Catecholamines Research Articles

Non-functional paraganglioma of urinary bladder managed by transurethral resection.

ABSTRACTPurpose As a rare bladder tumor, paraganglioma of the urinary bladder (PUB) is frequently misdiagnosed as bladder cancer, particularly for the non-functional type. To date, transurethral resection remains a controversial treatment for non-functional PUB. This study aimed to identify the clinical features, pathological characteristics, prognosis, and safe/effective treatment of non-functional PUB using transurethral resection of the bladder tumor (TURBT).Materials and Methods The clinical records, radiological data, pathological characteristics and follow-up times were retrospectively reviewed in 10 patients with clinically and pathologically proven non-functional PUB in our hospital from January 2008 to November 2016. All patients underwent TURBT treatment.Results The incidence of non-functional PUB in patients with bladder cancer was 0.17%. The mean age at diagnosis was 44.5 ± 13.6 years (range, 29-70 years), and the patient population had a female: male ratio of 3: 2. No patients had excess catecholamine (CA) whilst four patients had painless hematuria. All neoplasms were completely resected via TURBT. The majority of samples were positive for immunohistochemical markers including chromogranin A (CgA) and Synaptophysin (Syn), but were negative for cytokeratins (CKs). Only a single recurrence was observed from the mean follow-up period of 36.4 ± 24.8 months.Conclusion Complete TURBT is a safe and efficient treatment that serves both diagnostic and therapeutic purposes. Histopathological and immunohistochemistry examinations are mandatory for diagnostic confirmation. Long-term follow-up is recommended for patients with non-functional PUB.

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

Clinical effect of carvedilol in treatment of children with severe hand-foot-mouth disease caused by enterovirus 71 infection

To study the clinical effect of carvedilol in the treatment of children with severe hand-foot-mouth disease (HFMD) caused by enterovirus 71 (EV71) infection. A retrospective analysis was performed for the clinical data of 86 children with severe HFMD caused by EV71 infection who were admitted to the hospital from April 2016 to August 2017. According to whether carvedilol was used, the children were divided into conventional treatment group with 51 children and carvedilol treatment group with 35 children. A total of 56 healthy children who underwent physical examination at the outpatient service during the same period were enrolled as the control group. The two treatment groups were compared in terms of clinical features and levels of catecholamines (norepinephrine, adrenaline and dopamine), and the levels of catecholamines were compared between these two treatment groups and the control group. Before treatment, the conventional treatment group and the carvedilol treatment group had significantly higher levels of norepinephrine and adrenaline than the control group (P<0.05). After treatment, both the conventional treatment group and the carvedilol treatment group had significant reductions in norepinephrine, adrenaline, blood glucose, systolic pressure, diastolic pressure, heart rate, body temperature and leukocyte count (P<0.05). Compared with the conventional treatment group, the carvedilol treatment group had significantly lower dopamine level, blood glucose, heart rate and respiratory rate after treatment (P<0.05). Changes in norepinephrine and adrenaline might be involved in the pathogenesis of severe HFMD caused by EV71 infection. Carvedilol, in addition to the conventional treatment, can improve respiration, heart rate and blood glucose in children with severe HFMD caused by EV71 infection.

A Novel Biomarker Renalase and Its Relationship with its Substrates in Schizophrenia.

SummaryBackgroundSchizophrenia, particularly the form related to excessive dopamine (DA), is a chronic psychotic disorder affecting millions of people worldwide. Renalase metabolizes its catecholamine (CA) substrates, including DA, suggesting that there might be an association between renalase levels and schizophrenia occurrence. Therefore, the current study aimed to evaluate the renalase and CA levels in the serum of patients with schizophrenia.MethodsThe study was conducted with thirty-three schizophrenia patients and an age- and gender-matched group of thirty-one controls. Renalase and CA levels were measured by using an enzyme-linked immunosorbent assay (ELISA).ResultsRenalase levels were significantly lower in the schizophrenia patients than in the control group (p<0.05), whereas DA levels were significantly higher (p<0.05). The epinephrine (Epi) levels of both groups were similar (p=0.186), while the norepinephrine levels in patients with schizophrenia were significantly lower than those in the control group (p<0.05). The areas under the curves for the renalase-dopamine, renalase-norepinephrine and renalase-epinephrine ratios were 0.805, 95% confidence interval (CI): 0.699–0.912 (p<0.001); 0.726, 95% CI: 0.594–0.859 (p=0.032); and 0.656, 95% CI: 0.520–0.791 (p=0.02).ConclusionsThe high DA levels in patients with schizophrenia might be due to low renalase levels. Renalase enzyme levels may play a substantial role in the pathophysiology of schizophrenia. Thus, this enzyme might be a new future target for the treatment and diagnosis of schizophrenia after intrabrain renalase and DA dynamics have been further evaluated.

