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P J Blankestijn, M L Bots
The rationale behind catheter-based renal denervation is that afferent and efferent renal nerves play a role in the pathogenesis and maintenance of high blood pressure, and that this can be prevented by blocking the function of the renal nerves. Since the introduction of catheter-based renal denervation, several observational and a small number of randomised controlled trials have been conducted. The available evidence does not allow for a definitive conclusion regarding its efficacy. There have been no serious side-effects reported...
2016: Nederlands Tijdschrift Voor Geneeskunde
Sven Jarius, Marius Ringelstein, Jürgen Haas, Irina I Serysheva, Lars Komorowski, Kai Fechner, Klaus-Peter Wandinger, Philipp Albrecht, Harald Hefter, Andreas Moser, Eva Neuen-Jacob, Hans-Peter Hartung, Brigitte Wildemann, Orhan Aktas
BACKGROUND: Recently, we described a novel autoantibody, anti-Sj/ITPR1-IgG, that targets the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in patients with cerebellar ataxia. However, ITPR1 is expressed not only by Purkinje cells but also in the anterior horn of the spinal cord, in the substantia gelatinosa and in the motor, sensory (including the dorsal root ganglia) and autonomic peripheral nervous system, suggesting that the clinical spectrum associated with autoimmunity to ITPR1 may be broader than initially thought...
October 24, 2016: Journal of Neuroinflammation
Marius Schwerg, Anna Slagman, Karl Stangl, Verena Stangl
BACKGROUND: Renal denervation is used as a treatment option for patients with resistant hypertension. But only a subgroup of patients benefits from RDN. Biomarkers might be helpful to identify patients who respond to RDN. Copeptin as a surrogate for vasopressin levels is increased in hypertension and other cardiovascular diseases. This study aims to evaluate the effect of RDN on Copeptin and its prognostic value for response to RDN. METHOD AND RESULTS: A total of 40 patients have been included in the study...
October 24, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Haruo Nishijima, Tatsuya Ueno, Shinya Ueno, Fumiaki Mori, Yasuo Miki, Masahiko Tomiyama
Long-term administration of levodopa for Parkinson's disease is associated with various motor and non-motor complications. We examined the dendritic spine morphology of pyramidal tract-type neurons in the prefrontal cortex in a rat model of Parkinson's disease chronically treated with levodopa. Dendritic spines showed decreased density and increased average volume after dopamine denervation and levodopa treatment. These morphologic alterations suggest that the prefrontal neurons may maladaptively respond to excitatory input, which might be one of the mechanisms underlying various levodopa-induced complications in patients with Parkinson's disease...
October 20, 2016: Neuroscience Research
Stefano Strano, Alessandra Fanciulli, Massimiliano Rizzo, Paolo Marinelli, Paolo Palange, Dorina Tiple, Giuseppe De Vincentis, Giovanni Calcagnini, Federica Censi, Giuseppe Meco, Carlo Colosimo
BACKGROUND: The clinical presentation of Parkinson's disease (PD) includes a wide spectrum of non-motor features, including cardiovascular autonomic failure. OBJECTIVE: To evaluate cardiovascular autonomic status and cardiac functional capacity in drug-naïve PD patients. METHODS: 18 newly-diagnosed PD patients underwent laboratory cardiovascular autonomic function tests using power spectral analysis of the R-R interval, blood pressure (BP) short-term variability and non-invasive baroreflex sensitivity (BRS)...
November 15, 2016: Journal of the Neurological Sciences
Lorenza Brocca, Luana Toniolo, Carlo Reggiani, Roberto Bottinelli, Marco Sandri, Maria Antonietta Pellegrino
Muscle atrophy is a complex process that is in common with many different catabolic diseases including disuse/inactivity and ageing. The signalling pathways that control the atrophy program in the different disuse/inactivity conditions have not yet been completely dissected. It has been recently reported that inhibition of FoxO only partially spared muscle mass after denervation. The purposes of this study were: (i) to determine the involvement of FoxOs in hindlimb suspension disuse model, (ii) to define whether the molecular events of protein breakdown are shared among different unloaded muscles and finally (iii) to compare the data obtained in this model with another model of inactivity such as denervation...
