Urinary Catecholamine Concentrations Research Articles

Experiences of Discrimination and Urinary Catecholamine Concentrations: Longitudinal Associations in a College Student Sample.

Experiences of discrimination are a risk factor for subsequent cardiovascular disease. However, there is a lack of longitudinal research examining associations between discrimination and urinary catecholamines. This is surprising given the likely mediating role of sympathetic nervous system dysregulation in the association between psychosocial stress and cardiovascular morbidity. The current study examined the 3 year longitudinal association between experiences of discrimination and urinary catecholamines. The sample included 149 college students (mean age at baseline = 18.8, standard deviation = 0.96; 45% Black/African American; 55% White/European American). Concentrations of epinephrine and norepinephrine-urinary catecholamines with established links to psychosocial stress exposure and subsequent morbidity-were determined from 12 hr overnight samples. Results indicated that experiences of discrimination were associated with increases in both epinephrine (β = .284, standard error [SE] = .117, p = .015) and norepinephrine (β = .306, SE = .114, p = .001). These longitudinal associations persisted after adjusting for negative affect, depression, and rejection sensitivity and did not vary as a function of race/ethnicity. Results suggest that examination of overnight urinary catecholamines as a biological mediator of associations between experiences of discrimination and cardiovascular morbidity is warranted.

The effects of desynchronosis on the gut microbiota composition and physiological parameters of rats

BackgroundAll living organisms experience physiological changes regulated by endogenous circadian rhythms. The main factor controlling the circadian clock is the duration of daylight. The aim of this research was to identify the impact of various lighting conditions on physiological parameters and gut microbiota composition in rats. 3 groups of outbred rats were subjected to normal light-dark cycles, darkness and constant lighting.ResultsAfter 1 and 3 months we studied urinary catecholamine levels in rats; indicators of lipid peroxidation and antioxidant activity in the blood; protein levels of BMAL1, CLOCK and THRA in the hypothalamus; composition and functional activity of the gut microbiota. Subjecting the rats to conditions promoting desynchronosis for 3 months caused disruptions in homeostasis.ConclusionsChanging the lighting conditions led to changes in almost all the physiological parameters that we studied. Catecholamines can be regarded as a synchronization super system of split-level circadian oscillators. We established a correlation between hypothalamic levels of Bmal1 and urinary catecholamine concentrations. The magnitude of changes in the GM taxonomic composition was different for LL/LD and DD/LD but the direction of these changes was similar. As for the predicted functional properties of the GM which characterize its metabolic activity, they didn’t change as dramatically as the taxonomic composition. All differences may be viewed as a compensatory reaction to new environmental conditions and the organism has adapted to those conditions.

Urine catecholamines in children with severe Enterovirus A71 infection: comparison with paediatric septic shock

Purpose: Hypercatecholaminemia-related heart failure has been proposed as the main cause of enterovirus A71-related (EV-A71) early mortality. The purpose of this study was to measure urine catecholamine concentrations in severe EV-A71-infected children. Methods: A total of 35 children, aged 2.5 ± 2.1 years, were divided into three groups. Group I: 15 septic shock patients, group II: 17 EV-A71-stage-2 patients, and group III: 3 EV-A71-stage-4 patients. The laboratory results, cardiac biomarkers and urine catecholamine concentrations were statistically analysed. Results: Group I had the highest C-reactive protein (CRP) levels and group II had the lowest B-type natriuretic peptide (BNP) and its N-terminal prohormone among the groups (p = 0.039, <0.01 and <0.01, respectively). Group III patients had significantly higher urine catecholamine and troponin-I values among the groups. If urine epinephrine (Epi) >134 ug/gCr, norepinephrine (NE) >176 ug/gCr and vanillylmandelic acid (VMA) >11.7 mg/gCr were used as the cutoff points to differentiate groups II and III, the sensitivities and specificity were all 100%. Conclusions: The significantly elevated urine catecholamine concentrations in EV-A71-stage-4 patients support the hypothesis that hypercatecholaminemia-related heart failure is involved in severe EV-A71 infection. Urine catecholamines could be used as reliable biomarkers for differentiation of severe EV-A71 infection with or without heart failure and septic shock.

