Plasma Dopamine Levels Research Articles

Subthalamic Nucleus Deep Brain Stimulation Modulate Catecholamine Levels with Significant Relations to Clinical Outcome after Surgery in Patients with Parkinson's Disease.

AimsAlthough subthalamic nucleus deep brain stimulation (STN-DBS) is effective in patients with advanced Parkinson’s disease (PD), its physiological mechanisms remain unclear. Because STN-DBS is effective in patients with PD whose motor symptoms are dramatically alleviated by L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, the higher preoperative catecholamine levels might be related to the better clinical outcome after surgery. We aimed to examine the correlation between the preoperative catecholamine levels and postoperative clinical outcome after subthalamic nucleus deep brain stimulation. The effectiveness of STN-DBS in the patient who responded well to dopaminergic medication suggest the causal link between the dopaminergic system and STN-DBS. We also examined how catecholamine levels were modulated after subthalamic stimulation.MethodsIn total 25 patients with PD were enrolled (Mean age 66.2 ± 6.7 years, mean disease duration 11.6 ± 3.7 years). Mean levodopa equivalent doses were 1032 ± 34.6 mg before surgery. Cerebrospinal fluid and plasma catecholamine levels were measured an hour after oral administration of antiparkinsonian drugs before surgery. The mean Unified Parkinson’s Disease Rating Scale scores (UPDRS) and the Parkinson’s disease Questionnaire-39 (PDQ-39) were obtained before and after surgery. Of the 25 patients, postoperative cerebrospinal fluid and plasma were collected an hour after oral administration of antiparkinsonian drugs during on stimulation at follow up in 11 patients.ResultsMean levodopa equivalent doses significantly decreased after surgery with improvement in motor functions and quality of life. The preoperative catecholamine levels had basically negative correlations with postoperative motor scores and quality of life, suggesting that higher preoperative catecholamine levels were related to better outcome after STN-DBS. The preoperative plasma levels of L-DOPA had significantly negative correlations with postoperative UPDRS- III score in off phase three months after STN-DBS. The preoperative cerebrospinal fluid (CSF) 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxytryptamine (5-HT) levels had significantly negative correlations with postoperative UPDRS- III score in off phase one year after STN-DBS and the preoperative CSF homovanilic acid (HVA) levels had significant negative correlations with postoperative UPDRS- III score in on phase three months after STN-DBS. In PDQ-39 SI (summary index), preoperative plasma dopamine (DA) level had significantly negative correlations with postoperative PDQ-39 SI one year after STN-DBS suggesting that higher preoperative plasma DA level resulted in better quality of life (QOL) one year after STN-DBS. The stepwise multiple linear regression study revealed that higher preoperative plasma HVA levels had negative influence on the postoperative motor symptoms (i.e., increase in the score of UPDRS), whereas higher preoperative CSF L-DOPA levels had positive influence on the postoperative motor symptoms and QOL (decrease in the score of UPDRS and PDQ-39 SI) The catecholamine levels were not significantly reduced postoperatively in 11 patients despite the significant reduction in levodopa equivalent doses. Unexpectedly, CSF HVA levels significantly increased from 0.00089±0.0003 ng/μl to 0.002±0.0008 ng/μl after STN-DBS.ConclusionThe preoperative catecholamine levels might affect the postoperative motor symptoms and quality of life. The catecholamine levels were not significantly reduced postoperatively despite the significant reduction in levodopa equivalent doses.

Quantitative determination of dopamine in human plasma by a highly sensitive LC–MS/MS assay: Application in preterm neonates

The determination of dopamine facilitates better understanding of the complex brain disorders in the central nervous system and the regulation of endocrine system, cardiovascular functions and renal functions in the periphery. The purpose of this study was to develop a highly sensitive and reliable assay for the quantification of dopamine in human neonate plasma. Dopamine was extracted from human plasma by strong cation exchange (SCX) solid phase extraction (SPE), and subsequently derivatized with propionic anhydride. The derivatized analyte was separated by a Waters Acquity UPLC BEH C18 column using gradient elution at 0.4ml/min with mobile phases A (0.2% formic acid in water [v/v]) and B (MeOH–ACN [v/v, 30:70]). Analysis was performed under positive electrospray ionization tandem mass spectrometer (ESI–MS/MS) in the multiple reaction monitoring (MRM) mode. The stable and relatively non-polar nature of the derivatized analyte enables reliable quantification of dopamine in the range of 10–1000pg/ml using 200μl of plasma sample. The method was validated with intra-day and inter-day precision less than 7%, and the intra-day and inter-day accuracy of 91.9–101.9% and 92.3–102.6%, respectively. The validated assay was applied to quantify dopamine levels in two preterm neonate plasma samples. In conclusion, a sensitive and selective LC–MS/MS method has been developed and validated, and successfully used for the determination of plasma dopamine levels in preterm neonates.

