Case Report: Concomitant Alzheimer's and Lewy-Related Pathology Extending the Spectrum of Underlying Pathologies of Corticobasal Syndrome

Corticobasal syndrome (CBS) is clinically characterized by progressive asymmetric rigidity and apraxia together with symptoms suggestive of cortical involvement and basal ganglia dysfunction. The spectrum of neurodegenerative diseases that can manifest with CBS is wide. The associations of CBS with corticobasal degeneration, progressive supranuclear palsy, Alzheimer's disease, frontotemporal lobar degenerations, Creutzfeldt–Jakob disease, or diffuse Lewy body pathology have been reported. We describe the case of a 71-year-old woman with CBS. The histopathological examination of brain tissue revealed concomitant pathology corresponding to the limbic stage of Lewy-related pathology and the intermediate stage of Alzheimer's-type pathology. To date, there have been only a few cases with a similar combination of pathology manifesting with the CBS phenotype that have been described in the literature. The extent and distribution of pathological changes in these cases were somewhat different from ours, and significance for clinical manifestation was attributed to only one of these pathologies. In our case, we assume that both types of pathology contributed to the development of the disease, considering the presumed specific spread of both types of pathological processes according to Braak's staging. Our case expands the spectrum of neurodegenerative pathological processes that may manifest with the typical CBS phenotype. Also, it points out the importance of identifying specific biomarkers that would enable more accurate in vivo differential diagnosis and more accurate determination of the underlying pathological processes of these diseases.

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Harnessing PET to track micro- and nanoplastics in vivo

Scientific Reports ◽

10.1038/s41598-021-90929-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Outi Keinänen ◽

Eric J. Dayts ◽

Cindy Rodriguez ◽

Samantha M. Sarrett ◽

James M. Brennan ◽

...

Keyword(s):

Sea Water ◽

Accurate Determination ◽

Nuclear Imaging ◽

Imaging Data ◽

Biodistribution Studies ◽

Positron Emission ◽

20 Nm ◽

Pharmacokinetic Behavior

AbstractThe proliferation of plastics in the environment continues at an alarming rate. Plastic particles have been found to be persistent and ubiquitous pollutants in a variety of environments, including sea water, fresh water, soil, and air. In light of this phenomenon, the scientific and medical communities have become increasingly wary of the dangers posed to human health by chronic exposure to microplastics (< 5 mm diameter) and nanoplastics (< 100 nm diameter). A critical component of the study of the health effects of these pollutants is the accurate determination of their pharmacokinetic behavior in vivo. Herein, we report the first use of molecular imaging to track polystyrene (PS) micro- and nanoplastic particles in mammals. To this end, we have modified PS particles of several sizes—diameters of 20 nm, 220 nm, 1 µm, and 6 µm—with the chelator desferrioxamine (DFO) and radiolabeled these DFO-bearing particles with the positron-emitting radiometal zirconium-89 (89Zr; t1/2 ~ 3.3 d). Subsequently, positron emission tomography (PET) was used to visualize the biodistribution of these radioplastics in C57BL/6J mice at 6, 12, 24, and 48 h after ingestion. The imaging data reveal that the majority of the radioplastics remain in the gastrointestinal tract and are eliminated through the feces by 48 h post-ingestion, a result reinforced by acute biodistribution studies. Ultimately, this work suggests that nuclear imaging—and PET in particular—can be a sensitive and effective tool in the urgent and rapidly growing effort to study the in vivo behavior and potential toxicity of micro- and nanoplastics.

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Sensitive and accurate determination of neurotransmitters from in vivo rat brain microdialysate of Parkinson's disease using in situ ultrasound-assisted derivatization dispersive liquid–liquid microextraction by UHPLC-MS/MS

RSC Advances ◽

10.1039/c6ra23808d ◽

2016 ◽

Vol 6 (110) ◽

pp. 108635-108644 ◽

Cited By ~ 20

Author(s):

Xian-En Zhao ◽

Yongrui He ◽

Ping Yan ◽

Na Wei ◽

Renjun Wang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rat Brain ◽

Accurate Determination ◽

Ultrasound Assisted ◽

Dispersive Liquid Liquid Microextraction ◽

Liquid Microextraction

In situ UA-DDLLME coupled with UHPLC-MS/MS has been developed for simultaneous determination of neurotransmitters and baicalein from Parkinson's disease rats.

