Effects of exposure to pyrethroid cyfluthrin on serotonin and dopamine levels in brain regions of male rats.

The effects of cyfluthrin oral exposure (1, 5, 10 and 20mg/kg bw, 6 days) on brain region monoamine levels of male rats were examined. Cyfluthrin-treated rats (1, 5 and 10mg/kg bw, orally 6 days), had no visible injury, i.e., no clinical signs of dysfunction were observed. However, rats treated with cyfluthrin at the highest dose (20mg/kg bw, orally 6 days) showed skeletal muscle contraction in the hind limbs, slight movement incoordination without any signs of dyskinesia and tremor after 1-2h of treatment. These signs were reversible at 6h after dose. After last dose of cyfluthrin, dopamine (DA) and serotonin (5-HT) and its metabolites levels were determined in brain regions hypothalamus, midbrain, hippocampus, striatum and prefrontal cortex by HPLC. Cyfluthrin (1mg/kg bw, orally 6 days) did not affect the DA, 5-HT and metabolites levels in the brain regions studied. Cyfluthrin (5, 10 and 20mg/kg bw, orally 6 days) caused a statistically significant decrease in DA and its metabolites DOPAC and HVA levels and in 5-HT and its metabolite 5-HIAA levels in a brain region- and dose-related manner. Moreover, cyfluthrin (20mg/kg bw, orally 6 days) evoked a statistically significant increase in 5-HT turnover in striatum and midbrain, and in DA turnover in striatum and prefrontal cortex. These findings indicate that serotoninergic and dopaminergic neurotransmission is affected by exposure to cyfluthrin and may contribute to the overall spectrum of neurotoxicity caused by this pyrethroid.

Evidence for dose-additive effects of a type II pyrethroid mixture. In vitro assessment.

Despite the widespread use of pyrethroid insecticides that led to common exposure in the population, few studies have been conducted to quantitatively assess dose-additive effects of pyrethroids using a funcional measure involved in the common toxic mode of action. The aim of this study was to evaluate the potency and efficacy of 6 Type II pyretroids (α-cypermethrin, cyfluthrin, λ-cyhalothrin, deltamethrin, cyphenothrin and esfenvalerate) to evoke induction of both nitric oxide and lipid peroxides levels measured as malondialdehyde in three in vitro models (SH-SY5Y, HepG2 and Caco-2 human cells) as well as to test the hypothesis of dose additivity for mixtures of these same 6 pyrethroids. Concentration-responses for 6 pyrethroids were determined as well as the response to mixtures of all 6 pyrethroids. Additivity was tested assuming a dose-additive model. The human neuroblastoma SH-SY5Y cell line was the most sensitive in vitro model. The rank order of potency for cell SH-SY5Y viability MTT assay was deltamethrin>cyphenothrin>λ-cyhalothrin>cyfluthrin>esfenvalerate>α-cypermethrin. When 6 pyrethroids were present in the mixture at an equitoxic mixing ratio, the action on nitric oxide (NO) and lipid peroxides measured as malondialdehyde (MDA) production was consistent with a dose-additive model. The results of the present study are consistent with previous reports of additivity of pyrethroids in vivo e in vitro.

Management of non-hepatic distant metastases in neuroendocrine neoplasms.

Neuroendocrine neoplasms represent an uncommon disease with an increasing incidence. Thanks to improvements in diagnostic and therapeutic methods, metastases previously considered uncommon, such as bone metastases, or even very rare, such as brain, orbital and cardiac metastases, are more frequently found in daily practice. Due to the great heterogeneity of these neoplasms, there is a lack of high-quality evidence on the management of patients with these types of metastases. The aim of this review is to provide the current state of the art, reviewing neuroendocrine neoplasm specific studies and useful information from other tumor types and to propose a treatment recommendation with algorithms to consider in daily clinical practice.

Long-term antibody response following SPUTNIK V primary vaccination in healthcare workers with and without history of SARS-CoV-2 infection: Prospective cohort study from a hospital in Argentina.