Direct laboratory evidence that pregnancy-induced hypertension might be associated with increased catecholamines and decreased renalase concentrations in the umbilical cord and mother’s blood

Abstract Background Renalase (RNL) is a controversial enzyme as to whether it oxidizes catecholamines (CAs) (as is generally accepted) in the blood or not. CAs (dopamine [DPMN], epinephrine [EPI] and norepinephrine [NEPI]) are associated with hypertension, including pregnancy-induced hypertension, which occurs in 8–10% of all pregnancies. Therefore, the aim of the study was to compare CAs and renalase concentration in (i) normotensive controls (C), (ii) patients with preeclampsia (PE) and (iii) patients with severe preeclampsia (SPE), which is one of the well-known symptoms of hypertension. Methods This case-control study involved 90 women divided into three groups – 30 C, 30 PE and 30 SPE – whose age and body mass indexes (BMIs) were similar. A total of 270 blood samples (90 maternal samples, 90 umbilical cord artery samples and 90 umbilical cord vein samples) were obtained. CAs and RNL concentrations of the biological samples were measured by enzyme-linked immunosorbent assay (ELISA). Results Comparing the amounts of CAs, RNL and systolic blood pressure (SBP)/diastolic blood pressure (DBP) between healthy control pregnant women and pregnant women with PE and SPE (SBP/DBP was 120/80 mm Hg for C, above 140/90 mm Hg for PE and above 160/110 mm Hg for SPE), the levels of CAs were significantly increased whereas RNL was reduced. The correlation between SBP/DBP and the amount of RNL in pregnant women with PE and SPE was negative. Conclusions These novel results are evidence that hypertension seen in PE and SPE is directly related to increased levels of CAs and reduced RNL concentrations. The use of RNL preparations may be preferred in future to prevent maternal and perinatal morbidity and mortality due to pregnancy-induced hypertension.

High-fat diet promotes adrenaline production by visceral adipocytes.

Catecholamines (CA) play a major role in metabolism and immune response. Recent reports showing adipose tissue can synthetize CA enlighten new roles for these amines in obesity. This study aimed to evaluate the expression of both tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) and CA content along preadipocytes differentiation, under normal and obesigenic conditions. 8-9week-old male C57BL/6 mice were divided in two groups: one fed with a high-fat diet (HFD) and other with a standard diet (SD) for 20weeks. Afterwards, both TH and PNMT expression, localization, and CA content in adipocytes, were evaluated. qPCR results showed no changes for TH and PNMT expression during the differentiation process for visceral and subcutaneous preadipocytes from mice fed with SD. Comparing to SD, HFD increased TH gene expression of subcutaneous preadipocytes and PNMT gene expression of both visceral preadipocytes and adipocytes. HPLC-ED analyses revealed HFD increased visceral adipocytes noradrenaline intracellular content comparing with preadipocytes (p = 0.037). When compared with SD, HFD raised and decreased noradrenaline content, respectively, in visceral adipocytes (p = 0.004) and subcutaneous preadipocytes (p = 0.001). Along the differentiation process, HFD increased visceral adrenaline intracellular content comparing with SD (p < 0.001). HFD increased visceral comparing to subcutaneous adrenaline content for both preadipocytes (p = 0.004) and adipocytes (p = 0.001). TH and PNMT expression in adipose tissue is differently modulated in visceral and subcutaneous adipose depots, and seems to depend on diet. Differences observed in visceral adipose CA handling in HFD-fed mice might uncover novel pharmacological/nutritional strategies against obesity and cardiovascular risk.

