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BMJ Case Reports Oct 2015We report a case of phaeochromocytoma associated with hypercortisolism and hypercalcaemia in a 62-year-old man. The patient presented to clinic, with a 3-year history of...
We report a case of phaeochromocytoma associated with hypercortisolism and hypercalcaemia in a 62-year-old man. The patient presented to clinic, with a 3-year history of exertional headaches, and a 4-month history of increasing fatigue, sweating and palpitations, loss of appetite and weight, and sleepiness. He did not have a medical, family or social history that could account for these symptoms. 24 h urinary catecholamines, plasma metanephrines, 24 h urinary cortisol and adjusted serum calcium, were elevated. Overnight low-dose dexamethasone suppression test did not suppress morning plasma cortisol. Serum intact parathyroid hormone and parathyroid hormone-related peptide were low, and adrenocorticotropic hormone was normal. The patient was treated with intravenous 0.9% sodium chloride and disodium pamidronate to control hypercalcaemia. CT showed a 10 cm left adrenal mass. Following inpatient treatment with phenoxybenzamine, he underwent a left adrenectomy and histology confirmed a phaeochromocytoma. Postoperatively, he required long-term steroids for contralateral adrenal suppression. Adjusted serum calcium returned to normal postoperatively.
Topics: Adrenal Gland Neoplasms; Calcium; Follow-Up Studies; Humans; Hydrocortisone; Hypercalcemia; Male; Middle Aged; Pheochromocytoma
PubMed: 26446319
DOI: 10.1136/bcr-2014-208657 -
Annals of Cardiac Anaesthesia 2015
Topics: Adrenergic alpha-Agonists; Cardiac Surgical Procedures; Humans; Hypotension; Perioperative Care; Phenoxybenzamine; Tachycardia
PubMed: 26440247
DOI: 10.4103/0971-9784.166473 -
Journal of Feline Medicine and Surgery Feb 2017Case series summary Four cats that presented with severe cluster seizures developed neurogenic urinary retention in the postictal phase. None of the cats had previous...
Case series summary Four cats that presented with severe cluster seizures developed neurogenic urinary retention in the postictal phase. None of the cats had previous seizures. Micturition was reported as normal in all cats for 3 or more years before seizure onset. All cats required a continuous rate infusion of propofol to control the seizure activity. In all cats manual bladder expression was performed every 8 h until recovery of normal micturition. One cat was started on phenoxybenzamine to reduce internal urethral sphincter tone. All cats recovered normal micturition within 4 weeks of the last cluster of seizures. Relevance and novel information Transient neurogenic urinary retention has not previously been reported in cats or dogs following severe cluster seizures. Urinary retention should be considered a potential postictal deficit, requiring prompt recognition and treatment to avoid urinary tract infection and detrusor muscle atony.
Topics: Animals; Cat Diseases; Cats; Female; Male; Seizures; Spinal Cord Injuries; Urinary Retention; Urinary Tract Infections
PubMed: 26337374
DOI: 10.1177/1098612X15602739 -
Journal of Clinical Hypertension... Sep 2015Management of blood pressure in children with pheochromocytoma and other catecholamine-secreting tumors (CSTs) is unique and challenging. The authors report a...
Management of blood pressure in children with pheochromocytoma and other catecholamine-secreting tumors (CSTs) is unique and challenging. The authors report a single-center experience using sequential α-adrenergic blockade (phenoxybenzamine), increased fluid intake, and β-blockade for presurgical management of 10 CSTs in children. In this retrospective review, mean duration for blood pressure control in preparation for surgery was 4.5±2.6 weeks. Intraoperative hypertension was noted transiently (<2 hours) in eight patients (80%) and was treated with continuous infusion of short-acting antihypertensive agents. Two (20%) patients required vasopressor medication infusion to manage intraoperative hypotension. Only two (20%) patients developed postoperative hypotension and required vasopressor medication infusion for <24 hours. All antihypertensive medications were discontinued in the immediate (≤4 days) postoperative period in 80% of patients. In conclusion, a systematic and multidisciplinary approach utilizing adrenergic blockade is effective in treating children with CSTs.
