http://jdr.sagepub.com/content/57/9/899.abstract Influence of Fluoride upon Plaque and Gingivitis in theMessage 1 of 1 , Mar 17, 2012View Source
Influence of Fluoride upon Plaque and Gingivitis in the Beagle Dog
Two studies were conducted to explore the effects of twice daily topical applications of NaF, SnF 2, and an amine fluoride at equivalent fluoride concentrations (0.1%) upon plaque and gingivitis in the dog. Although some trends toward modest benefits were noted in certain instances, none of the agents exerted a significant effect upon either parameter
There have been numberous of studies evaluated the effects of various topical fluorides on gingivitis in children. J.J. Murray in 1969 investigate the prevalence of gingivitis in 15 year old children from high fluoride (1.5 to 2 ppm) and low fluoride (0.2 ppm) areas. He reported that up to the level of 2 ppm, fluoride in drinking water has no influence on prevalence of gingivitis, on its extent or on the relative distribution of gingivitis in individual labial papillae and the margins associated with anterior teeth in 15 year old children. This study was in agreement with James et al. in 1960 who reported that there was no significant increase in incidence and severity of gingivitis in children living in the high fluoride areas. On the contrary, Ast and Schlesinger in 1954 measured gingivitis in children aged 6-9 years from the fluoride city of Newburgh (1-1.2 ppm F) and the control city of Kingston (F= .1ppm) and concluded that a slight but significantly more gingivitis was observed amongst Kingston children than among those in Newburgh. Russell in 1957 carried out a similar study involving school children of 7-14 yrs old and found that proportions of children free form overt signs of periodontal disease (including gingivitis) were higher throughout the age range in children of high fluoride city than the low fluoride city. It is rather difficult to assess whether the lower prevalence of gingivitis observed in children from fluoride areas is directly or indirectly associated with the F content of drinking water. One theory would be since application of fluoride involved involved mainly tooth brushing, the effect of gingival inflammation may well be a result of mechanical oral hygiene effort. Fluoride treatment, nevertheless, have not been shown to have significant effect on periodontal surgical healing in animal. Fluoride actually causes healing time to increase (delay wound healing). Another area of application of fluoride is hypersensitivity teeth. The use of sodium fluoride has been reported in many studies as an effective agent in treatment dentinal hypersensitivity (Stout et al. in 1955, Hoyt et al. in 1943).
A large number of studies reported no detrimental effects of fluorides on periodontal tissue. Side effect included staining, mild blanching of the gingiva when high concentration of SnF2 were applied topically (only on 5% of subjects), sloughing of gingival tissue of children within an hour of topical application of APF. This effect was related to the presence of inflammation, the more inflammation, the more sloughing. Crevicular epithelium was more susceptible to sloughing than the papillary gingiva. Branemark studied the effect of commonly used topical fluoride solutions on intact connective tissue, damaged connective tissue, and epithelium in hamster, rabbits, and humans. Changes noted varied with concentration of NaF and went from slight and reversible trauma to definite destruction of tissue cells leading to necrosis and subsequent proliferative reparative phenomena. Prolonged contact with fluoride solution may aggravate the existing chronic inflammation. Finally, titanium does not withstand certain acidic fluoride prophylactic agents. The use of fluoride near the implant restoration should be avoided. Lothar Probster et al. in 1992 examined the use of sodium fluoride gel, amino-fluoride gel, sodium fluoride solution, aminofluoride solution, and sodium fluoride lacquer. Drops of 4mm in diameter were placed on the polished titanium surfaces. Surface roughness was investigated with profilometer and SEM. They also placed and IMZ implant and its transmucosal abutment in Oral B fluor gel for 24 hours. The results showed significant increase of surface roughness in acidulated fluoride agent. Scannic electron microscope illustrated the corrosive effect of the acidic agent. The implant and abutment which was stored for 24 hours in Oral B gel showed massive corrosion and the effect is compatible to the cast titanium used in the study. Acidic fluoride agents should not be used in patients with titanium implants or restoration.
