phenylephrine-hydrochloride and Parkinson-Disease

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, and in an effort to identify novel therapeutic target for this disease in recent years, human microbiota has attracted much interest. This paper briefly summarizes the main findings concerning the differences of human microbiome across several important mucosal interfaces, including nose, mouth, and gut between PD patients and controls as obtained from a total of 13 studies published since 2015, which covered a total of 943 PD patients and 831 matched controls from 6 countries. Overall, these studies supported the differences of gut microbiota between PD patients and matched controls, while significantly altered bacterial taxa among studies were not identical. Due to relatively limited number of available studies and covered patients, the associations between oral and nasal microbiota and PD remain inconclusive. The therapeutic and diagnostic potentials of gut microbiota for PD are discussed. More well-designed clinical studies recruiting large-scale PD patients are encouraged in future.

Topics: Humans; Intestines; Microbiota; Mouth; Nose; Parkinson Disease

Olfactory dysfunction (OD) in Parkinson's disease (PD) appears several years before the presence of motor disturbance. Olfactory testing has the potential to serve as a tool for early detection of PD, but OD is not specific to PD as it affects up to 20% of the general population. Olfaction includes an orthonasal and a retronasal components; in some forms of OD, retronasal olfactory function is preserved. We aimed to evaluate whether combined testing components allows for discriminating between PD-related OD and non-Parkinsonian OD (NPOD). The objective of this study is to orthonasal and retronasal olfactory function in PD patients and compare them to a NPOD group and to healthy controls. We hypothesized that this combined testing allows to distinguish PD patients from both other groups. We included 32 PD patients, 25 NPOD patients, and 15 healthy controls. Both olfactory components were impaired in PD and NPOD patients, compared with controls; however, NPOD patients had significantly better orthonasal scores than PD patients. Furthermore, the ratio of retronasal/orthonasal score was higher in PD than in both other groups. In the NPOD group, orthonasal and retronasal scores were significantly correlated; no such correlation could be observed in PD patients. In summary, PD patients seem to rely on compensatory mechanisms for flavor perception. Combined orthonasal and retronasal olfactory testing may contribute to differentiate PD patients from patients with NPOD.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Female; Humans; Male; Middle Aged; Nose; Olfaction Disorders; Parkinson Disease; Smell; Trigeminal Nerve

Patients with Parkinson's disease (PD) oftentimes develop olfactory dysfunction in their early stages, converting the nasal environment into a useful source of potential biomarkers. Here we determined the possible application of nasal fluid cells for PD biomarker identification. Thirty PD patients and 13 age-matched healthy controls were enrolled in this study. Messenger RNA levels of selected PD-related genes were monitored through real-time quantitative PCR. Target gene transcripts can be efficiently amplified from the cDNA library from human nasal fluid cell pellets. And subsequent analysis showed both a marked downregulation of parkin transcripts and an upregulation of AIMP2 in PD patients when compared to controls (cutoff value = 1.753 for with 84.2% sensitivity and 84.6% specificity; 0.359 for parkin with 76.7% sensitivity and 76.9 specificity). Moreover, alteration pattern of parkin and AIMP2 in PD was distinct from another neurodegenerative disease, multiple system atrophy. Analysis in both the early and late stages of PD cases reported that parkin levels inversely correlated with PD stages. Our results validate the practical value of easily accessible nasal fluid cells and the utility of both AIMP2 and parkin as potential biomarkers for PD diagnosis.

Topics: Aged; Biomarkers; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Nose; Nuclear Proteins; Parkinson Disease; Sensitivity and Specificity; Ubiquitin-Protein Ligases; Up-Regulation

Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD.. To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals.. Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed.. Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms.. Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Topics: Aged; Case-Control Studies; Cohort Studies; Female; Gastrointestinal Microbiome; Humans; Male; Middle Aged; Nose; Parkinson Disease; REM Sleep Behavior Disorder; RNA, Ribosomal, 16S; RNA, Ribosomal, 18S

Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD.. The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs.. Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (. Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD.

Topics: Administration, Intranasal; Animals; Brain; Disease Models, Animal; Dopamine Agonists; Drug Carriers; Drug Delivery Systems; Lactoferrin; Male; Nanoparticles; Neuroprotective Agents; Nose; Parkinson Disease; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Tetrahydronaphthalenes; Thiophenes; Tissue Distribution

Human nasal chemosensation is mediated by two separate, though interacting sensory pathways: the trigeminal and olfactory systems. Trigeminal sensitivity and olfacto-trigeminal interactions have not yet been well studied in idiopathic Parkinsons disease (IPD).. The aim of this study was to assess odour detection thresholds in elderly IPD patients, and compare them to the odour detection thresholds of healthy controls. Finally, we investigated potential interactions between trigeminal and olfactory sensitivity.. 89 IPD patients aged over 65 and 89 matched healthy participants were enrolled in the study. Odour detection thresholds to 3 stimuli differentially activating olfactory and trigeminal afferents (Phenyl-ethyl alcohol, n-Butanol and Pyridine) were assessed, using an ascending staircase, binary forced-choice procedure.. Detection threshold scores were able to discriminate between elderly IPD and controls. Pyridine was less effective than the two other odorants, suggesting that trigeminal pathway is less impaired than the olfactory system. We found that the detection thresholds were significantly different between IPD patients with good autonomy, and patients with impaired autonomy.

