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Endocrinology, Diabetes and Metabolism... Jun 2023Traumatic brain injury (TBI) was associated with increased plasma agonist autoantibodies targeting the serotonin 2A receptor. Repeated TBI exposure is associated with...
OBJECTIVES
Traumatic brain injury (TBI) was associated with increased plasma agonist autoantibodies targeting the serotonin 2A receptor. Repeated TBI exposure is associated with high risk for neurodegenerative and neuropsychiatric complications. Here we tested a hypothesis that repeated TBI is associated with plasma agonist autoantibodies targeting more than one kind of catecholamine G-protein coupled receptor.
METHODS
Protein-A affinity chromatography was used to isolate the IgG fraction of plasma in forty-two middle-aged and older adults who had experienced one or more TBI exposures. The Ig (1/40 dilution=7.5 ug/mL) were tested for neurotoxicity in mouse neuroblastoma cells using an acute neurite retraction assay indicative of Gq11/IP3/Ca2+ and RhoA/Rho kinase signaling pathways' activation. Three different linear synthetic peptides corresponding to the second extracellular loop of the alpha 1A, alpha 2A or serotonin 2A receptors were used as target antigen in different enzyme-linked immunoassays. The second extracellular loop receptor peptides themselves (alpha 1A, alpha 2A) or a fragment (serotonin 2A) were tested for ability to prevent Ig-induced neurite retraction.
RESULTS
Patients who had experienced either repeated TBI (N=10) or a single TBI with a co-morbid autoimmune disease (N=5) were significantly more likely to harbor neurotoxic plasma autoantibodies targeting both alpha 1 adrenergic and serotonin 2A receptors vs. patients having only a single TBI. Ig-induced neurotoxicity was significantly prevented by co-incubation with either 850 nM prazosin (alpha 1 adrenergic receptor) and/or 500 nM M100907 (serotonin 2A receptor) antagonists. Alpha 1 adrenergic receptor and serotonin 2A receptor Ig immunoreactive level and titer were significantly increased in repeated TBI and single TBI/autoimmune patients (N=7-8) compared to age-matched TBI patients without neurotoxic plasma Ig (N=4). SN.8, a linear synthetic peptide corresponding to a conserved region of the second extracellular loop (ECL) of the serotonin 2A receptor completely prevented neurite retraction induced by repeated TBI plasma Ig. A repeated TBI patient harboring alpha adrenergic receptor AAB alone experienced prospective steep decline in cognitive function over two years.
CONCLUSIONS
Repeated TBI and TBI with associated autoimmunity harbored more than one kind of neurotoxic catecholaminergic agonist GPCR autoantibody each associated with high risk for steep rate of cognitive decline. Specific immunoassays using the second extracellular receptor loop as target antigen are needed to detect each specific different GPCR autoantibody. A fragment of the second ECL of the serotonin 2A receptor (SN.8) neutralized Ig-induced neurotoxicity in repeated TBI or TBI with associated systemic autoimmunity.
PubMed: 37560352
DOI: 10.31038/EDMJ.2023722 -
Journal of Postgraduate Medicine Apr 2024Pheochromocytoma and paraganglioma (PPGL) are rare tumors, and data on ambulatory blood pressure monitoring (ABPM) in these patients and the effect of blocking on ABPM...
CONTEXT/AIMS
Pheochromocytoma and paraganglioma (PPGL) are rare tumors, and data on ambulatory blood pressure monitoring (ABPM) in these patients and the effect of blocking on ABPM parameters is limited. We aimed to describe ABPM parameters in a cohort of PPGL at our center in western India.
METHODS
Retrospective study of patients with PPGL whose ABPM data was available. Demographic details, secretory status, and ABPM data were retrieved. Coefficient of variability (CV) was calculated as standard deviation/mean in percentage.