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A Corticobasal Syndrome Variant of Familial Creutzfeldt-Jakob Disease with Stroke-Like Onset

Case Reports in Neurological Medicine ◽

10.1155/2016/4167391 ◽

2016 ◽

Vol 2016 ◽

pp. 1-3 ◽

Cited By ~ 3

Author(s):

Ján Necpál ◽

Martin Stelzer ◽

Silvia Koščová ◽

Michal Patarák

Keyword(s):

Corticobasal Degeneration ◽

Early Death ◽

Prnp Gene ◽

Corticobasal Syndrome ◽

Progressive Dementia ◽

Rare Presentation ◽

Alien Hand ◽

Jakob Disease ◽

Neurological Features ◽

Characteristic Features

Creutzfeldt-Jakob disease (CJD) is an untreatable rare human prion disease characterized by rapidly progressive dementia along with various neurological features, including myoclonus and sometimes other movement disorders. The clinical course is typically insidious and rapid, leading to an early death. In general, the most common form is sporadic CJD; however, Slovakia is typical for a high percentage of genetic cases. We present an unusual case report of a 65-year-old man with a sudden, stroke-like onset of motor aphasia with right-sided levodopa unresponsive parkinsonism, alien hand, and other characteristic features of corticobasal syndrome (CBS), with rapid deterioration and death on the 32nd day of the disease. Various neurodegenerative disorders are manifested with CBS as a clinical phenotype, including corticobasal degeneration (CBD), progressive supranuclear palsy, Alzheimer’s disease, and CJD. In our patient, mutation E200K and M129M polymorphism of the PRNP gene and typical immunohistochemical findings pointed to a diagnosis of CJD. The patient’s mother died of CJD many years ago. Several CBS-CJD cases were described, but the atypical stroke-like onset of CBS-CJD, an extremely rare presentation of CJD, makes our case unique worldwide.

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Use of 13C-labeled glucose for estimating glucose oxidation: some design considerations

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.5.1725 ◽

1987 ◽

Vol 63 (5) ◽

pp. 1725-1732 ◽

Cited By ~ 69

Author(s):

J. J. Robert ◽

J. Koziet ◽

D. Chauvet ◽

D. Darmaun ◽

J. F. Desjeux ◽

...

Keyword(s):

Glucose Oxidation ◽

Accurate Determination ◽

Metabolic States ◽

Series Of Experiments ◽

Time Required ◽

Infusion Protocol ◽

The Ideal ◽

Expired Air

Use of 13C-labeled glucose for estimating in vivo rates of glucose oxidation faces several difficulties, particularly the accurate determination of the output of 13C in expired air. In an investigation of wholebody glucose metabolism in healthy adult humans, using a continuous intravenous infusion of D-[U-13C]glucose, we found that a precise estimate of the rate of glucose oxidation was difficult to achieve when the study included infusions with unlabeled glucose. Problems arose 1) as a result of the slow rate at which the 13CO2 released by glucose oxidation reaches an equilibrium in expired air CO2 and 2) due to the contribution to 13CO2 output by the natural 13C in the unlabeled glucose that was infused. In a subsequent series of experiments in healthy young adults, we found that the entry of 13CO2 released by the tissues into the bicarbonate pool and into the expired air is relatively slow and a tracer infusion protocol of approximately 6 h is required for determination of glucose oxidation. This applies when metabolic states are changed acutely during the experiment or when unlabeled glucose is infused. However, for resting subjects in the basal postabsorptive state we confirmed that the time required to achieve a steady state in the 13C enrichment of expired air can be shortened significantly by the use of a NaH13CO3 priming dose, even when this dose varies from the ideal.

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Targeted LC-MS/MS platform for the comprehensive determination of peptides in the kallikrein-kinin system

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-021-03231-9 ◽

2021 ◽

Author(s):

Tanja Gangnus ◽

Bjoern B. Burckhardt

Keyword(s):

Healthy Volunteers ◽

Clinical Symptoms ◽

Matrix Effects ◽

Accurate Determination ◽

Kinin System ◽

Carry Over ◽

Kallikrein Kinin System ◽

The Impact

AbstractThe kallikrein-kinin system (KKS) is involved in many physiological and pathophysiological processes and is assumed to be connected to the development of clinical symptoms of angioedema or COVID-19, among other diseases. However, despite its diverse role in the regulation of physiological and pathophysiological functions, knowledge about the KKS in vivo remains limited. The short half-lives of kinins, their low abundance and structural similarities and the artificial generation of the kinin bradykinin greatly hinder reliable and accurate determination of kinin levels in plasma. To address these issues, a sensitive LC-MS/MS platform for the comprehensive and simultaneous determination of the four active kinins bradykinin, kallidin, des-Arg(9)-bradykinin and des-Arg(10)-kallidin and their major metabolites bradykinin 2-9, bradykinin 1-7 and bradykinin 1-5 was developed. This platform was validated according to the bioanalytical guideline of the US Food and Drug Administration regarding linearity, accuracy, precision, sensitivity, carry-over, recovery, parallelism, matrix effects and stability in plasma of healthy volunteers. The validated platform encompassed a broad calibration curve range from 2.0–15.3 pg/mL (depending on the kinin) up to 1000 pg/mL, covering the expected concentrations in disease states. No source-dependent matrix effects were identified, and suitable stability of the analytes in plasma was observed. The applicability of the developed platform was proven by the determination of endogenous levels in healthy volunteers, whose plasma kinin levels were successfully detected in the low pg/mL range. The established platform facilitates the investigation of kinin-mediated diseases (e.g. angioedema, COVID-19) and enables the assessment of the impact of altered enzyme activities on the formation or degradation of kinins. Graphical abstract