Topics: Aged; Female; Humans; Male; Nose; Odorants; Olfaction Disorders; Olfactory Perception; Olfactory Receptor Neurons; Parkinson Disease; Research Design; Sensory Thresholds; Smell; Trigeminal Nerve

The gut with its variety of microbiota may serve as an etiological origin of diseases. Gut microbes may also play a role in the pathogenesis of diseases beyond their simple nutritional maintenance and support. For example, gut protein aggregation, possibly aided by microbes as well as nasal influences, might be linked to disease that may move to the brain through the vagus nerve. To this end, Braak has offered a "dual-hit" hypothesis that proposes a novel etiology for Parkinson's disease (PD). The hypothesis places the initial origin of the disease in the nose and the gastrointestinal tract (GI) after infection by an unknown pathogen that could aggregate in the gut and then eventually spread to the brain via the autonomic plexuses. Gut health functioning, therefore, may affect brain status and behavior. A protein known as alpha-synuclein accumulates in brains of people with Parkinson's disease that is also present in the GI before the onset of motor symptoms. Therefore, the stomach, previously thought to be a stable mechanism throughout life, might explain some etiological origins of disease. Finally, the vagus nerve of the autonomic system that extends from the brain to the abdomen and exercises both sympathetic and parasympathetic roles might be associated with PD diagnosis along with Lewy body influences.

Topics: Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Models, Biological; Nasal Mucosa; Nose; Parkinson Disease; Vagus Nerve

Parkinson's disease (PD) is associated with neuropathological changes in olfactory and gastrointestinal tissues, and PD patients frequently suffer from hyposmia, hyposalivation, and dysphagia. Since hyposmia and gastrointestinal dysfunction are frequently premotor symptoms, it has been speculated that an external, for example microbial, agent could trigger the pathologic process in the corresponding organs, subsequently spreading to the central nervous system. We recently showed evidence for compositional differences between the fecal microbiota of PD patients and control subjects. In this study, our objective was to explore a possible connection between nasal and oral microbiota and PD.. We compared the oral and nasal bacterial communities of PD patients (oral: n = 72, nasal: n = 69) and control subjects (oral: n = 76, nasal: n = 67) using a 16S rRNA gene amplicon sequencing approach.. Oral and nasal microbiota differed markedly from each other, with no notable similarity within subjects. Oral microbiota of PD patients and control subjects had differences in beta diversity and abundances of individual bacterial taxa. An increase in the abundance of opportunistic oral pathogens was detected in males, both with and without PD. Our data did not reveal convincing differences between the nasal microbiota of control subjects and PD patients.. The oral microbiome deserves additional research regarding its connection to PD and its biomarker potential. The higher abundance of oral pathogens in men underlines the importance of monitoring and promoting male dental health.

Topics: Aged; Female; Humans; Male; Microbiota; Middle Aged; Nasal Cavity; Nose; Parkinson Disease; Sex Factors; Statistics, Nonparametric; Surveys and Questionnaires

To assess nasal cycle, nasal mucosal pH and mucociliary clearance time in patients with Parkinson's disease and healthy control subjects.. Patients with idiopathic Parkinson's disease and healthy control subjects were recruited. Presence of the nasal cycle, nasal mucosa pH and mucociliary clearance time were investigated in all participants.. The study included 27 patients and 24 control subjects. The nasal cycle was present in significantly fewer patients than controls. Nasal pH and mucociliary clearance time were significantly higher in patients than in controls.. Parkinson's disease is associated with alterations in nasal cycle, nasal mucosa pH and mucociliary clearance time. Measurements of these nasal parameters may be useful for the early diagnosis of autonomic and olfactory dysfunction in Parkinson's disease.

Topics: Aged; Case-Control Studies; Demography; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Mucociliary Clearance; Nasal Mucosa; Nose; Parkinson Disease

A patient is presented who used apomorphine, a potent dopamine agonist in the treatment of Parkinson patients. He suffered of severe dystonia of the legs, which did not respond to conservative treatment. The apomorphine was delivered bij intranasal spray. The patient developed an allergic reaction with swollen nose and lips, which disappeared within one day after discontinuation of the treatment. Subcutaneous administration caused no symptoms. Cutaneous challenge with apomorphine caused a positive reaction. We raise the hypothesis that the allergic reaction was due to the binding of apomorphine to certain proteins in cutis or nasal mucosa.

Topics: Administration, Intranasal; Angioedema; Apomorphine; Humans; Injections, Subcutaneous; Lip; Male; Middle Aged; Nose; Parkinson Disease

The pathogenesis of "random" fluctuations in parkinsonian mobility, which are not clearly related to the dosing schedule of levodopa, has not been determined. We rated parkinsonian mobility and assayed plasma dopa in one patient with clinically random fluctuations during two modes of administration of levodopa/carbidopa: (1) standard oral route and (2) direct duodenal delivery via nasoduodenal tube. During oral therapy, mobility varied unpredictably in relation to levodopa dosing, suggesting a clinically random pattern. During duodenal delivery, however, a predictable and dramatic pattern of recurrent end-of-dose deterioration was observed; each intraduodenal levodopa dose resulted in 60 to 90 minutes of benefit. Plasma dopa levels correlated closely with mobility ratings for both modes of administration. Our findings indicate that erratic gastric emptying of levodopa is responsible for apparently "random" oscillations in mobility in at least one patient with Parkinson's disease and probably in others.

Topics: Absorption; Administration, Oral; Dihydroxyphenylalanine; Duodenum; Gastric Emptying; Humans; Intubation; Levodopa; Male; Middle Aged; Nose; Parkinson Disease