Plasma Dopamine Research Articles

Effect of dopamine on intracerebral glutamate uptake ability in rats with minimal hepatic encephalopathy and the pathogenesis of minimal hepatic encephalopathy

Objective: To investigate the effect of dopamine (DA) on the glutamate (Glu) uptake ability of neural cells, as well as its effect on cognitive impairment in rats with minimal hepatic encephalopathy (MHE) via related pathways. Methods: A total of 45 Sprague-Dawley rats were randomly divided into control group, MHE model group, and DA intervention model group, with 15 rats in each group. The rats in the MHE model group were given intraperitoneal injection of thioacetamide (TAA), those in DA intervention model group were given intraventricular injection of DA, and those in the control group were given intraperitoneal injection of physiological saline, with a frequency of twice a week for 8 weeks. Cerebral microdialysis was used to measure the change in the content of Glu in the brain in MHE rats and rats with DA intervention; RT-PCR and Western blotting were used to measure the relative mRNA and protein expression of trace amine-associated receptor 1 (TAAR1) and excitatory amino acid transporter 2 (EAAT2); the changes in the expression of EAAT2 and extracellular Glu level were measured after intracerebroventricular injection of TAAR1 siRNA and TAAR1 plasmid in MHE rats and rats with DA intervention. One- way analyses of variance for comparison among different groups were performed, categorical data between groups were compared using nonparametric tests. Results: Compared with the control group, the MHE model group had significant increases in the content of DA in liver tissue, plasma, and brain tissue (4.90 ± 0.13 ng/g vs 1.20 ± 0.13 ng/g, P < 0.05; 16.32 ± 1.01 pmol/ml vs 5.50 ± 0.82 pmol/ml, P < 0.05; 732.45 ± 78.85 ng/g vs 387.00 ± 23.36 ng/g, P < 0.05). There was a significant increase in the extracellular Glu level within 40-120 minutes after intracerebral injection of DA in the DA intervention model group. Compared with the control group, the MHE model group and the DA intervention model group had a significant increase in the relative protein expression of TAAR1 (3.72 ± 0.50/4.18 ± 0.43 vs 0.96 ± 0.40, both P < 0.05) and a significant reduction in the expression of EAAT2 (0.46 ± 0.16/0.51 ± 0.20 vs 0.92 ± 0.11, P = 0.013 and 0.036). Compared with the model group treated with empty vector, the MHE model group and the DA intervention model group had a significant increase in the relative protein expression of EAAT2 after TAAR1 siRNA intervention (0.86±0.142 vs 0.56 ± 0.060, P = 0.028; 0.99 ± 0.056 vs 0.43 ± 0.098, P = 0.0010) and a significant reduction in the extracellular Glu level in the brain at 60-120 minutes after injection, while after TAAR1 plasmid intervention, the MHE model group and the DA intervention model group had a significant reduction in the relative protein expression of EAAT2 (0.20 ± 0.040 vs 0.48 ± 0.08, P = 0.006; 0.24 ± 0.05 vs 0.54 ± 0.07, P = 0.004) and a significant increase in the extracellular Glu level in brain at 60-100 minutes after injection. Conclusion: DA interacts with TAAR1 in brain tissue to induce extracellular accumulation of Glu, thus leading to the disorder of the TAAR1-EAAT2 signaling pathway in brain tissue and ultimately injuring the cognitive function of MHE rats.

Plasma & urinary catecholamines & urinary vanillylmandelic acid levels in patients with generalized vitiligo.