Irinotecan–temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial

Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or dinutuximab to irinotecan-temozolomide in patients with relapsed or refractory neuroblastoma. For this open-label, randomised, phase 2 selection design trial of the Children's Oncology Group (COG; ANBL1221), patients had to have histological verification of neuroblastoma or ganglioneuroblastoma at diagnosis or have tumour cells in bone marrow with increased urinary catecholamine concentrations at diagnosis. Patients of any age were eligible at first designation of relapse or progression, or first designation of refractory disease, provided organ function requirements were met. Patients previously treated for refractory or relapsed disease were ineligible. Computer-based randomisation with sequence generation defined by permuted block randomisation (block size two) was used to randomly assign patients (1:1) to irinotecan and temozolomide plus either temsirolimus or dinutuximab, stratified by disease category, previous exposure to anti-GD2 antibody therapy, and tumour MYCN amplification status. Patients in both groups received oral temozolomide (100 mg/m2 per dose) and intravenous irinotecan (50 mg/m2 per dose) on days 1-5 of 21-day cycles. Patients in the temsirolimus group also received intravenous temsirolimus (35 mg/m2 per dose) on days 1 and 8, whereas those in the dinutuximab group received intravenous dinutuximab (17·5 mg/m2 per day or 25 mg/m2 per day) on days 2-5 plus granulocyte macrophage colony-stimulating factor (250 μg/m2 per dose) subcutaneously on days 6-12. Patients were given up to a maximum of 17 cycles of treatment. The primary endpoint was the proportion of patients achieving an objective (complete or partial) response by central review after six cycles of treatment, analysed by intention to treat. Patients, families, and those administering treatment were aware of group assignment. This study is registered with ClinicalTrials.gov, number NCT01767194, and follow-up of the initial cohort is ongoing. Between Feb 22, 2013, and March 23, 2015, 36 patients from 27 COG member institutions were enrolled on this groupwide study. One patient was ineligible (alanine aminotransferase concentration was above the required range). Of the remaining 35 patients, 18 were randomly assigned to irinotecan-temozolomide-temsirolimus and 17 to irinotecan-temozolomide-dinutuximab. Median follow-up was 1·26 years (IQR 0·68-1·61) among all eligible participants. Of the 18 patients assigned to irinotecan-temozolomide-temsirolimus, one patient (6%; 95% CI 0·0-16·1) achieved a partial response. Of the 17 patients assigned to irinotecan-temozolomide-dinutuximab, nine (53%; 95% CI 29·2-76·7) had objective responses, including four partial responses and five complete responses. The most common grade 3 or worse adverse events in the temsirolimus group were neutropenia (eight [44%] of 18 patients), anaemia (six [33%]), thrombocytopenia (five [28%]), increased alanine aminotransferase (five [28%]), and hypokalaemia (four [22%]). One of the 17 patients assigned to the dinutuximab group refused treatment after randomisation; the most common grade 3 or worse adverse events in the remaining 16 patients evaluable for safety were pain (seven [44%] of 16), hypokalaemia (six [38%]), neutropenia (four [25%]), thrombocytopenia (four [25%]), anaemia (four [25%]), fever and infection (four [25%]), and hypoxia (four [25%]); one patient had grade 4 hypoxia related to therapy that met protocol-defined criteria for unacceptable toxicity. No deaths attributed to protocol therapy occurred. Irinotecan-temozolomide-dinutuximab met protocol-defined criteria for selection as the combination meriting further study whereas irinotecan-temozolomide-temsirolimus did not. Irinotecan-temozolomide-dinutuximab shows notable anti-tumour activity in patients with relapsed or refractory neuroblastoma. Further evaluation of biomarkers in a larger cohort of patients might identify those most likely to respond to this chemoimmunotherapeutic regimen. National Cancer Institute.

Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia.