Analysis of clinical characteristics for hypertensive attack during pheochromocytoma and paraganglioma operation: a single center case report of 219 cases

Objective To analyze the clinical characteristics for hypertensive attack during operation and clinical experience of preoperative evaluation and preparation in patients with pheochromocytoma and paraganglioma(PHEO/PGL). Methods A total 219 PHEO/PGL cases from September 2016 to September 2018 were retrospectively reviewed. It included 99 males and 120 females, aged 13 to 76(average 47)years old.The mean diameter of tumor was 5.3 cm(1.5-18.0 cm).140 cases were unilateral PHEO, 6 cases were bilateral PHEO, 68 cases were PGL(jugular, mediaphragm, heart, retroperitoneum, pelvic and bladder) and 5 cases were PHEO combined with PGL. Preoperative highest systolic blood pressure (SBP)was 240 mmHg(1 mmHg=0.133 kPa) and highest diastolic blood pressure(DBP) was 160 mmHg. 20 cases were occult PHEO without hypertension. 217 cases accepted preoperative preparation of alpha-blocker [phenoxy-benzamine, dosage ranging from 5 mg Q12h to 40 mg Q8h, maximum dosage not exceeding 1 mg/(kg·24 h)]. 2 cases did not accept preoperative preparation. All cases accepted open or endoscope surgery. The patients were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack. Results Histopathological results showed that all cases were PHEO or PGL, while 205 cases were benign, 14 cases were malignant. Hypertensive attack were recorded in 112 cases(51%). The diameter of tumors in the hypertensive attack group were larger than that in the non-hypertensive attack group[(6.70±2.95)cm vs.(3.95±1.70)cm, P=0.005]. There was no significant difference between the two groups among age[(51.0±10.8)years vs.(38.5±17.6)years, P=0.105], preoperative catecholamine level [norepinephrine (111.20±41.49)μg/24 h vs.(419.15±154.81)μg/24 h, P=0.075], time of use of alpha blockers[(53.0±7.5)d vs.(38.0±6.4)d, P=0.139], daily dosage of alpha blocker[(40.0±7.2)mg vs.(27.1±1.8)mg, P=0.111] and blood pressure at diagnosis[(173.75±26.69)mmHg vs.(155.0±20.75)mmHg, P=0.139]. Among 219 cases, 2 case had emergency hemostasis after operation, 1 case had catecholamine cardiomyopathy after operation for occult pheochromocytoma, and no perioperative death occurred. Conclusions Patients with large tumor tend to have hypertensive attack during operation so that should be better prepared. Key words: Pheochromocytoma; Paraganglioma; Alpha-blockade; Hypertension

Analysis of risk factors for intraoperative hemodynamic instability in adrenal incident pheochromocytoma