Gingivitis in 15-year-old children from high-fluoride and low-fluoride areas
Evidence concerning the influence of fluoride drinking water on gingivitis is inconsistent. In order to determine whether fluoride in drinking water up to the level of 2 ppm has any effect on the prevalence, extent or pattern of gingivitis in anterior labial units, the gingival health of 386 15-year-old children, continuously resident in West Hartlepool, a high fluoride area (1.52.00 ppm F), was compared with that of 38115-year-old children from York, a low fluoride area (0.2 ppm F).
The method of measurement was that described by Jackson (1965).
It was concluded that fluoride in drinking water, at least up to the level of 2 ppm, has no influence of clinical significance on the prevalence of gingivitis, on the extent, or on the pattern of gingivitis in individual papillae and margins associated with incisor and canine teeth in 15-year-old-children.
In both communities prevalence of gingivitis was higher in boys than in girls. However, when only those children with a good standard of oral cleanliness were considered this sex difference disappeared, suggesting that the observed sex difference could be due to differences in the standards of oral cleanliness between boys and girls.
A distinctive pattern of gingivitis in papillae and margins associated with anterior teeth was observed in all four groups studied, and this pattern was essentially the same as that observed independently by Jackson (1965) and Sutcliffe (1968), suggesting that this pattern is universally true.
Gingivitis and gingival recession in adults from high-fluoride and low-fluoride areas
The prevalence of gingivitis and gingival recession in 1884 dentate adults, aged 1565 yr, continuously resident in the natural fluoride area of Hartlepool (1.52.0 ppm F.) was compared with that in 2015 dentate adults from the low-fluoride town of York (0.150.28 ppm F.).
The measurement of gingivitis was restricted to the anterior labial gingival sites, after the method described by Jackson (1965). The prevalence of gingivitis did not vary with increasing age. Therefore, data for all age groups were combined. Eighty nine per cent in Hartlepool and 87 per cent in York had one or more gingival sites inflamed. In both communities, the slightly higher prevalence of gingivitis in males than in females disappeared when only those with good oral cleanliness were considered. In Hartlepool, the site prevalence of gingivitis was 37.2 per cent and in York 35.4 per cent. In those with good oral cleanliness, the site prevalence of gingivitis was 21.8 per cent in Hartlepool and 19.8 per cent in York. The maximum divergence between the two communities was 0.4 gingival units.
No sex difference in the prevalence of gingival recession was observed in either community. Therefore, data for males and females were combined. In Hartlepool at 1519 yr of age, 3.0 per cent were affected by gingival recession; at 6065 yr, virtually 100 per cent were affected. The trend with age in York followed exactly the same pattern as that observed in Hartlepool. The percentage of teeth with gingival recession also increased steadily with age. In Hartlepool at 1519 yr of age, 0.2 per cent of teeth had gingival recession. At 6065 yr, 66.7 per cent of teeth were affected. The corresponding values in York were 0.2 per cent and 63.8 per cent. No significant differences were observed between Hartlepool and York data.
It was concluded that fluoride in drinking water, at least up to the level of 2 ppm, has no effect of clinical significance on the prevalence of gingivitis or gingival recession in adults.
PFPC NEWSLETTER #9:
", & Oral Cancer"
© 2002 PFPC http://184.108.40.206/pfpc/html/newsletter_9.html
and periodontal disease are the oral diseases requiring most urgent intervention. Over 90% of the U.S. population over 13 is affected. Strong links have been made to heart disease and low birth weight and infant mortality. For heart disease the association with is stronger than the one for smoking or high cholesterol. As heart disease is the #1 killer in the US, many efforts are undertaken to reduce this alarming figure. In Canada large pictures of a diseased heart are placed on cigarette packs alerting to the fact that smoking causes heart disease.
It is of great importance that warning labels and pictures of periodontal disease, oral cancer, diseased hearts, pituitary and thyroid glands, as well as Alzheimer's brains - just to name a few - are placed on all oral care products containing.
