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Article ; Online: Correction to: Baroreflex‑sympathoneural dysfunction characterizes at‑risk individuals with preclinical central Lewy body diseases.

Goldstein, David S / Sharabi, Yehonatan

Clinical autonomic research : official journal of the Clinical Autonomic Research Society

2023 Volume 33, Issue 1, Page(s) 79

Language	English
Publishing date	2023-02-01
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	1080007-4
ISSN	1619-1560 ; 0959-9851
ISSN (online)	1619-1560
ISSN	0959-9851
DOI	10.1007/s10286-022-00917-7
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Article ; Online: SnapShot: Autonomic nervous system disorders.

Sharabi, Yehonatan / Vatine, Gad D / Ashkenazi, Avraham

Neuron

2022 Volume 110, Issue 8, Page(s) 1432–1432.e1

MeSH term(s)	Autonomic Nervous System Diseases ; Humans
Language	English
Publishing date	2022-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2022.03.007
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Baroreflex-sympathoneural dysfunction characterizes at-risk individuals with preclinical central Lewy body diseases.

Goldstein, David S / Sharabi, Yehonatan

Clinical autonomic research : official journal of the Clinical Autonomic Research Society

2022 Volume 33, Issue 1, Page(s) 41–49

Abstract: Purpose: In central Lewy body diseases (LBDs) such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), by the time parkinsonism or cognitive dysfunction becomes manifest, substantial central neurodegeneration has already occurred. ... ...

Abstract	Purpose: In central Lewy body diseases (LBDs) such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), by the time parkinsonism or cognitive dysfunction becomes manifest, substantial central neurodegeneration has already occurred. Cardiovascular autonomic biomarkers might detect preclinical central LBDs in at-risk individuals, enabling possibly effective disease-modifying treatment. Methods: In the prospective, longitudinal PDRisk study, 59 participants provided information about family history of PD, olfactory dysfunction, dream enactment behavior, and orthostatic intolerance or hypotension at a protocol-specific website and were screened as outpatients. Thirty-four had three or more confirmed risk factors and were followed until PD was diagnosed or up to 7.5 years. Dependent measures included assessments of baroreflex-sympathoneural function, via the blood pressure recovery time (PRT) after release of the Valsalva maneuver and baroreflex areas; and baroreflex-cardiovagal function, via heart rate variability in the time and frequency domains and Valsalva baroslopes. Data were compared from groups with or without a subsequent diagnosis of a central LBD (LBD+, N = 9; LBD-, N = 25) and PDRisk participants with fewer than three confirmed risk factors (PDRisk-, N = 25). Results: The LBD+ group had larger orthostatic falls in systolic blood pressure than did the LBD- and PDRisk- groups (p < 0.0001 each). The LBD+ group had increased PRTs (p = 0.0114 versus LBD-, p = 0.0094 versus PDRisk-) and baroreflex areas after the Valsalva maneuver (p = 0.0225 versus LBD-, p = 0.0028 versus PDRisk-), whereas the groups did not differ in indices of baroreflex-cardiovagal function. Conclusion: Orthostatic hypotension and baroreflex-sympathoneural dysfunction characterize at-risk individuals who go on to be diagnosed with a central LBD during longitudinal follow-up.
MeSH term(s)	Humans ; Baroreflex/physiology ; Prospective Studies ; Lewy Bodies ; Heart ; Parkinson Disease ; Lewy Body Disease
Language	English
Publishing date	2022-12-12
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1080007-4
ISSN	1619-1560 ; 0959-9851
ISSN (online)	1619-1560
ISSN	0959-9851
DOI	10.1007/s10286-022-00912-y
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Article ; Online: Cardiac noradrenergic deficiency revealed by 18F-dopamine positron emission tomography identifies preclinical central Lewy body diseases.

Goldstein, David S / Holmes, Courtney / Sullivan, Patti / Lopez, Grisel / Gelsomino, Janna / Moore, Sarah / Isonaka, Risa / Wu, Tianxia / Sharabi, Yehonatan

The Journal of clinical investigation

2024 Volume 134, Issue 1

MeSH term(s)	Humans ; Dopamine ; Prospective Studies ; Lewy Bodies ; Positron-Emission Tomography/methods ; Parkinson Disease/diagnostic imaging ; Norepinephrine
Chemical Substances	Dopamine (VTD58H1Z2X) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI172460
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Ua VI Zs.184: Show issues

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Article: [PSEUDOPHEOCHROMOCYTOMA - AN UNCOMMON FORM OF HYPERTENSION].

