Urinary Dopamine Research Articles

Inhalation of printer-emitted particles impairs cardiac conduction, hemodynamics, and autonomic regulation and induces arrhythmia and electrical remodeling in rats

BackgroundUsing engineered nanomaterial-based toners, laser printers generate aerosols with alarming levels of nanoparticles that bear high bioactivity and potential health risks. Yet, the cardiac impacts of printer-emitted particles (PEPs) are unknown. Inhalation of particulate matter (PM) promotes cardiovascular morbidity and mortality, and ultra-fine particulates (< 0.1 μm aerodynamic diameter) may bear toxicity unique from larger particles. Toxicological studies suggest that PM impairs left ventricular (LV) performance; however, such investigations have heretofore required animal restraint, anesthesia, or ex vivo preparations that can confound physiologic endpoints and/or prohibit LV mechanical assessments during exposure. To assess the acute and chronic effects of PEPs on cardiac physiology, male Sprague Dawley rats were exposed to PEPs (21 days, 5 h/day) while monitoring LV pressure (LVP) and electrocardiogram (ECG) via conscious telemetry, analyzing LVP and heart rate variability (HRV) in four-day increments from exposure days 1 to 21, as well as ECG and baroreflex sensitivity. At 2, 35, and 70 days after PEPs exposure ceased, rats received stress tests.ResultsOn day 21 of exposure, PEPs significantly (P < 0.05 vs. Air) increased LV end systolic pressure (LVESP, + 18 mmHg) and rate-pressure-product (+ 19%), and decreased HRV indicating sympathetic dominance (root means squared of successive differences [RMSSD], − 21%). Overall, PEPs decreased LV ejection time (− 9%), relaxation time (− 3%), tau (− 5%), RMSSD (− 21%), and P-wave duration (− 9%). PEPs increased QTc interval (+ 5%) and low:high frequency HRV (+ 24%; all P < 0.05 vs. Air), while tending to decrease baroreflex sensitivity and contractility index (− 15% and − 3%, P < 0.10 vs. Air). Relative to Air, at both 2 and 35 days after PEPs, ventricular arrhythmias increased, and at 70 days post-exposure LVESP increased. PEPs impaired ventricular repolarization at 2 and 35 days post-exposure, but only during stress tests. At 72 days post-exposure, PEPs increased urinary dopamine 5-fold and protein expression of ventricular repolarizing channels, Kv1.5, Kv4.2, and Kv7.1, by 50%. Conclusions: Our findings suggest exposure to PEPs increases cardiovascular risk by augmenting sympathetic influence, impairing ventricular performance and repolarization, and inducing hypertension and arrhythmia. PEPs may present significant health risks through adverse cardiovascular effects, especially in occupational settings, among susceptible individuals, and with long-term exposure.

Особливості лікування хворих з артеріальною гіпертензією із супутнім ожирінням: невідоме про відоме

Introduction. Arterial Hypertension is the most common disease of the circulatory system. Today we can talk about it as a non-infectious epidemic. Obesity is a risk factor and a frequent comorbid condition in hypertension. The aim. Given the role of dopamine metabolism as one of the pathogenetic triggers of hypertension and obesity, to study the effect of a dopamine receptor agonist bromocriptine in this category of patients. Materials and methods. We examined 111 hypertensive patients with concomitant obesity and 18 hypertensive patients without obesity with dopamine (DA) metabolism disorders. 24 patients with concomitant obesity received the dopamine receptor agonist bromocriptine and the calcium antagonist amlodipine to correct their DA metabolism disorders. The level of DA was determined according to the daily excretion of DA in the urine by fluorometric method. Determination of angiotensin II (ATII) was performed using enzyme-linked immunosorbent assay. The concentration of lipids was determined using the enzymatic colorimetric method, blood pressure was assessed using Daily Monitoring of Blood Pressure (ABPM), the condition of the endothelium was determined using D.S Celermajer’s endothelium-dependent vasodilation assessment. Results. Concomitant obesity leads to a deeper impairment in the dopaminergic system, RAAS, lipid spectrum and endothelial status. Bromocriptine and amlodipine treatment resulted in a significant increase in urinary DA excretion by 1.77 times (77.4%) and a trend towards blood ATII increase, which confirms the assumption of similar mechanism of action of dopamine agonists and angiotensin II receptor antagonist; positivization of lipid spectrum parameters: significant reduction of total cholesterol by 5.7%, TG by 14.01%, LDL by 5.5%. Regarding other lipid metabolism, such as HDL, there was a trend towards increase by 4.6%, combined with a significant improvement in endothelium-dependent vasodilation by 54.8%, lower blood pressure and a positive modulating effect of the combination of these drugs on the daily blood pressure profile against the background of a significant decrease in body weight by 8.8%.