Objective To evaluate the risk factors for intraoperative hemodynamic instability (HI) in patients with adrenal incident pheochromocytoma. Methods Perioperative clinical parameters of patients undergoing surgery for adrenal incident pheochromocytoma at the First Hospital of Peking University from January 2001 to July 2018 were analyzed. There were 39 males and 41 females, with mean age of 45.1 years (13-76 years old). The median tumor length was 5.1 cm (1.5-14.0 cm), with 25 cases (31.3%) on the left side , 55 cases (68.8%) on the right side. There were 37 cases combined with coronary heart disease or diabetes or BMI≥24 kg/m2. Patients were divided into hemodynamic instability (HI group) and hemodynamic stability group (HS group) by whether intraoperative hemodynamic instability occurred. The differences of demographic characteristics and clinical parameters between the two groups were compared. Logistic regression analysis was done for seeking the risk factors for hemodynamic instability during surgery. Results There were 54 cases (67.5%) in the HS group and 26 cases (32.5%) in the HI group. Univariate analysis showed that there was no significant difference in age [(44.06±13.58) years old vs. (47.35±16.11) years old], combined with coronary heart disease or diabetes or BMI≥24 kg/m2 [50.0% (27/54) vs. 38.5% (10/26)], tumor long diameter [median 5.0 cm(1.5-14.0 cm) vs. 6.0cm(1.5-13.5 cm)], tumor location[left: 29.6% (16/54) vs. 34.6% (9/26)], preoperative catecholamine test positive [44.4% (20/45) vs. 50.0% (10/20)], open surgery [27.8% (15/54) vs. 34.6% (9/26)]and preoperative non-alpha blockers[13.0%(7/54) vs. 30.8%(8/26)] between HS group and HI group (P>0.05). Further logistic regression analysis was used to analyze the risk factors of intraoperative hemodynamic instability. Multivariate analysis found that patients who preoperative non-alpha blockers before surgery were independent risk factor for HI (OR=4.574, 95%CI 1.273-16.432, P=0.020). Conclusions Preoperative non-alpha blocker in patients with adrenal incidental pheochromocytoma could be independent risk factor for intraoperative hemodynamic instability. Therefore, it is recommended that patients with adrenal incidental tumors, especially those who fail to rule out pheochromocytoma, take preoperative alpha blockers. Key words: Pheochromocytoma; Adrenal incidentaloma; Hemodynamic; Alpha blocker

SUN-174 Severe Insulin Resistance and Diabetic Ketoacidosis after Brentuximab Vendotin and Cyclosporin Treatment

Introduction: Brentuximab Vendotin(BV) is antibody-drug conjugate that selectively delivers cytotoxic agent, monomethyl auristatin E, targeting cells expressing surface CD30, treatment approved for refractory Hodgkin’s lymphoma. Previous research suggested MDR1 inhibition (cyclosporine) can overcome BV resistance. Case: 23 year old male with relapsed and refractory classical Hodgkin lymphoma underwent clinical trial with BV and Cyclosporin( CyA). He was given one dose of BV( 1.8mg/kg) and CyA ( 725mg 2 times a day for 5 days). A week after BV and 3 days after the last dose of CyA, patient had acute onset of hyperglycemia and ketoacidosis; glucose 435 mg/dL, bicarbonate 14 mmol/L, anion gap 14( 8-14), beta hydroxybutyrate 40.3 mg/dL (0.0-3.0 mg/dL), urine ketone +3, C-peptide 9.0 ng/ml (0.8-3.5 ng/ml). Serum cyclosporine level was high as 453 ng/ml (150-300ng/ml) at the time of presentation, which was reduced to 116 ng/ml within a week. He had no previous diabetes history. His severe hyperglycemia and metabolic acidosis persisted after aggressive hydration and multiple daily insulin injections. He was started on modified intravenous insulin infusion protocol. Within 24 hours, his glycemic control was improved at goal requiring average 34 units/h of regular insulin with NPO status. This was transitioned to U500 regular insulin divided dose injection every 8 hours with holding criteria. 10 days after initial clinical presentation, patient's insulin requirement was abruptly reduced and eventually discontinued. Patient was discharged and glucose level remained within reference range (80-128 mg/dl) without additional medical management from follow-up. Patient had completed given clinical trial with reduced dose of BV and CyA, and there was no further similar episode. During the hospital course, underlying endocrine disease related to insulin resistance was ruled out including thyroid, glucagon, cortisol, catecholamine, or growth hormone excess. Autoimmune workup was negative except elevated ESR. Insulin autoantibody panels were negative. Pancreatitis and infections were also ruled out. Lymphocytes were reduced and monocytes were increased in CBC during the episode. Peripheral blood mononuclear cell (PBMC) analysis by flow cytometry showed that absolute B and T cell counts were low but in the residual CD4+ and CD8+ T cells, expression of CD25 and PD-1 was increased. Major portion of the PBMC did not stain with our standard immune phenotype panel, which may include plasma cells, NKT, or dendritic cells. Discussion: Adverse events ≥ Grade 3 hyperglycemia (12%) has been reported with BV treatment. On the other hand, CyA is known to be related to insulin resistance as well. This is the first case report of a patient who developed rare condition of severe insulin resistance and diabetic ketoacidosis in the context of hyperinsulinemia likely due to impaired insulin signaling induced by BV and CyA.