October 21, 2016: Journal of Physiology
Elżbieta Lorenc-Koci, Anna Czarnecka, Kinga Kamińska, Joanna Knutelska, Małgorzata Zygmunt, Magdalena Dudek
BACKGROUND: Interaction between dopaminergic and nitrergic neurotransmission in the brain plays a crucial role in the control of motor function and in the regulation of blood pressure (BP). In Parkinson's disease (PD), dopaminergic denervation of the striatum leads to disturbances in the nitrergic system in the basal ganglia. Recently, it has been demonstrated that addition of a low dose of the nitric oxide donor molsidomine to l-DOPA therapy improves dopaminergic neurotransmission in the denervated nigrostriatal system and weakens dyskinesias in rodent models of the disease...
September 28, 2016: Pharmacological Reports: PR
Naokata Sumitomo
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is induced by emotions or exercise in patients without organic heart disease and may be polymorphic or bidirectional in nature. The prognosis of CPVT is not good, and therefore prevention of sudden death is of utmost importance. Genetic variants of CPVT include RyR2, CASQ2, CALM2, TRD, and possibly KCNJ2 and ANK2 gene mutations. Hypotheses that suggest the causes of CPVT include weakened binding of FKBP12.6 and RyR2, a store overload-induced Ca(2+) release (SOICR), unzipping of intramolecular domain interactions in RyR2, and molecular and functional abnormalities caused by mutations in the CASQ2 gene...
October 2016: Journal of Arrhythmia
Yongkeun Cho
Medications such as ß-blockers are currently the primary treatment for patients with hereditary arrhythmia syndromes such as long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, these drugs are ineffective in some patients, and the other treatment option, that is implantable cardioverter defibrillator (ICD) implantation, is associated with significant complications in young and active patients. Left cardiac sympathetic denervation (LCSD) may reduce the wide gap between life-long ß-blocker medication and ICD implantation...
October 2016: Journal of Arrhythmia
Alan Pestronk, Richard Keeling, Rati Choksi
OBJECTIVE: We studied mitochondrial impairment as a factor in the pathologic equivalent of sarcopenia, muscle fiber atrophy associated with increased age. METHODS: Mitochondrial oxidative enzyme activities and coenzyme Q10 levels were measured in frozen human proximal limb muscles with combined age and atrophy, age alone, atrophy alone, denervation, immune myopathies, and mitochondrial disorders with ophthalmoplegia. RESULTS: Sarcopenia (age and atrophy) had reduced mean activities of mitochondrial Complexes I, II, and II+III, with severe reduction of Complex I activity in 54% of patients...
October 19, 2016: Muscle & Nerve
Suma Babu, Erik P Pioro, Jianbo Li, Yuebing Li
INTRODUCTION: We compared the yield of limb and thoracic paraspinal muscles for revealing lower motor neuron (LMN) dysfunction on electromyography (EMG) in amyotrophic lateral sclerosis (ALS). METHODS: A retrospective review of 354 patients with clinically definite or probable ALS was performed. Seventeen limb muscles and thoracic paraspinal muscles were evaluated for the presence of both active and chronic denervation. RESULTS: Distal limb muscles showed the highest electrodiagnostic sensitivities of LMN dysfunction in ALS regardless of onset region and diagnostic certainty at the time of diagnosis...
October 19, 2016: Muscle & Nerve
Mai Michishita, Kazuo Yano, Ken-Ichi Tomita, Osamu Matsuzaki, Ken-Ichi Kasahara
AIMS: For patients with benign prostatic hyperplasia (BPH), storage symptoms due to bladder dysfunction are bothersome, and that mechanism elucidation is needed. Piezo1, a mechanically activated ion channel, is believed to play a role in sensing bladder distension. To investigate the involvement of Piezo1 in bladder dysfunction, we examined the expression and distribution of Piezo1 and neurofilament (NF-L) to understand pathological alterations in rat bladders with partial bladder outlet obstruction (pBOO), an animal model of BPH...
