatory reactions. However, the association between those factors has not yet been investigated. Therefore, the aim of this study was to evaluate the acetylcholinesterase (AChE) activity in blood and lymphocytes and the activity of butyrylcholinesterase (BChE) in serum of rats experimentally infected with T. gondii during the acute phase of infection. For that, an in vivo study was performed with evaluations of AChE and BChE activities on days 5 and 10 post-infection (PI). The activity of AChE in blood was increased on day 5 PI, while in lymphocytes its activity was enhanced on days 5 and 10 PI (P<0.05). No significant difference was observed between groups regarding to the activity of BChE in serum. A positive (P<0.01) correlation was observed between AChE activity and number of lymphocytes. The role of AChE as an inflammatory marker is well known in different pathologies; thus, our results lead to the hypothesis that AChE has an important role in modulation of early immune responses against T. gondii infection.

prognostic value of the Glasgow coma scale, serum acetylcholinesterase and leukocyte levels in acute organophosphorus poisoning

Organophosphate poisoning [OP] is a serious clinical condition that may sometimes be fatal. The aim of this study was to determine whether the Glasgow coma scale [GCS], and serum acetylcholinesterase and leukocyte levels have prognostic value in acute OP poisoning. Retrospective review of records of patients admitted to the intensive care unit of Selcuk University, Meram Medical Faculty, Emergency Department, Konya, Turkey, between January 2006 and January 2009. We studied acutely OP-poisoned patients admitted within 24 hours after OP exposure. The mean age of the 25 patients was 37 years [range, 20-80 years]. Three [12%] of the 25 patients [male-female ratio, 12:13] died. The mean GCS values of the patients who died were significantly lower compared to those of the group that survived [4 vs 11.7, respectively P<.05]. While the mean serum acetylcholinesterase levels were lower in the patients who died, the difference in the mean serum acetylcholinesterase levels between the patients who died and the ones who survived was not statistically significant [3841 IU/L vs. 1768 IU/L, respectively]. Although serum cholinesterase values can be used in the quick diagnosis, their efficiency at predicting outcome in patients with OP poisoning has not been established. It has also been determined that serum leukocyte values have no prognostic value in OP poisoning, but GCS values have been found to be effective in predicting the outcome

Evaluación bioquímica de trabajadores rurales expuestos a pesticidas / Biochemical evaluation on rural workers exposed to pesticides

Los pesticidas utilizados en agricultura pueden representar un riesgo potencial para la salud de los agricultores expuestos y para el medio ambiente. El objetivo de este trabajo fue evaluar trabajadores frutihortícolas expuestos a plaguicidas, categorizados por: exposición directa (n = 45), exposición indirecta (n = 50) y controles (n = 50) mediante biomarcadores de exposición y efecto: colinesterasa (ChE), acetilcolinesterasa (AChE), catalasa (CAT), peroxidación de lípidos (TBARS), Indice de Daño Ensayo Cometa (IDEC) e Indice de Daño Ensayo Reparación (IDER). Los resultados indican: a) inhibición significativa de AChE (p < 0.001) en expuestos directos e indirectos; b) aumento en los niveles de TBARS (p < 0.001) en los directos; c) reducción de CAT significativa (p < 0.01) y d) aumento de IDEC e IDER (p < 0.001) en ambos grupos. Los resultados obtenidos reflejan modificaciones en el balance oxidativo junto con daño al ADN en los trabajadores estudiados. Estos hallazgos representan una contribución en la evaluación subclínica de exposición a agroquímicos en nuestro país.

Pesticides are used in agriculture to protect crops but may represent a potential risk to farmers and the environment. The aim of this work was to evaluate horticultural workers exposed to pesticide, categorized by: direct exposure (n = 45), indirect exposure (n = 50) and controls (n = 50) using exposure and effect biomarkers: cholinesterase (ChE), acetylcholinesterase (AChE), catalase (CAT), lipid peroxidation (TBARS), Damage Index Comet Assay (IDEC) and Damage Index Repair Assay (IDER). Our results show: a) an AChE inhibition in directly and indirectly exposed population (p < 0.001), b) significant increase in the levels of TBARS in direct exposure (p < 0.001), c) the CAT reduction was significant (p < 0.01), d) a significant increase in IDEC and IDER in both exposed groups (p < 0.001). Our results evidence variations in oxidative balance and DNA damage in exposed workers. These findings represent a contribution to the sub-clinical evaluation of subjects exposed to agrochemicals in our country.

Propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function: Attenuation by Withania somnifera.

Propoxur (2-isopropoxyphenyl N-methylcarbamate) is widely used as an acaricide in agriculture and public health programs. Studies have shown that sub-chronic exposure to propoxur can cause oxidative stress and immuno-suppression in rats. Carbamates are also known to exhibit inhibitory effect on cholinesterase activity, which is directly related to their cholinergic effects. In the present study, the effect of Withania somnifera (Ashwagandha), a widely used herbal drug possessing anti-stress and immuno-modulatory properties was studied on propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function in rats. Male Wistar rats were divided into four groups. Group I was treated with olive oil and served as control. Group II was administered orally with propoxur (10 mg/kg b.wt.) in olive oil, group III received a combination of propoxur (10 mg/kg b.wt.) and W. somnifera (100 mg/kg b.wt.) suspension and group IV W. somnifera (100 mg/kg b.wt.) only. All animals were treated for 30 days. Cognitive behaviour was assessed by transfer latency using elevated plus maze. Blood and brain acetylcholine esterase (AChE) activity was also assessed. Oral administration of propoxur (10 mg/kg b.wt.) resulted in a significant reduction of brain and blood AChE activity. A significant prolongation of the acquisition as well as retention transfer latency was observed in propoxur-treated rats. Oral treatment of W. somnifera exerts protective effect and attenuates AChE inhibition and cognitive impairment caused by sub-chronic exposure to propoxur.

Peripheral nerve dysfunction among workers with long term occupational exposure to pesticides

A comparative cross-section study was carried out on 36 workers with long-term exposure to pesticide [pesticide sprayers] and 20 pesticide unexposed controls, from Dekernes, Dakahlia Governorate, Egypt. General medical examination and neurological evaluation were performed to elicit sensory, motor manifestation; as well as neurophysiological study including nerve conduction and electromyography. Plasma cholinesterase level was estimated and correlated to neurological findings. Carbamates and Organophosphates were sprayed by most pesticide sprayers. Most of them had practiced pesticide application with improper personal hygiene, concerning: storage, mixing and preparation, spraying, disposal, and after work cleaning up. Symptoms of neuropathy; lower limbs sensory nerve signs; ankle hyporeflexia were insignificantly prevalent among pesticide sprayers while no motor signs were detected among them. A highly significant decrease of the conduction velocity and amplitude of motor unit action potential [MUAP] of the lower limbs examined nerves, and insignificant decrease of their terminal latencies was observed among pesticide sprayers compared to the control. This picture is not evident in the upper limbs examined nerves, in which the conduction velocities are decreased but with no statistical significant difference. This was consistent with axonal neuropathic affection of the examined lower limbs nerves. As regards sensory nerve conduction study there was a highly significant increase of the terminal latency; highly statistical significant decrease of the CV and amplitude of the superficial peroneal nerves and significant decrease of amplitude of upper limbs examined nerves among pesticide sprayers when compared with that of controls. Accordingly peripheral poly neuropathies were found to be more prevalent among pesticide sprayers [38.9%] compared to the control [5.0%]. Of them, 78.6% were subclinical neuropathies and 21.4% were possible neuropathies. Pesticide sprayers had a highly statistically significant lower plasma AChE mean level [1548.9 +/- 801.7 mu/ml] compared to the controls [6751.7 +/- 990.8 mu/ml]. The pesticide sprayers who worked from 15-20 years had the lowest AChE mean level, but the difference was statistically insignificant. Among pesticide sprayers, the means of AChE levels were significantly lower in the workers with neuropathy [981.7 +/- 524.9 mu/ml] more than those without neuropathy [1911.9 +/- 742.5 mu/ml]. Neuropathy was more prominent among sprayers who exposed for long duration [more than 5 years] [11.1 +/- 4.5 years]. Pesticide sprayers are vulnerable to develop peripheral neuropathy 2.78 folds increase when compared to controls. So reduction and legislative control of the pesticide use and disposal seem the best options to protect pesticide sprayers, farmers and the environment from the adverse effects of pesticides. Also the use of protective equipment, the adoption of safety practices during field work, the health education programs about the risks of pesticide exposure, will help a lot to decrease the risk from the exposure to pesticides among pesticide sprayers. Pre-employment measurement of AChE, Occupational health surveillance and periodic medical monitoring with emphasis on the peripheral nervous system are recommended for all pesticide sprayers