Chronic intermittent hypoxia (IH) induces activation of the sympathoadrenal system, which plays a pivotal role in attenuating hypoxic pulmonary vasoconstriction (HPV) via central β1-adrenergic receptors (AR) (brain) and peripheral β2AR (pulmonary arteries). Prolonged hypercatecholemia has been shown to upregulate β3AR. However, the relationship between IH and β3AR in the modification of HPV is unknown. It has been observed that chronic stimulation of β3AR upregulates inducible nitric oxide synthase (iNOS) in cardiomyocytes and that IH exposure causes expression of iNOS in RAW264.7 macrophages. iNOS has been shown to have the ability to dilate pulmonary vessels. Hence, we hypothesized that chronic IH activates β3AR/iNOS signaling in pulmonary macrophages, leading to the promotion of NO secretion and attenuated HPV. Sprague-Dawley rats were exposed to IH (3-min periods of 4–21% O2) for 8 h/d for 6 weeks. The urinary catecholamine concentrations of IH rats were high compared with those of controls, indicating activation of the sympathoadrenal system following chronic IH. Interestingly, chronic IH induced the migration of circulating monocytes into the lungs and the predominant increase in the number of pro-inflammatory pulmonary macrophages. In these macrophages, both β3AR and iNOS were upregulated and stimulation of the β3AR/iNOS pathway in vitro caused them to promote NO secretion. Furthermore, in vivo synchrotron radiation microangiography showed that HPV was significantly attenuated in IH rats and the attenuated HPV was fully restored by blockade of β3AR/iNOS pathway or depletion of pulmonary macrophages. These results suggest that circulating monocyte-derived pulmonary macrophages attenuate HPV via activation of β3AR/iNOS signaling in chronic IH.

Victims of lethal hypothermia have decreased levels of thrombomodulin in myocardium and urine

Severe cold stress has been shown to cause changes in the expression and secretion of thrombomodulin (TM), an endothelial protein regulating haemostasis and inflammation. To further evaluate TM as a cold stress indicator, relative TM mRNA and TM protein levels in the myocardium and the concentrations of TM in serum and urine were analysed in different causes of death (hypothermia main cause, n = 80; hypothermia contributory cause, n = 26; cardiovascular disease (CVD) main cause, n = 94; trauma main cause, n = 45; other main cause, n = 25). Urinary catecholamine concentrations and myocardial heat shock factor 1 (HSF1) transcript levels were also studied. The TM mRNA and the TM protein levels in myocardium and urine were significantly lower in hypothermia deaths than those in the controls. Post-mortem interval did not correlate with urinary TM concentration. The sensitivity and specificity of urinary TM assay to detect hypothermia deaths were 70.8 and 70.3%, respectively. Catecholamine concentrations in urine correlated significantly with TM concentration in urine and TM mRNA levels in all groups excluding CVD deaths. There were no differences in the HSF1 transcript levels and no correlation to TM levels. These findings provide further evidence that cold stress and hypothermia affect TM expression and secretion and that they are possibly linked to catecholamine action. Thus, measuring post-mortem TM levels may provide additional support to diagnosing hypothermia in medico-legal examination. The results may also provide additional knowledge for the treatment of hypothermic patients and the use of hypothermia for medical purposes.

Phaeochromocytoma revealed by a stellate neuroretinitis

A 28-year-old woman presented with bilateral progressive decrease in visual acuity for 1 month. She had a history of headache, palpitations, profuse sweating, and abdominal pain for 3 months. Visual acuity was 20/800 in both eyes. On funduscopy (fi gure A) we saw a prominent bilateral optic disc swelling (black arrowheads) with marked macular hard exudates in a star shape (white arrowheads). Several hyperpigmented lesions (Siegrist streaks; white arrows) were scattered in the temporal midperipheral retina, suggesting marked ischaemia over choroidal arteries. We also noted a mild and diff use arterial narrowing with some intraretinal haem orrhages. This presentation was consistent with a stellate neuroretinitis, which is defi ned by optic disc swelling and macular hard exudates in a star shape. Fluorescein angiography (fi gure B) showed, a bilateral papillary hyperfl uorescence (black arrowheads) with some areas of delayed choroidal fi lling (white arrows) and several well-defi ned hypofl uorescent lesions (Elschnig fl ecks; white arrowheads) suggestive of a hypertensive choroidopathy. Optical coherence tomography (fi gure C) revealed a bilateral mild macular oedema (white arrows) with many perimacular exudates (white arrowheads). Blood count, erythrocyte sedimentation rate, serum lysozyme concentration, serum angiotensin-converting enzyme concentration, and fasting glucose concentration showed no abnormal results. Serology for Bartonella, syphilis, Lyme disease, and leptospirosis, quantiferon gold for tuberculosis, and cerebral CT were all normal. The patient’s blood pressure was 240/130 mm Hg. Abdominal ultra sonography showed a right adrenal mass that was hyperechoic and highly vascularised, measuring 50 mm by 52 mm and displacing the kidney (fi gure D). An abdominopelvic CT scan showed a hypodense right adrenal lesion with areas of necrosis, no intratumoural calcifi cations, and measuring 60 mm in diameter. Urinary catecholamine concentrations were high (metanephrine 107·1 μmol/24 h; normetanephrine 17·22 μmol/24 h). Neck ultrasonography, calcitonin concentration, parathyroid hormone concentration, blood and urinary calcium concentration and phosphorus concentration were normal, discounting medullary thyroid carcinoma and primary hyperparathyroidism. We did a right laparoscopic adrenalectomy; pathological examination confi rmed Phaeochromocytoma. At 3-month follow-up, blood pressure was normal (100/80 mm Hg) and visual acuity was 20/63 (right eye) and 20/200 (left eye). In our patient, the ocular symptoms were related to the high blood pressure, with a subsequent breakdown of the blood–retinal barrier leading to stellate neuroretinitis (which is a grade 4 hypertensive retinopathy). Presentation with bilateral stellate neuroretinitis should lead to measurement of blood pressure. Additional presence of Menard’s triad (headache, palpitations, and sweating) should be recognised as suggestive of phaeochromocytoma.