Plasma Norepinephrine and Dopamine Levels in Prepubertal Male Children with Attention-Deficit Hyperactivity Disorder do not Change with 8 Weeks of Methylphenidate Treatment

ABS TRACT: Plasma norepinephrine and dopamine levels in prepubertal male children with attention-deficit hyperactivity disorder do not change with 8 weeks of methylphenidate treatment Objectives: The aim of this study was to determine plasma norepinephrine and dopamine levels at baseline and after 8 weeks of stimulant treatment in pre-pubertal male children with ADHD. Methods: The study group consisted of 50 children (6-12 years old) diagnosed with ADHD. The control group comprised students from a primary school within the epidemiological catchment area of the clinic and was matched for class and age to the ADHD patients. The Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) was used to diagnose ADHD and allowed comorbidities. Mental retardation was ruled out with the Wechsler Intelligence Scale for Children-Revised (WISC-R) and impaired functioning. We evaluated disorder severity at the time of assessment using the Clinic Global Impression Scale (CGI). The DuPaul ADHD Rating Scale-IV (ARS) was also used. All patients were treatment-naive. The parents were advised to use OROS methylphenidate daily with no drug holidays during weekends. No rescue medications (immediate-release methylphenidate) were allowed. The dose started at 18 mg and was titrated to 54 mg in 4 weeks to yield average doses of 1 mg/kg/ day. Baseline and endpoint plasma DA and NE were measured. Results: Baseline plasma NE and DA levels had no statistically significant differences between ADHD patients `and controls (232.0±67.3 versus 232.2±65.3 pg/mL and 169.3±48.4 versus 186.9±40.5 pg/mL). Plasma NE levels in all ADHD subgroups decreased with 8 weeks of stimulant treatment, while changes in DA levels were more complex. Plasma DA levels decreased with treatment in the ADHD-inattentive subgroup but were elevated in the hyperactive/impulsive and combined subgroups. There were no statistically significant differences between ADHD subgroups for these variables. Endpoint NE levels were correlated with endpoint DA levels. There were no statistically significant differences between ADHD subgroups. Plasma NE levels were not related to symptom severity or treatment response. In contrast, baseline DA levels were negatively correlated with ARS total scores. Conclusions: We found no statistically significant differences between plasma levels of NE and DA in a prepubertal male sample with ADHD and controls. Plasma DA and NE levels were correlated at both baseline and the endpoint. Although there was a signal that baseline DA levels may correlate with ADHD symptoms as evaluated via ARS, this was not true for endpoint analyses. Because this negative correlation disappeared after treatment, this finding about baseline DA levels may also be evaluated as an early treatment neuromarker. The negative results could also be explained by our focus on plasma. The recent consensus is that urinary levels of NE and DA may be more informative in patients with ADHD and that concurrent evaluation of multiple neurotransmitter systems (i.e., neuropeptide Y and NE) may be more informative. Further studies may benefit from concurrent measurements of plasma and urinary levels of catecholamines and their metabolites.

Serum Catecholamines and Dysautonomia in Diabetic Gastroparesis and Liver Cirrhosis