A patent by the pharmaceutical company Sepracor discloses that concentrations of s from fluoridated toothpastes and mouthwashes activate G proteins in the oral cavity, thereby promoting and periodontitis, as well as oral cancer. Incomprehensibly, this vital information is being withheld from the public by all parties involved, including the company, at least two well-known Universities, and numerous oral disease experts. This includes a much-decorated ADA scientist who was involved in setting the CDC recommendations for intake in children, served as head of a Food and Drug Administration subcommittee that decides which dental products to make available to the public, and who chaired the panel on safe use of for the Centers for Disease Control (CDC, 2001).
An extensive section of this Newsletter deals with biochemical aspects [Part 4].
ORAL CANCER - Statistics
FLUORIDATION AND ORAL CANCER
BRIEF LITERATURE REVIEW - EVIDENCE
BIOCHEMISTRY - G PROTEINS
Oral Cancer - The ras oncogene
G q/11 Diseases
Dentists & Oral Cancer
Richard Gracer, MD
THYROID HORMONES &
Many of our children have experienced oral diseases which miraculously disappeared whenintake was curtailed. For example, some had consistent "white spots" on their gums which vanished upon elimination of fluoridated toothpaste, but returned as soon as such toothpaste was used again.
Some of these white spots and patches were diagnosed as pre-cursors to oral cancer (squamous cell carcinomas), while others were deemed to be "allergic reactions" by medical professionals. Yet other doctors identified oral yeast infections (Candidiasis).
When we investigated the scientific literature ontoxicity we found that such oral conditions have been related to intake countless times. There is extensive evidence of such disease in humans from areas with water fluoridation, from toothpaste and mouthrinse use, as well as in workers exposed to s.[See:Part 3]
Studies in workers exposed to Asthma.have shown that the severity of periodontal disease is directly correlated to the levels in systemic fluids (i.e. Domazalska, 1972). The more in the system - the more severe the periodontal disease. The same findings have been made for
In 1996 three biochemists (Aberg, Jerussi & McCullough, 1998), working for the pharmaceutical company Sepracor, speculated on implications in periodontal disease. Realizing that s activate G proteins, they reasoned that s would also be involved in the activation of those G proteins which regulate the pathways involved in and periodontitis - and they decided to test for the ability of to activate two integral receptors involved in periodontal disease - the prostaglandin E2 receptor (PGE2) and the thromboxane A2 (TXA2) receptor. Both are coupled to G proteins called G q/11.
The scientists conducted a test with sodium HL-60 cells. These are Human Leukemia cells often used in biochemistry investigations, as one can observe fundamental and critical signals involved in the activation of the body's immune system - because of the cells' ability to respond to foreign organisms.based on a well-established in-vitro protocol model involving
The authors reported:
- "We found that , in the concentration range in which it is used for the prevention of dental caries, stimulates production of prostaglandins and thereby excaberates the inflammatory response in and periodontitis.... Thus, the inclusion of in toothpastes and mouthwashes for the purpose of inhibiting the development of caries may, at the same time, accelerate the process of chronic, destructive periodontitis."
A very important finding as it relates to public health!
In the 1986 National Institute of Health (NIH) survey, 93% of adults indicated that their children used toothpaste with, obviously putting all at risk. and periodontal disease constitute THE major public oral health problems in the US.
The patent findings supply the biochemical explanation for earlier reports by many researchers who had found increasedand gum inflammation due to fluoridated water, or other sources of .
Even T. Dean himself - the so-called "Father of Fluoridation", made such observations.[see: Part 3]
However, instead of alerting the public health officials to their findings, those men apparently decided to take another avenue.
They went looking for an agent which would counteract the adverse effects ofand therefore could be used together WITH . After all, was/is the "proven caries fighter"!
They chose a non-steroidal anti-inflammatory agent (NSAID) called ketoprofin, conducted more studies to see if ketoprofin was efficient in off-setting the damagingeffects, and then filed a patent on their new concoction now containing both and ketoprofin (Aberg et al, 1998).
