Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that involves the autoreactive T-cell attack on axonal myelin sheath. Lesions or plaques formed as a result of repeated damage and repair mechanisms lead to impaired relay of electrical impulses along the nerve, manifesting as clinical symptoms of MS. Evidence from studies in experimental autoimmune encephalomyelitis (EAE) models of MS strongly suggests that mitochondrial dysfunction presents at the onset of disease and throughout the disease course. The aim of this study was to determine if mitochondrial dysfunction occurs before clinical symptoms arise, and whether this is confined to the CNS. EAE was induced in C57B/L6 mice, and citrate synthase and mitochondrial respiratory chain (MRC) complex I-IV activities were assayed at presymptomatic (3 or 10 days post first immunisation (3 or 10 DPI)) and asymptomatic (17 days post first immunisation (17 DPI) time-points in central nervous system (CNS; spinal cord) and peripheral (liver and jaw muscle) tissues. Samples from animals immunised with myelin oligodendrocyte glycoprotein (MOG) as EAE models were compared with control animals immunised with adjuvant (ADJ) only. Significant changes in MOG compared to control ADJ animals in MRC complex I activity occurred only at presymptomatic stages, with an increase in the spinal cord at 10 DPI (87.9%), an increase at 3 DPI (25.6%) and decrease at 10 DPI (22.3%) in the jaw muscle, and an increase in the liver at 10 DPI (71.5%). MRC complex II/III activity changes occurred at presymptomatic and the asymptomatic stages of the disease, with a decrease occurring in the spinal cord at 3 DPI (87.6%) and an increase at 17 DPI (36.7%), increase in the jaw muscle at 10 DPI (25.4%), and an increase at 3 DPI (75.2%) and decrease at 17 DPI (95.7%) in the liver. Citrate synthase activity was also significantly decreased at 10 DPI (27.3%) in the liver. No significant changes were observed in complex IV across all three tissues assayed. Our findings reveal evidence that mitochondrial dysfunction is present at the asymptomatic stages in the EAE model of MS, and that the changes in MRC enzyme activities are tissue-specific and are not confined to the CNS.

Multiple sclerosis and oral health: an update.

Multiple sclerosis is a chronic, neurodegenerative disease seen in 69.1 per 100,000 person-years in the world. As multiple sclerosis and periodontal disease both have an inflammatory origin, dental professionals should be aware of the link between these two diseases. In patients unable to carry out effective oral hygiene, dental treatment should be done by dental hygienists and/or dentists to prevent dental caries and periodontal disease. It is hoped that by identifying multiple sclerosis patients in dental clinics, the required support and treatment could be provided to these patients to improve their quality of life and that dental professionals would feel comfortable treating patients with multiple sclerosis.

Increased Risk for Acute Periapical Abscesses in Multiple Sclerosis Patients and the Possible Association with Epstein-Barr Virus.

INTRODUCTION: Multiple sclerosis (MS) is a severe inflammatory neuroimmune degenerative condition affecting more than 2 million individuals worldwide. The purpose of this study was to assess the prevalence of acute periapical abscesses in patients with MS and to evaluate whether acute periapical abscesses (PAs) are more likely to affect patients who were previously infected by Epstein-Barr virus (EBV). METHODS: Integrated data of hospital patients were used. Data from the corresponding diagnosis codes for MS and acute PA were retrieved by querying the appropriate International Classification of Diseases, Tenth Revision codes in the database. RESULTS: Of the total hospital patient population, 0.18% were diagnosed with a history of MS. Females were more affected than males 3.25-fold. Whites were more affected than African Americans 6-fold. Whites were more affected than African Americans combined with other ethnicities 3.6-fold. The odds ratio (OR) for acute PAs in patients with a history of MS was 2.2 (P < .0001). After adjustment for diabetes mellitus comorbidity, the OR for acute PAs in patients with a history of MS was 2.6. After adjustment for cardiovascular disease comorbidity, the OR for acute PAs in patients with a history of MS was 1.27. Of the patients who presented with PAs, 0.2% were diagnosed with a history of EBV infection. The OR was 3.98, and the difference in prevalence was statistically significant (P < .0001). CONCLUSIONS: Under the conditions of this cross-sectional study, it appears that the prevalence of acute PAs is higher in patients with MS and that EBV may play a role.

Anti-phospholipid Antibodies and Smoking: An Overview.