Topics: Adolescent; Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Antihypertensive Agents; Blood Pressure; Catecholamines; Child; Child, Preschool; Female; Humans; Hypertension; Hypotension; Infant; Intraoperative Period; Male; Phenoxybenzamine; Pheochromocytoma; Postoperative Period; Retrospective Studies; Treatment Outcome; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 26010736
DOI: 10.1111/jch.12571 -
PloS One 2015Drug repositioning has shorter developmental time, lower cost and less safety risk than traditional drug development process. The current study aims to repurpose...
Drug repositioning has shorter developmental time, lower cost and less safety risk than traditional drug development process. The current study aims to repurpose marketed drugs and clinical candidates for new indications in diabetes treatment by mining clinical 'omics' data. We analyzed data from genome wide association studies (GWAS), proteomics and metabolomics studies and revealed a total of 992 proteins as potential anti-diabetic targets in human. Information on the drugs that target these 992 proteins was retrieved from the Therapeutic Target Database (TTD) and 108 of these proteins are drug targets with drug projects information. Research and preclinical drug targets were excluded and 35 of the 108 proteins were selected as druggable proteins. Among them, five proteins were known targets for treating diabetes. Based on the pathogenesis knowledge gathered from the OMIM and PubMed databases, 12 protein targets of 58 drugs were found to have a new indication for treating diabetes. CMap (connectivity map) was used to compare the gene expression patterns of cells treated by these 58 drugs and that of cells treated by known anti-diabetic drugs or diabetes risk causing compounds. As a result, 9 drugs were found to have the potential to treat diabetes. Among the 9 drugs, 4 drugs (diflunisal, nabumetone, niflumic acid and valdecoxib) targeting COX2 (prostaglandin G/H synthase 2) were repurposed for treating type 1 diabetes, and 2 drugs (phenoxybenzamine and idazoxan) targeting ADRA2A (Alpha-2A adrenergic receptor) had a new indication for treating type 2 diabetes. These findings indicated that 'omics' data mining based drug repositioning is a potentially powerful tool to discover novel anti-diabetic indications from marketed drugs and clinical candidates. Furthermore, the results of our study could be related to other disorders, such as Alzheimer's disease.
Topics: Adrenergic alpha-2 Receptor Antagonists; Cyclooxygenase 2 Inhibitors; Data Mining; Databases, Pharmaceutical; Diabetes Mellitus; Drug Repositioning; Gene Expression Profiling; Genome-Wide Association Study; Humans; Hypoglycemic Agents; Metabolomics; Proteomics; Receptors, N-Methyl-D-Aspartate
PubMed: 25946000
DOI: 10.1371/journal.pone.0126082 -
Medicine May 2015Cardiac pheochromocytoma is relatively rare. Few reports describe the intraoperative and postoperative progression of patients experiencing a life-threatening...
Pheochromocytoma crisis with severe cyclic blood pressure fluctuations in a cardiac pheochromocytoma patient successfully resuscitated by extracorporeal membrane oxygenation: a case report.
Cardiac pheochromocytoma is relatively rare. Few reports describe the intraoperative and postoperative progression of patients experiencing a life-threatening pheochromocytoma crisis treated with extracorporeal membrane oxygenation (ECMO).A 35-year-old man was referred to our facility for paroxysmal hypertension with a 10-year history of sweating, headaches, cardiac palpitations, and postexercise dyspnea. The patient initially underwent urine catecholamine measurement and an isotope scan, somatostatin receptor scintigraphy, and 18F-fluorodeoxyglucose positron emission tomography/computer tomography (CT), which indicated a multiple, cardiac pheochromocytoma. Echocardiography, cardiac magnetic resonance imaging (MRI), CT reconstruction, and a coronary CT angiography revealed several lesions at the aortic root and along the cardiac vasculature.Multifocal cardiac pheochromocytoma was diagnosed and pheochromocytoma crisis with severe cyclic blood pressure fluctuation occurred during surgery.Surgical resection of multiple pheochromocytomas in the right medial carotid sheath, mediastinum between the main and pulmonary arteries, and between the abdominal aorta and inferior vena artery was performed. To ensure cardiac perfusion and avoid severe circulatory fluctuation, the cardiac paraganglioma resection was prioritized. After resecting the cardiac pheochromocytoma, a severe pheochromocytoma crisis with rapid cyclic blood pressure fluctuation developed. ECMO and intraaortic balloon pump (IABP) were initiated to stabilize circulation and perfusion. Phenoxybenzamine, norepinephrine, epinephrine, and fluid resuscitation were administered to support cardiovascular function.The magnitude of blood pressure fluctuation steadily decreased with treatment. IABP was discontinued after 3 days, and ECMO was discontinued after 16 days. The patient was discharged 3 months postoperatively.This case indicates that mechanical life support with ECMO is a valuable option for pheochromocytoma-induced cardiac shock and should be considered as an effective therapeutic choice in patients with highly unstable hemodynamic function.