Cardiotoxicity of acute organophosphate poisoning

To study the cardiotoxicity of acute organophosphate [OP], poisoning, this study was designed to evaluate 46patients who presented to the Benha poisoning control unit over a 14 months period from the 1st of March, 2007 to 30 April 2008, with acute OP poisoning and discus their associated cardiac complication and electrocadiographical [ECG] abnormalities. The serum level of cholinesterase [AChE] was significantly lower than the normal value. At the same time serum creatinine kinase [CK-MB] and cardiac trophonin I [CTnI] levels were significantly elevated at the time of admition indicating the presence some degree of cardiac injury. ECG changes confirmed the presence of cardiac injury. These was sinus tachycardia [34.78%] which the most common ECG abnormality, sinus bradycardia occurred in 9 patients [19.56%], hypertension developed in 6 patients [14.04%] and hypotension in 6 patients [13.04%]. OP induced impaired cardiac conductivity inform of prolongation of the QTc interval [32.61%] and prolonged PR interval [8.70%] and increased cardiac excitability in the form of extracystole [6.52%], ventricular tachycardia [2.17%] and atrial fibrillation [4.35%] and also induced myocardial cell injury manifested by elevated ST segment [15.22%]. Cardiac trophonin I [CTnI] level is indicated for diagnosis of cardiac injury due to OP poising when the patient is seen 3 days after intoxication. Most of cardiac complications associated with organophosphate occur during the first few hours after exposure. Sympathetic, parasymathatic over activity hypoxemia, acidosis and electrolyte derangements and a direct toxic effect of the OP on the myocardium are major predisposing factors for the development of these complications. The cardiac complications and ECG abnormalities all returned to normal before the patients were discharged. Initial complete ECG is recommended and should be obtained immediately in the Poison Control Unit in patients with acute OP or poisoning

Evaluation of suspected chronic pesticide poisoning among residents near agriculture fields

The present study was performed to evaluate the incidence of organophosphorus toxicity among agrarian and non agrarian subjects residing near agriculture fields. The location of this study was Nawakot village, Multan. From the cotton producing area of Multan, 225 volunteers [farmers] including 103 females and 122 males were selected. Children <12 years of age constitute 15% of the population. A total of 100 volunteers [non agrarians] from Multan city were taken as control. Blood [4 ml] was drawn from the volunteers to test the level of acetylcholine estrase [Ach E] in plasma. The blood samples were then analysed at the laboratory of National Poison Control Center [NPCC]. Organo-phosphate [OP] and carbamates [CM] both act to block Ach E hydrolysis, necessary for synaptic response in the CNS. Acute illnesses were seen in 6 [2.67%], children [group 1]. They had fever and signs of pulmonary infections. Generalised weakness was found in 9 males and 13 females. Paraesthesia was found in 11 volunteers of group IV. Blood sampling test revealed that 6 volunteers [2.67%] had plasma Ach E below 5300 IU/ml [< 50% reduction], whereas 4 volunteers had Ach E level between 5300 - 5500 IU/ml [< 45% reduction], 81 volunteers fall in group "c", and 126 individuals had an Ach E reduction of at least 25% and 8 volunteers had the serum cholinesterase level above 10000 IU/ml. None of volunteers had the value above 11000 IU whereas plasma Ach E level of control population was between 11500 - 13500 IU/ml. Medical tests of the level of Ach E in plasma suggest that the overall incidence of poisoning from exposure to OP and CM is quite high, and appears to be consistent with the results from other studies in other developing countries

biochemical, cognitive, and psychiatric effects of anticholinergics benzhexol hydrochloride and biperiden hydrochloride in schizophrenic patients

