Neuroprotective effects of hydrogen sulfide on Parkinson’s disease rat models

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra (SN). The present study was designed to examine the therapeutic effect of hydrogen sulfide (H₂S, a novel biological gas) on PD. The endogenous H₂S level was markedly reduced in the SN in a 6‐hydroxydopamine (6‐OHDA)‐induced PD rat model. Systemic administration of NaHS (an H₂S donor) dramatically reversed the progression of movement dysfunction, loss of tyrosine‐hydroxylase positive neurons in the SN and the elevated malondialdehyde level in injured striatum in the 6‐OHDA‐induced PD model. H₂S specifically inhibited 6‐OHDA evoked NADPH oxidase activation and oxygen consumption. Similarly, administration of NaHS also prevented the development of PD induced by rotenone. NaHS treatment inhibited microglial activation in the SN and accumulation of pro‐inflammatory factors (e.g. TNF‐α and nitric oxide) in the striatum via NF‐κB pathway. Moreover, significantly less neurotoxicity was found in neurons treated with the conditioned medium from microglia incubated with both NaHS and rotenone compared to that with rotenone only, suggesting that the therapeutic effect of NaHS was, at least partially, secondary to its suppression of microglial activation. In summary, we demonstrate for the first time that H₂S may serve as a neuroprotectant to treat and prevent neurotoxin‐induced neurodegeneration via multiple mechanisms including anti‐oxidative stress, anti‐inflammation and metabolic inhibition and therefore has potential therapeutic value for treatment of PD.     

Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Adult human endometrial derived stem cells (HEDSC), a readily obtainable type of mesenchymal stem‐like cell, were used to generate dopaminergic cells and for transplantation. Cells expressing CD90, platelet derived growth factor (PDGF)‐Rβ and CD146 but not CD45 or CD31 were differentiated in vitro into dopaminergic neurons that exhibited axon projections, pyramidal cell bodies and dendritic projections that recapitulate synapse formation; these cells also expressed the neural marker nestin and tyrosine hydroxylase, the rate‐limiting enzyme in dopamine synthesis. Whole cell patch clamp recording identified G‐protein coupled inwardly rectifying potassium current 2 channels characteristic of central neurons. A 1‐methyl 4‐phenyl 1,2,3,6‐tetrahydro pyridine induced animal model of PD was used to demonstrate the ability of labelled HEDSC to engraft, migrate to the site of lesion, differentiate in vivo and significantly increase striatal dopamine and dopamine metabolite concentrations. HEDSC are a highly inducible source of allogenic stem cells that rescue dopamine concentrations in an immunocompetent PD mouse model.     

Nitric oxide synthase regulation and diversity: Implications in Parkinson’s disease

Nitric oxide (NO) is a janus faced chemical messenger, which, in the recent years, has been the focus of neurobiologists for its involvement in neurodegenerative disorders in particular, Parkinson's disease (PD). Nitric oxide synthase, the key enzyme involved in NO production exists in three known isoforms. The neuronal and inducible isoforms have been implicated in the pathogenesis of PD. These enzymes are subject to complex expressional and functional regulation involving mRNA diversity, phosphorylation and protein interaction. In the recent years, mRNA diversity and polymorphisms have been identified in the NOS isoforms. Some of these genetic variations have been associated with PD, indicating an etiological role for the NOS genes. This review mainly focuses on the NOS genes - their differential regulation and genetic heterogeneity, highlighting their significance in the pathobiology of PD.     

Association between oral health, cognitive impairment and oral health-related quality of life