Background & objectives:Vitiligo is an acquired skin disease characterized by depigmented areas of the skin. Increased release of catecholamines from autonomic nerve endings in microenvironment of melanocytes in affected skin might be involved in the aetiopathogenesis of vitiligo. Levels of catecholamines are considered as being related to onset or worsening of the disease. Therefore, in this study, the role of catecholamines was evaluated in mapping disease stability and outcome of vitiligo patients undergoing melanocyte transfer.Methods:In this study, circulatory and urinary levels of catecholamine (CA) and vanillylmandelic acid (VMA) were determined in 45 individuals (30 vitiligo patients and 15 healthy controls) using ELISA.Results:A significant increase for plasma and urinary catecholamines along with VMA was observed as compared to healthy controls. When the pre- and post-intervention levels were analyzed in responders and non-responders, respectively, only dopamine showed significant decline in urine, rest of the molecules in plasma as well as urine showed non-significant decline except VMA which showed insignificant increase.Interpretation & conclusions:Levels of plasma/urinary epinephrine, and plasma dopamine, could not be established as biomarkers for disease stability or successful outcome of autologous melanocyte transfer in generalized vitiligo patients. However, dopamine (urine) might be of help in determining the stability in patients with generalized vitiligo undergoing melanocyte transfer. Further studies need to be done on a large sample of patients to confirm our findings.

Copper nanoclusters conjugated silica nanoparticles modified on carbon paste as an electrochemical sensor for the determination of dopamine

An electrochemical sensor based on modification of carbon paste electrode by glutathione‐capped copper nanoclusters silica nanoparticles (CuNCs/SiO2NPs) composite for determination of dopamine in the presence of ascorbic acid was presented. Transmission electron microscopy, scanning electron microscopy, energy dispersive X‐Ray analysis, X‐ray photoelectron spectroscopy, Fourier‐transform infrared spectroscopy, X‐ray diffraction and electrochemical impedance spectroscopy were used for characterization of the developed electrode. The electrochemical behavior of dopamine on CuNCs/SiO2NPs/carbon paste electrode was investigated by cyclic voltammetry and differential pulse voltammetry. Dopamine was determined in the range of 10.0 – 900.0 μM, and the limit of detection was obtained as 0.43 μM. The electrochemical behaviors of the coexisting electroactive species, which often cause interference with the determination of dopamine, were investigated. The results show that the developed electrode does not show any interference with respect to coexisting species, even in the presence of ascorbic acid. The developed electrochemical sensor was further employed for the determination of dopamine in human blood plasma, with a good recovery.

Effect of transportation on the sympatho-adrenal system responses in horses

The objective of current study was to evaluate the effect of transportation stress on the circulating adrenaline (A), noradrenaline (NA) and dopamine (DA) responses of stallions, according to the different distances. Forty-two stallions were studied before and after road transportation of 100, 200 and 300km, for a period of 1–3h. An increase in plasma A after 100km (P<0.001) was observed. A similar result was seen in plasma NA after 100km (P<0.001), and 300km (P<0.001). Increases in plasma DA after 100 and 200km (P<0.0001) were observed, with a decrease after 300km (P<0.0001). Significant interactions among groups and times for A (P<0.0001), NA (P<0.0006) and DA (P<0.0001) changes were observed. These results indicate that the sympatho-adrenal system response of horses was greater after short (100km), than medium-longer period of transportation (200 and 300km). This may indicate an adaptation process during transport, considering A and NA as the primary candidate neurotransmitters for the maintenance of homeostatic process to alleviate the effects of the perceived transportation stress.

Quantification of dopamine in biological samples by surface-enhanced Raman spectroscopy: Comparison of different calibration models

In this contribution, an attempt was made to quantify dopamine (DA) in complex biological samples (i.e., plasma and urine) using surface-enhanced Raman spectroscopy. Silver nanoparticles modified with iron-nitrilotriacetic acid (DA-selective probe) and 4-mercaptobenzoic acid (internal standard) were used as enhancing substrate. The performance of different calibration models for the quantification of DA in plasma and urine samples spiked with DA was evaluated and compared. The calibration models investigated were univariate ratiometric model based on the intensity ratio between the characteristic SERS peaks of DA and 4-mercaptobenzoic acid, PLS models built on the raw, standardized or pre-processed SERS measurements, and multiplicative effects model for surface-enhanced Raman spectroscopy (MEMSERS). Experimental results showed that among the models considered in this contribution, only MEMSERS achieved quite accurate and precise concentration predictions for DA in the spiked plasma and urine samples with recovery rates varying within the range of 91.9–112%, surprisingly better than the corresponding values of the quantitative results obtained by LC-MS/MS. This work provided further evidence of the effectiveness of MEMSERS in solving the problem of poor accuracy of quantitative SERS assays.