It is estimated that 45 million people suffer from schizophrenia around the world; it is among the top ten leading causes of disability. By 2050, this number will have grown to approximately 71 million people. Mental illnesses contribute more to the global burden of disease than all cancers combined. The present study has been planned to evaluate the effect of anticholinergic parkinol [benzhexol hydrochloride] and akineton [biperiden hydrochloride] on erythrocyte acetyl cholinesterase [AChE] activity and serum activities of gamma-glutamyl transferase [GOT], alanine transaminase [ALT], aspartate transaminase [AST], and alkaline phosphatase [ALP] in schizophrenic patients treated with haloperidol, and also to study the effect of the previously mentioned two anticholinergics on both the cognitive functions and psychiatric symptoms in such patients. The study was carried out on 30 male schizophrenic patients who were divided into two main groups [group 1 and group 2] each of 15 patients of comparable age. The present results revealed that the total score of [PANSS] showed a significant decrease in all studied groups. The total score of [MMSE] showed a significant increase in all studied groups. The AChE activity didn't show any significant difference in all comparisons in all studied groups. In our study, there was a significant elevation of serum GGT, ALT, AST and ALP levels in some groups of treated patients as compared to pretreatment groups. The results obtained in our study showed a significant increase in serum GGT, ALT, AST, and ALP levels in groups treated with either [haloperidol + benzhexol hydrochloride] or [haloperidol + biperiden hydrochloride] as compared to the corresponding levels in groups treated with haloperidol only, respectively. From all results we can concluded that the biochemical parameters used in this study are useful in detecting any side effects of antipsychotic and anticholinergic drugs on liver functions. The treatment with [haloperidol + benzhexol hydrochloride] and [haloperidol + biperiden hydrochloride] are effective in decreasing the positive and negative symptoms of schizophrenia

Testosterone production and spermatogenic damage induced byorganophosphorate pesticides

Parathion is an organophosphorate pesticide amply used in agriculture. Many alterations induced by organophosphorate pesticides have been described, such as: cytogenetic alterations in germinal cells, oligozoospermia and teratozoospermia in the mouse. The effect of Parathion, both pure (PP) and commercial (PC), on mouse interstitial cell testosterone production was evaluated in vivo and in vitro. Male mice were intraperitoneally injected with a single dose of 1/3 LD50 of Parathion, both PP and PC. The animals were sacrificed at 1, 8 and 40 days post injection to evaluate the impact of disrupting testosterone production on spermatogonia, spermatocytes and elongated spermatids. The plasma testosterone was assayed by standard radioimmunoanalysis. The same method was used to assay testosterone in the culture medium of interstitial cells obtained from the control and Parathion treated animals at the same time intervals. Sperm count, sperm teratozoospermia and tubular blockage were analyzed for an appraisal of spermatogenesis. Increase in the teratozoospermia and tubular blockage was detected in the PP and PC group at 8 and 40 days post injection. Plasma testosterone levels drop significantly at 8 days and recovered slowly at 40 days only in PP animals as detected in vivo, implying interference of testicular steroidogenesis due to the toxicant. Recuperation of normality occurs at long time intervals. In conclusion, Parathion disturbs the synthesis of testosterone in mice affecting qualitatively the spermatogenesis.

Hematological and biochemical studies on workers occupationally exposed to pesticides

Pesticides can cause many problems in exposed individuals. Twenty-tour workers exposed to pesticides have been investigated. They were divided into two groups. The first group is the applicators of pesticides [14 workers] and the second group is the salesmen who sale pesticides in the market [10 workers]. Ten non-exposed individuals were used as control. Hemoglobin content [Hb], hematocrit value [Hct], red blood cells [ABCs], white blood cells counts [WBCs], mean corpuscular volume [MCVI, mean corpuscular hemoglobin [MCH], and mean corpuscular hemoglobin concentration [MCHC] were measured. Biochemical liver functions: Serum aspartate aminotransferases [ASTI, and alanine aminotransferases [ALTI, renal functions: creatinine [CR] and uric acid [UAJ, acetyl cholinesterase [AChE] activity, and total protein [TP] were estimated in the occupationally and non-occupationally exposed groups. Significant decrease was observed in the hematological parameters [Hb, RBCs, WBCs], plasma AChE activity, and the total protein. In contrast, significant increase in serum AST activity, creatinine, and uric acid concentrations were recorded in the exposed groups when compared with the non-exposed groups. Also, significant increase in MCV and MCH values of the two exposed groups was found. Salesmen were more affected than the applicator group. These results suggested that Salesmen group were exposed to various pesticides and for a long time during day by different routes of exposure