Plasma catecholamine influences autonomic function and control, but there are few reports correlating them. In this study, 47 individuals (mean age, 38 years) were studied: 19 diabetes mellitus (DM) patients with gastroparesis, 16 with liver disease and 12 control subjects. Noninvasive autonomic function was assessed for sympathetic adrenergic functions as peripheral vasoconstriction in response to cold stress test and postural adjustment ratio (PAR) and cholinergic function as Valsalva ratio, represented by change in R-R intervals. Measurements were compared by analysis of variance and Spearman's correlation, and results were reported as mean ± standard error. Plasma norepinephrine (1902.7 ± 263.3; P = 0.001) and epinephrine (224.5 ± 66.5; P = 0.008) levels, as well as plasma dopamine levels (861.3 ± 381.7), and total plasma catecholamine levels were highest for patients with liver disease, who also had significant negative correlation between norepinephrine level and vasoconstriction (P = 0.01; r = -0.5), PAR1 (P = 0.01; r = -0.5), sympathetic adrenergic functions (P = 0.005; r = -0.6), total autonomic index (P = 0.01-0.5) and total autonomic function (P = 0.01; r = -0.2) and also negative correlation between epinephrine plasma level and total autonomic function (P = 0.04; r = 0.4). DM patients were next highest in norepinephrine level (133.26 ± 7.43), but lowest for plasma catecholamine; a positive correlation between dopamine level and PAR1 (P = 0.008; r = 0.6) was also seen in this group. Plasma dopamine levels and spider score correlated negatively (P = 0.04; r = -0.5) and total plasma catecholamine positively with encephalopathy (P = 0.04; r = 0.5) in patients with liver disease. Plasma catecholamine levels correlated with adrenergic functions in control subjects and patients with DM and liver disease, with no significant correlation seen for cholinergic function.

Plasma Catecholamine Profile of Subarachnoid Hemorrhage Patients with Neurogenic Cardiomyopathy

Purpose: To investigate the connection between sympathetic function and neurogenic cardiomyopathy (NC), and to determine whether NC is mediated primarily by circulating adrenal epinephrine (EPI) or neuronally transmitted norepinephrine (NE), following subarachnoid hemorrhage (SAH). Methods: This is a prospective observational investigation of consecutive severe-grade SAH patients. All participants had transthoracic echocardiography and serological assays for catecholamine levels - dopamine (DA), NE and EPI - within 48 h of hemorrhage onset. Clinical and serological independent predictors of NC were determined using multivariate logistic regression analyses, and the accuracy of predictors was assessed by receiver operating characteristic (ROC) curves. Multivariate linear regression analyses were used to evaluate correlations among the catecholamines. Results: The investigation included a total of 94 subjects: the mean age was 55 years, 81% were female and 57% were Caucasian. NC was identified in approximately 10% (9/94) of cases. Univariate analyses revealed associations between NC and worse clinical severity (p = 0.019), plasma DA (p = 0.018) and NE levels (p = 0.024). Plasma NE correlated with DA levels (ρ = 0.206, p = 0.046) and EPI levels (ρ = 0.392, p < 0.001), but was predicted only by plasma EPI in bivariate [parameter estimate (PE) = 1.95, p < 0.001] and multivariate (PE = 1.89, p < 0.001) linear regression models. Multivariate logistic regression analyses consistently demonstrated the predictive value of clinical grade for NC (p < 0.05 for all analyses) except in models incorporating plasma NE, where NC was independently predicted by NE level (OR 1.25, 95% CI 1.01-1.55) over clinical grade (OR 4.19, 95% CI 0.874-20.1). ROC curves similarly revealed the greater accuracy of plasma NE [area under the curve (AUC) 0.727, 95% CI 0.56-0.90, p = 0.02] over clinical grade (AUC 0.704, 95% CI 0.55-0.86, p = 0.05) for identifying the presence or absence of NC. Conclusions: Following SAH, the development of NC is primarily related to elevated plasma NE levels. Findings implicate a predominantly neurogenic process mediated by neuronal NE (and not adrenal EPI), but cannot exclude synergy between the catecholamines.

Hedonic sensitivity to natural rewards is affected by prenatal stress in a sex-dependent manner.

Palatable food is a strong activator of the reward circuitry and may cause addictive behavior leading to eating disorders. How early life events and sex interact in shaping hedonic sensitivity to palatable food is largely unknown. We used prenatally restraint stressed (PRS) rats, which show abnormalities in the reward system and anxious/depressive-like behavior. Some of the hallmarks of PRS rats are known to be sex-dependent. We report that PRS enhanced and reduced milk chocolate-induced conditioned place preference in males and females, respectively. Male PRS rats also show increases in plasma dihydrotestosterone (DHT) levels and dopamine (DA) levels in the nucleus accumbens (NAc), and reductions in 5-hydroxytryptamine (5-HT) levels in the NAc and prefrontal cortex (PFC). In male rats, systemic treatment with the DHT-lowering drug finasteride reduced both milk chocolate preference and NAc DA levels. Female PRS rats showed lower plasma estradiol (E2 ) levels and lower DA levels in the NAc, and 5-HT levels in the NAc and PFC. E2 supplementation reversed the reduction in milk chocolate preference and PFC 5-HT levels. In the hypothalamus, PRS increased ERα and ERβ estrogen receptor and CARTP (cocaine-and-amphetamine receptor transcript peptide) mRNA levels in males, and 5-HT2C receptor mRNA levels in females. Changes were corrected by treatments with finasteride and E2 , respectively. These new findings show that early life stress has a profound impact on hedonic sensitivity to high-palatable food via long-lasting changes in gonadal hormones. This paves the way to the development of hormonal strategies aimed at correcting abnormalities in the response to natural rewards.