Subsequently, a study was instigated at the Harvard School of Dental Medicine (funded by Sepracor), documenting the `wonderful' effects of ketoprofin upon. The first study on beagles included one of the three co-inventors (McCullough) together with two Assistant Professors from two separate well-respected Universities, and was subsequently published in the Journal of Clinical Periodontology in 1997 (Paquette et al, 1997).
In the study not one word is mentioned aboutbeing a causative/promoting agent of , as stated in the patent claims.
Another study - this time on rats, and again as a direct result of the patent research - was conducted involving yet another of the three co-inventors from Sepracor (Jerussi).
This time the study was done with two professionals from the University of Rochester, one being Prof. Bowen, the much-adorned and decorated ADA scientist involved in setting the 2001 CDC recommendations on intake.
Results of this study were published recently in the Journal of Oral Diseases (Bowen et al, 2000) Full Text
Again, not one single word aboutpromoting and causing appears in the entire text.
According to the National Institute of Dental and Craniofacial Research (NIDCR; Brown et al, 1996), over 90% of persons 13 years or older experience some form of periodontal disease.
74.9 % of all people between 35 and 44 years suffer from periodontal disease (Fig.4.7, Oral Health Report, 2000). 29% of males and 15 % of females between 35 and 44 years old have destructive periodontal disease (Healthy People 2010-Conference Edition).
60% of all people between 18 and 44 suffer from periodontal disease (Figure 4.8, OHR).
Compared to these figures - up to 46% of adults over 18 years old have untreated caries (Figure 4.5, OHR).
Not surprisingly, periodontal disease has recently become the primary focus for dental researchers because of the very strong links which have been made to other conditions such as heart disease (Loesche 1994, 1998; Herzberg and Meyer 1996), as well as infants with low birth weight and premature births. For heart disease the association is stronger than for smoking (Loesche et al, 1998).
The NID(C)R, in their 1999 appeal to the Appropriation Committee for $276,518,000 in funding, stated that gum disease is now also known as a high risk factor for low birth weight babies. Said Crawford in his plea for the big money:
- "Care of low birth weight babies costs the nation approximately $5 billion dollars each year. If we can lower the incidence of low birth weight babies by treating gum disease it will mean that 1:10 babies born in the US have a better chance of a healthy start in life."
Further, he reasoned:
- "As we come to the end of this, century, 50% of heart attacks (the number one cause of death in the Western World) and 25% of low birth weight babies have no aditional risk factors associated with them. We now have strong evidence that gum disease is a risk factor for both these conditions - in fact - as strong a risk factor for heart disease as elevated cholesterol or smoking!"(Crawford, 1999)
This clearly means that (PFPC, 2001). Biochemical investigations have identified the pathways.s - by promoting - also contribute to heart disease and low birth weight. Heart disease has long been known to be higher in workers exposed to s, or caused by s in medications
The patent findings implicating the"topical" activation of G proteins in the oral cavity have many far-reaching and serious implications - not only for periodontal disease, but also for oral cancers - which involve "mutated" G proteins, and which are activated by , often even "preferring" activation.[see Part 4: Biochemistry]
ORAL CANCER - Statistics
Oral cancer is the sixth most frequent cancer in the world (Buffalo Sisters Hospital, 2000).
Oral cancer claims the life of one American every hour. Over thirty thousand Americans are diagnosed with oral or pharyngeal (throat) cancer every year and 8,000 people die annually from these cancers. Only half survive more than five years. This overall 5-year survival rate (52 percent) has not changed in the past five decades - coincident with the appearance ofas a `preventive treatment' for caries.
Black people have higher incidence and mortality rates than other subgroups (OHR, 2000; Caplan et al. 1993; NIH Press Release, 1996), as they do with most thyroid hormone-related disorders, including, of course, "dental fluorosis" (PFPC, 2000).