Synthesis of semicarbazide catechol derivative as a potential electrode modifier: application in electrocatalysis of catechol amine drugs

2-(1-(3,4-Dihydroxyphenyl)ethylidene)hydrazine-1-carboxamide was synthesized as a precursor for generation of redox polymer. In acidic media, the opposite charge on the surface of this monomer and graphene quantum dots make feasible monomer electrodeposition. Fourier transform infrared spectroscopy and field-emission scanning electron microscopy were used for chemical band identification and morphological characteristics of coated film at electrode. Polymer-modified electrode enhances electron-transfer process of catechol amines such as dopamine and dobutamine selectively. Graphene quantum dots/polymer film-modified electrode produce more oxidation current compared to polymer-modified electrode alone. Under optimized condition, the concentration of dobutamine and its oxidation signal was well fitted to the linear regression function in the range of 0.05–35.0 µM with the detection limit of 0.01 µM. The accuracy evaluation of modified electrode was determined by measuring concentration of dobutamine in serum samples.

EPHB6 controls catecholamine biosynthesis by up-regulating tyrosine hydroxylase transcription in adrenal gland chromaffin cells

EPHB6 is a member of the erythropoietin-producing hepatocellular kinase (EPH) family and a receptor tyrosine kinase with a dead kinase domain. It is involved in blood pressure regulation and adrenal gland catecholamine (CAT) secretion, but several facets of EPHB6-mediated CAT regulation are unclear. In this study, using biochemical, quantitative RT-PCR, immunoblotting, and gene microarray assays, we found that EPHB6 up-regulates CAT biosynthesis in adrenal gland chromaffin cells (AGCCs). We observed that epinephrine content is reduced in the AGCCs from male Ephb6-KO mice, caused by decreased expression of tyrosine hydroxylase, the rate-limiting enzyme in CAT biosynthesis. We demonstrate that the signaling pathway from EPHB6 to tyrosine hydroxylase expression in AGCCs involves Rac family small GTPase 1 (RAC1), MAP kinase kinase 7 (MKK7), c-Jun N-terminal kinase (JNK), proto-oncogene c-Jun, activator protein 1 (AP1), and early growth response 1 (EGR1). On the other hand, signaling via extracellular signal-regulated kinase (ERK1/2), p38 mitogen-activated protein kinase, and ELK1, ETS transcription factor (ELK1) was not affected by EPHB6 deletion. We further report that EPHB6's effect on AGCCs was via reverse signaling through ephrin B1 and that EPHB6 acted in concert with the nongenomic effect of testosterone to control CAT biosynthesis. Our findings elucidate the mechanisms by which EPHB6 modulates CAT biosynthesis and identify potential therapeutic targets for diseases, such as hypertension, caused by dysfunctional CAT biosynthesis.

Parsing the functional specificity of Siderocalin/Lipocalin 2/NGAL for siderophores and related small-molecule ligands

Siderocalin/Lipocalin 2/Neutrophil Gelatinase Associated Lipocalin/24p3 is an innate immune system protein with bacteriostatic activity, acting by tightly binding and sequestering diverse catecholate and mixed-type ferric siderophores from enteric bacteria and mycobacteria. Bacterial virulence achieved through siderophore modifications, or utilization of alternate siderophores, can be explained by evasion of Siderocalin binding. Siderocalin has also been implicated in a wide variety of disease processes, though often in seemingly contradictory ways, and has been proposed to bind to a broader array of ligands beyond siderophores. Using structural, directed mutational, and binding studies, we have sought to rigorously test, and fully elucidate, the Siderocalin recognition mechanism. Several proposed ligands fail to meet rigorous binding criteria, including the bacterial siderophore pyochelin, the iron-chelating catecholamine hormone norepinephrine, and the bacterial second messenger cyclic diguanylate monophosphate. While possessing a remarkably rigid structure, in principle simplifying analyses of ligand recognition, understanding Scn recognition is complicated by the observed conformational and stoichiometric plasticity, and instability, of its bona fide siderophore ligands. Since the role of Siderocalin at the early host/pathogen interface is to compete for bacterial ferric siderophores, we also analyzed how bacterial siderophore binding proteins and enzymes alternately recognize siderophores that efficiently bind to, or evade, Siderocalin sequestration – including determining the crystal structure of Bacillus cereus YfiY bound to schizokinen. These studies combine to refine the potential physiological functions of Siderocalin by defining its multiplexed recognition mechanism.