doi: 10.1111/j.1741‐2358.2011.00542.x
Association between oral health, cognitive impairment and oral health–related quality of life Objective: Investigating oral health–related quality of life’s (OH‐QoL) relationship with cognitive state. Background: Oral health affects OH‐QoL and is poor in institutionalised and cognitively impaired people. Material and Methods: This was a cross‐sectional study involving 215 institutionalised elderly (82.9 mean age), who were interviewed, examined and cognitively screened using the Pfeiffer test. Results: Mean GOHAI score was 53.1; only 43.7% of the participants reported having a good OH‐QoL. Needing help with dressing or washing (OR 2.14; p = 0.004), having one to nine teeth (OR 4.65; p ≥ 0.001), eight or less occluding pairs (OR 2.74; p = 0.002), one to three caries (OR 1.85; p = 0.005) and being cognitive impaired (OR 0.54; p = 0.034) were significantly associated with altered OH‐QoL in bi‐variate analysis. Being edentulous (OR 3.18; p = 0.0046), having 1–9 teeth (OR 2.62; p = 0.056) and presenting mild cognitive impairment (MCI) (OR 0.32; p = 0.016) appeared as predictive variables in logistic regression for having an altered OH‐QoL. Conclusions: Participants having MCI had significantly better GOHAI score than cognitively normal residents. Performing cognitive screening parallel to applying any OH‐QoL instrument would make the results more reliable and would benefit cognitively impaired people.     

Factors associated with the oral health-related quality of life in elderly persons in dental clinic: validation of a Mandarin Chinese version of GOHAI

Gerodontology 2011; doi: 10.1111/j.1741‐2358.2009.00360.x
Factors associated with the oral health‐related quality of life in elderly persons in dental clinic: validation of a Mandarin Chinese version of GOHAI Objectives: To translate the original English version of Geriatric Oral Health Assessment Index (GOHAI) into Mandarin Chinese and assess its reliability and validity for use among the elderly in inland China and to explore the factors associated with oral health‐related quality of life (OHRQoL). Methods: The original English version of GOHAI was translated, back‐translated and cross‐culturally adapted. The psychometric properties of GOHAI‐M were assessed in a sample of 263 people aged 60 years and over and OHRQoL was examined in 221 subjects using GOHAI‐M. Multiple regression analysis was conducted. Results: Internal consistency of the GOHAI‐M was excellent (Cronbach’s α : 0.81). Split‐half reliability coefficient was 0.80, and item‐scale correlation coefficient ranged from 0.25 to 0.71. Self‐rated oral health was significantly associated with OHRQoL (r_s = 0.505, p < 0.01). The relation coefficient between GOHAI‐M and self‐perceived need for dental treatment and number of missing teeth were 0.231 and ?0.653, respectively (p < 0.05). Multiple regression analysis found that better OHRQoL was significantly associated with better self‐ratings of oral health (β = 0.497, p = 0.01), number of missing teeth (β = 0.187, p < 0.01) and life satisfaction (β = 0.132, p < 0.05). Conclusion: The Mandarin Chinese version of GOHAI demonstrates acceptable reliability and validity. OHRQoL is associated with self‐rated oral health, number of missing teeth and satisfaction with life.     

Informing the debate on oral health care for older people: a qualitative study of older people’s views on oral health and oral health care

doi: 10.1111/j.1741‐2358.2009.00274.x
Informing the debate on oral health care for older people: a qualitative study of older people’s views on oral health and oral health care Background: Older people represent a growing and diverse section of the population. As age increases, people are more likely to experience health and mobility problems and be at higher risk of developing oral disease. Nevertheless, few older people utilise primary oral healthcare services. It is therefore important to understand the value older people place on oral health and dental services to inform providers and planners of oral health care. This research was conducted as part of a study to identify potential ways of minimising barriers to oral health care in older people. Objectives: To explore perceptions of oral health and oral healthcare services amongst older people living in a socially deprived inner city area and how these are related to service utilisation. Methods: A qualitative approach was utilised to explore the range of issues related to older people’s perceptions of oral health and their views on health care. This involved a combination of focus groups and semi‐structured individual interviews with older people and their carers. Data analysis was conducted using the Framework approach. Results:

• ? Response: Thirty‐nine older people and/or their carers participated in focus groups.
• ? Oral health perception: Oral health was associated with the presence of natural teeth, the absence of pain, practical/social functioning, preferably supported by positive assessment by a dentist.
• ? Oral health life‐course: Older people have a long and complex dental history. Past negative experiences with oral health care, especially in childhood, strongly influenced present attitudes towards dentistry and dental personnel.
• ? Citizenship and right to health care: There was a strong perception that, as ‘British citizens’, older people should have a right to free health care and that the National Health Service (NHS) should support them in this phase of their life.