Protein–inorganic nano hybrid sheets of Pd embedded BSA as a robust catalyst in water for oxidase mimic activity and C–C coupling reactions, and as a sustainable material for micromolar sensing of dopamine

A new nano-hybrid sheet material using palladium and BSA protein (Pd_NP@BSAsheet) was developed as a sustainable catalyst for C–C coupling reactions in water, as an oxidase enzyme mimic and for the detection of dopamine in buffer, human serum and urine.

90 Transient severe mitral regurgitation caused by an exclusively dopamine secreting paraganglioma

Abstract INTRODUCTION A 93 year old woman presented to the hospital because of severe dyspnea with a sudden onset. Her medical history was positive for a sick sinus syndrome for which she received a DDD pacemaker in 2014. Furthermore an intra-abdominal paraganglioma (PGL) was discovered a year earlier which was treated conservatively because of her age and lack of symptoms. On physical examination, a sinus rhythm of 88 bpm (pacemaker rhythm) and oxygen saturation of 80% was noted. Blood pressure was 66/38 mmHg. An urgent blood gas analysis showed an elevated blood lactate concentration of 5.5 mmol/l. Her signs and symptoms were compatible with a cardiogenic shock. Transthoracic echocardiography (TTE) revealed a notable hyperdynamic left ventricular (LV) function and a severe mitral regurgitation (MR) (ERO 0,7 cm2), based on restriction and tenting of both the anterior and posterior mitral leaflet with a systolic pulmonary artery pressure (PAPs) of 70mmHg + CVP. Because of her age and a written declaration of will, only a supportive therapy with oxygen and morphine was given. After 45minutes however, the patient suddenly and completely recuperated. Her vital signs stabilized with a blood pressure of 110/60 mmHg and oxygen saturation of 95%. A second TTE showed only a mild MR without any restriction of the mitral leaflets and a normalized PAPs of 30mmHg +CVP. The patient was hospitalized for further investigation. COURSE DURING HOSPITALIZATION During the next 48 hours, four similar episodes with acute dyspnea and signs and symptoms of cardiogenic shock were documented. Each time, TTE revealed a hyperdynamic LV function with a severe MR, based on tenting of both mitral valve leaflets. These episodes always terminated spontaneously with only a mild residual MR afterwards. An angiography was performed and showed no coronary lesions. DIFFERENTIAL DIAGNOSIS Because of the paroxysmal episodes, documentation of a hyperdynamic LV function with severe hypotension and the known PGL, a 24h urine collection was performed. The results demonstrated a markedly elevated urine dopamine concentration (5300 µg/l) with normal concentrations of adrenaline (3.5 µg/l) and noradrenaline (64.3 µg/l). 3-Methoxytyramine, the metabolite of dopamine, was also highly elevated (4700 µg/l). As such, the diagnosis of a dopamine producing PGL was made. The patient refused any treatment and she went home in a palliative setting. CONCLUSION Dopamine-secreting PGL is a very rare entity without a classic clinical presentation. This is the first case report showing a severe MR with cardiogenic shock, leading to the diagnosis of a dopamine secreting PGL. The mechanism of the MR is still unclear, but strain measurements did show an exacerbation of the RV pacing induced dyssynchrony during the episodes of shock, hypothesizing that dopamine release exacerbated the pacing induced asynchrony of the papillary muscles, leading to a functional MR.

A sensitive resonance Rayleigh scattering sensor for dopamine in urine using upconversion nanoparticles

AbstractA highly sensitive resonance light scattering method for detecting dopamine in urine was developed by using a novel probe based on lanthanide‐doped upconversion nanoparticles (UCNPs) linked to dopamine–quinone (DQ) by hydrogen bonding and electrostatic interactions. Adding dopamine to a solution containing UCNPs decreases their size and the intensity of their resonance light scattering signals. Based on the decrease, dopamine can be determined in Tris–HCl buffer and in urine samples spiked with analyte concentrations over the range 0–300 μM with a limit of detection of 1.62 μM. As‐prepared UD can thus provide an effective platform for biosensor development, drug discovery, and rapid diagnosis of Parkinson's and Alzheimer's disease, among other medical conditions.