Differential Co-release of Two Neurotransmitters from a Vesicle Fusion Pore in Mammalian Adrenal Chromaffin Cells

Co-release of multiple neurotransmitters from secretory vesicles is common in neurons and neuroendocrine cells. However, whether and how the transmitters co-released from a single vesicle are differentially regulated remains unknown. In matrix-containing dense-core vesicles (DCVs) in chromaffin cells, there are two modes of catecholamine (CA) release from a single DCV: quantal and sub-quantal. By combining two microelectrodes to simultaneously record co-release of the native CA and ATP from a DCV, we report that (1) CA and ATP were co-released during a DCV fusion; (2) during kiss-and-run (KAR) fusion, the co-released CA was sub-quantal, whereas the co-released ATP was quantal; and (3) knockdown and knockout of the DCV matrix led to quantal co-release of both CA and ATP even in KAR mode. These findings strongly imply that, in contrast to sub-quantal CA release in chromaffin cells, fast synaptic transmission without transmitter-matrix binding is mediated exclusively via quantal release in neurons.

Metabolic effects of epinephrine on the crab Neohelice granulata

Although widely known for their involvement in the control of carbohydrate and lipid metabolism of vertebrates, the participation of catecholamines (CAs) in the metabolism of invertebrates is less understood. This study was designed to identify the physiological role of Epinephrine (E) in the intermediary metabolism of the burrowing crab Neohelice granulata and how E regulates the metabolism in crabs fed with a high-carbohydrate (HC) or a high-protein (HP) diet. To answer these questions, we evaluated in vivo the effects of E injections on glucose and triglycerides in the hemolymph and tissue glycogen levels of crabs fed with HC or HP diet. An in vitro investigation was carried out to assess the direct effects of E on glycogenolysis, lipolysis and glycolysis pathways in the hepatopancreas, mandibular muscle and anterior and posterior gills of this crab. E injections increased glucose and did not affect triglycerides levels in the hemolymph of either group of crabs, and E decreased glycogen in the hepatopancreas and mandibular muscle only in HP crabs, suggesting that these effects may be mediated by the crustacean hyperglycemic hormone (CHH). When the tissues were incubated with different concentrations of E, the concentration of glucose released to the medium decreased in the hepatopancreas and posterior gills, while glucose oxidation increased in the posterior gills of HP crabs. Incubation with E did not alter any parameter in tissues of HC crabs. These effects suggest that E may be involved in the metabolic response to osmotic stress.

Telmisartan induces browning of fully differentiated white adipocytes via M2 macrophage polarization

Telmisartan is a well-known anti-hypertensive drug acting as an angiotensin 2 receptor blocker (ARB), but it also possesses partial PPARγ agonistic activity and induces insulin sensitivity. In the present study, we investigated the effects of telmisartan on macrophage polarization in association with its browning capacity, because PPARγ plays a key role in M2 polarization and in the browning of white adipocytes. Telmisartan induced M2 marker expression in murine macrophages concentration dependently, which was confirmed by flow cytometry. Both PPARγ and PPARδ activations appear to be responsible for telmisartan-induced M2 polarization. Telmisartan-treated conditioned medium (Tel-CM) of RAW264.7 cells and of bone marrow derived macrophages (BMDM) induced the expressions of browning markers in fully differentiated white adipocytes with reduced lipid droplets, and increased oxygen consumption rate and mitochondrial biogenesis. Levels of catecholamines (CA) released into the conditioned medium as well as intracellular tyrosine hydroxylase (TH) mRNAs were found to be increased by telmisartan, and browning effects of Tel-CM were lessened by β3 receptor antagonist (L-748,337), suggesting CA secreted into CM play a role in Tel-CM-induced adipocyte browning. Acute administration of telmisartan (2 weeks, p.o.) to C57BL/6J mice increased the expressions of browning markers and M2 markers in white adipose tissues, whereas macrophage depletion by clodronate liposome pretreatment attenuated the telmisartan-induced expressions of browning markers. Together, telmisartan was observed to induce the browning of fully differentiated white adipocytes, at least in part, via PPAR activation-mediated M2 polarization.