Background: In December 2020, Sputnik V was incorporated to the National COVID-19 Immunization Plan in Argentina. Studies had shown 98% of antibody response rate. To date, data on immunogenicity and antibody persistence in Argentina are scarce.The objective was to assess humoral immune response after two doses of Sputnik V in Health Care Workers (HCWs) at the Ricardo Gutierrez Children's Hospital (RGCH). Methods: A prospective, cohort study in HCWs immunized with two doses of Sputnik V between February and March 2021. The following variables were assessed: age, gender, risk factors for severe COVID-19 or mortality, immunosuppressive therapy and history of SARS-CoV-2. Blood samples were drawn on the day of the first dose, 28 days and 180 days after the second. Anti-Spike IgG was measured using an ELISA assay. Differences in immune response were evaluated according to study variables. Comparison analyses between groups with or without history of infection were performed, with T-test and ANOVA or Mann-Whitney tests. For each subject, we compared baseline values with 28 days and 180 days after the second vaccine.STATA version 14 and R Sofware were used for data analyses. Results: We included 528 individuals, mean age 41.5 years, 82.9% female, 14.4% (76/528) reported previous SARS-CoV-2 infection.All subjects developed antibodies post-vaccination. At day 28, concentrations were significantly higher in previously infected than naïve subjects (p < 0.001) with no differences according to age, gender and comorbidities.At day 180, 17% (95% CI 13.17-21.53) of naïve subjects were negative. Antibody concentrations decreased significantly in all subjects except in those who reported SARS-CoV-2 infection after vaccination (n = 31). This last group had significantly higher antibody concentrations. Conclusion: This study assessed immune response to a new COVID-19 vaccine in real life in a cohort of subjects. Antibody concentrations varied according to history of SARS-COV-2 infection and decreased over time.

[Hereditary hemorragic telangiectasia: the state of art]. / Teleangectasia emorragica ereditaria: stato dell'arte.

Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber syndrome, is a multisystemic vascular dysplasia. The disease is transmitted as a dominant autosomic character. The Hereditary Hemorrhagic Telangiectasia is differentiated in two subclasses: (1) HHT1, which is caused by mutation of ENG gene. This gene is localized on long arm of chromosome 9: (2) HHT2, which is caused by mutation of ALK-1 gene. This gene is located on long arm of chromosome 12. These two genes codify for two receptorial proteins: the endoglin and the activin-like protein 1; these proteins belong to receptorial superfamily of TGF-beta, which is involved in vascular remodelling and angiogenesis. Clinically, the consequences of these mutations are represented by the formation of cutaneous and/or mucous telangiectases and artero-venous fistulas. In both cases histological alteration is the same: extremely ectatic venules with numerous layers of myocytes around them. Arterioles communicate with venules directly without a capillary filter. Essentially, telangiectases manifest themselves with hemorrhages, while more common consequences of fistulas are secondary to formation of shunts with a possible thromboembolism; that is particularly serious in case of pulmonary artero-venous malformations. In 2000. Shovlin published 4 diagnostic criteria (criteria of Curaçao): (1) spontaneous and recurrent epistaxis; (2) multiple telangiectases; (3) visceral artero-venous malformations; (4) familiarity for HHT. Actually there is no possibility for a genetic therapy of HHT. Therefore, the therapeutic efforts are turned to control of symptoms and to the prevention of complications.

[Therapy of dyslipidemia in post-infarction: state of the art]. / Terapia delle dislipidemie nel post-infarto: stato dell'arte.

Between the risks factors involved in the atherogenesis LDL-cholesterol is determinant because highly associated to cardiovascular events. The primary target for the prevention of coronary diseases is a reduction of LDL-cholesterol because that reduces the cardiovascular mortality and the total mortality. The NCEP ATP III 2004 guide-lines propose as therapeutic target for the high-risk patients the reduction of plasma levels of LDL-cholesterol under 100 mg/dl and according to new trials under 70 mg/dl. The dyslipidaemia treatments are based on two approaches, i.e., the therapeutic lifestyle change and the pharmacological therapy. The available drugs are statins, fibrates, anion exchange resins, nicotinic acid. In the acute coronary syndrome patients is desirable to start immediately a therapy with statins since the hospital phase and direct the treatment to aggressive therapy. Unfortunately, the statin doses used in the most secondary prevention trials allow to get LDL-cholesterol under 100 mg/dl in the only half high-risk patients. The innovative therapeutic approach to hypercholesterolemia today is based on a double inhibition of cholesterol synthesis and absorption combining a statin with ezetimibe.

Fipronil sulfone induced higher cytotoxicity than fipronil in SH-SY5Y cells: Protection by antioxidants.