Leshem, Yehoshuaq Shuki / Sharabi, Yehonatan

Harefuah

2021 Volume 160, Issue 4, Page(s) 245–249

Abstract: Introduction: Pseudopheochromocytoma is an uncommon form of hypertension. In contrast to the more well-known pheochromocytoma, no unequivocal etiologic factor or a clear physiological abnormality can be identified. This disorder manifests in sudden, ... ...

Abstract	Introduction: Pseudopheochromocytoma is an uncommon form of hypertension. In contrast to the more well-known pheochromocytoma, no unequivocal etiologic factor or a clear physiological abnormality can be identified. This disorder manifests in sudden, recurrent, episodes of significant, sometimes extreme, increase in blood pressure, both systolic and diastolic, lasting from minutes to hours, with no consistent trigger that the patient or the doctor is aware of, and is accompanied by typical symptoms. These symptoms include, but are not limited to, headaches, fever, flushing, weakness, with or without an accelerated heart rate. Patients with this disorder have increased sympathetic activity, from an adrenal source or sympathetic nerve endings, as well as hyper-responsiveness of the heart and blood vessels to this activation. There is an increased secretion of epinephrine and dopamine in the case of an adrenal source, and norepinephrine in the case of the sympathetic nerve endings. It is important to perform the differential diagnosis of this condition to rule out pheochromocytoma by testing plasma and urinary metanephrines. Additional diagnoses that need to be excluded are anxiety attacks, fluctuating-episodic hypertension, and baroreflex failure. The therapeutic approach of this disorder includes a combination of drugs to lower and control blood pressure, especially drugs that block alpha and beta-adrenergic receptors, along with antianxiety and antidepressants. Psychological intervention, as well as techniques that are aimed to reduce anxiety, have a place in therapy, especially among those patients who can relate the manifestations of the disorder to mental and emotional factors that contribute to the clinical manifestations.
MeSH term(s)	Adrenal Gland Neoplasms/diagnosis ; Adrenal Gland Neoplasms/therapy ; Blood Pressure ; Epinephrine ; Humans ; Hypertension/diagnosis ; Hypertension/etiology ; Pheochromocytoma/diagnosis ; Pheochromocytoma/therapy
Chemical Substances	Epinephrine (YKH834O4BH)
Language	Hebrew
Publishing date	2021-04-25
Publishing country	Israel
Document type	Journal Article ; Review
ZDB-ID	953872-0
ISSN	0017-7768
ISSN	0017-7768
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Zs.B 291: Show issues

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Article ; Online: Chronic and acute exposure to rotenone reveals distinct Parkinson's disease-related phenotypes in human iPSC-derived peripheral neurons.

Saleh, Mahmood Ali / Amer-Sarsour, Fatima / Berant, Asaf / Pasmanik-Chor, Metsada / Kobo, Hila / Sharabi, Yehonatan / Vatine, Gad D / Ashkenazi, Avraham

Free radical biology & medicine

2024 Volume 213, Page(s) 164–173

Abstract: Peripheral autonomic nervous system (P-ANS) dysfunction is a critical non-motor phenotype of Parkinson's disease (PD). The majority of PD cases are sporadic and lack identified PD-associated genes involved. Epidemiological and animal model studies ... ...

Abstract	Peripheral autonomic nervous system (P-ANS) dysfunction is a critical non-motor phenotype of Parkinson's disease (PD). The majority of PD cases are sporadic and lack identified PD-associated genes involved. Epidemiological and animal model studies suggest an association with pesticides and other environmental toxins. However, the cellular mechanisms underlying toxin induced P-ANS dysfunctions remain unclear. Here, we mapped the global transcriptome changes in human induced pluripotent stem cell (iPSC) derived P-ANS sympathetic neurons during inhibition of the mitochondrial respiratory chain by the PD-related pesticide, rotenone. We revealed distinct transcriptome profiles between acute and chronic exposure to rotenone. In the acute stage, there was a down regulation of specific cation channel genes, known to mediate electrophysiological activity, while in the chronic stage, the human P-ANS neurons exhibited dysregulation of anti-apoptotic and Golgi apparatus-related pathways. Moreover, we identified the sodium voltage-gated channel subunit SCN3A/Nav1.3 as a potential biomarker in human P-ANS neurons associated with PD. Our analysis of the rotenone-altered coding and non-coding transcriptome of human P-ANS neurons may thus provide insight into the pathological signaling events in the sympathetic neurons during PD progression.
MeSH term(s)	Animals ; Humans ; Parkinson Disease/metabolism ; Rotenone/toxicity ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology ; Neurons/metabolism ; Phenotype
Chemical Substances	Rotenone (03L9OT429T)
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2024.01.016
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Zs.A 2109: Show issues