Topics: Adrenal Gland Neoplasms; Adult; Blood Pressure; Diagnosis, Differential; Diagnostic Imaging; Extracorporeal Membrane Oxygenation; Fluid Therapy; Heart Neoplasms; Humans; Intra-Aortic Balloon Pumping; Male; Pheochromocytoma
PubMed: 25929929
DOI: 10.1097/MD.0000000000000790 -
Journal of Pharmacological Sciences Mar 2015This study was conducted to identify the characteristic pharmacological features of GT-0198 that is phenoxymethylbenzamide derivatives. GT-0198 inhibited the function of...
This study was conducted to identify the characteristic pharmacological features of GT-0198 that is phenoxymethylbenzamide derivatives. GT-0198 inhibited the function of glycine transporter 2 (GlyT2) in human GlyT2-expressing HEK293 cells and did not bind various major transporters or receptors of neurotransmitters in a competitive manner. Thus, GT-0198 is considered to be a comparatively selective GlyT2 inhibitor. Intravenous, oral, and intrathecal injections of GT-0198 decreased the pain-related response in a model of neuropathic pain with partial sciatic nerve ligation. This result suggests that GT-0198 has an analgesic effect. The analgesic effect of GT-0198 was abolished by the intrathecal injection of strychnine, a glycine receptor antagonist. Therefore, GT-0198 is considered to exhibit its analgesic effect via the activation of a glycine receptor by glycine following presynaptic GlyT2 inhibition in the spinal cord. In summary, GT-0198 is a structurally novel GlyT2 inhibitor bearing a phenoxymethylbenzamide moiety with in vivo efficacy in behavioral models of neuropathic pain.
Topics: Analgesics; Animals; Benzamides; Disease Models, Animal; Glycine Plasma Membrane Transport Proteins; HEK293 Cells; Humans; Ligation; Male; Mice, Inbred ICR; Neuralgia; Phenoxybenzamine; Piperidines; Sciatic Nerve; Spinal Cord; Strychnine
PubMed: 25837937
DOI: 10.1016/j.jphs.2015.02.010 -
International Journal of Clinical and... 2014To investigate methods for improving the preoperative management of patients with pheochromocytoma.
OBJECTIVE
To investigate methods for improving the preoperative management of patients with pheochromocytoma.
METHODS
We collected 155 cases diagnosed as adrenal pheochromocytoma and with hypertension. During preoperative preparation, 85 patients had antihypertensive therapy by using the selective α1-blocker doxazosin controlled-release tablets; 70 patients was controlled by using the nonselective α-blocker phenoxybenzamine; All 155 patients underwent qualitative diagnosis by determination of 24-hour urinary vanilmandelic acid (VMA) or [11C]meta-hydroxyephedrine (mHED) positron emission tomography computed tomography (PET-CT) and underwent computed tomography (CT) for tumor localization;
RESULTS
In doxazosin group, with the exception of two patients who had radical fluctuations in blood pressure during surgery, other patients showed a smooth blood pressure control during surgery. No hypertensive crisis and hypotensive shock appeared after surgery. In phenoxybenzamine group, ten patients had sharp fluctuations in blood pressure during surgery, and no hypertensive crisis and hypotensive shock appeared after surgery.
CONCLUSION
Compared with phenoxybenzamine, doxazosin has minimal adverse reactions, with high security as a preoperative preparation for adrenal pheochromocytoma, and it is easy to be taken. MHED PET-CT examination has a clear diagnostic value for patients with normal 24-hour urinary VMA.