Fipronil is a broad spectrum insecticide from the phenyl pyrazole family, which targets GABA receptor. Limited information is available about the metabolite fipronil sulfone cytotoxic actions. This study examined in vitro neurotoxicity of fipronil and fipronil sulfone and evaluated Trolox (vitamin E analog) (0.3, 1µM), N-acetyl-cysteine (0.5, 1mM), melatonin (0.1, 1µM) and Tempol (superoxide dismutase analog) (0.3, 0.5mM) protective role in SH-SY5Y cells. MTT and LDH assays were carried out to assess the cytotoxicity of fipronil and fipronil sulfone at 3-100µM concentrations. Fipronil sulfone was more toxic than fipronil. Tempol showed the best neuroprotectant profile against fipronil (50 and 150µM) and fipronil sulfone (3 and 10µM) reaching control levels. Fipronil (100µM) and fipronil sulfone (3µM) treatments induced a 4.7- and 5-fold increases in lipid peroxides measured as malondialdehyde (MDA) and a 2.2- and 2.0-fold increases in the levels of nitric oxide (NO). These results suggest that oxidative stress observed may be one of the major mechanisms of fipronil-induced neurotoxicity and it may be attributed in part to fipronil disposition and metabolism. Our results led us postulate that metabolite fipronil sulfone might be responsible for the fipronil-induced toxicity rather than fipronil itself.

Immunological and endocrinological disturbances in patients after prolonged coma following head injury.

It has been previously reported that following severe brain damage, a deficit of cellular immunity could be detected in the early phase after the occurence of the lesion. We report here the results of a cross-sectional study on long term effects of severe brain damage on immunological and neuro-endocrine changes in patients who recovered from prolonged coma caused by head injury. Results obtained from post-comatose (PC) patients were compared with those obtained from two control groups made up of spinal-cord injury (SCI) patients and healthy subjects, respectively. The following parameters were studied: lymphomonocyte subsets; interleukin 2 (IL-2) production; natural killer (NK) activity and serum levels of adrenocorticotrophic hormone (ACTH), cortisol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, tri-iodothyronine (T3) and thyroxine (T4). With respect to healthy controls the PC1 subgroup, i.e. patients examined 3-6 months after injury, showed a statistically significant decrease in IL-2 production, NK activity and CD25+ lymphocytes. Similar immunological disturbances were observed in SCI but not in the PC2 subgroup, i.e. patients examined later than 6 months after injury. The same sub-group of PC1 patients showed high serum levels of cortisol and PRL. These results could be related to the immunological status and may be interpreted as a transient but prolonged condition of chronic stress or "chronic alarm reaction". Copyright Rapid Science Ltd

Determinants of sit-to-stand capability in the motor impaired elderly.

Among the healthy elderly, sit-to-stand (STS) movement largely depends on: (a) trunk bending momentum, (b) centre of gravity (CG) position before the body rises and (c) lower limb extensor muscle strength. Because determining whether (c) improvement would affect STS capability in the motor impaired elderly (MIE) has been recommended, we studied the relative importance of (a), (b) and (c) in determining a successful fast STS movement comparing the healthy elderly with MIE with orthopaedic disorders studied before and after a rehabilitation program. Force platform was used to measure body's posture and kinematics during a STS test and therefore to assess (a), (b) and maximum vertical velocity (VVpeak), assumed as outcome measurement. Knee extensor maximal isometric voluntary contraction normalized by body mass (nMVC) was an indicator of (c). A multiple regression model was built to predict VVpeak from the three determinants of STS movement. In both groups, the model significantly determined VVpeak, with (a) and (c) being significant predictors of VVpeak and (a) being the major predictor. Rehabilitation was effective in improving nMVC. This process resulted in a change of the relative importance of (a) and (c), strength becoming the major predictor of VVpeak. In conclusion the present study demonstrates that a rehabilitative intervention aimed at increasing strength is effective in improving STS capability in MIE.

Exercise induced muscle damage and recovery assessed by means of linear and non-linear sEMG analysis and ultrasonography.