One-pot green synthesis of supramolecular β-cyclodextrin functionalized gold nanoclusters and their application for highly selective and sensitive fluorescent detection of dopamine

We report here one-pot synthetic method for preparing gold nanoclusters (AuNCs) by employing pristine β-cyclodextrin (β-CD) as reducing-cum-stabilizing agent for the first time. The developed AuNCs were used as a selective and sensitive fluorescent probe for sensing dopamine (DA) based on β-CD supramolecular interaction and quenching effect. The as-synthesized β-CD protected gold nanoclusters (β-CD@AuNCs) showed good monodispersity with ultra-small size < 2.0nm and exhibited strong fluorescence intensity at 450nm β-CD@AuNCs have been systematically characterized by UV–vis absorption spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. DA can trigger significant fluorescence quenching of β-CD@AuNCs on the basis of photo-induced electron transfer (PET) mechanism. Fluorescence lifetimes characterization of β-CD@AuNCs and DA/β-CD@AuNCs conjugate were performed to confirm the proposed PET process. A good linearity range (100.0nM to 80.0μM) for DA detection was obtained by applying the Stern-Volmer equation with lower LOD (3σ/s) of 20.0nM, revealing the high sensitivity of the method. This fluorescent AuNCs sensing probe for DA demonstrates excellent selectivity among 24 biological interferents owing to the specificity of steric host-guest interactions between DA and the nanocavity of β-CD capped on AuNCs. The developed nanosensor was successfully applied in the detection of DA in human serum plasma and injection dosage forms, indicating its good practicability for DA detection in biological and pharmaceutical research.

The effect of low-frequency electrical stimulation at acupoints on the plasma DA of stroke survivors with insomnia: A clinical trial

Objective To compare the therapeutic effect of low-frequency electrical stimulation at the acupoints with that of conventional Western medication among patients with post-stroke insomnia, and explore the underlying mechanism. Methods Totally 120 stroke survivors with insomnia were randomly divided into an intervention group, a medication group and a placebo group, each of 40. The intervention group received low-frequency electrical stimulation at the Dazhui and Shenshu acupoints once a day for 30 consecutive days. The medication group received 1mg estazolam capsules and the placebo group took 1mg starch capsules. The average levels of plasma dopamine (DA) of the 3 groups were compared before and after the intervention and therapeutic efficacy was estimated. Results After the intervention, the total effective rate of the intervention group was 95% (38/40). For the medication group it was 92.5% (37/40) and for the placebo group it was 17.9% (7/39). The former two treatments were significantly more effective than no treatment (the placebo). There was no significant change in the average level of plasma DA before and after the treatment in the placebo group, but significant improvement was observed in the other two groups. There was no significant difference in plasma DA between the two treatment groups after the treatment. Conclusion Low-frequency electrical stimulation at acupoints is safe and equally as effective as estazolam for treating post-stroke insomnia. Both may alleviate post-stroke insomnia by increasing plasma DA levels. Key words: Insomnia; Low-frequency electric stimulation; Acupoints; Dopamine; Randomized controlled trials

Associations between the DBH gene, plasma dopamine β-hydroxylase activity and cognitive measures in Han Chinese patients with schizophrenia

The dopamine (DA) and norepinephrine (NE) systems modulate cognitive function. Dopamine β-hydroxylase (DβH) converts DA to NE, and its activity is under strong genetic control. This study examines the association of plasma DβH (pDβH) activity, DBH gene polymorphisms (−1021C>T, rs1611115 and 444G>A, rs1108580) and cognitive deficits in Han Chinese patients with schizophrenia. We assessed pDβH activity and cognitive function using the Verbal Fluency Test (VFT), Trail Making Test (TMT) A-B, Stroop color-word test and Wisconsin Card Sorting Test (WCST) in 200 patients with schizophrenia before and after 8weeks of antipsychotic treatment (96 patients completed assessments at baseline and post-treatment). We found that rs1611115 was significantly associated with pDβH activity, and there was strong LD between rs1611115 and rs1108580 polymorphisms. Correlation analysis indicated that pDβH activity correlated nominally with improvement in VFT score after 8weeks antipsychotic treatment. Moreover, there was a significant genotype effect of the rs1108580 on VFT: the VFT score of patients with AA genotype was higher than that of patients with AG/GG genotype either at baseline or the end of 8 weeks after treatment. However, this difference was not observed for rs1611115. Our findings confirm a strong association between genotype at rs1611115 and pDβH activity in Chinese patients with schizophrenia. Our data also suggest the rs1108580 polymorphism may influence some aspects of cognitive function in schizophrenia.