Electrochemical determination of urinary dopamine from neuroblastoma patients based on Cu nanoplates encapsulated by alginate-derived carbon

Precisely monitoring dopamine (DA) with high sensitivity, selectivity, and low cost from real life biological samples such as urine to investigate the suspected catecholamine-secreting tumor remains a big challenge. Here, for the first time, we synthesize a DA sensor based on Cu nanoplatelets (Cu@CNP) encapsulated by carbon nanoparticles (CNP) that are pre-modified by a benzimidazolium-1-acatate ionic liquid (BAIL). The simple scalable route (freeze-drying followed by a temperature-switchable carbonization process) enables the CNP shells with controlled thickness to form upon the Cu nanoplatelets. Among the resulting products, Cu@CNP-600 (Cu@CNP carbonized at 600 °C) shows a high concentration of exposed {111} Cu crystal planes, surface defects with quadrupole and dipolar plasmons multipoles, and graphitic layers. Once deposited onto the lead pencil electrode (LPE), the Cu@CNP-600 modified with highly conductive BAIL synergistically allows highly sensitive and selective detection of DA. We successfully apply this novel electrode to monitor the DA from the urine of neuroblastoma patients with high sensitivity. The designed electrode can be used not only in the diagnosis of suspected catecholamine-secreting tumors but also in the evaluation of drugs’ efficacy.

Graphene Modified Molecular Imprinting Electrochemical Sensor for Determining the Content of Dopamine

Background: The unnatural levels of dopamine (DA) result in serious neurological disorders such as Parkinson’s disease. Electrochemical methods which have the obvious advantages of simple operation and low-cost instrumentation were widely used for determination of DA. In order to improve the measurement performance of the electrochemical sensor, molecular imprinting technique and graphene have always been employed to increase the selectivity and sensitivity. Methods: An electrochemical sensor which has specific selectivity to (DA) was proposed based on the combination of a molecular imprinting polymer (MIP) with a graphene (GR) modified gold electrode. The performance and effect of MIP film were investigated by differential pulse voltammetry (DPV) and cyclic voltammetry (CV) in the solution of 5.0 ×10-3 mol/L K3[Fe(CN)6] and K4[Fe(CN)6] with 0.2 mol/L KCl at room temperature. Results: This fabricated sensor has well repeatability and stability, and was used to determine the dopamine of urine. Under the optimized experiment conditions, the current response of the imprinted sensor was linear to the concentration of dopamine in the range of 1.0×10-7 ~ 1.0×10-5 mol/L, the linear equation was I (µA) = 7.9824+2.7210lgc (mol/L) with the detection limit of 3.3×10-8 mol/L. Conclusion: In this work, a highly efficient sensor for determination of DA was prepared with good sensitivity by GR and great selectivity of high special recognization ability by molecular imprinting membrane. This proposed sensor was used to determine the dopamine in human urine successfully.

Urinary catecholamines during stress and ambulatory blood pressure in children born full term but small for gestational age: a pilot study.

Increased sympathetic activity is proposed to be a mechanism of high blood pressure in children born small for gestational age. Ambulatory blood pressure monitoring is a form of blood pressure measurement that can detect high blood pressure outside the hospital in patients with normal office blood pressure. This condition is called masked hypertension. There are limited data on association between ambulatory blood pressure and urinary catecholamines during exposure to stress in children born small for gestational age. Nineteen children born small for gestational age and 17 healthy controls ages 6-14 years old were included. Demographic data and office blood pressure were collected. Urinary catecholamines were collected before and after exposure to stress including mathematical test and venipuncture. Afterwards, ambulatory blood pressure monitoring was performed to obtain 24-hour blood pressure profiles. All children had normal office blood pressure but ambulatory blood pressure monitoring revealed masked hypertension in six children born small for gestational age (32%) and two controls (11.7%). After stress, median percentage of increase in urine norepinephrine levels was greater in children born small for gestational age with masked hypertension than that of children born small for gestational age without masked hypertension (9.2 vs. -13.2 μg/g creatinine, P = 0.05). There was no increase in urine norepinephrine levels in controls with masked hypertension. Among children born small for gestational age, awake SBP z-scores had significant positive correlations with pre- and post-stress urinary dopamine levels (r = 0.530, P = 0.02 and r = 0.597, P = 0.007, respectively). Masked hypertension is not uncommon in children born small for gestational age. After stress, urinary norepinephrine levels were increased in children born small for gestational age with masked hypertension.