This study was aimed at investigating the time-course and recovery from eccentric (EC) exercise induced muscle damage by means of surface electromyography (sEMG), ultrasonography (US), and blood enzymes. Five subjects (EC Group) performed two bouts of 35 EC maximum contractions with the biceps brachii of their non dominant arm, five subjects were tested without performing EC (Control Group: CNT). The maximal isometric force (MVC) was measured. Force and sEMG signals were recorded during 80% MVC isometric contractions. In EC and CNT subjects US assessment on non-dominant biceps brachii was performed; creatin kinase (CK) and lactic dehydrogenasis (LDH) plasma levels were also assessed. Force, sEMG and CK-LDH measurements were performed before EC and after it periodically for 4 weeks. The sEMG was analysed in time and frequency domains; a non-linear analysis (Lyapunov 1st exponent, L1) of sEMG was also performed. After EC, the MVC was reduced by 40% on average with respect to the pre-EC values. A significant decrease in the initial frequency content, and in the MDF and L1 decay (13-42% less than the pre-EC values, respectively) was also observed. The sEMG amplitude (Root Mean Square, RMS) was unchanged after EC. The US revealed an increase in muscle belly thickness and in local muscle blood flow after EC. A complete recovery of all the considered parameters was achieved in two weeks. In conclusion sEMG analysis was confirmed as an early indicator of muscle damage. Muscle recovery from damage is followed by both sEMG and US and this may have useful clinical implications. Non linear analysis (L1) was revealed to be sensitive to early sEMG modifications induced by EC as well as able to follow the post EC changes in the sEMG.

Cost of walking and locomotor impairment.

The aim of the present study was to evaluate the importance and the necessity of metabolic measurements to quantify locomotor impairment in a clinical context. Oxygen consumption, heart rate, pulmonary ventilation and walking speed were measured during locomotion in 14 normal subjects, used as a control group, and 82 patients with different pathologies [hemiparetic, paraparetic, tetraparetic, orthopaedic and paraplegic patients, who walked using a reciprocating gait orthosis (RGO)]. The subjects were characterized on the basis of a cumulative impairment score (CIS), based on clinical scales commonly used to evaluate impairment and disability in locomotion. Appropriate indices of energy, cardiac and ventilatory costs expressed per metre walked, globally called physiological costs, were obtained. It resulted that the most comfortable speed (MCS) of normal subjects was significantly higher than that of each group of patients. Normal subjects' physiological costs were found to be significantly lower than those of patients who needed either a device or the help of a person to walk. All measured parameters correlated significantly with each other. The MCS was found to be the most correlated parameter with the CIS (r = 0.8), and therefore it must be considered the best single measurement, if only one is to be used. Measurements more precise than MCS, such as the physiological costs, may be necessary in clinical trials.

Serologic evidence of coronavirus infection in New York and New England dairy cattle with winter dysentery.

Acute and convalescent sera were collected from 8 dairy herds with classic clinical features of winter dysentery. An enzyme-linked immunosorbent assay was used to measure coronavirus antibody titers, employing calf diarrhea coronavirus as antigen. Twenty-two of the 35 animals tested (63%) showed a greater than or equal to 4-fold seroconversion. Adult cattle in all 8 herds seroconverted. These findings complement previously reported immunoperoxidase and electron microscopic evidence, suggesting an etiologic role for an enteric coronavirus in this disease.

Primary neuroblastoma presenting as a paratesticular tumor.

A 3-month-old boy was operated on for an inguinal tumor. Histological diagnosis was neuroblastoma. This is the second known case of primary paratesticular neuroblastoma reported in the literature. The treatment of choice for Evan's stage I is surgery.

1-Octadecene as a solvent for ferrofluids for intraocular use.

PURPOSE: 1-Octadecene is a hydrocarbon with one double bond in its structure that could serve as a solvent for ferrofluids. The aim of this pilot study was to obtain preliminary information on intraocular tolerance to 1-octadecene. METHODS: Vitreous compression with perfluoropropane gas was achieved in 20 eyes of albino rabbits. Four days after gas injection a fluid-gas exchange was undertaken. Sixteen eyes received 1-octadecene. Four eyes received balanced salt solution. Eyes were obtained at 3, 7, 14 and 30 days. The samples were fixed in 10% buffered formalin, processed in paraffin and sections were stained with hematoxylin and eosin. RESULTS: Emulsification of the oil bubble was observed in 31.25% of the cases by the fifth day; light microscopy showed normal retinal architecture in all the eyes and epiretinal and vitreous macrophages in 50% of the eyes. CONCLUSIONS: 1-Octadecene does not appear to have any retinal cytotoxic effect but elicits an inflammatory response in the vitreous activity.