Treadmill exercise produces neuroprotective effects in a murine model of Parkinson’s disease by regulating the TLR2/MyD88/NF-κB signaling pathway

Parkinson’s disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer’s disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Eight weeks of treadmill exercise improved motor deficits and reduced α-synuclein expression, a major causative factor of PD-like symptoms, in MPTP mice. Treadmill exercise also down-regulated the expression of toll-like receptor 2 and its associated downstream signaling molecules, including myeloid differentiation factor-88, tumor necrosis factor receptor-associated factor 6, and transforming growth factor-β-activated protein kinase 1. These effects were associated with reduced ionized calcium-binding adapter molecule 1 expression, decreased IκBα and nuclear transcription factor-κB phosphorylation, decreased tumor necrosis factor α and interleukin-1β expression, and decreased NADPH oxidase subunit expression in the SNpc and striatum. Additionally, it promoted the expression of tyrosine hydroxylase and the dopamine transporter, as well as plasma dopamine levels, in MPTP mice; these effects were associated with decreased caspase-3 expression and cleavage, as well as increased Bcl-2 expression in the SNpc. Taken together, our data suggest that treadmill exercise improves MPTP-associated motor deficits by exerting neuroprotective effects in the SNpc and striatum, supporting the notion that treadmill exercise is useful as a non-pharmacological tool for the management of PD.

Impact of special aviation gymnastics instruments training on selected hormones in cadets' blood serum and plasma.

This study has aimed at investigating the impact of the Special Aviation Gymnastics Instruments (SAGI) training scheme on the blood serum cortisol, testosterone, insulin, and plasma adrenaline, noradrenaline, and dopamine in comparison with a control group. Fifty-five cadets, aged 20 years old, participated in the study. Cadets were divided into 2 groups: A (N = 41) - the SAGI-trained, and B (N = 14) - the control group. In both groups, blood was the examined material, sampled twice: before the training session (BT) and after the training session (AT), at the beginning (training session I), during (training session II), and after completion of the SAGI training session (training session III). Commercially available kits were used for assaying serum cortisol, testosterone, and insulin as well as plasma adrenaline, noradrenaline, and dopamine. Cadets' physical fitness was assessed by means of Aero-Synthetic Efficiency Tests. In group A, a significant decrease in serum cortisol (training session III) and insulin in three training sessions AT in comparison with the values BT was seen. A statistically significant increase in testosterone and catecholamines was noted in all 3 training sessions AT in comparison with the values BT. In group B, a statistically significant increase in cortisol (training session II), testosterone, and catecholamines was observed in all 3 training sessions AT vs. the values in training session BT. In group B, serum levels of all assayed hormones were higher in training session III than those in group A. In the examined group, the SAGI training produced fewer hormonal changes dependent on the intensity and exercise type and physical efficiency improvement than in the control group. Int J Occup Med Environ Health 2017;30(4):655-664.

Involvement of PKCα and ERK1/2 signaling pathways in EGCG’s protection against stress-induced neural injuries in Wistar rats

Stress-induced neural injuries are closely linked to the pathogenesis of various neuropsychiatric disorders and psychosomatic diseases. We and others have previously demonstrated certain protective effects of epigallocatechin-3-gallate (EGCG) in stress-induced cerebral impairments, but the underlying protective mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of PKCα and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in EGCG-mediated protection against restraint stress-induced neural injuries in rats. In both open-field and step-through behavioral tests, the restraint stress-induced neuronal impairments were significantly ameliorated by administration of EGCG or green tea polyphenols (GTPs), which was associated with a partial restoration of normal plasma glucocorticoid, dopamine and serotonin levels. Furthermore, the stress-induced decrease of PKCα and ERK1/2 expression and phosphorylation was significantly attenuated by EGCG and to a less extent by GTP administration. Additionally, EGCG supplementation restored the production of adenosine triphosphate (ATP) and the expression of a key regulator of cellular energy metabolism, the peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), in stressed animals. In conclusion, PKCα and ERK1/2 signaling pathways as well as PGC-1α-mediated ATP production might be involved in EGCG-mediated protection against stress-induced neural injuries.