Systematic assessment of urinary catecholamines in type 2 diabetic nephropathy and neuropathy patients by liquid chromatography tandem mass spectrometry

Objective To investigatethe relationship between urinary catecholamine levels and type Ⅱ diabetic nephropathy and neuropathy. Methods Allsubjects were collected fromTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,and were divided into two groups: type Ⅱ diabetic patients (For 24 h urine, n=130, aged 27-81 years old, 75 men, 55 female; for random urine, n=115, aged 27-77 years old, 75 men, 40 female) and healthy control (For 24 h urine, n=118, aged 27-76 years old, 67 men, 51 female; for random urine, n=93, aged 25-74 years old, 57 men, 36 female).Based on the results of urinary albumin excretion, type Ⅱ diabetic patients were prospectively divided into two independent groups: patients with nephropathy (For 24 h urine, n=37; for random urine, n=32) and patients without nephropathy (For 24 h urine, n=32; for random urine, n=35). According to questionnaires, quantitative sensory testing and autonomic function test, type Ⅱ diabetic patients were divided into two different groups: patients with neuropathy (For 24 h urine, n=31; for random urine, n=23) and patients without neuropathy (For 24 h urine, n=30; for random urine, n=35). Urinary catecholamines(CAs) levels, including epinephrine (E), norepinephrine (NE), dopamine (DA) and total catecholamines (total CAs) levels, were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS). The CAs levels in different groups have been discussed. The results were analyzed using χ2 test, independent t test and Mann-Whitney non-parametric test. Results Type Ⅱ diabetic patients with nephropathy show lower E (0.74±0.24) μg/24 h, NE(9.22±4.02) μg/24 h, DA(64.77±21.68) μg/24 h and total CAs(74.72±25.65) μg/24 h in 24-hour urine in comparison with the group without nephropathy(For E, 4.23±0.50 μg/24 h, U=10, P<0.001; for NE, (32.31±1.74) μg/24 h, t=-2.72, P=0.011; for DA, (219.58±27.51) μg/24 h, t=-2.88, P=0.007; fro CAs, (256.02±30.65) μg/24 h, t=-3.02, P=0.005) and the differences were statistically significant (P<0.05). The differences of NE, DA and total CAs between type Ⅱ diabetic patients with nephropathyand without nephropathy were statistically significant in random urine(P<0.05). Conclusion These results suggested that urine CAs levels in diabetic patients with nephropathy is lower than that in patients without nephropathy, which may be related to the occurrence and development of diabetic nephropathy. Key words: Diabetic nephropathies; Diabetic neuropathies; Diabetes mellitus, type 2; Catecholamines; Chromatography, liquid; Tandem mass spectrometry

Association Between Urinary Catecholamine Excretion and Urine Volume.

Several confounders must be considered in the evaluation of urinary catecholamine excretion. However, literature is contradictory about potential confounders. The aim of the present study was to assess correlations between catecholamine excretion and anthropometric or clinical parameters with special attention to urine volume. A total of 967 24-h urinary catecholamine measurements were performed in 593 patients for diagnostic purposes. The indication for urine examination was suspicion of secondary hypertension, phaeochromocytoma, or paraganglioma. From the patients examined, 57% were females and 43% were males. The patients' age ranged between 15 and 87 years with a median [Q1; Q3] of 51 [39; 62] years. Seventy-eight percent of the patients suffered from hypertension. Seventy percent of patients took one or more antihypertensive drugs. The most commonly used drugs were ACE inhibitors (43%), while α-blockers (15%) were the least used drugs. Urinary excretion was between 500 and 11 950 ml/24 h with a median of 2200 [1600; 2685] ml/24 h. The median body mass index (BMI) was 26.7 [24.0; 30.4] kg/m2. The excretion of all catecholamines was greater in men than in women (all p<0.0001). Epinephrine (p=0.0026), dopamine (p<0.0001), and metanephrine (p=0.0106) excretion decreased with age. BMI was associated with urinary excretion of dopamine (p<0.0001), norepinephrine (p=0.0026), normetanephrine (p<0.0001), and homovanillylmandelic acid (HVMA; p=0.0251). Urine volume correlated with urinary dopamine (p=0.0127), metanephrine (p<0.0001), normetanephrine (p=0.0070), and HVMA (p<0.0028) excretion. In addition to the established associations between urinary catecholamine excretion and age, gender, and BMI in the present study, urinary catecholamine excretion correlated also with urine volume.