[Analysis of proliferating cell nuclear antigen (PCNA) expression in 24 cases of primary non-small cell pulmonary carcinomas and correlation with survival]. / Análisis de la expresión del antígeno nuclear de proliferación celular (PCNA) en 24 carcinomas primarios de pulmón de células no pequeñas y correlación con la supervivencia.

Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein involved in DNA replication that is believed to provide an indication of proliferation in some neoplasms. This study analyzes PCNA expression in 24 cases of primary non-small cell lung cancer using monoclonal PC-10 antibodies in paraffin embedded material. We found significant inter- and intra-tumoral variations in PCNA expression, and no statistically significant relation between the amount of PCNA expression and the size and location of tumors, index of mitosis, histological tumor type or patient age. We found a statistically significant relation (r = 0.47; p < 0.05) between survival and amount of PCNA expression in a sample of 19 cases, but no statistically significant differences in survival related to whether PCNA expression was slight (0-25), moderate (25%-50%) or high (> 50%), and no prognostic value for degree of PCNA expression.

Pharmacokinetics of amoxycillin and the rate of depletion of its residues in pigs.

Six pigs were used in a two-period crossover study to investigate the pharmacokinetics of amoxycillin after single intravenous and oral doses of 20 mg/kg bodyweight. Twelve pigs were used to study the residues of the drug in muscle, kidney, liver and fat after they had received daily oral doses of 20 mg/kg amoxycillin for five days. The mean (sd) elimination half life (t1/2beta) and mean residence time of amoxycillin in plasma were 3.38 (0.30) and 3.54 (0.43) hours, respectively, after intravenous administration and 4.13 (0.50) and 4.47 (0.30) hours, respectively, after oral administration. After oral administration, the maximum plasma concentration (Cmax) was 7.37 (0.42) microg/ml and it was reached after 0.97 (0.29) hours. Six days after the last oral dose, the mean concentration of amoxycillin in the pigs' kidneys was 21.38 ng/g and in the liver it was 12.32 ng/g, but no amoxycillin could be detected in fat or muscle; the concentrations of amoxycillin in edible tissues were less than the European Union maximal residue limit of 50 microg/kg.

[Reactivity of serologic tests for the detection of syphilis in patients infected with the human immunodeficiency virus]. / Reactividad de las pruebas serológicas para detección de sífilis en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND: The coexistence of syphilis and infection by the human immunodeficiency virus (HIV) appears to modify the natural history of both diseases. The aim of this study was to know the prevalence of syphilis in a population of patients with HIV infection, the possible association with certain risk practices and the validity of the reaginic test in such patients. METHODS: Three hundred sixty-seven patients with HIV infection who went for the first time to a monographic clinic of a university hospital were studied. Syphilis serology was carried out: rapid plasma reaginic (RPR) and hemagglutination (MHA-TP) tests. RESULTS: Out of all the patients 26 (7.1%) had positive MHA-TP. The proportion of homosexuals was greater among those who had a positive treponemic test (69%) than among those who were negative (6.4%; odds ratio [OR] = 32.6; confidence interval 95%: 16.2-65.4). The positivity of MHA-TP was more frequent among those presenting criteria of the acquired immunodeficiency syndrome (AIDS) at the diagnosis (18% versus 5.6%; OR = 3.6 [1,5-8,9]). Seventy-four false positive reactions were observed with the RPR (20%) corresponding almost exclusively (96%) to intravenous drug users who presented false positivity in 25% of the cases. CONCLUSIONS: The prevalence of syphilis detected by treponemic serology among subjects with infection by the human immunodeficiency virus is related with homosexuality as the principal practice of risk. One quarter of the intravenous drug users with infection by the human immunodeficiency virus presented false positive results to the reaginic test thus leading to the recommendation that therapeutic measures should not be initiated without confirmation with a treponemic test.

[The prognostic factors and evolution of the quality of life in primary biliary cirrhosis]. / Factores pronósticos y evolución de la calidad de vida en la cirrosis biliar primaria.