October 15, 2016: Life Sciences
Michael Böhm, Christian Ukena, Sebastian Ewen, Dominik Linz, Ina Zivanovic, Uta Hoppe, Krzysztof Narkiewicz, Luis Ruilope, Manuela Negoita, Roland Schmieder, Bryan Williams, Uwe Zeymer, Andreas Zirlik, Guiseppe Mancia, Felix Mahfoud
OBJECTIVES: Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with hypertension. The effects on resting and ambulatory heart rate (HR), also regulated by the sympathetic nervous system, are not established. METHODS: Herein, we report 12-month outcomes from the Global SYMPLICITY Registry on office and ambulatory HR and BP in patients with uncontrolled hypertension (n = 846). RESULTS: HR declined in correlation with the HR at baseline and at 12 months, in particular, in patients in the upper tertile of HR (>74 bpm)...
October 15, 2016: Journal of Hypertension
Jonathan G Moss, Anna-Maria Belli, Antonio Coca, Michael Lee, Giuseppe Mancia, Jan H Peregrin, Josep Redon, Jim A Reekers, Costas Tsioufis, Dierk Vorwerk, Roland E Schmieder
Renal denervation (RDN) was reported as a novel exciting treatment for resistant hypertension in 2009. An initial randomized trial supported its efficacy and the technique gained rapid acceptance across the globe. However, a subsequent large blinded, sham arm randomized trial conducted in the USA (to gain Food and Drug Administration approval) failed to achieve its primary efficacy end point in reducing office blood pressure at 6 months. Published in 2014 this trial received both widespread praise and criticism...
October 17, 2016: Journal of Hypertension
Seong Hwan Kim
Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the concurrent use of three antihypertensive agents of different classes at optimal dosing, of which one should be a diuretic. Accordingly, it is not synonymous with uncontrolled hypertension. Among a variety of risk factors, obstructive sleep apnea (OSA), which is a common type of sleep-disordered breathing, has been recognized a well-established risk factor for resistant hypertension. Indeed, both European and American guidelines for the management of arterial hypertension stated that OSA is a modifiable cause of resistant hypertension...
September 2016: Journal of Hypertension
Byeong-Keuk Kim
Catheter-based renal sympathetic denervation (RDN) has opened the new world in the treatment of resistant or refractory hypertension. However, SYMPLICITY HTN-3, 2:1 randomization, blinded and sham-controlled study did not show a significant reduction of systolic blood pressure (BP) in patients with resistant hypertension 6 months after RDN as compared with a sham control. After that, substudy investigating the predictors of BP responses in SYMPLICITY HTN-3 trial was reported; racial difference and optimal medical treatment were issued for the optimal denervation therapy...
September 2016: Journal of Hypertension
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
Yu Hasegawa, Shokei Kim-Mitsuyama
OBJECTIVE: Although hypertensive patients show significant elevation of blood pressure (BP) in acute phase after cerebral infarction, it is still unknown how it should be managed to carry the best prognosis. To address this issue, we investigated the effect of acute control of elevated BP by bilateral renal denervation (RD) against ischemic stroke in SHRSP rats with 90 minutes transient middle cerebral arterial occlusion (MCAO). DESIGN AND METHOD: Seventy-five male SHRSP rats of 15 weeks of age were assigned to sham-operated (control, n = 15) and MCAO + sham (sham, n = 30), and MCAO + RD (RD, n = 30)...
September 2016: Journal of Hypertension
George Bakris
Renal denervation started out as a very promising approach to treat resistant hypertension with a very strong conceptual and basic science frame work from Gerald DiBona's lab and extending into the early non shame clinical studies demonstrating proof of concept in SYMPLICITY HTN-1 and 2. SYMPLICITY-HTN 3 a properly done, sham control trial failed to show a benefit on further reduction of BP compared to the sham group. The conclusion the procedure doesn't work. How could this be-it was clearly effective in animal models but why not in man...
September 2016: Journal of Hypertension
Markus Schlaich
Accumulating evidence from mainly uncontrolled and unblinded clinical studies with various types of ablation catheters have shown that renal denervation (RDN) can be applied safely and is effective in lowering blood pressure (BP) in most patients with treatment resistant hypertension. Sustained BP lowering has been documented up to 3 years at this stage. Furthermore, RDN has been associated with regression of target organ damage, such as left ventricular hypertrophy, arterial stiffness and others. Several studies indicate potential benefit in other common clinical conditions associated with increased sympathetic tone including chronic kidney disease and heart failure...
September 2016: Journal of Hypertension
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