MON-383 Sporadic Bilateral Pheochromocytoma with Renal Pelvis Paraganglioma: A Rare Coexisting Occurrence

Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare neuroendocrine catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla and the extra-adrenal autonomic paraglanglia respectively. The natural course of this disease increases morbidity and mortality. Most cases are sporadic, unicentric and unilateral and occur in the 4th and 5th decade of life. Hereditary disease typically presents at a younger age and are likely to be bilateral and linked to germline genetic mutations. This is the case of a 26 year-old lady with history of early onset high blood pressure (HTN) in the setting of bilateral (B/L) adrenal masses. At 21 years old, she was diagnosed with HTN accompanied with symptoms of depression, cry spells, anxiety, tachycardia and episodes of chest pain that warranted frequent ER visits. She was started on labetalol, lisinopril and hydrochlorothiazide. The work-up for early onset HTN prompted urine fractionated catecholamine collection that revealed normal metanephrines but elevated normetanephrines more than 10 times above the upper limit of normal. SPECT CT abdomen and pelvis showed a 3 cm left adrenal mass lesion compatible with a pheochromocytoma and a 4.5cm complex but dominantly low right adrenal mass with no significant uptake suggestive of a benign adenoma. Dexamethasone suppression test, 24-hour urine free cortisol, aldosterone, plasma renin activity, calcitonin, calcium and PTH levels were within normal limits. Repeated testing showed urine norepinephrine 793 mcg/24h (normal 15-100), urine dopamine 641mcg/24h (normal 52-480), normal urine epinephrine, plasma normetanephrines 2383pg/ml (normal <148) and normal plasma metanephrines. With the diagnosis of Normetanephrine secreting PHEO, She was alpha blocked to undergo left adrenalectomy. Final pathology confirmed left PHEO. After surgery lisinopril was restarted due to HTN, and cathecholamines mildly improved but remained elevated. 7 month later CT abdomen w/wo contrast plus PET CT described status post left adrenalectomy; interval decrease in size of the right adrenal mass now avidly positive reflecting an additional PHEO and an enhancing mass in the left renal pelvis and left renal calyx consistent with a PGL, retrospectively also present in prior imaging. Interestingly no germline mutation was identified in genetic analysis. Simultaneous PGL and PHEO is rare with an incidence of 0.3 and 1 per 100000. Our detailed literature review found only two cases with bilateral PHEO and PGL. Less than 17 cases with renal PGL have been published. Our case is the first sporadic B/L PHEO with renal PGL ever reported. Although no specific genetic mutation was found in our patient, we propose close monitoring with imaging and to be continued in patients with a hereditary pattern. As genetic technology continues to evolve we will be able to identify a clear mutation in this type of patients.

SUN-283 FH Variant in a Child with Family History of Early-Onset Pheochromocytoma

Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors associated with many genes. Recently, the fumarate hydratase gene (FH) has been implicated. We describe a case of a child evaluated for PCC who was found to have a variant in FH. A 7y5mo female was referred to our pediatric endocrinology clinic for evaluation of possible PCC. Family history included 3 relatives with reported early-onset PCC (ages 8-15), including mother (alive), maternal uncle and maternal grandfather (both deceased). There was reported thyroid disease in maternal grandmother, but no other family history of conditions seen with PCC-related syndromes. The patient was healthy aside from obesity until developing headaches 5 mo prior to visit with us. Given her family history, 24-hr urine collection for catecholamines was done which showed marked elevations in urine metanephrines, normetanephrines, norepinephrine, and dopamine compared to lab reference ranges. Contrast-enhanced abdominal CT was normal by report. At the time of her visit, headaches had improved. Exam was notable for high BP at >95th percentile for height (no prior hypertension diagnosis) and obesity; there were no mucosal neuromas and thyroid exam was normal. We arranged for plasma fractionated metanephrine and normetanephrine testing and checked prolactin, gastrin, calcitonin, calcium, phosphorus, and vitamin D levels. All labs were unremarkable. MIBG scan was normal. 24-hr urine free metanephrine testing was repeated and normal. She was seen in our genetics division and tested for PCC-associated genes. A heterozygous variant in FH, c.925C>T (p.Pro309Ser), was found. This variant was classified as of uncertain significance and is present in population databases but has not been described with FH-related disease. FH is associated with autosomal dominant hereditary leiomyomatosis and renal cell cancer (HLRCC), and has early evidence of correlation with hereditary PCC/PGL. We present a case of a child who was initially suspected to have PCC based on family history, headaches, and elevated urine catecholamines but who had normal results on confirmatory testing. She was found to have a FH variant, p.Pro309Ser, classified as uncertain in significance but which we believe may be disease-causing in this family; testing for the variant in her mother is being pursued. To our knowledge, only one case of a FH mutation associated with PCC in a child has been published. On a practical note, the patient’s fluctuating urine catecholamines may have been due to large volume on initial sample, which did not occur on the second sample; it is important to consider urine volume when interpreting urine catecholamine results. This case also highlights the impact on management that targeted genetic testing can have: knowledge of FH’s association with non-PCC conditions prompts consideration of additional screening that might not be performed for PCC alone.

SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma

Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. More than 30% of patients with PPGL have a hereditary predisposition. To date, at least 14 tumor susceptibility genes have been described. Mutations in the succinate dehydrogenase complex iron sulfur subunit B gene (SDHB) are more associated with paragangliomas and metastatic disease. Patients who are young, with larger tumors (>6 cm), positive genetic testing (especially SDHB) or paraganglioma have a higher risk of metastasis development. Case Report: A 14-yr-old boy was referred to investigate severe hypertension and paroxysmal headache, pallor and tachycardia. Biochemical testing for catecholamine-secreting PPGLs showed: 24h urine metanephrines 1.9 µg (normal range, 0.05 to 1.2), plasma normetanephrine 13.3 nmol/L (<0.9 nmol/L), plasma metanephrine <0.2 nmol/L (<0.5 nmol/L), 24h urine norepinephrine 987 µg (14 to 80), 24h urine epinephrine 0 (0.5 to 20 µg) and 24h urine dopamine 391 µg (65 to 400). Magnetic resonance imaging (MRI) revealed a 6.5 cm heterogenous and high-vascular mass in right adrenal gland topography. A strong positive uptake was evidenced in the metaiodobenzylguanidine (MIBG) scintigraphy. A selective α1-receptor blocker (prazosin) was started to control blood pressure and adrenergic symptoms. The patient underwent laparoscopic surgery and anatomopathological analysis revealed a 5.5 cm paraganglioma (PASS criteria= 3). The normal right adrenal gland was identified in the histopathology and there was no continuity between normal adrenal gland and neoplasia. After one year of follow-up, the patient is in complete remission. Genetic analysis by Sanger automated sequencing revealed no pathogenic variants in VHL and SDHD genes. We identified a heterozygous germline synonymous variant c.540 G>A (p.L180=), involving a G>A transition in the last nucleotide of SDHB exon 5. This synonymous variant results in alternative splicing of the SDHB primary transcript. This germline variant was previously reported in a 12-yr-old patient with isolated jugulotympanic paraganglioma, but it has not been associated with catecolamine-secreting paraganglioma. Neck MRI revealed no abnormalities in our patient. Conclusion: We report here a synonymous pathogenic variant in SDHB exon 5 associated with an abdominal functioning paraganglioma. Annual screening for multifocal disease (abdominal and neck PPGLs) and malignancy should be performed.

Hyperprolactinemic African elephant (Loxodonta africana) females exhibit elevated dopamine, oxytocin and serotonin concentrations compared to normal cycling and noncycling, low prolactin elephants†.

Many zoo elephants do not cycle normally, and for African elephants, it is often associated with hyperprolactinemia. Dopamine agonists successfully treat hyperprolactinemia-induced ovarian dysfunction in women, but not elephants. The objective of this study was to determine how longitudinal dopamine, serotonin, and oxytocin patterns in African elephants are related to ovarian cycle function. We hypothesized that dopamine concentrations are decreased, while oxytocin and serotonin are increased in non-cycling, hyperprolactinemic African elephants. Weekly urine and serum samples were collected for eight consecutive months from 28 female African elephants. Females were categorized as follows: (1) non-cycling with average prolactin concentrations of 15 ng/ml or greater (HIGH; n=7); (2) non-cycling with average prolactin concentrations below 15 ng/ml (LOW; n=13); and (3) cycling with normal progestagen and prolactin patterns (CYCLING; n=8). Both oxytocin and serotonin were elevated in hyperprolactinemic elephants. Thus, we propose that stimulatory factors may play a role in the observed hyperprolactinemia in this species. Interestingly, rather than being reduced as hypothesized, urinary dopamine was elevated in hyperprolactinemic elephants compared to CYCLING and LOW prolactin groups. Despite its apparent lack of regulatory control over prolactin, this new evidence suggests that dopamine synthesis and secretion are not impaired in these elephants, and perhaps are augmented.

Surgical strategy for an adult patient with a catecholamine-producing ganglioneuroblastoma and a cerebral aneurysm: a case report