RESULTS
In the 39 included patients, mean age at presentation was 39.3 ± 14.2 yr; 20 (51.3%) were males, 25 (64.1%) hypertensive, and mean tumor diameter was 5.3 cm. In 18 patients whose baseline ABPM was done without medications, those with nocturnal blood pressure dipping (6/18, 33%) had higher serum metanephrines (median 313.2 vs. 34.7 pg/ml, P = 0.028). Despite normal office blood pressure (BP), 8.9% of systolic BP readings were >140 mmHg, and 1.2% were >160 mmHg. Among 29 patients with both pre and post-block ABPM, mean BP (systolic 121.6 vs. 132.5 mmHg, P = 0.014; diastolic 68.9 vs. 76.4 mmHg, P = 0.005) and percentage of BP readings above 140 mmHg (median 9.4% vs. 24.4%, P = 0.016) were significantly lowered after the preoperative blockade in hypertensive ( n = 19) patients, whereas CV was similar. The post-blockade ABPM characteristics were similar in patients blocked with amlodipine or prazosin.
CONCLUSION
ABPM provides additional information about BP characteristics in PPGL. The preoperative blocking decreases the magnitude of BP excursions but does not affect BP variability.
Topics: Humans; Pheochromocytoma; Male; Female; Blood Pressure Monitoring, Ambulatory; Adult; Retrospective Studies; Middle Aged; Adrenal Gland Neoplasms; Paraganglioma; Hypertension; Blood Pressure; India
PubMed: 37555422
DOI: 10.4103/jpgm.jpgm_208_23 -
Current Problems in Cardiology Nov 2023The BRASH (bradycardia, renal failure, atrioventricular block, shock, and hyperkalaemia) syndrome is a recently recognized condition which may lead to life-threatening...
The BRASH (bradycardia, renal failure, atrioventricular block, shock, and hyperkalaemia) syndrome is a recently recognized condition which may lead to life-threatening complications if not correctly identified and treated early. We report here the case of a 74-year-old woman with type 2 diabetes, hypertension and atrial flutter who presented to the emergency department with 2-day history of dizziness, presyncope, and bradycardia, and a junctional rhythm at 61 beat per minute on initial ECG. She was on apixaban, digoxin, prazosin, and telmisartan. Serum biochemistry revealed severe hyperkalaemia with a potassium 8.4 mmol/L, creatinine 161 mmol/L, glucose 15.3 mmol/L and an upper normal digoxin level of 1.2 mmol/L (ref. 0.6-1.2). Arterial blood pH was 7.2. Given the constellation of biochemical and clinical findings a diagnosis of BRASH syndrome was made, though her blood pressure values at presentation were rather high (180/65-179/59 mmHg). The patient was rapidly stabilised with the administration of intravenous insulin and dextrose, fluid resuscitation, and zirconium cyclosilicate (SZC), followed by haemodialysis. Following the correction of the serum potassium to 4.7 mmol/L, a further ECG performed 6 hours later, showed a restoration of sinus rhythm with a rate of 65 bpm, normalization of the QRS duration. The digoxin and telmisartan were discontinued, and the patient was commenced on a calcium channel antagonist for hypertension. Clinicians should be alerted to patients who present with either a BRASH (shock) or BRAHH (hypertensive manifestation) where timely intervention is essential to avoid life-threatening brady-and tachyarrhythmias in these patients.
Topics: Aged; Female; Humans; Arrhythmias, Cardiac; Bradycardia; Diabetes Mellitus, Type 2; Digoxin; Hyperkalemia; Hypertension; Potassium; Telmisartan
PubMed: 37473946
DOI: 10.1016/j.cpcardiol.2023.101984 -
Vascular Pharmacology Aug 2023Sympathomimetic amines, including β-phenylethylamine (PEA), constrict animal blood vessels but their mechanism of action is not now thought to be through...
Sympathomimetic amines, including β-phenylethylamine (PEA), constrict animal blood vessels but their mechanism of action is not now thought to be through α-adrenoceptors and release of noradrenaline but via trace amine-associated receptors (TAARs). This information is not available for human blood vessels. Functional studies were therefore performed on human arteries and veins to establish whether they constrict to PEA and whether any constrictions are adrenoceptor-mediated. Isolated internal mammary artery or saphenous vein rings were set up in Kreb's-bicarbonate solution at 37 ± 0.5 °C gassed with O:CO (95:5) under class 2 containment. Isometric contractions were measured and cumulative concentration-response curves for PEA or the α-adrenoceptor agonist, phenylephrine were established. PEA showed concentration-related contractions. The maximum was significantly greater in arteries (1.53 ± 0.31 g, n = 9) than veins (0.55 ± 0.18 g, n = 10), but not when plotted as % of KCl contractions. PEA showed slowly developing contractions plateauing at 17,3 ± 3.7 min in mammary artery. The reference α-adrenoceptor agonist, phenylephrine, exhibited more rapid onset (peak 5.0 ± 1.2 min) but non-sustained contractions. In saphenous veins, PEA (62.8 ± 10.7%) and phenylephrine (61.4 ± 9.7%, n = 4) displayed the same maximum, but phenylephrine was more potent. The α-adrenoceptor antagonist, prazosin (1 μM), blocked phenylephrine contractions of mammary arteries but not PEA contractions in either vessel. PEA causes substantial vasoconstriction of human saphenous vein and mammary artery, which explains its vasopressor actions. This response, however, was not mediated via α-adrenoceptors, but likely due to TAARs. The classification of PEA as a sympathomimetic amine on human blood vessels is therefore no longer valid and requires revision.