PubMed: 25664068
DOI: No ID Found -
FEMS Microbiology Ecology Dec 2014Obtaining a better understanding of mechanisms involved in bacterial infections is of paramount importance for the development of novel agents to control disease caused...
Obtaining a better understanding of mechanisms involved in bacterial infections is of paramount importance for the development of novel agents to control disease caused by (antibiotic resistant) pathogens in aquaculture. In this study, we investigated the impact of catecholamine stress hormones on growth and virulence factor production of pathogenic vibrios (i.e. two Vibrio campbellii strains and two Vibrio anguillarum strains). Both norepinephrine and dopamine (at 100 μM) significantly induced growth in media containing serum. The compounds also increased swimming motility of the tested strains, whereas they had no effect on caseinase, chitinase, and hemolysin activities. Further, antagonists for eukaryotic catecholamine receptors were able to neutralize some of the effects of the catecholamines. Indeed, the dopaminergic receptor antagonist chlorpromazine neutralized the effect of dopamine, and the α-adrenergic receptor antagonists phentolamine and phenoxybenzamine neutralized the effect of norepinephrine, whereas the β-adrenergic receptor antagonist propranolol had limited to no effect. Finally, pretreatment of pathogenic V. campbellii with catecholamines significantly increased its virulence toward giant freshwater prawn larvae. However, the impact of catecholamine receptor antagonists on in vivo virulence was less clear-cut when compared to the in vitro experiments. In summary, our results show that—similar to enteric pathogens—catecholamines also increase the virulence of vibrios that are pathogenic to aquatic organisms by increasing motility and growth in media containing serum.
Topics: Adrenergic alpha-Agonists; Animals; Aquaculture; Artemia; Chlorpromazine; Dopamine; Dopamine Agents; Dopamine Antagonists; Larva; Norepinephrine; Phentolamine; Random Allocation; Vibrio; Virulence
PubMed: 25264299
DOI: 10.1111/1574-6941.12432 -
British Journal of Pharmacology Feb 2015The transmembrane protein LINGO-1 is a negative regulator in the nervous system mainly affecting axonal regeneration, neuronal survival, oligodendrocyte differentiation...
BACKGROUND AND PURPOSE
The transmembrane protein LINGO-1 is a negative regulator in the nervous system mainly affecting axonal regeneration, neuronal survival, oligodendrocyte differentiation and myelination. However, the molecular mechanisms regulating its functions are poorly understood. In the present study, we investigated the formation and the role of LINGO-1 cis-dimers in the regulation of its biological activity.
EXPERIMENTAL APPROACH
LINGO-1 homodimers were identified in both HEK293 and SH-SY5Y cells using co-immunoprecipitation experiments and BRET saturation analysis. We performed a hypothesis-driven screen for identification of small-molecule protein-protein interaction modulators of LINGO-1 using a BRET-based assay, adapted for screening. The compound identified was further assessed for effects on LINGO-1 downstream signalling pathways using Western blotting analysis and AlphaScreen technology.
KEY RESULTS
LINGO-1 was present as homodimers in primary neuronal cultures. LINGO-1 interacted homotypically in cis-orientation and LINGO-1 cis-dimers were formed early during LINGO-1 biosynthesis. A BRET-based assay allowed us to identify phenoxybenzamine as the first conformational modulator of LINGO-1 dimers. In HEK-293 cells, phenoxybenzamine was a positive modulator of LINGO-1 function, increasing the LINGO-1-mediated inhibition of EGF receptor signalling and Erk phosphorylation.
CONCLUSIONS AND IMPLICATIONS
Our data suggest that LINGO-1 forms constitutive cis-dimers at the plasma membrane and that low MW compounds affecting the conformational state of these dimers can regulate LINGO-1 downstream signalling pathways. We propose that targeting the LINGO-1 dimerization interface opens a new pharmacological approach to the modulation of its function and provides a new strategy for drug discovery.
Topics: Cell Line, Tumor; Dimerization; HEK293 Cells; Humans; Membrane Proteins; Molecular Structure; Molecular Weight; Nerve Tissue Proteins; Phenoxybenzamine; Signal Transduction; Stereoisomerism; Structure-Activity Relationship
PubMed: 25257685
DOI: 10.1111/bph.12945