Histological and hormonal changes in the European eel (Anguilla anguilla) after exposure to environmental cocaine concentration.

The aim of this study was the assessment of histological and hormonal changes induced in the European eel from environmental concentrations of cocaine. Silver eels were exposed to 20ngL(-1) of cocaine during 50days; at the same time, control, vehicle control and two post-exposure recovery groups (3 and 10days) were made. The general morphology of the skin and the intestine, and the plasma levels of prolactin, cortisol and dopamine were evaluated. In the skin, cocaine decreased the number and size of mucous cells, increased the thickness of the epidermis and altered the club cells and the basal lamina. In the intestine, cocaine increased the thickness of the epithelium and the number of mucous cells and reactivated the structure of the intestine and of the intestinal musculature. Moreover, cocaine increased plasma prolactin, cortisol and dopamine levels. These results suggest that cocaine induced histological changes, directly and/or through the hormonal changes observed. Considering the complex life cycle of the eel, the changes induced by cocaine in the skin, the intestine and the endocrine system could threaten the ability of the eel to successfully migrate and reproduce.

Biological variations in adrenal gland response to immobilization and glucoprivation stressors in rats

The aim of the present study was to investigate the potential variation in adrenal gland response to two different types of acute stressors, immobilization and glucoprivation. Twenty-four adult male albino rats were randomly divided into three main groups (8 rats/group): a) control, i.e. non-stressed group, b) immobilized group (IS), and c) glucoprivated (GS) group. Plasma catecholamines (CAs), including epinephrine (E), norepinephrine (NE), dopamine (DA), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), sodium, potassium, and glucose were measured. Adrenals weight, CAs levels, and nitric oxide (NO) content were also determined. Immobilized group of rats showed significantly higher plasma NE and DA levels along with asignificantly lower adrenal NE content than GS group. On the other hand, GS group was associated with significantly higher plasma E, ACTH, CORT, glucose, and Na+ levels as well as higher adrenal DA and NO levels along with significantly lower plasma K+ levels and adrenal E content in comparison with IS group. Stress response is unique according to the nature of the stressor. Adrenal glands play akey role in this stress-induced differentiated response probably via modulation of its adreno-medullary and/or adrenocortical hormone levels in order to assign the body cope with different types of stress challenges during the life.

Caffeine links dopamine and serotonin release during passive heat loading

Caffeine links dopamine and serotonin release during passive heat loading

Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder

Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18pg/ml) and dopamine (34.87±3.57pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72pg/ml and 20.40±3.53pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine.

Platelet hyperactivity, neurobehavioral symptoms and depression among Indian women chronically exposed to low level of arsenic

The prevalence of neurobehavioral symptoms (NBS) and depression has been investigated in premenopausal rural women of West Bengal, India enrolled from arsenic (As) endemic (groundwater As 11–50μg/L; n=342) and control areas (As level≤10μg/L; n=312). The subjective symptoms questionnaire and Beck's 21-point depression inventory-II were used for the detection of NBS and depression, respectively. Platelet P-selectin expression was measured by flow cytometry, plasma neurotransmitter activity with high performance liquid chromatography and groundwater As level by atomic absorption spectroscopy. The As level in groundwater was 2.72±1.18μg/L in control and 28.3±13.51μg/L in endemic areas (p<0.0001). Women residing in endemic areas demonstrated a higher prevalence of depressive symptoms (39.8 vs. 19.9%, p<0.001) and anxiety (43.3 vs. 18.0% in control, p<0.001), fatigue (68.4 vs. 23.4%, p<0.0001), reduced sense of taste (15.8 vs. 4.5%, p<0.0001) and smell (14.9 vs. 5.8%, p<0.001); burning sensation (36.8 vs. 5.4%, p<0.0001) and tingling or numbness in the extremities (25.1 vs. 5.1%, p<0.0001); and transient loss of memory (69.9 vs. 28.2%, p<0.001). As-exposed women had 1.6-times more plasma epinephrine and norepinephrine (p<0.05), 1.8-times higher level plasma serotonin with 28.9% lower intraplatelet serotonin (p<0.05 for both), but their plasma dopamine level was not significantly different (p>0.05) from that of controls. Moreover, women from endemic areas had 2.3-times more P-selectin-expressing platelets in their circulation (p<0.001). After controlling the potential confounders, chronic low level As (11–50μg/L) exposure showed a positive association with the prevalence of neurobehavioral symptoms and depression among Indian women in their child-bearing age.