"White Patches" - Cancer
As was mentioned in the INTRO, many of our kids have had these "white patches" in the mouth, often diagnosed as "precursors" for an `oral squamous carcinoma'.
A benign squamous papilloma is the obligate precursor of squamous cell carcinoma, and again, numerous laboratory investigations have shown that these are brought about by. Mere ras oncogene activation is sufficient to produce the papilloma phenotype in skin cancers, and is known to act additively with the ras oncogene in producing this papilloma (Camp & Hoffman, 1993). (-> Cancer promotion).
[see Part 4: Biochemistry]
FLUORIDATION AND ORAL CANCER
In 1981 Dr. John Yiamouyiannis and Dean Burk, chief chemist emeritus of the National Cancer Institute (NCI), first showed very convincingly that there was an increase in oral cancer in fluoridated areas.
An investigation done by the Battelle Institute on behalf of the National Toxicology Program (NTP) (NTP, 1991; also see: Yiamouyiannis, 1993) showed a clear dose-response relationship between oral cancers andintake in the animals tested.
According to the late Yiamouyiannis, the National Cancer Institute (NCI) - in response to the NTP findings - decided to examine the incidence of oral cancer in fluoridated and non-fluoridated areas. The resulting data showed at least a 33% to 50% increase in the incidence of oral cancers in fluoridated areas, indicating at least an additional 5000 - 7500 or more cases or oral and pharyngeal cancer per year as a result of fluoridation alone (Yiamouyiannis, 1993).
An increase in oral carcinomas and their precursors has also been observed in workers exposed tos.[see next section]
BRIEF LITERATURE REVIEW - EVIDENCE
(Compiled by Wendy Small)
and oral diseases due to excess have been reported many times in the world literature.
In 1936 Dean - the "father of fluoridation" himself - wrote in the Journal of the American Medical Association:
- "From observations that I made in areas of relatively high concentration (more than 4 parts per million of fluorine) there is sufficient evidence to suggest that there is an apparent tendency toward a higher incidence of ."
Remember, at that time water withat 4ppm was thought to produce a total intake of 4 mg/day. In 1991 the US PHS estimated that TOTAL intake exceeded 6.5 mg/day in U.S. cities having one part per million (1ppm) of in their water supply!
Similar observations of the link betweenand periodontal disease have been made many times since (Dean & Arnold, 1943; Day, 1940; Spira, 1953; Ramseyer et al, 1957; de Toledo, 1970; Grimbergen et al, 1974; Poulsen & Moller,1974; Waldbott et al, 1978; Olsson, 1979; Reddy et al, 1985; Wei et al, 1986; Yiamouyiannis, 1993).
In 1953 Leo Spira had identifiedand bleeding gums as signs of chronic poisoning. In 1957 Ramseyer observed in older rats drinking water fluoridated at 1 ppm. By 1982 Domazalska observed a direct correlation between the severity of periodontal disease and levels in systemic fluids.
From around the world...
"Most children in both urban and rural areas had...Children who brush their teeth every day were 88.5% in urban and 72.8% in rural areas and most of them used tooth paste."
Suksu-art N, Arkasuwan N - "Survey on the oral health status of primary school children in urban and rural areas, Hat Yai, Songkhla" Research/Government Report, Thailand (2000)
"A significant relationship between the concentration of F- in dental plaque...and the condition of periodontal tissues was established."
Borysewicz-Lewicka M, Kobylanska M - "Periodontal Disease, Oral Hygiene AndContent Of Dental Deposits In Aluminum Workers" 16(1):5-10 (1983)
"Fluorosis was endemic...Periodontal disease was moderate at 15 yr of age, but seemed to be a predisposing factor in caries from the late teens onward. ... More than half of persons in the 55-64 yr age group required full maxillary and mandibular dentures while 10% already possessed them."