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Effects and Characterization of Some Topical Ointments Based on Vegetal Extracts on Incision, Excision, and Thermal Wound Models

Molecules ◽

10.3390/molecules25225356 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5356

Author(s):

Calin Vasile Andritoiu ◽

Corina Elena Andriescu ◽

Constanta Ibanescu ◽

Cristina Lungu ◽

Bianca Ivanescu ◽

...

Keyword(s):

Wistar Rats ◽

Histopathological Examination ◽

Contraction Rate ◽

Thermal Burn ◽

Arctium Lappa ◽

Ointment Base ◽

The One

The present paper aims to formulate and characterize four phytotherapeutic ointments based on Hippophae fructus, Calendulae flos, Bardanae folium, and Millefolii herba, which are included in a novel ointment base. In order to investigate the healing properties of the ointments, in vivo experimental wound models of linear incision, circular excision, and thermal burn were performed on Wistar rats. Topical treatment was performed daily for 21 days. Determination of the wound contraction rate (WCR), the period of reepithelization, and histopathological examination were achieved. Additionally, for the tested ointments, oscillatory and rotational rheological tests were carried out, and for the extracts, HPLC analysis was performed. The results demonstrate that the tested novel ointments are safe for use and the most effective ointment proved to be the one based on Arctium lappa, followed by that of Calendulae flos.

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In vivo retention of 18F-AV-1451 in corticobasal syndrome

Neurology ◽

10.1212/wnl.0000000000004264 ◽

2017 ◽

Vol 89 (8) ◽

pp. 845-853 ◽

Cited By ~ 51

Author(s):

Ruben Smith ◽

Michael Schöll ◽

Håkan Widner ◽

Danielle van Westen ◽

Per Svenningsson ◽

...

Keyword(s):

Basal Ganglia ◽

Motor Cortex ◽

Cortical Thickness ◽

Corticospinal Tract ◽

Corticobasal Degeneration ◽

Corticobasal Syndrome ◽

Cortical Atrophy ◽

Class Iii ◽

Body Side

Objective:To study the usefulness of 18F-AV-1451 PET in patients with corticobasal syndrome (CBS).Methods:We recruited 8 patients with CBS, 17 controls, 31 patients with Alzheimer disease (AD), and 11 patients with progressive supranuclear palsy (PSP) from the Swedish BioFINDER study. All patients underwent clinical assessment, 18F-AV-1451 PET, MRI, and quantification of β-amyloid pathology. A subset of participants also underwent 18F-FDG-PET.Results:In the 8 patients with CBS, 6 had imaging findings compatible with the corticobasal degeneration pathology and 2 with typical AD pathology. In the 6 patients with CBS without typical AD pathology, there were substantial retentions of 18F-AV-1451 in the motor cortex, corticospinal tract, and basal ganglia contralateral to the most affected body side. These patients could be clearly distinguished from patients with AD dementia or PSP using 18F-AV-1451. However, cortical atrophy was more widespread than the cortical retention of 18F-AV1451 in these CBS cases, and cortical AV-1451 uptake did not correlate with cortical thickness or glucose hypometabolism. These results are in sharp contrast to AD dementia, where 18F-AV-1451 retention was more widespread than cortical atrophy, and correlated well with cortical thickness and hypometabolism.Conclusions:Patients with CBS without typical AD pathology exhibited AV-1451 retention in the motor cortex, corticospinal tract, and basal ganglia contralateral to the affected body side, clearly different from controls and patients with AD dementia or PSP. However, cortical atrophy measured with MRI and decreased 18F-fluorodeoxyglucose uptake were more widespread than 18F-AV-1451 uptake and probably represent earlier, yet less specific, markers of CBS.Classification of evidence:This study provides Class III evidence that 18F-AV-1451 PET distinguishes between CBS and AD or PSP.