Topics: Animals; Humans; Mammary Arteries; Vasoconstriction; Saphenous Vein; Phenylephrine; Norepinephrine; Receptors, Adrenergic
PubMed: 37399882
DOI: 10.1016/j.vph.2023.107191 -
The Korean Journal of Physiology &... Jul 2023α-adrenoceptors link via the G-protein Gq/G to both Ca entry and release from stores, but may also activate Rho kinase, which causes calcium sensitization. This study...
α-adrenoceptors link via the G-protein Gq/G to both Ca entry and release from stores, but may also activate Rho kinase, which causes calcium sensitization. This study aimed to identify the subtype(s) of α-adrenoceptor involved in Rho kinase-mediated responses in both rat aorta and mouse spleen, tissues in which contractions involve multiple subtypes of α-adrenoceptor. Tissues were contracted with cumulative concentrations of noradrenaline (NA) in 0.5 log unit increments, before and in the presence of an antagonist or vehicle. Contractions produced by NA in rat aorta are entirely α-adrenoceptor mediated as they are competitively blocked by prazosin. The α-adrenoceptor antagonist RS100329 had low potency in rat aorta. The α-adrenoceptor antagonist BMY7378 antagonized contractions in rat aorta in a biphasic manner: low concentrations blocking α-adrenoceptors and high concentrations blocking α-adrenoceptors. The Rho kinase inhibitor fasudil (10 μM) significantly reduced aortic contractions in terms of maximum response, suggesting inhibition of α-adrenoceptor mediated responses. In the mouse spleen, a tissue in which all 3 subtypes of α-adrenoceptor are involved in contractions to NA, fasudil (3 μM) significantly reduced both early and late components to the NA contraction, the early component involving α- and α-adrenoceptors, and the late component involving α- and α-adrenoceptors. This suggests that fasudil inhibits α-adrenoceptor mediated responses. It is concluded that α- and α-adrenoceptors interact in rat aorta and α-, α- and α-adrenoceptors interact in the mouse spleen to produce contractions and these interactions suggest that one of the receptors preferentially activates Rho kinase, most likely the α-adrenoceptor.
PubMed: 37386830
DOI: 10.4196/kjpp.2023.27.4.325 -
World Journal of Surgical Oncology Jun 2023Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors characterized by hemodynamic instability, caused by the paroxysmal release of...
BACKGROUND
Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors characterized by hemodynamic instability, caused by the paroxysmal release of catecholamines. Patients may develop cardiovascular complications in the perioperative phase due to the massive release of catecholamines, particularly during anesthetic induction and surgical manipulation of the tumor. The aim of this retrospective study was to evaluate the risk factors involved in perioperative hemodynamic instability in patients who underwent surgery for chromaffin tumors.
METHODS
Forty patients (median age 55 [36.50-64.50]) undergone surgery for PHEO/abdominal PGL from January 2011 to December 2016 at the AOU Careggi (Florence, Italy) were retrospectively evaluated. Systolic, diastolic, and mean blood pressure were considered at baseline and during surgery. Patients with blood pressure steadily < 140/90 mmHg before surgery were considered "adequately prepared". A preoperative therapy with doxazosin, a selective alpha-1 blocker, was started in all patients for at least 14 days prior to the surgery. The presence of hemodynamic instability was reported.
