Urinary Dopamine Excretion Rate Decreases during Acute Dietary Protein Deprivation and Is Associated with Increased Plasma Pancreatic Polypeptide Concentration

Background: Dopamine, a key neurotransmitter in the autonomic nervous system participating in the homeostatic balance between sympathetic and parasympathetic divisions, is involved in food intake regulation. Objective: We investigated whether dopamine is altered by acute fasting or overfeeding diets with varying macronutrient content. Design: Ninety-nine healthy subjects underwent 24-h dietary interventions including eucaloric feeding, fasting, and five different overfeeding diets in a crossover design. Overfeeding diets (200% of eucaloric requirements) included one diet with 3%-protein (low-protein high-fat overfeeding—LPF: 46%-fat), three diets with 20%-protein, and a diet with 30%-protein (44%-fat). Urine was collected for 24 h and urinary dopamine concentration was quantified by high-performance liquid chromatography. Plasma pancreatic polypeptide (PP) concentration, an indirect marker of parasympathetic activity, was measured prior to and after each diet after an overnight fast. Results: During 24-h of fasting, dopamine decreased on average by ~14% compared to eucaloric conditions, whereas PP increased by two-fold (both p < 0.001). Lower dopamine during 24-h fasting correlated with increased PP (r = −0.40, p < 0.001). Similarly, on average urinary dopamine decreased during LPF by 14% (p < 0.001) and lower dopamine correlated with increased PP (r = −0.31, p = 0.01). No changes in dopamine and PP concentrations were observed during other overfeeding diets (all p > 0.05). Conclusions: Dopamine concentrations decrease during short-term fasting and overfeeding with a low-protein diet. As both dietary conditions have in common protein deficit, the correlation between dopamine and PP suggests a compensatory mechanism underlying the shift from sympathetic to parasympathetic drive during dietary protein deprivation.

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.

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.

Effects of Forest Bathing on Cardiovascular and Metabolic Parameters in Middle-Aged Males

In the present study, we investigated the effects of a forest bathing on cardiovascular and metabolic parameters. Nineteen middle-aged male subjects were selected after they provided informed consent. These subjects took day trips to a forest park in Agematsu, Nagano Prefecture, and to an urban area of Nagano Prefecture as control in August 2015. On both trips, they walked 2.6 km for 80 min each in the morning and afternoon on Saturdays. Blood and urine were sampled before and after each trip. Cardiovascular and metabolic parameters were measured. Blood pressure and pulse rate were measured during the trips. The Japanese version of the profile of mood states (POMS) test was conducted before, during, and after the trips. Ambient temperature and humidity were monitored during the trips. The forest bathing program significantly reduced pulse rate and significantly increased the score for vigor and decreased the scores for depression, fatigue, anxiety, and confusion. Urinary adrenaline after forest bathing showed a tendency toward decrease. Urinary dopamine after forest bathing was significantly lower than that after urban area walking, suggesting the relaxing effect of the forest bathing. Serum adiponectin after the forest bathing was significantly greater than that after urban area walking.

INTERFERON ALPHA2B INDUCED DOPAMINE CHANGES IN CUTANEOUS MELANOMA PATIENTS

Objective. The authors interest was focused on interferon impact on dopamine status and on the relation between negative emotional state and dopamine in melanoma patients. Methods. 60 patients diagnosed with malignant melanoma in 1st or 2nd clinical stage were included in the first 56 days after surgical removal of the tumor in an observational prospective study. The patients were divided in 2 groups: group A that included 30 cases treated with 10MU interferon alpha2b/mp three times a week for one year and group B that included 30 cases with no adjuvant treatment. Urinary dopamine (ELISA) was evaluated before treatment with interferon alpha2b, after 1, 6, 12 months of treatment and after 6 months from the end of the treatment. Neuropsychiatric disorders were grouped according to their frequency in melanoma patients. Results. Neuropsychiatric disorders associated with the treatment with interferon were: irritability, asthenia and fatigability, sleep disorders, anxiety, cognitive disorders, somatic symptoms. The treatment with interferon altered dopamine metabolism. Dopamine returned to the pretherapeutical values at six months after interferon was stopped. Patients with low levels of urinary dopamine had a high, statistically significant risk of developing depression during interferon treatment (OR=2.647, IC=2.186-3.014, p=0.0216). Conclusions. Low dopamine might have a major role in the development of depression secondary to interferon treatment.