Catecholamine levels and delay discounting forecast drug use among African American youths

To test hypotheses about the contributions of the catecholamines epinephrine and norepinephrine [which serve as biological markers of life stress through sympathetic nervous system (SNS) activation], delay discounting and their interaction to the prediction of drug use among young African American adults. A 1-year prospective study that involved assessment of SNS activity and collection of self-report data involving delay discounting and drug use. Rural communities in the southeastern United States. A total of 456 African Americans who were 19 years of age at the beginning of the study. At age 19, participants provided overnight urine voids that were assayed for epinephrine and norepinephrine. Participants were also assessed for hyperbolic temporal discounting functions (k) and drug use. At age 20, the participants again reported their drug use. Linear regression analyses revealed that (i) catecholamine levels at age 19 forecast increases in drug use [B = 0.087, P < 0.01, 95% confidence interval (CI) = 0.025, 0.148] and (ii) among young men, catecholamine levels interacted positively with delay discounting to forecast increases in drug use (simple slope = 0.113, P < 0.001, 95% CI = 0.074, 0.152). Higher urinary catecholamine concentrations in their adulthood predict higher levels of drug use a year later among young African American men in the United States who engage in high, but not low, levels of delay discounting.

Reduced Insulin Sensitivity in Adults With Pseudohypoparathyroidism Type 1a

Disruption of the Gsα maternal allele leads to severe obesity and insulin resistance in mice and early-onset obesity in patients with pseudohypoparathyroidism (PHP) type 1a. However, insulin resistance and glucose metabolism have not been systematically characterized in patients with PHP1a. In a cross-sectional, case-control study, we examined insulin sensitivity, β-cell function, energy expenditure (EE), and sympathetic nervous system activity in adults with PHP1a. PHP1a patients (n = 8) and healthy control subjects (n = 24) matched for age (41 ± 7 vs 41 ± 7 years [mean ± SD]), gender, and percent body fat. Insulin sensitivity (SI), acute insulin response to glucose, and disposition index were assessed during a frequently sampled iv glucose tolerance test. Oral glucose insulin sensitivity (OGIS) was measured during a mixed meal. EE was measured using whole-room indirect calorimetry. Body composition was assessed via dual-energy x-ray absorptiometry and sympathetic nervous system activity by measuring 24-hour urinary catecholamine concentrations. PHP1a patients were less insulin-sensitive than their matched controls based upon SI and OGIS. Nondiabetic PHP1a patients tended to have a lower SI (P = .09) and reduced OGIS (P = .03). Disposition index, a composite measure of β-cell function, also tended to be lower in patients (P = .07). Total caloric intake, resting EE, total EE, meal-induced thermogenesis, and 24-hour urinary catecholamine concentrations were not significantly different between the groups. Adults with PHP-1a have reduced insulin sensitivity compared with their matched controls that may contribute to the pathogenesis of glucose intolerance and diabetes in these patients.