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and anti-ß2 glycoprotein-I antibodies. Antiphospholipid syndrome can occur on its own or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). A connection between cigarette smoking and anti-phospholipid antibodies (aPL) was first reported in the late1980s. Systemic lupus erythematosus patients with aPL are more likely to be smokers than those without aPL. These patients have a particularly high frequency of vascular events. Recently, a potential link between periodontitis, tobacco, and aPL has been proposed. Research has also suggested that periodontitis and Porphyromonas gingivalis infection are associated with citrullination through the action of peptidylarginine deiminase. A strong correlation between smoking and the presence of citrillunated autoantibodies, which are characteristic of rheumatoid arthritis, has also been observed. While many studies have investigated possible links between infection and aPL in patients with autoimmune diseases, the association of smoking with aPL has not been systematically examined. The fact that both aPL and tobacco are risk factors for thrombosis has complicated efforts to evaluate these factors separately. Also, there has been great variability in measurement techniques, and laboratories lack routine methods for differentiating transient and persistent aPL; both of these factors can make interpretation of autoantibody results quite challenging. This review summarizes the clinical evidence supporting a posited link between aPL and smoking, both in patients with a systemic autoimmune disease and in patients with other medical conditions.

Dental amalgam and multiple sclerosis: a case-control study in Montreal, Canada.

BACKGROUND: The aetiology of multiple sclerosis (MS) remains poorly understood. Dental amalgams containing mercury have recently been suggested as a possible risk factor for MS. METHODS: In a case-control study conducted between 1991 and 1994, we interviewed a total of 143 MS patients and 128 controls, to obtain information on socio-demographic characteristics and the number of dental amalgams and the time since installation based on dentists' records. RESULTS: Neither the number nor the duration of exposure to amalgams supported an increased risk of MS. After adjustment for age, sex, smoking, and education those who had more than 15 fillings had an odds ratio (OR) of 2.57 (95% CI: 0.78-8.54) compared to those who had none; for individuals whose first amalgam was inserted more than 15 years prior to the study, we found an OR of 1.34 (95% CI: 0.38-4.72). CONCLUSIONS: Although a suggestive elevated risk was found for those individuals with a large number of dental amalgams, and for a long period of time, the difference between cases and controls was not statistically significant.

Immunological basis for the therapy of multiple sclerosis.

Much progress is currently being made in different areas of clinical and experimental multiple sclerosis (MS) research, including epidemiology and genetics, immunological mechanisms, possible role of infectious agents, imaging, clinical trials and development of new therapeutic agents. This article reviews some principles of MS pathogenesis and immunotherapy.

Multiple sclerosis and oral care.

Multiple sclerosis is a complex neurological condition affecting sensory and motor nerve transmission. Its progression and symptoms are unpredictable and vary from person to person as well as over time. Common early symptoms include visual disturbances, facial pain or trigeminal neuralgia and paraesthesia or numbness of feet, legs, hands and arms. These, plus symptoms of spasticity, spasms, tremor, fatigue, depression and progressive disability, impact on the individual's ability to maintain oral health, cope with dental treatment and access dental services. Also, many of the medications used in the symptomatic management of the condition have the potential to cause dry mouth and associated oral disease. There is no cure for multiple sclerosis, and treatment focuses on prevention of disability and maintenance of quality of life. Increasingly a multi-disciplinary team approach is used where the individual, if appropriate his/her carer, and the specialist nurse are key figures. The dental team plays an essential role in ensuring that oral health impacts positively on general health.

Personalization of multiple sclerosis treatments: using the chelation therapy approach.

Though Multiple Sclerosis (MS) sufferers are probably genetically predisposed, toxic metal poisoning (TMP) does seem an increasingly likely environmental trigger. The technique for measuring and clearing TMP was chelation therapy using ethylene-diamine-tetracetic acid (EDTA), which revealed aluminum accumulation in both cases. The first patient, initially benefiting from removing dental fillings that had leaked mercury, also showed gadolinium accumulation from scan contrast medium, and a genomic deficiency of glutathione transferase M1. Glutathione production was impaired and hence also liver detoxification functions. The personal protocol involved glutathione administration and deutrosulfazyme to enhance oxygenation and alleviate oxidative stress. As aluminum began to clear with EDTA infusion, the extracellular/intracellular water ratio was carefully monitored, and carbohydrates limited. In the second case, aluminum poisoning responded to EDTA chelation therapy with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), multivitamins, and glutathione administration, again followed by deutrosulfazyme, water ratio control, and dietary correction. The two personalized protocols presented here tend to confirm the hypothesis of TMP as an environmental or iatrogenic trigger for MS, especially when inadequate detoxification lies at the root. Cleansing by chelation therapy, properly understood, can be efficacious, especially bearing in mind the altered cellular water ratio.

Revolutionary advances in the prevention of demyelinating diseases.

This collective review focuses on three major factors that influence the incidences of multiple sclerosis (MS) to include ultraviolet radiation (UVR), vitamin D3 supplementation, and vitamin D receptor gene (VDRG) polymorphisms. In general, the rate of MS increases with latitude. Individuals tend to carry their original risk with them if they migrate to a different latitude after adolescence. It is important to emphasize that UVR increases the synthesis of vitamin D3, which has a known immune suppressant action via the VDRG. Clinical studies have pointed out that vitamin D deficiency may exacerbate the development of MS. Because vitamin D3 is an inhibitor of MS, providing supplemental D3 for individuals at risk for MS should be mandatory. There is unanimous agreement that exposure to UVR and vitamin D3 supplementation can reduce the incidence of MS. Although there is debate regarding the association of MS with the use of silver mercury fillings, there is general agreement throughout the world that there is a need for dental-patient informed-consent brochures for all dentists who use dental restoration materials. For the dentists who remove silver mercury amalgam from their patients, there is a uniform international agreement that all dental offices should use reliable debris collection devices that prevent pollution of our environment.