Experimental study of biochemical effects of insecticides in albino rats

To detect the acute toxicity of some insecticide rats were divided into ten treatments each one contained six rats. These rats administered a single oral dose of 1/10 LD[50], 1/4 LD[50] and the LD[50] of primiphos-methyl, Chlorpyriphos-methyl and fenitrothion. After 24 hr treated rats were sacrificed. The activity of some biochemical parameters glutamic oxaloacetic transaminase [GOT], glutamic pyruvic transaminase [GPT], alkaline phosphatase [Alk. Ph.], creatinine, urea, total protein and total cholesterol] were detected in blood serum. The results indicated that all treatments caused significant increase in the activity of GOT, GPT and [Alk. Ph.], as well as the level of creatinine, urea and total cholesterol as compared by control ones. While the results indicated that 1/4 LD[50] and 1/10 LD[50] of the three tested insecticides caused significant decrease in total protein concentration. These detected differences observed on values between enzymes tested of liver and kidney function by increase or decrease it is considered a sign and pronounced that treated animals affected by oral dose through 24 hr

Evaluation of the severity of organophosphous insecticide intoxication using poisoning severity scoring, laboratory and therapeutic parameters

Organophosphorus [OP] compounds are the most widely used insecticides that cause poisoning after accidental, occupational or suicidal exposure. Poisoning is particularly common in the developing countries where more potent agents are widely available for agricultural and household purposes. The aim of the study was to evaluate the role of poisoning severity score [PSS], different laboratory and therapeutic measures in assessment of severity of OP poisoning, and to determine the need for intensive care management in cases of OP intoxication. One hundred patients suffering from acute OP poisoning were interviewed and categorized clinically according to PSS into three grades. Routine laboratory tests were done including arterial blood gases, random blood sugar and serum potassium on admission. Specific tests were estimation of pseudo choline sterase activity on admission and serum amylase on admission and after six hours. The studied patients received different lines of treatment in the form of general measures plus atropine or atropine and pralidoxime with or without assisted mechanical ventilation.55% of patients had the mildest degree of OP intoxication [PSS1], 31% had PSS2 and 14% were graded as PSS3. Significant correlation was detected between the degree of poisoning assessed by PSS and different laboratory investigations as well as the lines of treatment used. Cases having the highest score of severity [PSS3] had the lowest psudocholinesterase activity with more pronounced hyperglycemia, hypoxia, metabolic acidosis and hypokalemia. Acute pancreatitis occurred specifically in them. They needed atropine and pralidoxime in addition to assisted mechanical ventilation with longer stay in hospital than other cases. Accordingly, all these parameters including clinical scoring[PSS], laboratory findings and lines of treatment needed can be used for determination of the severity of OP poisoning. They are recommended to be applied in all OP-intoxicated patients

Comparative account of certain enzymes in the serum of homo-iothermal vertebrates subjected to production of myocardial infarction by isoproterenol hydrochloride.

Myocardial infarction was produced by subcutaneous administration of isoproterenol hydrochloride (85 mg/kg b.w. for two consecutive days). The myocardial damage was proved by observing increase in the activity of SGOT and SGPT in serum whereas AChE activity was inhibited by increasing Km, without affecting Vmax. The inhibition of AChE and inhibitory kinetic may be useful in the diagnosis and management of salvage of myocardium.

Oxidative damage in intermediate syndrome of acute organophosphorous poisoning.

BACKGROUND & OBJECTIVES: The main cause of morbidity due to organophosphate poisoning is intermediate syndrome (Type II paralysis) that can occur 48-72 h after poisoning. Mechanisms that underlie the intermediate syndrome are not known. This study investigates the role of oxidative damage to muscles as a possible mechanism underlying the development of the intermediate syndrome. METHODS: Nineteen patients with acute organophosphate poisoning were evaluated from admission to discharge from intensive care for the severity of poisoning and the development and duration of the intermediate syndrome. Blood cholinesterases and parameters of oxidative stress were studied daily and their temporal profiles analysed according to the severity of poisoning and the development and duration of the intermediate syndrome. RESULTS: Fifteen patients had severe poisoning and 16 developed intermediate syndrome. There was a positive association between the severity of poisoning and the occurrence of intermediate syndrome. There was no association between the organophosphate ingested and the development of intermediate syndrome. Erythrocyte membrane acetylcholinesterase and serum butyrylcholinesterase levels at admission and over the course of poisoning were significantly (P < 0.001) reduced in patients compared to controls. There were significantly (P < 0.05) higher levels of lipid peroxidation, conjugated dienes and protein thiols in erythrocyte membranes of patients who developed the intermediate syndrome compared to healthy controls, in patients who developed intermediate syndrome compared to those who did not and in patients with long compared to short duration intermediate syndrome. INTERPRETATION & CONCLUSION: In acute organophosphate poisoning, severe and prolonged acetylcholinesterase inhibition is associated with oxidative stress, detected in erythrocyte membranes, that occurs early in the course of poisoning and may contribute to the development and severity of intermediate syndrome.