Effects of dexmedetomidine on patients undergoing radical gastrectomy

BackgroundSurgical stress may cause immunosuppression especially in patients who have surgery for primary tumor removed. This study aimed to explore the effects of dexmedetomidine on immune and inflammatory response in patients undergoing radical gastrectomy. MethodsAfter the institutional review board approval and written informed consent, forty patients undergoing radical gastrectomy were equally randomized to receive dexmedetomidine infusion (Dex group; 0.5 μg·kg−1 initial dose followed by a maintenance dose of 0.4 μg·kg−1 h−1) or normal saline infusion (NS group). Helper T lymphocytes (T helper 1 [Th1] and T helper 2 [Th2]), tumor necrosis factor-α, and interleukin-6 were measured during and after surgeries. Plasma catecholamine levels were also measured during surgery. Postoperative pain was measured by a visual analog scale. ResultsThe percentage of Th1 increased significantly at the end of surgery, 24 h after surgery (P = 0.045 and 0.048, respectively), and Th2 decreased notably at the end of surgery in the Dex group (P = 0.030). Plasma levels of tumor necrosis factor-α (P = 0.045 and 0.036, respectively) and interleukin-6 (P = 0.049 and 0.042, respectively) differed significantly at the end of surgery and 24 h after surgery. Plasma epinephrine and norepinephrine levels decreased significantly at the beginning of surgery in the Dex group (P = 0.020 and 0.015, respectively). At the end of surgery, plasma dopamine levels decreased significantly in the Dex group (P = 0.048), but increased in the NS group. The visual analog scale pain score was lower in the Dex group than in the NS group 24 h after surgery (P = 0.046). ConclusionsDexmedetomidine has been shown to reduce surgical stresses and maintain Th1/Th2 balance. It has been shown to reduce inflammatory responses and exerts immunoprotective effect.

One dose of oral hexarelin protects chronic cardiac function after myocardial infarction

Both hexarelin and its natural analog ghrelin exert comparable cardioprotective activities. A single dose of ghrelin administered at the very acute phase after experimental myocardial infarction positively affects cardiac function in chronic heart failure. Therefore, this study aimed to determine whether a single dose of oral hexarelin has the same effect in the chronic disease phase. Myocardial infarction or sham operation was generated by left coronary artery ligation in male C57BL/6J mice, which subsequently received one dose of hexarelin or vehicle treatment by oral gavage 30min after operation. Although the mortality within 14 days after myocardial infarction did not differ between the groups, hexarelin treatment protected cardiac function in the chronic phase as evidenced by higher ejection fraction and fractional shortening, as well as lower lung weight/body weight and lung weight/tibial length ratios, compared with vehicle treatment. Hexarelin treatment concurrently lowered plasma epinephrine and dopamine levels, and shifted the balance of autonomic nervous activity toward parasympathetic nervous activity as evidenced by a smaller low/high-frequency power ratio and larger normalized high-frequency power on heart rate variability analysis. The results first demonstrate that one dose of oral hexarelin treatment potentially protects chronic cardiac function after acute myocardial infarction, and implicate that activating growth hormone secretagogue receptor 1a might be beneficial for cardioprotection, although other mechanism may also be involved.

Effects of repeated tooth pulp stimulation on concentrations of plasma catecholamines, corticosterone, and glucose in rats

In this study, we examined whether tooth pulp stimulation (TPS) affects the stress responses in anesthetized rats. As for stress response indices, we monitored changes in the concentrations of plasma catecholamines (CAs) (adrenaline, noradrenaline, and dopamine), corticosterone (CS), and glucose (Glu). We observed that repeated TPS attenuated plasma adrenaline, dopamine, CS, and Glu levels compared with those of sham-TPS. After administering naloxone, an opioid antagonist, repeated TPS reversed the decreases in plasma CAs, CS, and Glu. These findings showed that the effects of repeated TPS may be mediated by endogenous opioid administration. Our findings suggest that repeated TPS can induce stress-analgesia and that an endogenous descending pain modulation system exists.