Erratum to: HPLC Determination of Bioactive Sulfur Compounds, Amino Acids and Biogenic Amines in Biological Specimens.

There is an increasing interest for analytical methods aimed to detect biological sulfur-containing amines, because of their involvement in human diseases and metabolic disorders. This work describes an improved HPLC method for the determination of sulfur containing amino acids and amines from different biological matrices. We optimized a pre-column derivatization procedure using dabsyl chloride, in which dabsylated products can be monitored spectrophotometrically at 460 nm. This method allows the simultaneous analysis of biogenic amines, amino acids and sulfo-amino compounds including carnosine, dopamine, epinephrine, glutathione, cysteine, taurine, lanthionine, and cystathionine in brain specimens, urines, plasma, and cell lysates. Moreover, the method is suitable for the study of physiological and non-physiological derivatives of taurine and glutathione such as hypotaurine, homotaurine, homocysteic acid and S-acetylglutathione. The present method displays good efficiency of derivatization, having the advantage to give rise to stable products compared to other derivatizing agents such as o-phthalaldehyde and dansyl chloride.

HPLC Determination of Bioactive Sulfur Compounds, Amino Acids and Biogenic Amines in Biological Specimens.

There is an increasing interest for analytical methods aimed to detect biological sulfur-containing amines, because of their involvement in human diseases and metabolic disorders. This work describes an improved HPLC method for the determination of sulfur containing amino acids and amines from different biological matrices. We optimized a pre-column derivatization procedure using dabsyl chloride, in which dabsylated products can be monitored spectrophotometrically at 460 nm. This method allows the simultaneous analysis of biogenic amines, amino acids and sulfo-amino compounds including carnosine, dopamine, epinephrine, glutathione, cysteine, taurine, lanthionine, and cystathionine in brain specimens, urines, plasma, and cell lysates. Moreover, the method is suitable for the study of physiological and non-physiological derivatives of taurine and glutathione such as hypotaurine, homotaurine, homocysteic acid and S-acetylglutathione. The present method displays good efficiency of derivatization, having the advantage to give rise to stable products compared to other derivatizing agents such as o-phthalaldehyde and dansyl chloride.With this method, we provide a tool to study sulfur cycle from a metabolic point of view in relation to the pattern of biological amino-compounds, allowing researchers to get a complete scenario of organic sulfur and amino metabolism in tissues and cells.

Indices of the antioxidant system and dopamine in blood plasma in the dynamics of microwave resonance therapy in patients with alcoholism

To study effects of microwave resonance therapy (MWRT) on the level of dopamine and some indices of the antioxidant system of blood plasma in patients with alcohol dependence. Dopamine, reduced glutathione, activities of catalase and superoxidismutase (SOD) were measured in blood plasma of alcoholic patients (50 men) before and after therapy. Plasma of 25 physically and mentally healthy men matched for age was used as control. In alcoholic patients in withdrawal state, the significant increase in dopamine (p=0.03), activity of catalase and SOD (p<0.05) as well as a decrease in reduced glutathione (p<0.01) in blood plasma in comparison with controls were found. The level of dopamine decreased significantly as after conventional therapy, as well after the therapy with addition of MWRT. After MWRT, the level of glutathione in blood plasma increased significantly and activities of catalase and SOD decreased practically up to the control level while after conventional therapy (without MWRT), the indices of the antioxidant system did not change significantly. The inclusion of MWRT in complex treatment of patients with alcoholism contributes to the normalization of the activity of catalase and SOD and increases the level of reduced glutathione, but has no significant effect on blood plasma dopamine level.