Study of some biochemical and genetic aspects of schizophrenic disorders

Molecular genetics and Biochemistry have been devoted to establish the genetic contribution to aetiology of schizophrenia. The biochemical changes in brain neurotransmitters may contribute to the patho genesis of schizophrenia. The human platelets contain monoamine oxidase [MAO] which is similar in many physiochemical properties to that of the brain, the similarity was also established between brain catechol-O-methytransferase [COMT] and acetyicholinesterase [AChE] and that of RBCs. So, this study was directed towards monitoring the platelet MAO and RBCs, COMT and AchE as possible indices for the CNS cellular events. The present study was carried out on 144 subjects classified into normal control group free of any psychiatric manifestation and schizophrenic patients group. Assessment of the changes in neurotransmitters metabolism, was tested e.g. that of catecholamine and acetylcholine by determination of the activity of the enzymes involved in its catabolism e.g. MAO, COMT and AChE either by fluorimetric method or colorimetric method. Our results indicated a highly significant reduction in platelets MAO activity among schizophrenic patients than control group [P<0.001]. Concerning the COMT activity, there was no statistical significant difference between control and patients group. Assessment of AChE activity indicated a significant reduction in patients group [P<0.02]. So, the changes in cholinergic activity in relation of that catecholamine may play a role in the explanations of schizophrenic dysfunction. The genetic contribution was conducted by phenotyping of group specific component [Gc] and phosphoglucomutase I [PGMI] as genetic makers of schizophrenia using isoelectro focusing techniques. In the present study analyzing the distribution of different Gc genotypes among control and schizophrenic groups demonstrated the increase of Gc 2-1 genotype frequency among schizophrenics [P<0.001] with a relative risk factor of RR=2.56. There was significant difference in distribution of PGM1 1+1+ between normal control group and schizophrenic group [P<0.001]. No correlation could be detected between MAO, COMT, AChE enzyme activity and Gc genotypes or PGM1 phenotypes

Contact exposure of red Baladi rabbits to diazinon induces physiological and histopathological changes

Diazinon are widely used as pesticides in agriculture. So, the current work aimed to investigate the effects of diazinon exposure on some physiological aspects, histopathological changes and histochemical acetyl- cholinesterase in red Baladi rabbits. Seventy-two red Baladi bucks were distributed into three groups, the rabbits of the first group were dipped into tap water and served as control group. The rabbits of the second and the third groups were dipped in diazinon at concentrations of 0.6 mg [DLC] and 3 mg [DHC] dissolved in one litter of water, respectively for 10 sec. This step was repeated after 10 days. The animals were sacrificed by jugular vein incision after 0, 1, 3, 7, 15 and 21 day following the second dipping of rabbits in diazinon. In whole blood, diazinon decreased rabbits's RBC's [P<0.01] and Hb [P<0.05], while MCV and MCH were elevated [P<0.01] for both tested concentrations, but PCV values were increased only [P<0.01] in the DHC group. In plasma TP was decreased [P<0.01] in both tested concentrations, however cholesterol was increased [P<0.01] in the DLC and DHC groups. Meanwhile hydroxylamine and nitrite were increased only in the DHC treated group. Liver body weight ratio and cytochrome P-450 were decreased [P<0.01] in both tested concentrations, while microsomal protein was increased [P<0.01] in both concentrations. RBC's, PCV and microsomal protein were increased [P < 0.01] by the days of treatment. Meanwhile, MCV, MCH, MCHC, liver body weight ratio and cytochrom P-450 were decreased [P <0.01] by the days of treatment. There was no definite trend with days of treatment for WBC's, Hb, TP, cholesterol, hydroxylamine and nitrite. There was a highly significant effect of concentration X day interaction [P<0.01] on all tested parameters. Histopathological changes of liver, kidney and brain were observed after DHC dipping. Glycogen content was decreased in liver and increased in kidney Bowman's capsule. Furtheremore, the AChE activity was inhibited in brain tissue and decreased in liver and gradually increased in kidney glomeruli cells. Exposure of animals to diazinin caused extensive changes in physiological, histochemical and histopathological parameters, the kidney and brain were highly affected by the diazinon exposure when compared with liver. Diazinon lead to negative response on animal performance

Subacute toxicity of anilofos, a new organophosphorus herbicide, in male rats: effect on some physical attributes and acetylcholinesterase activity.