Impact of High Fat Diet-induced Obesity on the Plasma Levels of Monoamine Neurotransmitters in C57BL/6 Mice

Obesity is one of the most serious health problems in developed countries. It negatively affects diverse aspects of human wellbeing. Of these, a relationship between obesity and depression is widely recognized but biomarkers for assessment of obesityassociated mood changes in animal obesity models are rarely known. Here we explored the link between obesity and the plasma levels of monoamine neurotransmitters involved in mood control using a sensitive UPLC/MSMS technique in high fat diet (HFD)- induced obesity model in male C57BL/6 mice to explore the potential utility of plasma tests for obesity-associated mood change. HFD (60% of total calories, 8 weeks) induced significantly higher weight gains in body (+37.8%) and fat tissue (+306%) in male C57BL/6 mice. Bioanalysis of serotonin, dopamine and norepinephrine in plasma at 8 weeks of HFD revealed that serotonin decreased significantly in the obese mice when compared to normal diet-fed mice (2.7 ± 0.6 vs 4.3 ± 2.0 ng/ml, N=8). Notably, a negative correlation was found between the levels of serotonin and body weight gains. Furthermore, principal component analysis (PCA) with the individual levels of neurotransmitters revealed that plasma levels of dopamine and serotonin could apparently differentiate the obese mice from lean ones. Our study demonstrated that blood plasma levels of neurotransmitters can be employed to evaluate the mood changes associated with obesity and more importantly, provided an important clue for understanding of the relationship between obesity and mood disorders.

Tyrosine ameliorates heat induced delay in event related potential P300 and contingent negative variation

The efficacy of tyrosine, a catecholamine precursor, as a countermeasure in the reduction of cognitive decline during heat exposure (HE) using event-related potential P300, and contingent negative variation (CNV) was evaluated. Ten healthy males, age 20–30years participated in the study. Volunteers received placebo or tyrosine (6.5g) 90min prior to HE (1.5h in 45°C+30% RH). P300 latency was significantly increased (p<0.01) during exposure with placebo, which was reduced significantly (p<0.01) after tyrosine supplementation. There was an increase in CNV M100 latency (p<0.05) and reaction time (p<0.01) and decrease in M100 amplitude (p<0.01) during HE with placebo, which returns to near normal level with the tyrosine administration. A significantly higher plasma norepinephrine (p<0.05), dopamine and epinephrine levels were detected in tyrosine supplemented group post heat exposure. HE increases the brain catecholamine activity thereby reduces the plasma norepinephrine and dopamine level leading to a reduction in cognitive performances. Tyrosine supplementation increases the catecholamine level and reduces the impairment of cognitive performance during HE.

Infliximab, a TNF-α inhibitor, reduces 24-h ambulatory blood pressure in rheumatoid arthritis patients

Tumour necrosis factor-alpha (TNF-α) is an important mediator in the pathogenesis of rheumatoid arthritis (RA) and hypertension. TNF-α inhibitors improve clinical symptoms and inhibit joint destruction in RA, but their effect on blood pressure (BP) has not been fully investigated. We measured 24-h BP using an ambulatory BP monitor in 16 RA patients treated with a TNF-α inhibitor, infliximab, to investigate its influence on BP and its association with the regulatory factors of BP and renin-angiotensin-aldosterone and sympathetic nervous systems. Infliximab significantly reduced the 24-h systolic BP (SBP) from 127.4±21.8 to 120.1±23.4 mm Hg (P<0.0001). Particularly, morning BP (0600-0800 h) decreased from 129.7±19.7 to 116.9±13.4 mm Hg (P<0.0001), and daytime BP decreased from 131.8±15.1 to 122.5±13.7 mm Hg (P<0.0001). Infliximab significantly reduced the plasma level of norepinephrine and plasma renin activity (PRA) (from 347.5±180.7 to 283.0±181.8 pg ml(-1) and 2.6±2.7 to 2.1±2.9 ng ml(-1) h(-1), respectively) but did not significantly reduce the plasma levels of dopamine and epinephrine. The reduction in morning SBP correlated with the reduction in the norepinephrine level (P<0.05) but not with that in PRA and inflammatory parameters related to RA. This study shows the effect of infliximab on ambulatory BP, especially daytime BP, which may be partly accounted for by the reduction of sympathetic nerve activity after infliximab treatment.