Blood Pressure, Heart Rate, and Urinary Catecholamines in Healthy Dogs Subjected to Different Clinical Settings

Correct interpretation of blood pressure (BP) and heart rate (HR) recordings is important in a clinical environment, but little is known about effects of stress on BP and HR responses of dogs to different clinical settings. To investigate BP and HR responses in different clinical settings in dogs of 3 breeds, and to relate findings to urinary catecholamine concentrations measured by ELISA assays previously validated for use in human plasma and urine, after validation for use in dogs. Client-owned healthy dogs; 41 Labrador Retrievers, 33 Cavalier King Charles Spaniels (CKCS), and 15 Dachshunds. Prospective observational study. BP and HR were measured in 4 clinical settings with or without veterinarian and owner present. Urine samples were taken before and after examination. ELISA assays were validated for canine urine, and epinephrine/creatinine and norepinephrine/creatinine ratios were analyzed. BP and HR were higher when measured by veterinarian alone than when owner was present (P < .020). Urinary catecholamine/creatinine ratios were higher after examination, compared with before, in all dogs (P < .0001). Labrador Retrievers had lower diastolic BP than Dachshunds in 2 settings (P ≤ .041), lower HR than CKCSs in 3 settings (all P < .0001), and lower catecholamine/creatinine ratios after examination than both other breeds (P ≤ .035). The in-house validation showed mean spiked recovery of 96.5% for epinephrine and 83.8% for norepinephrine. BP and HR responses were related to breed as well as clinical setting. Breed differences were detected in urinary catecholamine/creatinine ratios. Further studies on breed differences are warranted.

810 EFFECT OF CILNIDIPINE ON SYMPATHETIC NERVOUS SYSTEM AND PLASMA ALDOSTERONE CONCENTRATION IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES MELLITUS

Objective: To investigate the effect of cilnidipine on the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) in hypertensive patients with type 2 diabetes mellitus (T2DM). Patients and methods: Thirty-three hypertensive outpatients with concomitant T2DM (27 men and 6 women, mean age 68.5 years) who had been treated with calcium channel blockers (CCBs) other than cilnidipine for more than 3 months were included. Patients’ medication was changed to cilnidipine 10 or 20 mg/day. Blood pressure, heart rate, serum and urinary concentrations of catecholamines, plasma renin concentration (PRC), aldosterone concentration (PAC), urinary albumin-creatinine ratio (ACR), and BNP were measured before and 3 months after the start of the new treatment. In addition, HbA1c, liver function, eGFR, creatinine kinase, uric acid, and lipid profiles were compared before and after the changeover as safety parameters. Results: After substitution of cilnidipine, systolic blood pressure decreased significantly from 137.3 to 133.4 mmHg, but diastolic blood pressure and heart rate did not change. Plasma noradrenaline (PNA) (0.45 to 0.39 ng/ml), urinary normetanephrine (UNMN) (0.21 to 0.15 mg/l), PAC (110.9 to 98.1 pg/ml), ACR (112.4 to 65.5 mg/gCr), and BNP (48.1 to 39.7 pg/ml) decreased significantly. Plasma adrenaline, dopamine, and urinary metanephrine concentrations did not change. There was no change in any of the safety parameters. Conclusion: Following the switch from other CCBs to cilnidipine, PNA, UNMN, and PAC decreased. At the same time, ACR and BNP also decreased. This indicates that cilnidipine might exert reno- and cardioprotective effects through the suppression of SNS and RAAS.

Urinary catecholamine concentrations in three beef breeds at slaughter

Animal welfare has become an important determinant of meat quality with poor animal temperament leading to huge economic losses to the meat industry due to carcass bruising and condemnation. Handling and transport of live animals is a stressful experience for animals. The temperaments of cattle affect their behaviour and differ between breeds, i.e. studies have shown that Bos indicus types are more temperamental than Sanga and Bos taurus types. Catecholamines (CAT’s) are considered as indicators of stress, because higher concentrations of CAT’s in brain tissue were noted in animals that are better adapted to stressful situations. In the present study, urinary CAT’s of three beef breeds were determined immediately post mortem. Brahman cattle represented Bos indicus types, Simmentaler cattle represented Bos taurus types and Nguni cattle represented the Sanga type. Nguni steers showed higher urinary norepinephrine (NE) and epinephrine (E) concentrations than Brahman and Simmentaler steers. Simmentaler steers showed a higher concentration of urinary dopamine (DA) than Br and Ng. The results suggest that Nguni cattle are less stress sensitive compared to the other beef breeds studied. These observations may be due to the process of domestication and selection for specific genes that influence tameability and consequently resulting in a shift in circulating concentrations of urinary CAT’s.Keywords: Animal welfare, breed divergence, animal temperament, stress

Case Scenario: Metastatic Pediatric Paraganglioma Presenting during the Course of an Elective Surgery

P HEOCHROMOCYTOMA and paraganglioma are neuroendocrine tumors rarely diagnosed in pediatric patients. The incidence of malignant pheochromocytoma and paraganglioma in childhood is approximately 0.02 cases per million every year. Coincidental intraoperative diagnosis of pheochromocytoma involves very high mortality rates, reaching 50%. We present a case of coincidental diagnosis of pediatric metastatic malignant paraganglioma during an elective surgical procedure. The evaluation and management of pheochromocytoma and paraganglioma are discussed.