RESULTS
Comparing males and females, a significant difference in doxazosin daily dose (p = 0.018), systolic blood pressure (p = 0.048), and in the proportion of adequately prepared patients (p = 0.031) emerged. A positive correlation between preoperative daily dose of doxazosin, tumor size (B = 0.60, p < 0.001), and urinary normetanephrine levels (B = 0.64, p < 0.001) was also observed. Hemodynamic instability occurred in 30.0% of patients. The absence of adequate preparation (p = 0.012) before surgery, urinary normetanephrine levels (NMNur p = 0.039), and surgery time (minutes) (p = 0.021) resulted as risk factors of hemodynamic instability in our series. The use of intraoperative drugs was higher in patients with hemodynamic instability (p < 0.001). A pre-surgical SBP level of > 133 mmHg (OR = 6 CI95% 1.37-26.20, p = 0.017) and an intraoperative SBP and MBP levels of > 127 mmHg (OR = 28.80 CI95% 2.23-371.0, p = 0.010) and > 90 mmHg (OR = 18.90 CI95% 1.82-196.0, p = 0.014), respectively, were identified as effective thresholds to recognize patients at higher risk of HI.
CONCLUSIONS
A preoperative therapy with alpha-blockers is useful, but not sufficient to avoid surgical risks. Patients with higher pre-surgical levels of NMNur, pre-surgical SBP > 133 mmHg, and/or intraoperative SBP > 127 mmHg and MBP > 90 mmHg, should be carefully monitored. A multidisciplinary approach is indispensable to optimize the management of PHEOs/abdominal PGLs in order to reduce surgical complications.
Topics: Male; Female; Humans; Middle Aged; Pheochromocytoma; Retrospective Studies; Doxazosin; Normetanephrine; Paraganglioma; Hemodynamics; Adrenal Gland Neoplasms; Catecholamines; Vascular Diseases
PubMed: 37370080
DOI: 10.1186/s12957-023-03072-z -
Urology Annals 2023The present retrospective study evaluates the effectiveness and tolerability of alpha-blockers as monotherapy in patients with benign prostatic hyperplasia associated...
Electronic medical records-based retrospective, longitudinal, observational study to understand the patient management of benign prostatic hyperplasia with alpha-blockers monotherapy in Indian population.
OBJECTIVE
The present retrospective study evaluates the effectiveness and tolerability of alpha-blockers as monotherapy in patients with benign prostatic hyperplasia associated with lower urinary tract symptoms (LUTS).
MATERIALS AND METHODS
A total of 335 male patients >50 years were categorized into four groups (Alfuzosin: 166, Silodosin: 67, Tamsulosin: 70, Prazosin: 32). The efficacy evaluated as a change in International Prostate Symptom Score (IPSS), peak flow rate (Qmax), residual urine volume, and relief from LUTS, and tolerability of the various alpha-blockers was assessed across the study group.
RESULTS
At baseline, most of the patients in alfuzosin (60%), silodosin (77%), and tamsulosin (90%) groups presented with severe IPSS (20-35), whereas patients in the prazosin group (69%) presented with a moderate score. At the end of the study, the mean IPSS gradually improved to moderate (41%, 62%, 66%, and 28%) and mild (59%, 38%, 28%, and 72%) in the alfuzosin, silodosin, tamsulosin, and prazosin groups, respectively ( = 0.004), with improvement in mean change in residual urine volume and complete relief from LUTS symptoms with no surgical or radiological interventions. Overall, 194 adverse events (AEs) were observed in 38.8% of patients. Of the total AEs, patients in the alfuzosin, silodosin, tamsulosin, and prazosin groups experienced 21%, 22%, 39%, and 18% of AEs, respectively.
CONCLUSION
The nonselective alpha-adrenergic receptor antagonist, alfuzosin, emerged as noninferior in effectiveness and superior in tolerability than other selective alpha-blockers, silodosin, tamsulosin, and prazosin.
PubMed: 37304518
DOI: 10.4103/ua.ua_114_21 -
Peptides Aug 2023Excessive activation of the sympathetic nervous system is involved in cardiovascular damage including cardiac hypertrophy. Natriuretic peptides are assumed to exert...