Effect of Sildenafil Citrate on Behavior and Excitatory and Inhibitory Amino Acids Levels in Albino Rat's Brain

Sildenafil is an active cGMP-specific phosphodiesterase type 5 inhibitor that is effective in the treatment of male erectile dysfunction. None of the previous studies havemeasured sildenafil or its possibly related neurochemical changes, but mainly they related their finding to sildenafil associated behavior changes. In this work, behavioral and brain neurochemical changes (excitatory and inhibitory neurotransmitters) associated with acute administration of sildenafil using male albino rats were investigated. Rats were divided into three groups (n=6); group1 received saline (1ml/kg), group2 received single doses of sildenafil (1.5mg/kg), while group 3 received single doses of sildenafil (100mg/kg). Administration was via the intraperitoneal route. Behavior scores using EPM and brain homogenate for neurotransmitters evaluation by HPLC were carried out 60min after administration. Sildenafil did not produce any changes in behavior using the EPM test; also it did not alter the brain levels of excitatory, inhibitory and dopamine. Sildenafil produced dose dependent decreases in plasma dopamine level by mechanism(s) needs more neurochemical investigation. The chronic effect of sildenafil should be taken into consideration.

Reversal of cardiac dysfunction and subcellular alterations by metoprolol in heart failure due to myocardial infarction

In order to examine the reversibility of heart failure due to myocardial infarction (MI) by β-adrenoceptor blockade, 12 weeks infarcted rats were treated with or without metoprolol (50 mg/kg/day) for 8 weeks. The depressed left ventricular (LV) systolic pressure, positive and negative rates of changes in pressure development, ejection fraction, fractional shortening and cardiac output, as well as increased LV end-diastolic pressure in 20 weeks MI animals were partially reversed by metoprolol. MI-induced decreases in septum (systolic) thickness as well as increase in LV posterior wall thickness and LV internal diameter were partially or fully reversible by metoprolol. Treatment of MI animals with metoprolol partially reversed the elevated levels of plasma norepinephrine and dopamine without affecting the elevated levels of epinephrine. Although sarcoplasmic reticular (SR) Ca(2+)-uptake, as well as protein content for SR Ca(2+)-pump and phospholamban, were reduced in the infarcted hearts; these changes were partially reversible with metoprolol. Depressed myofibrillar Ca(2+)-stimulated ATPase activity, as well as mRNA levels for SR Ca(2+)-pump, phospholamban and α-myosin heavy chain, were unaffected whereas increased mRNA level for β-myosin heavy chain was partially reversed by metoprolol. The results suggest that partial improvement of cardiac performance by β-adrenoceptor blockade at advanced stages of heart failure may be due to partial reversal of changes in SR Ca(2+)-pump function whereas partial to complete reverse cardiac remodeling may be due to partial reduction in the elevated levels of plasma catecholamines.

The role of tyrosine metabolism in the pathogenesis of chronic migraine

The pathogenesis of chronic migraine (CM) remains largely unknown. We hypothesized that anomalies of tyrosine metabolism, found in migraine without aura (MwwA) patients, play an important role in the transformation of MwwA into CM, since the increase in the number of MwwA attacks is the most predisposing factor for the occurrence of CM. To test our hypothesis we measured the plasma levels of dopamine (DA), noradrenaline (NE) and trace amines, including tyramine (TYR) and octopamine (OCT), in a group of 73 patients with CM, 13 patients with chronic tension-type headache (CTTH) and 37 controls followed in the Headache Centers of the Neurology Departments of Asti, Milan and Vicenza hospitals in Italy. The plasma levels of DA and NE were several-fold higher in CM patients compared with control subjects ( P > 0.001). The plasma levels of TYR were also extremely elevated ( P > 0.001); furthermore, these levels progressively increased with the duration of the CM. Our data support the hypothesis that altered tyrosine metabolism plays an important role in the pathogenesis of CM. The high plasma levels of TYR, a potent agonist of the trace amine associated receptors type 1 (TAAR1), may ultimately down-regulate this receptor because of loss of inhibitory presynaptic regulation, therein resulting in uncontrolled neurotransmitter release. This may produce functional metabolic consequences in the synaptic clefts of the pain matrix implicated in CM.