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Article ; Online: Parkinson's disease outside the brain: targeting the autonomic nervous system.

Sharabi, Yehonatan / Vatine, Gad D / Ashkenazi, Avraham

The Lancet. Neurology

2021 Volume 20, Issue 10, Page(s) 868–876

Abstract: Patients with Parkinson's disease present with signs and symptoms of dysregulation of the peripheral autonomic nervous system that can even precede motor deficits. This dysregulation might reflect early pathology and therefore could be targeted for the ... ...

Abstract	Patients with Parkinson's disease present with signs and symptoms of dysregulation of the peripheral autonomic nervous system that can even precede motor deficits. This dysregulation might reflect early pathology and therefore could be targeted for the development of prodromal or diagnostic biomarkers. Only a few objective clinical tests assess disease progression and are used to evaluate the entire spectrum of autonomic dysregulation in patients with Parkinson's disease. However, results from epidemiological studies and findings from new animal models suggest that the dysfunctional autonomic nervous system is a probable route by which Parkinson's disease pathology can spread both to and from the CNS. The autonomic innervation of the gut, heart, and skin is affected by α-synuclein pathology in the early stages of the disease and might initiate α-synuclein spread via the autonomic connectome to the CNS. The development of easy-to-use and reliable clinical tests of autonomic nervous system function seems crucial for early diagnosis, and for developing strategies to stop or prevent neurodegeneration in Parkinson's disease.
MeSH term(s)	Animals ; Autonomic Nervous System/metabolism ; Brain/metabolism ; Heart ; Humans ; Parkinson Disease ; alpha-Synuclein/metabolism
Chemical Substances	alpha-Synuclein
Language	English
Publishing date	2021-09-16
Publishing country	England
Document type	Journal Article ; Review ; Comment
ZDB-ID	2081241-3
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(21)00219-2
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Zs.A 5955: Show issues

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Article: [Re-organization of internal medicine wing in hospitals: a last-ditch effort or the beginning of reform?].

Sharabi, Yehonatan

Harefuah

2014 Volume 153, Issue 3-4, Page(s) 163–4, 239

Abstract: Over the last decade numerous publications have dealt with ongoing changes in the traditional practice of internal medicine. In general, in-hospital medicine has evolved into ambulatory or specialized care. In this volume of Harefuah, Yinon et al. ... ...

Abstract	Over the last decade numerous publications have dealt with ongoing changes in the traditional practice of internal medicine. In general, in-hospital medicine has evolved into ambulatory or specialized care. In this volume of Harefuah, Yinon et al. discuss trends at Shaare-Zedek Medical Center, focusing on the challenge of attracting residents to general internal medicine. Their model addresses local problems, but they have laid the groundwork for a more radical change. They present an evolutionary process that would transform hospital practice to become both more patient-centered and integrative, with an interdisciplinary team that translates the strengths of in-hospital (in- and out-patient care) vs. ambulatory or over-specialized care. Such reform should also include changes in clinical medical education, coupled with research and academic activities that can only take place in hospitals. The health care system is waiting for the next academic medical center that will take the lead in accepting this challenge and spearhead much needed reform.
MeSH term(s)	Academic Medical Centers/organization & administration ; Biomedical Research/organization & administration ; Education, Medical/organization & administration ; Health Care Reform ; Humans ; Internal Medicine/organization & administration ; Internship and Residency/organization & administration ; Israel ; Patient-Centered Care/organization & administration
Language	Hebrew
Publishing date	2014-03
Publishing country	Israel
Document type	Editorial ; English Abstract
ZDB-ID	953872-0
ISSN	0017-7768
ISSN	0017-7768
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Zs.B 291: Show issues

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Article ; Online: Dihydroxyphenylacetaldehyde Lowering Treatment Improves Locomotor and Neurochemical Abnormalities in the Rat Rotenone Model: Relevance to the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson's Disease.