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Evaluation of the Healing Effect of Ointments Based on Bee Products on Cutaneous Lesions in Wistar Rats

Pharmaceuticals ◽

10.3390/ph14111146 ◽

2021 ◽

Vol 14 (11) ◽

pp. 1146

Author(s):

Calin Vasile Andritoiu ◽

Cristina Lungu ◽

Maricel Danu ◽

Bianca Ivanescu ◽

Corina Elena Andriescu ◽

...

Keyword(s):

Histopathological Examination ◽

Experimental Models ◽

Point Of View ◽

Wound Contraction ◽

Cutaneous Lesions ◽

Beneficial Effects ◽

Drone Brood ◽

Histological Architecture

The wound-healing capacity of ointments based on bee products was investigated in vivo on three experimental models of incision, excision and heat burn. For this purpose, four ointments were prepared with propolis, honey, apilarnil (drone brood homogenate) and a mixture of these three apitherapy products. The ointments were applied topically for 21 days. Clinical and macroscopic evaluation was performed throughout the experiment, with the recording of the re-epithelialization period and determination of the wound contraction rate on days 6 and 9. The histopathological examination was performed on days 1, 3, 12 and 21 of the treatment. The topical formulations were also characterized from a rheological point of view in order to verify their stability. HPLC analysis of propolis revealed the presence of phenolic compounds, particularly ferulic acid and p-coumaric which were found in high amounts. All ointments had beneficial effects on wound contraction and the re-epithelialization period, but the most significant result, both macroscopically and especially in terms of histological architecture, was presented by the ointment that contains all three apitherapy products, due to their synergistic effect.

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Hemodynamic forces can be accurately measured in vivo with optical tweezers

Molecular Biology of the Cell ◽

10.1091/mbc.e17-06-0382 ◽

2017 ◽

Vol 28 (23) ◽

pp. 3252-3260 ◽

Cited By ~ 12

Author(s):

Sébastien Harlepp ◽

Fabrice Thalmann ◽

Gautier Follain ◽

Jacky G. Goetz

Keyword(s):

Optical Tweezers ◽

Cell Biology ◽

Accurate Determination ◽

Force Measurements ◽

Hemodynamic Forces ◽

Drag Forces ◽

Measured Flow ◽

Living Organisms

Force sensing and generation at the tissue and cellular scale is central to many biological events. There is a growing interest in modern cell biology for methods enabling force measurements in vivo. Optical trapping allows noninvasive probing of piconewton forces and thus emerged as a promising mean for assessing biomechanics in vivo. Nevertheless, the main obstacles lie in the accurate determination of the trap stiffness in heterogeneous living organisms, at any position where the trap is used. A proper calibration of the trap stiffness is thus required for performing accurate and reliable force measurements in vivo. Here we introduce a method that overcomes these difficulties by accurately measuring hemodynamic profiles in order to calibrate the trap stiffness. Doing so, and using numerical methods to assess the accuracy of the experimental data, we measured flow profiles and drag forces imposed to trapped red blood cells of living zebrafish embryos. Using treatments enabling blood flow tuning, we demonstrated that such a method is powerful in measuring hemodynamic forces in vivo with accuracy and confidence. Altogether this study demonstrates the power of optical tweezing in measuring low range hemodynamic forces in vivo and offers an unprecedented tool in both cell and developmental biology.

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Using Indentation and Intra-Vascular Ultrasound to Measure Arterial Response

MRS Proceedings ◽

10.1557/proc-662-mm2.4 ◽

2000 ◽

Vol 662 ◽

Author(s):

P.M. Anderson ◽

E.N. Glaser ◽

A.I. Veress ◽

G.M. Pharr ◽

D.G. Vince ◽

...

Keyword(s):

Mechanical Properties ◽

Contact Point ◽

Accurate Determination ◽

Initial Contact ◽

Vascular Ultrasound ◽

Internal Dissipation ◽

Microindentation Technique ◽

Micro Indentation

AbstractTwo alternatives to standard tensile testing of arteries are discussed. The first involves inflation of arteries and simultaneous measurement of radial displacement with intra-vascular ultrasound (IVUS). The second involves the measurement of load versus displacement during micro-indentation of the intimal surface. The IVUS technique is used to study the nonlinear stiffening of porcine coronaries during inflation and, ultimately, it may provide a method to determine mechanical properties in vivo. Processing of the IVUS data relies on accurate determination of the luminal/intimal and medial/advential boundaries during inflation. The microindentation technique is used to study the effect of loading rate on tissue stiffness, recovery, and internal dissipation. Ultimately, this technique may provide a method to measure local mechanical properties in the vicinity of an atherosclerotic plaque, for example. Accurate determination of the initial contact point between the indenter and intima is required, however. The techniques appear to successfully capture significant, nonlinear, time-dependent properties of arterial tissue.

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