BackgroundGanglioneuroblastomas, particularly those that produce catecholamine, are extremely rare in adults. Here, we report an interesting surgical case of an adult patient with a catecholamine-producing ganglioneuroblastomas in her adrenal gland, suspected to be a pheochromocytoma, and with a cerebral aneurysm.Case presentationThe patient was a 73-year-old woman under treatment for hypertension. During a health check-up, a cystic retroperitoneal tumor was incidentally found in the superior pole of her right kidney. Her blood adrenaline level was slightly elevated, and her urinary adrenaline, noradrenaline, and dopamine levels were above the upper reference limits. In addition, 24-h urinary excretion of metanephrine, normetanephrine, and vanillylmandelic acid were all increased. 123I-Meta-iodobenzylguanidine scintigraphy showed an abnormal accumulation of the marker in the cyst wall. She was, therefore, diagnosed with a pheochromocytoma and scheduled for tumor resection. However, preoperatively, 8-mm-diameter cerebral aneurysm was incidentally found in her basilar artery. This required careful preoperative discussion. The aneurysm was difficult to approach and treat, and based on its position, shape, and size, the risk of rupture was low. Because hypertension is a major risk factor for aneurysmal rupture, we decided to proceed with the tumor resection. A lumbar catheter was placed to monitor the cerebral aneurysm for intraoperative rupture, and her transcranial motor-evoked potential and somatosensory-evoked potentials were monitored to track her intraoperative neurological function. During surgery, we carefully monitored fluctuations in blood pressure and resected the tumor with minimal mobilization. Postoperatively, head computed tomography confirmed that there was no sign of rupture. Histopathologically, the tumor was diagnosed as a catecholamine-producing ganglioneuroblastoma. The postoperative course was good, and the patient’s blood pressure improved.ConclusionsCareful perioperative management is needed for a patient with both a catecholamine-producing tumor and cerebral aneurysm.

Co/Co‐N@Nanoporous Carbon Derived from ZIF‐67: A Highly Sensitive and Selective Electrochemical Dopamine Sensor

AbstractCo/Co‐N nanoparticles incorporated nitrogen‐doped nanoporous carbon (Co/Co‐N@NPC) nanostructures were fabricated via pyrolysis of metal organic framework, ZIF‐67, under argon atmosphere. The ZIF‐67 derived Co/Co‐N@NPC modified carbon paste electrode exhibited excellent performance during electroanalysis of dopamine, displaying two linear ranges; 10 nM to 50 μM, and 50 μM–500 μM with sensitivity of 12.4±0.3 μA/μM/cm2 and11.69±0.06 μA/μM/cm2, respectively. The modified electrodes were observed to be highly selective towards dopamine even in presence of other interfering biomolecules such as ascorbic acid, glucose and uric acid. To the best of our knowledge, the sensing ability of Co/Co‐N@NPC with a lower limit of detection as 6 nM is the best compared to the previously reported cobalt mediated sensors for dopamine. Practical feasibility of the sensor was demonstrated in real sample analysis of dopamine measurement in human urine samples and dopamine hydrochloride injection samples.

Strain-specific metastatic phenotypes in pheochromocytoma allograft mice

Somatostatin receptor-targeting endoradiotherapy offers potential for treating metastatic pheochromocytomas and paragangliomas, an approach likely to benefit from combination radiosensitization therapy. To provide reliable preclinical in vivo models of metastatic disease, this study characterized the metastatic spread of luciferase-expressing mouse pheochromocytoma (MPC) cells in mouse strains with different immunologic conditions. Bioluminescence imaging showed that, in contrast to subcutaneous non-metastatic engraftment of luciferase-expressing MPC cells in NMRI-nude mice, intravenous cell injection provided only suboptimal metastatic spread in both NMRI-nude mice and hairless SCID (SHO) mice. Treatment of NMRI-nude mice with anti-Asialo GM1 serum enhanced metastatic spread due to substantial depletion of natural killer (NK) cells. However, reproducible metastatic spread was only observed in NK cell-defective SCID/beige mice and in hairless immunocompetent SKH1 mice bearing disseminated or liver metastases, respectively. Liquid chromatography tandem mass spectrometry of urine samples showed that subcutaneous and metastasized tumor models exhibit comparable renal monoamine excretion profiles characterized by increasing urinary dopamine, 3-methoxytyramine, norepinephrine and normetanephrine. Metastases-related epinephrine and metanephrine were only detectable in SCID/beige mice. Positron emission tomography and immunohistochemistry revealed that all metastases maintained somatostatin receptor-specific radiotracer uptake and immunoreactivity, respectively. In conclusion, we demonstrate that intravenous injection of luciferase-expressing MPC cells into SCID/beige and SKH1 mice provides reproducible and clinically relevant spread of catecholamine-producing and somatostatin receptor-positive metastases. These standardized preclinical models allow for precise monitoring of disease progression and should facilitate further investigations on theranostic approaches against metastatic pheochromocytomas and paragangliomas.