Pheochromocytoma presenting as recurrent urinary tract infections : a case report

IntroductionPheochromocytomas are rare, potentially fatal, neuroendocrine tumors of the adrenal medulla or extra-adrenal paraganglia. Their clinical presentation varies greatly from the classic triad of episodic headache, diaphoresis and tachycardia to include a spectrum of non-specific symptomatology.Case presentationA 43-year-old Caucasian woman was referred to us from primary care services with a three-month history of recurrent urinary tract infections on a background of hypertension, latent autoimmune diabetes of adulthood and autoimmune hypothyroidism. At 38 years she required insulin therapy. Despite medication compliance and dietary control, she reported a recent history of increased insulin requirements and uncontrolled hypertension with concomitant recurrent urinary tract infections. A renal ultrasound examination, to rule out underlying renal pathology, revealed an incidental 8cm right adrenal mass of both solid and cystic components. A subsequent computed tomography of her abdomen and pelvis confirmed a solid heterogeneous mass consistent with a pheochromocytoma. There were no other features suggestive of multiple endocrine neoplasia. Urinary collection over 24 hours revealed grossly elevated levels of catecholamines and metabolites. Following an open right adrenalectomy, our patient's insulin requirements were significantly reduced and her symptoms resolved. Two weeks post-operatively, an iodine-131-metaiodobenzylguanidine scintigraphy was negative for residual tumor and metastatic disease. Urinary catecholamine and metabolite concentrations were within the normal range at a follow-up six months later.ConclusionPheochromocytoma is a rare catecholamine-producing tumor requiring a high index of suspicion for early diagnosis. Our case report serves to highlight the importance of considering pheochromocytoma as a differential diagnosis in the atypical setting of recurrent urinary tract infections and concomitant autoimmune disease.

Urinary Catecholamine and Metanephrine to Creatinine Ratios in Dogs with Hyperadrenocorticism or Pheochromocytoma, and in Healthy Dogs

Urinary catecholamines and metanephrines are used for the diagnosis of pheochromocytoma (PHEO) in dogs. Hyperadrenocorticism (HAC) is an important differential diagnosis for PHEO. To measure urinary catecholamines and metanephrines in dogs with HAC. Fourteen dogs with HAC, 7 dogs with PHEO, and 10 healthy dogs. Prospective clinical trial. Urine was collected during initial work-up in the hospital; in dogs with HAC an additional sample was taken at home 1 week after discharge. Parameters were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration. Dogs with HAC had significantly higher urinary epinephrine, norepinephrine and normetanephrine to creatinine ratios than healthy dogs. Urinary epinephrine, norepinephrine, and metanephrine to creatinine ratios did not differ between dogs with HAC and dogs with PHEO, whereas the urinary normetanephrine to creatinine ratio was significantly higher (P= .011) in dogs with PHEO (414, 157.0-925.0, median, range versus (117.5, 53.0-323.0). Using a cut-off ratio of 4 times the highest normetanephrine to creatinine ratio measured in controls, there was no overlap between dogs with HAC and dogs with PHEO. The variables determined in urine samples collected at home did not differ from those collected in the hospital. Dogs with HAC might have increased concentrations of urinary catecholamines and normetanephrine. A high concentration of urinary normetanephrine (4 times normal), is highly suggestive of PHEO.