Khashab, Rawan / Gutman-Sharabi, Naama / Shabtai, Zehava / Landau, Regev / Halperin, Reut / Fay-Karmon, Tsviya / Leibowitz, Avshalom / Sharabi, Yehonatan

International journal of molecular sciences

2023 Volume 24, Issue 15

Abstract: The catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease centers on accumulation of 3,4-dihydroxyphenylacetaldehyde (DOPAL) in dopaminergic neurons. To test the hypothesis, it is necessary to reduce DOPAL and assess if this improves ... ...

Abstract	The catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease centers on accumulation of 3,4-dihydroxyphenylacetaldehyde (DOPAL) in dopaminergic neurons. To test the hypothesis, it is necessary to reduce DOPAL and assess if this improves locomotor abnormalities. Systemic administration of rotenone to rats reproduces the motor and central neurochemical abnormalities characterizing Parkinson's disease. In this study, we used the monoamine oxidase inhibitor (MAOI) deprenyl to decrease DOPAL production, with or without the antioxidant N-acetylcysteine (NAC). Adult rats received subcutaneous vehicle, rotenone (2 mg/kg/day via a minipump), or rotenone with deprenyl (5 mg/kg/day i.p.) with or without oral NAC (1 mg/kg/day) for 28 days. Motor function tests included measures of open field activity and rearing. Striatal tissue was assayed for contents of dopamine, DOPAL, and other catechols. Compared to vehicle, rotenone reduced locomotor activity (distance, velocity and rearing); increased tissue DOPAL; and decreased dopamine concentrations and inhibited vesicular sequestration of cytoplasmic dopamine and enzymatic breakdown of cytoplasmic DOPAL by aldehyde dehydrogenase (ALDH), as indicated by DA/DOPAL and DOPAC/DOPAL ratios. The addition of deprenyl to rotenone improved all the locomotor indices, increased dopamine and decreased DOPAL contents, and corrected the rotenone-induced vesicular uptake and ALDH abnormalities. The beneficial effects were augmented when NAC was added to deprenyl. Rotenone evokes locomotor and striatal neurochemical abnormalities found in Parkinson's disease, including DOPAL buildup. Administration of an MAOI attenuates these abnormalities, and NAC augments the beneficial effects. The results indicate a pathogenic role of DOPAL in the rotenone model and suggest that treatment with MAOI+NAC might be beneficial for Parkinson's disease treatment.
MeSH term(s)	Rats ; Animals ; Parkinson Disease/drug therapy ; Parkinson Disease/etiology ; Parkinson Disease/metabolism ; Rotenone/pharmacology ; Dopamine/metabolism ; Selegiline ; Aldehyde Dehydrogenase/metabolism ; Monoamine Oxidase Inhibitors/pharmacology ; Acetylcysteine/pharmacology
Chemical Substances	Rotenone (03L9OT429T) ; Dopamine (VTD58H1Z2X) ; Selegiline (2K1V7GP655) ; Aldehyde Dehydrogenase (EC 1.2.1.3) ; Monoamine Oxidase Inhibitors ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2023-08-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241512522
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Article: High-Fructose Diet Increases Renal

Bier, Ariel / Shapira, Eliyahu / Khasbab, Rawan / Sharabi, Yehonatan / Grossman, Ehud / Leibowitz, Avshalom

Biology

2022 Volume 11, Issue 4

Abstract: Fructose consumption is associated with metabolic syndrome (MeS). Dysregulated lipid metabolism and ectopic lipid accumulation, such as in "fatty liver'', are pivotal components of the syndrome. MeS is also associated with chronic kidney disease (CKD). ... ...

Abstract	Fructose consumption is associated with metabolic syndrome (MeS). Dysregulated lipid metabolism and ectopic lipid accumulation, such as in "fatty liver'', are pivotal components of the syndrome. MeS is also associated with chronic kidney disease (CKD). The aim of this study was to evaluate kidney fructose metabolism and whether the addition of fructose leads to intrarenal fat accumulation. Sprague Dawley rats were fed either normal chow (Ctrl) or a high-fructose diet (HFrD). MeS features such as blood pressure and metabolic parameters in blood were measured. The kidneys were harvested for
Language	English
Publishing date	2022-04-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology11040618
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