Acute Adaption to Oral or Intravenous Phosphate Requires Parathyroid Hormone.

Phosphate (Pi) homeostasis is regulated by renal, intestinal, and endocrine mechanisms through which Pi intake stimulates parathyroid hormone (PTH) and fibroblast growth factor-23 secretion, increasing phosphaturia. Mechanisms underlying the early adaptive phase and the role of the intestine, however, remain ill defined. We investigated mineral, endocrine, and renal responses during the first 4 hours after intravenous and intragastric Pi loading in rats. Intravenous Pi loading (0.5 mmol) caused a transient rise in plasma Pi levels and creatinine clearance and an increase in phosphaturia within 10 minutes. Plasma calcium levels fell and PTH levels increased within 10 minutes and remained low or high, respectively. Fibroblast growth factor-23, 1,25-(OH)2-vitamin D3, and insulin concentrations did not respond, but plasma dopamine levels increased by 4 hours. In comparison, gastric Pi loading elicited similar but delayed phosphaturia and endocrine responses but did not affect plasma mineral levels. Either intravenous or gastric loading led to decreased expression and activity of renal Pi transporters after 4 hours. In parathyroidectomized rats, however, only intravenous Pi loading caused phosphaturia, which was blunted and transient compared with that in intact rats. Intravenous but not gastric Pi loading in parathyroidectomized rats also led to higher creatinine clearance and lower plasma calcium levels but did not reduce the expression or activity of Pi transporters. This evidence suggests that an intravenous or intestinal Pi bolus causes rapid phosphaturia through mechanisms requiring PTH and downregulation of renal Pi transporters but does not support a role of the intestine in stimulating renal clearance of Pi.

Nanostructured multilayer thin films of multiwalled carbon nanotubes/gold nanoparticles/glutathione for the electrochemical detection of dopamine

In the present study, multiwalled carbon nanotubes (MWCNTs), gold nanoparticles (AuNPs), and glutathione (GSH) were used to fabricate multilayer nanoscale thin films. The composite thin films were fabricated by layer-by-layer technique as the films were constructed by the alternate deposition of cationic and anionic polyelectrolytes. The MWCNTs were modified via a noncovalent surface modification method using poly(diallydimethylammonium chloride) to form a cationic polyelectrolyte. An anionic polyelectrolyte was prepared by the chemical reduction of HAuCl4 using sodium citrate as both the stabilizing and reducing agent to form anionic AuNPs. GSH was used as an electrocatalyst toward the electro-oxidation of dopamine. The constructed composite electrode exhibits excellent electrocatalytic activity toward dopamine with a short response time and a wide linear range from 1 to 100 μmol/L. The limits of detection and quantitation of dopamine are (0.316 ± 0.081) μmol/L and (1.054 ± 0.081) μmol/L, respectively. The method is satisfactorily applied for the determination of dopamine in plasma and urine samples to obtain the recovery in the range from 97.90% to 105.00%.

Selective Detection of Dopamine in the Presence of Ascorbic and Uric Acids through its Covalent Immobilization on Gold Mercaptopropionic Acid Self‐assembled Monolayer

AbstractA simple, stable and recoverable sensor is developed based on selective and covalent immobilization of dopamine (DA) on the gold (Au) electrode modified by mercaptopropionic acid (MPA) self‐assembled monolayers and then, activated with 1‐ethyl‐3(3‐(dimethylamino)propyl)‐carbodiimide hydrochloride (EDC)/n‐hydroxysuccinimide (NHS) activators. Fabrication steps and analytical application of this modified electrode toward quantitative determination of DA in the presence of ascorbic and uric acids are verified by cyclic and differential pulse voltammetry (CV and DPV) methods in the absence of any redox probe. The oxidation peak current of adsorbed DA changed linearly with the concentration of DA in the range of 0.5 to 600.0 μM with a detection limit of 0.064 μM, and the RSDs varied from 1.4 to 3.5 % for n=3 at each point. Finally, the fabricated sensor is used successfully for electroanalytical determination of DA in human blood plasma and pharmaceutical injection real samples.

Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains of rats with streptozotocin-induced diabetes

The central nervous system is one of the most vulnerable organs affected by the oxidative stress associated with diabetes mellitus. Healthy food provides an important source for antioxidants. Therefore, the protective effect of Cucumis melo var. flexuosus (C. melo var. flexuosus) leaf extract on the brains of diabetic rats was investigated. Adult male albino rats divided into 5 groups of 6 rats each were assigned into a normal control group and four diabetic groups. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60mg/kg bw). One of the four diabetic groups was left untreated and was considered as a diabetic control group while the three other groups were treated with C. melo var. flexuosus leaf extract at the doses of 30, 60 and 120mg/kg bw for a period of 30days. After completion of experimental duration plasma and brains were used for evaluating biochemical changes. The obtained data showed that C. melo var. flexuosus leaf extract treatment lowered blood glucose, glycated hemoglobin, brain tumor necrosis factor-alpha, interleukin levels, brain malondialdehyde content and caspase-3 activity. Furthermore, the treatment resulted in a marked increase in plasma dopamine, melatonin, brain vascular endothelial growth factor-A levels, brain catalase and superoxide dismutase activities. From the present study, it can be concluded that the C. melo var. flexuosus leaf extract exerts a neuroprotective effect against oxidative damage associated with diabetes.

Psychophysiological Investigation of Combat Veterans with Subthreshold Post-traumatic Stress Disorder Symptoms.

Military service members (SMs) with subthreshold combat-related post-traumatic stress disorder (PTSD) symptoms often have clinically significant functional impairment, even though they do not meet full PTSD criteria. We therefore assessed the psychophysical responses of SMs, upon their return from Afghanistan or Iraq, to a fear conditioning paradigm to better understand the biological underpinnings of symptom severity. Heart rate (HR), skin conductance, electromyography startle, and respiratory rate (RR) were monitored throughout three distinct phases of the paradigm-fear acquisition, fear inhibition, and fear extinction-while plasma catecholamines (epinephrine, norepinephrine, and dopamine) were measured at the end of fear inhibition. Those with higher PTSD symptom severity demonstrated elevations in HR and startle response to danger cues; elevated self-reported depression and anxiety; impaired functional status; poor skin conductance discrimination between danger and safety; and increases in HR and RR during fear extinction. Moreover, an inverse relationship was seen between plasma dopamine and HR during fear inhibition for those with high symptoms. Overall, the physiological responses we observed in our subthreshold PTSD population parallel what has been previously observed in full PTSD, making a case for addressing subthreshold PTSD symptoms in combat veterans.

Dopamine in plasma - a biomarker for myofascial TMD pain?

BackgroundDopaminergic pathways could be involved in the pathophysiology of myofascial temporomandibular disorders (M-TMD). This study investigated plasma levels of dopamine and serotonin (5-HT) in patients with M-TMD and in healthy subjects.MethodsFifteen patients with M-TMD and 15 age- and sex-matched healthy subjects participated. The patients had received an M-TMD diagnosis according to the Research Diagnostic Criteria for TMD. Perceived mental stress, pain intensity (0–100-mm visual analogue scale), and pressure pain thresholds (PPT, kPa) over the masseter muscles were assessed; a venous blood sample was taken.ResultsDopamine in plasma differed significantly between patients with M-TMD (4.98 ± 2.55 nM) and healthy controls (2.73 ± 1.24 nM; P < 0.01). No significant difference in plasma 5-HT was observed between the groups (P = 0.75). Patients reported significantly higher pain intensities (P < 0.001) and had lower PPTs (P < 0.01) compared with the healthy controls. Importantly, dopamine in plasma correlated significantly with present pain intensity (r = 0.53, n = 14, P < 0.05) and perceived mental stress (r = 0.34, n = 28, P < 0.05).ConclusionsThe results suggest that peripheral dopamine might be involved in modulating peripheral pain. This finding, in addition to reports in other studies, suggests that dopaminergic pathways could be implicated in the pathophysiology of M-TMD but also in other chronic pain conditions. More research is warranted to elucidate the role of peripheral dopamine in the pathophysiology of chronic pain.