Fructose modifies the hormonal response and modulates lipid metabolism during aerobic exercise after glucose supplementation

The metabolic response when aerobic exercise is performed after the ingestion of glucose plus fructose is unclear. In the present study, we administered two beverages containing GluF (glucose+fructose) or Glu (glucose alone) in a randomized cross-over design to 20 healthy aerobically trained volunteers to compare the hormonal and lipid responses provoked during aerobic exercise and the recovery phase. After ingesting the beverages and a 15-min resting period, volunteers performed 30 min of moderate aerobic exercise. Urinary and blood samples were taken at baseline (t(-15)), during the exercise (t(0), t(15) and t(30)) and during the recovery phase (t(45), t(75) and t(105)). Plasma insulin concentrations were higher halfway through the exercise period and during acute recuperation (t(15) and t(75); P<0.05) following ingestion of GluF than after Glu alone, without any differences between the effects of either intervention on plasma glucose concentrations. Towards the end of the exercise period, urinary catecholamine concentrations were lower following GluF (t(45); P<0.05). Plasma triacylglycerol (triglyceride) concentrations were higher after the ingestion of GluF compared with Glu (t(15), t(30), t(45) and t(105); P<0.05). Furthermore, with GluF, we observed higher levels of lipoperoxides (t(15), t(30), t(45) and t(105); P<0.05) and oxidized LDL (low-density lipoprotein; t(30); P<0.05) compared with after the ingestion of Glu alone. In conclusion, hormonal and lipid alterations are provoked during aerobic exercise and recovery by the addition of a dose of fructose to the pre-exercise ingestion of glucose.

Blood, semen, and an innocent man

In August, 2007, a 30-year-old doctoral student, from Nigeria but living in London, noticed bright red blood in his ejaculate. The problem persisted for 2 months, so he went to see his general practitioner. There was no history of injury to the genitals or the prostate; the patient had used barrier contraception with his current and previous two girlfriends. The patient was not physically examined, but was advised to attend a walk-in genitourinary clinic. When he did so, 3 days later, his blood pressure was 244/170 mm Hg. He was given 5 mg amlodipine, and sent to hospital. There, repeated measurements, with a manual sphygmomanometer, gave a blood pressure of around 239/141 mm Hg, in both arms. The patient’s blood pressure had last been measured 10 years before, when he had been told it was “a little high”. He had never taken antihypertensive drugs. He had been feeling entirely well, although, on close questioning, he described having had a nosebleed and headache 2 months before noticing the blood in his ejaculate. He had no other relevant medical history, and was a lifelong non-smoker. Inspection showed no signs of Cushing’s syndrome, acromegaly, or systemic sclerosis. Physical examination, including neurological, genital, and rectal examination, showed nothing abnormal— notably, radiofemoral delay and renal bruits were absent, and the patient scored 10/10 on the abbreviated mental test score. Dipstick testing of urine showed much protein, but not blood. Urine microscopy showed no casts. Blood tests showed nothing abnormal: notably, concentrations of calcium, creatinine, C-reactive protein, autoantibodies, and prostate-specifi c antigen were normal. Serological and immunological testing showed no evidence of HIV or tuberculosis, respectively. Microscopy and culture of urethral swabs showed no evidence of syphilis, chlamydia, or gonorrhoea. An electrocardiogram showed severe leftventricular hypertrophy; radiography of the chest showed no evidence of aortic coarctation. Fundoscopy showed bilateral papilloedema, but no haemorrhages. Ultrasonography showed kidneys of normal size, without cysts. CT of the abdomen showed nothing abnormal— and specifi cally, no adrenal masses. The patient’s blood pressure was lowered gradually, over several days, with amlodipine, ramipril, and intravenous glyceryl trinitrate; meanwhile, we took three 24-h urine collections: after the collections were done, we started treatment with atenolol, having stopped the glyceryl trinitrate. Urinary concentrations of catecholamines were normal, confi rming that the patient did not have a phaeochromocytoma. Retinal photography showed resolution of the papilloedema, but many cotton-wool spots and nerve-fi bre-layer (“fl ame”) haemorrhages (fi gure)—consistent with grade 3 hypertensive retinopathy. The plasma renin:aldosterone ratio is awaited. The diagnosis is essential hypertension or hyperaldosteronism. The patient was discharged 10 days after admission. When last seen by us, in late November, 2007, his blood pressure was around 150/96 mm Hg; he continued to feel well, and had no blood in his semen. Haematospermia is most commonly caused by infection or injury—including iatrogenic injury from taking biopsy samples of the prostate. Other causes include stones, cysts, vascular abnormalities—and severe hypertension, which causes an estimated 5% of cases. Malignant hypertension is defi ned as blood pressure over 180/100 mm Hg, with papilloedema or retinal haemorrhage. Although malignant hypertension can occur in essential hypertension, causes of secondary hypertension should always be sought. Apart from haemato spermia, our patient was asymptomatic—as are around 10% of people with malignant hypertension. Nonetheless, leftventricular hypertrophy, proteinuria, and retinopathy indicated pronounced end-organ damage, consistent with severe, longstanding hypertension.

Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): Modulation by a polyphenolic extract from pine bark (Pycnogenol®)

Our study tested the hypothesis that treatment with a potent polyphenol complex not only reduces hyperactivity of children, but also catecholamine excretion and oxidative stress. Urine catecholamine concentrations were measured in attention deficit hyperactivity disorder (ADHD) children and healthy controls. ADHD children received either placebo (PL) or Pycnogenol® (Pyc), a bioflavonoid extract from the pine bark, for one month. The study was performed in a randomized, double-blind, PL controlled design. Concentrations of catecholamines were higher in urine of ADHD patients compared to those of healthy children. Moreover, noradrenaline (NA) concentrations positively correlated with degree of hyperactivity of ADHD children. In ADHD patients, adrenaline (A) and NA concentrations positively correlated with plasma levels of oxidized glutathione. The treatment of ADHD children with Pyc caused decrease of dopamine (D) and trend of A and NA decrase and increased GSH/GSSG ratio. In conclusion, the data provide further evidence for the overactivity of the noradrenergic system in ADHD and demonstrate that A release may be increased, as well. Treatment of ADHD children with Pyc normalized catecholamine concentrations, leading to less hyperactivity, and, consequently, to reduced oxidative stress.

Changes in ear-pinna temperature as a useful measure of stress in sheep (Ovis aries)

AbstractActivation of the sympathetic nervous system, with associated increases in heart rate and the redistribution of blood in preparation for ‘fight or flight’, is an integral part of the ‘defence reaction’. In sheep, the defence reaction involves vasoconstriction in the ear-pinna. If decreases in ear-pinna temperature (Tp) can be used to indicate vasoconstriction, then it may be possible to use changes in Tpas a measure of the defence reaction. Ewe lambs were exposed to stressors including mustering into pens, moving between pens, isolation from conspecifics, and prolonged periods of exercise. Measurements of heart rate (HR), Tp, vaginal temperature (Tv), and salivary cortisol and urinary catecholamine concentrations were used to assess stress responses. A repeatable pattern of changes in HR, Tpand Tvwas observed in response to stressors. Short-term disturbances resulted in increased HR, reduced Tp, and increased Tv. More sustained disturbances — for example, prolonged periods of exercise — resulted in a sustained elevation in HR, a sustained decrease in Tp, and a sustained elevation in Tv. The highest levels of cortisol and catecholamines were associated with the treatments that resulted in the longest periods of decreased Tp. We infer that changes in Tpoccur largely in response to changes in sympathetic nervous activity, and that the potential exists to measure elements of stress responses by monitoring Tpin freely behaving animals. This is a minimally invasive measure that allows the monitoring of modest numbers of animals over prolonged periods with minimal handling.

Exaggerated response to cold stress in a congenic strain for the quantitative trait locus for blood pressure.

Stroke-prone spontaneously hypertensive rats (SHRSP) are known to have sympathetic hyperactivity to various stimuli. In the search for 'intermediate phenotypes' inferring the function of hypertension genes, the present study assessed responsiveness to cold stress in a congenic strain derived from SHRSP/Izm and Wistar-Kyoto/Izm (WKY/Izm). A congenic strain, WKYpch1.0, was established by 10 generations of backcrossing to transfer the chromosomal fragment between D1Wox29 and D1Arb21 of SHRSP to WKY. This fragment covered the 100:1 confidence interval of the quantitative trait locus (QTL) for blood pressure identified in a previous study. Response to cold stress was studied by exposing rats to 4 degrees C for 4 h. Blood pressure was monitored with telemetry. Urine was collected during the exposure, and urinary concentrations of catecholamines were measured by high-performance liquid chromatography. Under the cold stress, urinary excretion of norepinephrine (NE) and vanillylmandelic acid (VMA), as well as the plasma level of NE, was significantly greater in WKYpch1.0 than in WKY. The increase in blood pressure during the cold stress was also greater in WKYpch1.0 than in WKY. Further, neonatal chemical sympathectomy using guanethidine abolished the exaggerated response in blood pressure and in urinary excretion of NE and VMA in WKYpch1.0. These results suggested that the QTL region on rat chromosome 1 harbored genes responsible for the exaggerated response of the sympathetic nervous system to the cold stress. The relationship of this with the pathogenesis of hypertension should be elucidated in future studies.