Conclusions: The oral health life‐course of older people is an important influence on their perceptions of oral health and dental attendance. They consider oral health of importance and place great emphasis on their citizenship and rights of access to state funded oral health care. This raises important issues for the funding and delivery of NHS oral health care for older people.     

Oral health behind bars: a study of oral disease and its impact on the life quality of an older prison population

Objective: The principal aims of this study were to report on the prevalence of oral disease and its impact on the life quality of older (aged 60 and above) prisoners at Hong Kong SAR's elderly detention centre, China. Design: A cross‐sectional epidemiological survey involving clinical oral examinations and face‐to‐face interviews with 64 older prisoners at the centre. Clinical oral examinations were carried out following WHO criteria. The impact of oral health on life quality was assessed using the 14‐item Oral Health Impact Profile measure, OHIP‐14 Results: The prevalence of oral disease was high, the mean DMFT was 22.5 (SD 10.6) and 40% (18) of the dentate prisoners had shallow or deep periodontal pockets. Most (75%, 48) were in need of prosthetic treatment. Over half the prisoners experienced one or more oral health impacts on life quality during the previous year. This was associated with socio‐demographic factors: employment status prior to incarceration (P<0.01), oral health behaviour: smoking habits (P<0.01) and clinical oral health status: DMFT (P<0.05) and prosthetic need (P<0.05). Conclusion: Among inmates at Hong Kong's elderly detention centre, the prevalence of oral disease was high and the impact of oral health on their life quality was substantial. The impact of oral health on the life quality of the older prisoners was associated with prisoners socio‐demographic background, oral health behaviour and oral health status.     

Role of post-translational modifications on the alpha-synuclein aggregation-related pathogenesis of Parkinson’s disease

Together with neuronal loss, the existence of insoluble inclusions of alpha-synuclein (α-syn) in the brain is widely accepted as a hallmark of synucleinopathies including Parkinson’s disease (PD), multiple system atrophy, and dementia with Lewy body. Because the α-syn aggregates are deeply involved in the pathogenesis, there have been many attempts to demonstrate the mechanism of the aggregation and its potential causative factors including post-translational modifications (PTMs). Although no concrete conclusions have been made based on the previous study results, growing evidence suggests that modifications such as phosphorylation and ubiquitination can alter α-syn characteristics to have certain effects on the aggregation process in PD; either facilitating or inhibiting fibrillization. In the present work, we reviewed studies showing the significant impacts of PTMs on α-syn aggregation. Furthermore, the PTMs modulating α-syn aggregation-induced cell death have been discussed.      

The importance of oral health to older people's quality of life

Objectives This study was designed to determine whether older people perceive oral health as being important to Quality of Life (QoL) and if so, to identify the most important ways in which their lives are affected. In addition, to identify if subgroups of older people perceive its importance differently. Design: Nationwide qualitative face to face interviews with older people were carried out utilising the Office for National Statistics Omnibus survey in Great Britain. Subjects and methods 454 adults aged 65 or older took part in this study, part of a random probability sample of adults in the UK. Setting Respondents were interviewed in their homes. Results 72% (313) perceived their oral health status as important to their QoL through a variety of physical, social and psychological ways. Most frequently its impact on function: eating (29%, 126) and symptoms: comfort (14%, 59) were considered most important. Gender and social class variations were apparent (P<0.05). Conclusion Older people perceive oral health as being important to life quality in a variety of different ways. There are significant social class and gender variations which must be taken into consideration when assessing oral health needs of older people.     

A cross-sectional study of oral health and oral health-related quality of life among frail elderly persons on admission to a special oral health care programme in Copenhagen City, Denmark

doi: 10.1111/j.1741‐2358.2011.00486.x
A cross‐sectional study of oral health and oral health‐related quality of life among frail elderly persons on admission to a special oral health care programme in Copenhagen City, Denmark Aim: To describe the oral health and the oral‐health‐related quality of life (OHRQoL) of citizens in Copenhagen City on admission to a specific oral health‐care programme for disabled elderly persons. Further, to analyse how various factors influence the oral health and the OHRQoL among these patients. Methods: A cross‐sectional study of 189 persons (average 85 years) consecutively admitted to a special oral health‐care programme. Clinical data and data from interviews comprising social factors, life‐style, dental visit habits, oral hygiene practices and self‐perceived oral health were collected. A modified index on perceived dysfunction, discomfort and disability due to oral disorders was used. Results: Sixty‐eight per cent had natural teeth, among those 57% had decayed teeth and two out of three wore dentures. Smoking habits influence the number of teeth present and the OHRQoL (p < 0.05) of the patients. Edentulousness, decayed teeth, and presence of dentures did not seem to cause OHRQoL problems, while higher OHRQoL scores (more problems) were reported by those with 1–9 teeth and tooth mobility. Conclusion: OHRQoL of these patients can be increased by removal of loose teeth and provision of dentures to those with very few teeth rather than focus on traditional caries treatment.     