Speake JD, Malaki T - "Oral health in Tuvalu" Community Dent Oral Epidemiol 10(4):173-177 (1982)
"....We are more prone to caries...The incidence of dental fluorosis is on the rise in Bathinda. Experts reveal that the disease is commonplace due tocontamination in the ground water of the region. Studies indicate that nearly 90 per cent of the population ...is suffering from dental caries and chronic , which often leads to pyorrhoea [periodontitis]..."
Rishi, Shella - "We are more prone to caries" Bathinda/India; India Express - Thursday, July 20 (2000)
"There were some controversies in the results of fluoridation studies with one study reporting as high as 47.2% of the children to be afflicted with enamel fluorosis.... 93% of the 12-yr-olds had bleeding, 98% had calculus and 15% had shallow pockets, with 100% of the children needing prophylaxis."
Wei SH, Shi Y, Barmes DE - "Needs and implementation of preventive dentistry in China" Community Dent Oral Epidemiol 4(1):19-23 (1986)
"Teeth with moderate and severe fluorosis more frequently had dental caries than teeth with no or very mild and mild fluorosis....was seen in 97% of the children..."
Olsson B - "Dental findings in high-areas in Ethiopia" Community Dent Oral Epidemiol 7(1):51-6 (1979)
"The article deals with the problem of relation of the incidence and prevalence of various parodontal diseases in subjects with various degrees ofintake to the content of this element in various systemic fluids. ...A correlation was observed between the parodontopathy index of Kotzschke and F levels in the systemic fluids calculated by means of the correlation coefficient of Pearson."
Domazalska W - "Incidence of periodontal diseases in subjects with various degree of exposure tos" Czas Stomatol 25(10):1005-1011 (1972)
"Stomatological and mycological examinations of the workers [exposed to Leukoplakia [pre-cancerous growth] and candidiasis were the most common changes found on the mucous membrane in the oral cavity. Mycological investigations carried out on the Sabourand culture showed Candida albicans in 73.7% of cases."s]at the fusion department of the RZWM "Silesia" showed a considerable intensification of paradontium diseases (about 80% of cases).
Ilewicz L, Chrusciel H, Korycinska-Wronska W, Maniak B, Szlachta R, Mniszkowa M, Waszkiewicz-Golos H, Wrobel J - "Condition of the periodontium and mouth mucosa in workers exposed tos" Med Pr 33(1-3):153-6 (1982)
"...cancers of the oral cavity and pharynx, colon and rectum, hepato-biliary and urinary organs were positively associated with FD" [fluoridated drinking water]
Takahashi K, Akiniwa K, Narita K - "Regression analysis of cancer incidence rates and waterin the U.S.A. based on IACR/IARC (WHO) data (1978-1992). International Agency for Research on Cancer" J Epidemiol 11(4):170-9 (2000)
Krook L, Maylin GA, Lillie JH, Wallace RS - "Dental fluorosis in cattle" Cornell Vet 73(4):340-62 (1983)
"Five expressions of dental fluorosis are described in cattle exposed to industrialpollution: 1. Hypercementosis with tooth ankylosis, cementum necrosis and cyst formation; 2. Delayed eruption of permanent incisor teeth; 3 Necrosis of alveolar bone with recession of bone and gingiva; 4. Oblique eruption of permanent teeth, hypoplasia of teeth with diastemata; and 5. Rapid progression of dental lesions. The five entities are not recognized in the "standard for the classification of dental fluorosis" by the National Academy of Sciences. Since this classification it too limited and superficial, adherence to this standard has left severe cases of intoxication in cattle undetected in field surveys."
Chang YC, Chou MY - "Cytotoxicity ofon human pulp cell cultures in vitro" Oral Surg Oral Med Oral Pathol Oral Radiol Endod 91(2):230-4 (2001)
"OBJECTIVES: Numerous studies have revealed that conventional glass-ionomer cements might releaseinto an aqueous environment. The objective of this study was to examine the effects of on human pulp cells in vitro. STUDY DESIGN: H33258 fluorescence, cell proliferation, protein synthesis, and mitochondrial activity assay were used to investigate the pathobiological effects of on cultured human pulp cells. RESULTS: was found to be a cytotoxic agent to cultured human pulp cells by inhibiting cell growth, proliferation, mitochondrial activity, and protein synthesis. CONCLUSIONS: release has significant potential for pulpal toxicity."