Dopamine-induced sulfatase and its regulator are required for Salmonella enterica serovar Typhimurium pathogenesis

Catecholamine hormones enhance the virulence of pathogenic bacteria. Studies in the 1980s made intriguing observations that catecholamines were required for induction of sulfatase activity in many enteric pathogens, including Salmonella enterica serovar Typhimurium. In this report, we show that STM3122 and STM3124, part of horizontally acquired Salmonella pathogenesis island 13, encode a catecholamine-induced sulfatase and its regulator, respectively. Induction of sulfatase activity was independent of the well-studied QseBC and QseEF two-component regulatory systems. S. Typhimurium 14028S mutants lacking STM3122 or STM3124 showed reduced virulence in zebrafish. Because catecholamines are inactivated by sulfation in the mammalian gut, S. Typhimurium could utilize CA-induced sulfatase to access free catecholamines for growth and virulence.

Reproducibility in the cardiometabolic responses to high-intensity interval exercise in adults with type 1 diabetes

AimsPatients with type 1 diabetes (T1D) often report a rise in their blood glucose level following brief intense exercise. We sought to determine the reproducibility of the cardiometabolic responses to high-intensity interval training (HIIT). MethodsSixteen adults with T1D, using an optimized multiple daily injection with basal insulin glargine 300 U/mL (Gla-300), performed four fasted HIIT sessions over a 4–6-week period. Exercise consisted of high-intensity interval cycling and multimodal training over 25 min. ResultsHeart rate and rating of perceived exertion rose similarly in all sessions, as did lactate, catecholamine and growth hormone levels. Plasma glucose increased in response to HIIT in 62 of 64 visits (97%), with an overall increase of 3.7 ± 1.6 mmol/L (Mean ± SD) (P < 0.001). In within-patient comparisons, the change in plasma glucose among the four HIIT sessions was significantly correlated with a composite correlation of 0.58 ([r2 = 0.34]; 95% CI 0.35–0.80; P < 0.01). ConclusionsIntersession observations of four separate HIIT sessions showed high intrasubject reproducibility in the cardiometabolic responses to exercise, including the rise in plasma glucose, when adults with T1D perform the activity in a fasted state.

Impact of ginsenoside-Rg3 on catecholamine secretion in the perfused model of the rat adrenal medullae

Background: The present study was the first attempt to explore the characteristics of ginsenoside-Rg3 (Rg3) on release of catecholamines (CA) in the perfused rat adrenal medullae and also to verify the underlying action mechanism. Materials and Methods: The adrenal medulla was separated by some modification of the previous method and perfused with Krebs solution. CA was assayed directly by the fluorometry. Results: Rg3 reduced acetylcholine (ACh)-produced CA release in a dose- and time-dependent manner. Rg3 time-dependently depressed CA release produced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1,1-dimethyl-4-phenyl piperazinium iodide, and angiotensin II. In the presence of Rg3, the CA release produced by high K+, veratridine, cyclopiazonic acid, and methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4- (2-trifluoromethyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) was also markedly suppressed. However, during the simultaneous perfusion of Rg3 and Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME), the release of CA produced by ACh, angiotensin II, Bay-K-8644, and veratridine was restored closely to the level of each control, in contrast to that of Rg3-treatment alone. The nitric oxide (NO) release was significantly elevated by Rg3-treatment. Furthermore, in the coexistence of Rg3 and fimasartan, ACh-produced CA release was more significantly reduced as compared to that of fimasartan-treatment alone. Conclusions: We present the first evidence that Rg3 markedly depresses the CA secretion produced by activation of neuronal cholinergic and angiotensinergic receptors. Rg3-produced inhibition appears to be evoked not only by blocking the inflow of Na+ and Ca2+ into adrenomedullary cells but also by preventing the Ca2+ release from intracellular storage, partly through enhancement of NO release by NO synthase activation. Coadministration of Rg3 and fimasartan may be clinically beneficial for the treatment of cardiovascular diseases. Abbreviations used: Rg3: Ginsenoside-Rg3; VDCC: L-type voltage-dependent Ca2+ channels; Bay–K-8644: Methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5-carboxylate; ACh: Acetylcholine; McN-A-343: 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium; DMPP: 1.1-dimethyl-4-phenyl piperazinium; NO: Nitric oxide; L-NAME: Nω-nitro-l-arginine methyl ester; nNOS: Neuronal NO synthase.