Excessive activation of the sympathetic nervous system is involved in cardiovascular damage including cardiac hypertrophy. Natriuretic peptides are assumed to exert protective actions for the heart, alleviating hypertrophy and/or fibrosis of the myocardium. In contrast to this assumption, we show in the present study that both atrial and C-type natriuretic peptides (ANP and CNP) potentiate cardiac hypertrophic response to noradrenaline (NA) in rats. Nine-week-old male Wistar rats were continuously infused with subcutaneous 30 micro-g/h NA without or with persistent intravenous administration of either 1.0 micro-g/h ANP or CNP for 14 days. Blood pressure (BP) was recorded under an unrestrained condition by a radiotelemetry system. Cardiac hypertrophic response to NA was evaluated by heart weight/body weight (HW/BW) ratio and microscopic measurement of myocyte size of the left ventricle. Mean BP levels at the light and dark cycles rose by about 20 mmHg following NA infusion for 14 days, with slight increases in HW/BW ratio and ventricular myocyte size. Infusions of ANP and CNP had no significant effects on mean BP in NA-infused rats, while two natriuretic peptides potentiated cardiac hypertrophic response to NA. Cardiac hypertrophy induced by co-administration of NA and ANP was attenuated by treatment with prazosin or atenolol. In summary, both ANP and CNP potentiated cardiac hypertrophic effect of continuously infused NA in rats, suggesting a possible pro-hypertrophic action of natriuretic peptides on the heart.
Topics: Rats; Animals; Male; Rats, Wistar; Norepinephrine; Atrial Natriuretic Factor; Cardiomegaly; Blood Pressure; Natriuretic Peptide, C-Type; Natriuretic Peptide, Brain
PubMed: 37263541
DOI: 10.1016/j.peptides.2023.171035 -
JNMA; Journal of the Nepal Medical... Mar 2023Anti-hypertensive medications are prescribed for the management of high blood pressure which is the leading cause of mortality in chronic hemodialysis patients. The...
Antihypertensive Medications Use among Chronic Hemodialysis Patients Visiting the Outpatient Department of Nephrology of a Tertiary Care Centre: A Descriptive Cross-sectional Study.
INTRODUCTION
Anti-hypertensive medications are prescribed for the management of high blood pressure which is the leading cause of mortality in chronic hemodialysis patients. The objective of our study was to find out the prevalence of anti-hypertensive medication use among chronic hemodialysis patients visiting the outpatient Department of Nephrology of a tertiary care centre.
METHODS
This was a descriptive cross-sectional study conducted among chronic hemodialysis patients visiting the Department of Nephrology of a tertiary care centre from 2 April 2022 to 30 September 2022. Ethical approval was taken from the Institutional Review Committee (Reference number: 062-078/079). A convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated.
RESULTS
The prevalence of anti-hypertensive medications use was present in 102 (97.14%) (93.95-100, 95% Confidence Interval) patient undergoing hemodialysis. The three common drugs prescribed for hypertensive patients were amlodipine 79 (77.45%), torsemide 59 (57.84%), and prazosin 48 (47.05%).
CONCLUSIONS
The prevalence of antihypertensive medication use among patients undergoing hemodialysis was higher than other similar studies done in similar settings.
KEYWORDS
anti-hypertensive drugs; hemodialysis; prevalence.
Topics: Humans; Outpatients; Antihypertensive Agents; Cross-Sectional Studies; Nephrology; Tertiary Care Centers; Hypertension; Renal Dialysis
PubMed: 37203939
DOI: 10.31729/jnma.8095 -
Frontiers in Psychiatry 2023Post-traumatic stress disorder is a debilitating chronic illness that affects 6 out of 100 adults after a severe trauma. The alpha-adrenergic antagonist prazosin, which...
Post-traumatic stress disorder is a debilitating chronic illness that affects 6 out of 100 adults after a severe trauma. The alpha-adrenergic antagonist prazosin, which is prescribed off-label for flashbacks and nightmares due to trauma, is often continued indefinitely due to reports of symptoms returning upon discontinuation. There is no standard guidance for a trial of discontinuation of prazosin due to intolerance or side effects. In this case series, three patients are started on prazosin leading to remission of trauma-related symptoms, and symptoms continue to remit after treatment for an average of about 2 years followed by discontinuation of the medication. There are many similarities in these case reports which serve to provide guidance as to when a trial of prazosin discontinuation may be warranted.
PubMed: 37151970
DOI: 10.3389/fpsyt.2023.1172754