As we have stated many times in the past,is known as the "universal G protein activator" in biochemistry, meaning it can activate all G protein families. The only known receptor which is capable of doing the same, in the human organism, is the receptor for the thyroid-stimulating-hormone (TSH) (Gudermann et al, 1997).
This complex and multifunctional actvity of TSH is the reason why so many different diseases are associated with thyroid hormone dysfunction. It is also the reason why the same associations have been made in - poisoning being a TSH clone.
While for many years it was presumed that the TSH receptor was only expressed in the thyroid gland itself, TSH receptors have now been detected in liver, gastrointestinal tract (Duntas et al, 1998), orbital tissue and dermal fibroblasts (Paschke et al, 1994), peripheral lymphocytes, fat, cardiac muscle (Drvota et al, 1995), thymus, peripheral blood mononuclear cells, osteoblasts and osteosarcoma cells (Inoue et al, 1998), or the brain - where it is overexpressed in patients with Down Syndrome or Alzheimer's Disease (Labudova et al, 1999).
In order for us to understandpoisoning better, we have concentrated on the matter of Gq/11, as this is what TSH does - at elevated levels it activates the Gq/11-mediated pathways.
What are G q/11 proteins?
G q/11 proteins are membrane-associated proteins involved in signal transduction - the way cells communicate with each other.
Gq/11 are coupled to receptors which cross the cell membrane seven times ("transmembrane receptors"). Gq/11 proteins are located in the membrane of a cell.
Upon receptor activation, they may send information directly from the membrane to the cell's nucleus. Consider them an essential "relay station" for cell information, the initiators of other cascades of events. One such cascade involves the mitogen-activated-protein-kinase (MAPK). MAPKs are regarded as "switch" kinases in the phosphorylation cascade.
Gq/11 may be released directly from the plasma membrane to an intracellular location in response to activation by aluminocomplexes [AlF(x)], directly translocating immunoreactivity (i.e. Arthur et al, 1999).
not only directly augments the already existing hormonal (TSH) activation of Gq/11, it may activate such proteins even in the absence of TSH. [Without TSH, G proteins involved in thyroid hormone regulation are thought to be inactive (Utiger, 1995).]
G q/11 Diseases
Gq/11-regulated pathways have profound effects not only on the pathology of gum disease, but of chronic inflammation overall, as well as cancer, heart disease, stroke, diabetes, Alzheimer's Disease, Autism, etc. - in short - all those conditions which represent the most significant health care problems in the developed world today. We have come to describe this as the "G q/11 disease".
For example, in heart disease - which kills 725,192 people a year in the U.S. alone, making it the #1 cause of death (CDC, 2002) - it is G q/11 over-expression which leads to enlargement of the heart, in turn leading to congestive heart failure. Therefore recent pharmacological research has focused on creating so-called "decoys" for G q/11 - non-working versions of Gq to prevent the activation and reception of molecular signals that normally would produce such enlargement of the heart (Akhter et al, 1998; Adams et al, 2001).
It has been shown that on-going ("constitutive") G q/11 activation in heart muscle results in downsignalling of thyroid hormone T3 and inhibition of T3-dependent intra-cellular activities (i.e. Wu et al, 1997).
Needless to say, G q/11 are also involved in dental pulp and enamel formation and are also involved in the condition known as "dental fluorosis" (enamel hypoplasia) (Pozo et al, 2000; Bawden et al, 1996). Gq/11 have been unequivocally established to be the transducing G proteins for all Ca(2+)-mobilizing receptors (i.e. Exton,1993).
In Alzheimer's and Down Syndrome patients Gq/11 is elevated in the brain regions. Virtually all Down Syndrome patients suffer from Alzheimer's in their 40's.
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