Glutamate as a Neural Stress Factor in Humans and Animals

L-glutamic acid (glutamate-Glu) serves as one form with very strong stimulatory neurotransmitter (near aspartic, kainic, alpha-amino-3-hydroxy-5-me- thyl-4-izoxazole propionic acid (AMPA), chinolic and L-homocysteinic acid, glycine and D-serine) at the majority of neural excitatory synapse in the mammals and nonmammals central, sympathetic nervous system (CNS and SNS, respectively) and in different peripheral tissues and organ. It mediates interactions via stimulation a variety ionotropic N-methyl-D-As- partate (NMDA), AMPA and kainate receptors (ligand gated calcium channels) and III groups of the metabotropic glutamate receptors (mGluR1-8) family members (G-protein coupled receptors). It is good known different neuromodula-tion/interaction between Glu and norepinephrine (NE), dopamine (DA), gamma-amino-butyric acid (GABA), oxytocin/vasopressin (Oxy/AVP) and steroid receptors during stress in the central nervous system. In this review we describe the molecular structure of these glutamatergic receptors and discuss they neuropharmacology and clinical use probability of their antagonist, in stress particularly. On the other hand it was interesting if Glu can increase catecholamine (CA) release from motivational structures as stressoric factor in hypothalamo-pituitary adrenal axis (HPA) in the stress inducing processes. Our findings show that Glu more influences the brain’s motivational structure, which may indicate its contribution to the stress response by direct modulating the amount of catecholamine released.

Recent Concepts in Nutritional Therapy in Critically Ill Burn Patients

In developing countries such as India, burn injury is still a major and frequent cause of mortality and morbidity. Nutrition therapy aims to provide adequate and early nutrition for patients suffering from burn injuries. Metabolic support during heightened inflammatory state is essential to make sure adequate treatment of burn patients. It is essential to reduce the force and effects of the hypermetabolic response, aim for healing of wounds, and help to reduce negative catabolism effects. At the same time, care of surgical and medical needs of the patient is crucial for good clinical outcomes. Nutritional sustain is an essential and integral component of burn care that requires an aggressive multifaceted approach. Impaired wound healing, dysfunction of multiple organs, increased chances of infection, and death are largely prevented by an adequate nutrition care along with proper wound management. Catecholamine and corticosteroids, inflammatory mediator levels, are increased, and this hypermetabolic response leads to catastrophic results in the postburn injury period. A shift from preventing malnutrition to disease modulation in nutrition support in critically ill patients is being aimed at present. Uncontrolled inflammation causes severe metabolic derangement in burn patients. Major challenges are assessment of nutritional status of the patient and estimation of nutrient requirements. Careful decision-making for safe use of enteral or parenteral nutrition and an aggressive nutrient delivery are required. The course of disease can be altered favorably to a great extent by supplementation of specific nutrients. Nutritional factors with positive effects on immunity and in cell regulation include glutamine, arginine, and essential fatty acids, known as immunonutrients. They reduce the severity of illness and improve response to treatment of patients. Nutrition support specialists are trying to improve the management protocols and technological advances such as nanotechnology and biomarkers will take the nutrition management to greater advances.