In acute toxicity study, rats showed dose-dependent signs of cholinergic hyperactivity and behavioural alterations. Maximum intensity of symptoms was not associated with mortality. Oral LD50 was 1681 mg/kg. In subacute toxicity study, rats were orally administered 50, 100 or 200 mg/kg of anilofos once daily for 28 days. Signs and symptoms were observed mainly with 200mg/kg. At this dose, anilofos induced hypothermia and progressive weight loss. None of the anilofos-treated rats died. Weight of brain, lung, testis was not altered, while of liver, heart, spleen and kidney increased. Anilofos inhibited cholinesterase (ChE) activities of erythrocyte (41-67%), plasma (36%), blood (37-64%), brain (63-73%) and liver (28-48%). Total protein was decreased in plasma and liver. Results indicate moderate toxic potential of anilofos in mammals, substantial contribution of CNS-mediated effects in causing anilofos toxicity and no direct relationship between hypothermia and level of ChE inhibition.

Serial neuro-electrophysiological studies in acute organophosphate poisoning--correlation with clinical findings, serum cholinesterase levels and atropine dosages.

OBJECTIVES AND METHODS: A prospective evaluation of the correlation between the serial clinical findings, serum cholinesterase levels, electrodiagnostic abnormalities and the daily atropine requirement was undertaken in 29 patients with confirmed acute organophosphate poisoning (OPP). RESULTS: Clinical weakness conforming to the pattern found in 'Intermediate Syndrome' was noted in 19 patients (65.55%). It was associated with all types of organophosphate compounds and occurred in all patients in whom the serum cholinesterase on admission was less than 200 units. Three types of electrodiagnostic abnormalities were noted: single supramaximal electrical stimulus induced repetitive response, a decrement--increment response to 30 Hz repetitive nerve stimulation (RNS) and a decremental responses to 30 Hz RNS. The 30 Hz decremental response correlated best with the presence of clinically detectable weakness (sensitivity = 61.72%; specificity = 81.54%; positive predictive value = 73.91%; negative predictive value = 71.62%). Time trends evaluation revealed that the peak daily atropine dosages were given at a mean of 1.76 +/- 0.83 days in comparison to a mean nadir of serum cholinesterase of 2.48 +/- 1.97 days and a mean nadir of 9:1 ratio of 2.65 +/- 1.76 days. The 2-tailed correlation coefficient analysis and simple regression analysis revealed a positive correlation between serum cholinesterase levels and the 9:1 ratios (correlation coefficient: 0.59). A negative correlation was observed between the 9:1 ratios and the daily atropine requirement (correlation coefficient: -0.57) and between serum cholinesterase levels and daily atropine requirement (correlation coefficient: -0.49). CONCLUSIONS: At admission, level of serum cholinesterase of less than 200 units is a predictor and the 30 Hz RNS decremental response could be a useful marker for the 'Intermediate Syndrome'.

Biochemical alterations induced by a new phosphorothionate (RPR-II) in tissues of male and female rats.

This study was conducted to investigate the effect of a new phosphorothionate, the methyl ester of 2-butenoic acid-3-diethoxy phosphinothioyl (RPR-II) on membrane bound target enzymes aspartate amino transferase (ASAT), alanine amino transferase (ALAT) and RBC acetylcholinesterase (AChE) in different tissues of male and female albino wistar rats when treated orally with 0.014 (low), 0.028 (medium) and 0.042 (high) mg/kg daily for a period of 90 days. Repeated administration of RPR-II caused significant increase of ASAT and ALAT enzymes in serum, liver and kidney and significant decrease was recorded in lung in both male and female rats when measured after 45 and 90 days of treatment. This compound also caused significant inhibition of RBC AChE indicating its effect on nerve synapsis. Females were more susceptible than males with regard to ASAT and ALAT levels in serum and liver and also in kidney ASAT, whereas reverse trend was recorded in lung ALAT, suggesting sexual dimorphism in the treated rats. These studies also indicated that the levels of these affected enzymes were recovered to normal conditions after 28 days of post treatment (withdrawal study). Positive correlation was observed with regard to these enzymes between serum, liver and kidney, whereas in case of serum and lung a negative correlation was recorded. These enzymes profile elucidates lung necrosis whereas in other tissues the level of enzymes increased showing an adaptive mechanism due to the chemical stress.