Comments on the article "the toxicology of mercury and its chemical compounds" by Clarkson and Magos (2006).

Clarkson and Magos (2006) provide their perspectives on the toxicology of mercury vapor and dental amalgam. As scientists who are involved in preparing a German federal guideline regarding dental amalgam, we welcome additional scientific data on this issue. However, Clarkson and Magos do not present all the relevant studies in their review. The additional data provided here show that: (a) Dental amalgam is the main source of human total mercury body burden, because individuals with amalgam have 2-12 times more mercury in their body tissues compared to individuals without amalgam; (b) there is not necessarily a correlation between mercury levels in blood, urine, or hair and in body tissues, and none of the parameters correlate with severity of symptoms; (c) the half-life of mercury deposits in brain and bone tissues could last from several years to decades, and thus mercury accumulates over time of exposure; (d) mercury, in particular mercury vapor, is known to be the most toxic nonradioactive element, and is toxic even in very low doses, and (e) some studies which conclude that amalgam fillings are safe for human beings have important methodogical flaws. Therefore, they have no value for assessing the safety of amalgam.

Multiple sclerosis and prostate cancer: what do their similar geographies suggest?

Mortality rates from multiple sclerosis show a well-known north-south gradient, both within the United States and internationally. Mortality rates from prostate cancer show a similar gradient and are significantly correlated with multiple sclerosis (MS) mortality and MS prevalence. This finding adds prostate cancer to the set of diseases whose geographic distributions are significantly correlated with MS and whose members include colon cancer, dental caries, and Parkinson's disease. Review of the literature indicates that these clinically dissimilar diseases may share an aberration in vitamin (hormone) D. Recent evidence demonstrating a multi-faceted role for vitamin D in immunoregulation suggests that a vitamin D aberration may also contribute to the etiology of MS. A vitamin D hypothesis can illuminate several unexplained features of the epidemiology of MS and suggests opportunities for epidemiologic, laboratory, and clinical investigation.

Multiple sclerosis and dental amalgam: case-control study in Ferrara, Italy.

Dental amalgam fillings containing mercury have been suggested as a possible risk factor for multiple sclerosis (MS). In the context of a wider program of investigation into environmental risk factors and MS, we conducted a case-control comparison to investigate the alleged association between MS, dental caries, and amalgam fillings. We included 132 MS patients with onset during the last 16 years and 423 controls, matched to cases for sex, age and residence. Data were collected by a personal interview conducted by trained doctors. Cases and controls gave informed consent. Although we report a trend toward a higher number of dental fillings in cases than controls, odds ratios for subjects with exposures of different duration and with different numbers of amalgam fillings were not statistically significant. This case-control study failed to demonstrate an association between either the number of dental amalgam fillings or the duration of exposure to mercury amalgam and MS.

Human adjuvant disease: presentation as a multiple sclerosis-like syndrome.

Twenty-six women had a systemic disease with central nervous system (CNS) involvement at a mean age of 39.2 years (range, 23 to 64 years) after receiving silicone breast implants (n = 25) or silicone fluid injections into breasts (n = 1). The median latency period between breast surgery and onset of symptoms was 5.71 years (range, 3 months to 15 years). All patients had evidence of disseminated CNS lesions; 20 patients also had evidence of peripheral neuropathy. Additional problems included myalgia (n = 24), joint stiffness (n = 23), arthralgia (n = 22), sicca complex (dry eyes and dry mouth) (n = 19), headache (n = 16), skin rash (n = 15), joint swelling (n = 14), Raynaud's phenomena (n = 14), fever (n = 13), hair loss (n = 12), allergies (n = 11), sensitivity to sunlight (n = 10), and lymphadenopathy (n = 9). Magnetic resonance imaging brain scans were abnormal in 22 of 26 patients (21, white matter lesions; 1, ischemic lesions; 4, cerebral atrophy). Spinal tap revealed oligoclonal bands in 18 of 23 patients. Visual evoked responses were delayed in 14 of 23 patients, and autodirected antibodies were detected in 16 of 26. Sural nerve biopsy results showed loss of myelinated fibers in 15 of 15. Seventeen of 24 patients (71%) who had implant removal were found to have grossly ruptured implants. We believe our patients had a new syndrome triggered by the foreign material in their body. This syndrome appears as a systemic inflammatory autoimmune disease with central nervous system involvement resembling multiple sclerosis.