The Relationship between the Intrarenal Dopamine System and Intrarenal Renin-angiotensin System Depending on the Renal Function

Objective The mechanisms underlying the intrarenal renin-angiotensin system (RAS) activation depend on the conditions of kidney diseases. In angiotensin II (AngII) infusion models, the circulating AngII is filtered into the renal tubular lumens, activating intrarenal RAS. However, in the chronic kidney disease (CKD) models, plasma angiotensinogen (AGT) is filtered into the tubular lumens because of glomerular injury, activating intrarenal RAS. The intrarenal dopamine system activation reduces intrarenal AGT expression and suppresses the intrarenal RAS activity in AngII infusion models. However, the relationship between the intrarenal dopamine system and intrarenal RAS has not been elucidated. Therefore, this study was conducted to determine that relationship in CKD patients. Methods We recruited 46 CKD patients (age: 51.1±20.0 years; 16 men; causes of CKD: chronic glomerulonephritis, 34; diabetic nephropathy, 2; nephrosclerosis, 4; and others, 6) not undergoing dialysis or taking RAS blockers. The urinary dopamine (U-DOPA) level, an indicator of intrarenal dopamine activity, and the urinary AGT (U-AGT) level, a surrogate marker of intrarenal RAS activity, were measured. Results As the CKD stages progressed, the U-DOPA levels decreased while the U-AGT levels increased. The U-DOPA levels were significantly and negatively correlated with the U-AGT levels but significantly and positively correlated with the estimated glomerular filtration rate (eGFR). A multiple regression analysis revealed that the U-DOPA levels were associated with the U-AGT levels after adjusting for age, sex, body mass index, and blood pressure (β=-0.38, p=0.045). However, no correlation was observed when eGFR was also adjusted (β=-0.17, p=0.29). Conclusion The negative correlation between the intrarenal dopamine system and intrarenal RAS in CKD patients may be affected by the renal function.

Antihypertensive effect of etamicastat in dopamine D2 receptor-deficient mice.

Abnormalities of the D2R gene (DRD2) play a role in the pathogenesis of human essential hypertension; variants of the DRD2 have been reported to be associated with hypertension. Disruption of Drd2 (D2-/-) in mice increases blood pressure. The hypertension of D2-/- mice has been related, in part, to increased sympathetic activity, renal oxidative stress, and renal endothelin B receptor (ETBR) expression. We tested in D2-/- mice the effect of etamicastat, a reversible peripheral inhibitor of dopamine-β-hydroxylase that reduces the biosynthesis of norepinephrine from dopamine and decreases sympathetic nerve activity. Blood pressure was measured in anesthetized D2-/- mice treated with etamicastat by gavage, (10 mg/kg), conscious D2-/- mice, and D2+/+ littermates,and mice with the D2R selectively silenced in the kidney, treated with etamicastat in the drinking water (10 mg/kg per day). Tissue and urinary catecholamines and renal expression of selected G protein-coupled receptors, enzymes related to the production of reactive oxygen species, and sodium transporters were also measured. Etamicastat decreased blood pressure both in anesthetized and conscious D2-/- mice and mice with renal-selective silencing of D2R to levels similar or close to those measured in D2+/+ littermates. Etamicastat decreased cardiac and renal norepinephrine and increased cardiac and urinary dopamine levels in D2-/- mice. It also normalized the increased renal protein expressions of ETBR, NADPH oxidase isoenzymes, and urinary 8-isoprostane, as well as renal NHE3 and NCC, and increased the renal expression of D1R but not D5R in D2-/- mice. In conclusion, etamicastat is effective in normalizing the increased blood pressure and some of the abnormal renal biochemical alterations of D2-/- mice.

Simultaneous voltammetry detection of dopamine and uric acid in human serum and urine with a poly(procaterol hydrochloride) modified glassy carbon electrode

In the present study, procaterol hydrochloride (ProH) was successfully electropolymerized onto a glass carbon electrode (GCE) with simply cyclic voltammetry scans to construct a poly(procaterol hydrochloride) (p-ProH) membrane modified electrode. Compared with the bare GCE, much higher oxidation peak current responses and better peak potentials separation could be obtained for the simultaneous oxidation of dopamine (DA) and uric acid (UA), owning to the excellent electrocatalytic ability of the p-ProH membrane. And it's based on that a square wave voltammetry (SWV) method was developed to selective and simultaneous measurement of DA and UA. Under the optimum conditions, the linear dependence of oxidation peak current on analyte concentrations were found to be 1.0–100 μmol/L and 2–100 μmol/L, giving detection limits of 0.3 μmol/L and 0.5 μmol/L for DA and UA, separately. The as prepared modified electrode shows simplicity in construction with the merits of good reproducibility, high stability, passable selectivity and nice sensitivity. Finally, the proposed p-ProH membrane modified electrode was successfully devoted to the detection of DA and UA in biological fluids such as human serum and urine with acceptable results.