The prognostic factors and the evolution of the quality of life were evaluated in 38 patients with primary biliary cirrhosis (94.7% females, mean age 52.6 +/- 2.0 years) followed up for more than 36 months (mean 65.3 +/- 3.7 months). Karnofsky's index significantly declined during follow up (p less than 0.05) in a parallel fashion to modified Child's hepatic functional class (p less than 0.05) and to the days of hospital readmission (p less than 0.05). Eleven patients (28.9%) died, and the median survival was 88.7 months. The comparison of the actuarial curves showed the following to be significant poor prognostic factors at the time of diagnosis: a) clinical: more than one associated autoimmune disease, weight loss of more than 10% of the ideal weight, jaundice, upper gastrointestinal hemorrhage associated with portal hypertension, portal-systemic encephalopathy and a modified Child's hepatic functional class of 9 or more; b) biochemical: serum albumin lower than 3.5 g/dl and bilirubin higher than 2 mg/dl; c) histological: Total histological activity index of 10 or more and erosive necrosis index of 2 or more (Knodell et al.), lobular granulomas, and stage IV (Ludwig et al). A significant correlation was found (p less than 0.001) between the R index of the Mayo Clinic and the mean survival time of our patients. As a temporary policy, we indicate hepatic transplant when R is 9.2 or higher (life expectancy lower than 24 months), awaiting our own probabilistic prognostic model with the inclusion of quality of life criteria.

[Impact of zidovudine treatment and the pneumocystis carinii prophylaxis in natural history of patients with HIV infection]. / Influencia del tratamiento con zidovudina y de la profilaxis contra Pneumocystis carinii en la historia natural de los enfermos con infección por VIH.

INTRODUCTION: Early use of prophylactic regimens against Pneumocystis carinii and zidovudine therapy, may have modified the natural history of patients with HIV-1 infection. We describe the incidence of opportunistic infections and analize the mortality rate in those patients to check the occurrence of any change in the above mentioned natural history. PATIENTS: Clinical charts of patients with HIV-1 infection attending our hospital are reviewed, from november 1987 to june 1994. RESULTS: We found 200 patients with AIDS, documenting 64 (32%) deaths and 69 (34.5%) patients lost to follow-up. Seven HIV-1 infected patients (3.5%) received primary prophylaxis against Pneumocystis carinii and 17 (8.5%) zidovudine therapy before developing AIDS. Patients with AIDS receiving zidovudine therapy had a higher survival (median 50 months) than those not receiving such therapy (median 17 months; p < 0.001). Ninety one patients with tuberculosis receiving zidovudine therapy had also a higher survival than those not receiving antirretroviral therapy (p < 0.01). Eighty six patients with Pneumocystis carinii pneumonia receiving zidovudine had also a higher survival (p < 0.001). Likewise, patients on zidovudine treatment had a lower reduction on CD4 lymphocyte count. CONCLUSIONS: The spectrum of AIDS-defining illnesses is similar to the whole country. We have not found any difference in the incidence of opportunistic infections, but we observed a trend to reduction in the incidence rate of PCP. The introduction of zidovudine therapy seems to have a positive influence on the survival of AIDS patients. This advantage is highlighted in those patients more immunodeficients at first.

Effects of exposure to amitraz on noradrenaline, serotonin and dopamine levels in brain regions of 30 and 60 days old male rats.

The effects of amitraz oral exposure (20, 50 and 80mg/kg bw, 5 days) on brain region monoamine levels of male rats at 30 and 60 days of age were examined. The amitraz-treated rats at the oral doses of 20 and 50mg/kg bw had no visible injury, i.e., any clinical signs of dysfunction observed in any of the animals. However, rats treated with amitraz at the highest dose (80mg/kg bw, 5 days) showed a slight motor incoordination after 1-2h of treatment. These signs were reversible approximately at 6h after dose. After the last dose of amitraz, NE, DA and 5-HT and its metabolites levels were determined in the brain regions hypothalamus, midbrain, prefrontal cortex, striatum and hippocampus by HPLC. Amitraz caused changes in the NE, DA and 5-HT and their metabolite levels in a brain regional-, dose- and age-related manner. In the brain regions studied, amitraz induced a statistically significant increase in 5-HT, NE and DA content with age interaction, but the NE increases in prefrontal cortex and hippocampus was without age interaction. Moreover, in the brain regions studied, amitraz induced a statistically significant decrease in the metabolite 5-HIAA, MHPG, DOPAC and HVA levels displaying an age interaction, excepting the 5-HIAA decrease in midbrain and the DOPAC decrease in hypothalamus and striatum which were without age interaction. Furthermore, amitraz evoked a statistically significant decrease in 5-HT, NE and DA turnover in the brain regions studied. The present findings indicate that amitraz significantly altered CNS monoaminergic neurotransmitters in a brain regional-, dose- and age-related manner.