The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson’s disease

The concentration of neuromelanin (NM) in substantia nigra pars compacta (SNPC) has been measured in male and female normal subjects at different ages in the range 1–97 years old and in SNPC of parkinsonian patients. A very similar age trend of NM concentration was found in both sexes. In the first year of life NM was not detectable, between 10 and 20 years the NM levels were 0.3–0.8 μg/mg of SNPC, between 20 and 50 years were 0.8–2.3 μg/mg SNPC and between 50 and 90 were 2.3–3.7 μg/mg of SNPC. In parkinsonian subjects, the NM levels were 1.2–1.5 μg/mg of SNPC, which is less than 50% with respect to the age-matched controls. These data demonstrate a continuous NM accumulation in SNPC neurons during aging, the presence of large amounts of NM in SNPC and severe depletion of NM in Parkinson’s disease.     

Oral health‐related quality of life in patients receiving home‐care nursing: associations with aspects of dental status and xerostomia

doi:10.1111/j.1741‐2358.2009.00344.x
Oral health‐related quality of life in patients receiving home‐care nursing: associations with aspects of dental status and xerostomia Objective: To explore the differences in oral status, dental attendance and dry mouth problems between patients with long‐term disease with high and low scores on Oral Health Impact Profile 14 (OHIP 14) and how patients cope with oral problems such as xerostomia and a reduced ability to brush their teeth. Background: There has been a lack of studies of oral health and oral health‐related quality of life in the frail elderly within the community services. Materials and methods: A cross‐sectional questionnaire study was conducted with 137 patients receiving home‐care nursing. Structured interviews were conducted by student nurses using OHIP‐14, items from the Xerostomia Inventory and questions concerning dental visit habits, brushing of teeth and data from medical records. Results: Eighty‐three per cent of patients had natural teeth and 60% had only natural teeth. ‘Natural teeth only’ indicated a low score on OHIP‐14. Problems with brushing and items concerning xerostomia indicated a high score on OHIP‐14. Contrasts in the assessments concerning brushing of teeth and xerostomia indicated low priority from the patients themselves and the nursing staff. Conclusion: Community health services should focus upon oral health. Both patients and nurses should assess the need for regular brushing of teeth carried out by home‐care nurses. Assessment and treatment of dry mouth problems should have higher priority.     

Factors associated with negative self-perception of oral health among elderly people in a Brazilian community

Objective: Self‐perception of oral health is an important measurement for assessing the health and quality of life of elderly people. The aim of this study was to analyse associations between negative self‐perception of oral health and poor oral state, socio‐demographic variables, depression and use of medications. Method: In this cross‐sectional study, elderly people aged 60 to 74 years living in the urban zone of a city in southern Brazil were interviewed and examined. Functionally dependent individuals were excluded. Self‐perception was measured using the General Oral Health Assessment Index, and scores of 30 points or less were considered to represent negative perception. The physical, social and worry dimensions of this indicator were also analysed. Results: Two hundred and sixty‐seven elderly people (mean age 66.5 years, 59.9% female) were included in the study. Most of them had had little schooling. Negative self‐perception was identified in 18.7%, although none of the poor oral state was associated with this variable. In multivariate analysis, negative self‐perception was associated with female gender and depression. The women presented significantly lower means in the three dimensions analysed and individuals with depression, in the physical and social dimensions. Poor oral health (edentulism and absence of posterior occlusion) were associated with the physical dimension. Conclusion: Negative self‐perception of oral health was associated with gender and depression, but not with poor oral health. Therefore, gender and the presence of depression are factors to be taken into account in assessments involving this age group.