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Fluoride Deposition in the Aged Human Pineal Gland

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Abstract

The purpose was to discover whether fluoride (F) accumulates in the aged human pineal gland. The aims were to determine (a) F-concentrations of the pineal gland (wet), corresponding muscle (wet) and bone (ash); (b) calcium-concentration of the pineal. Pineal, muscle and bone were dissected from 11 aged cadavers and assayed for F using the HMDS-facilitated diffusion, F-ion-specific electrode method. Pineal calcium was determined using atomic absorption spectroscopy. Pineal and muscle contained 297+/-257 and 0.5+/-0.4 mg F/kg wet weight, respectively; bone contained 2,037+/-1,095 mg F/kg ash weight. The pineal contained 16,000+/-11,070 mg Ca/kg wet weight. There was a positive correlation between pineal F and pineal Ca (r = 0.73, p<0.02) but no correlation between pineal F and bone F. By old age, the pineal gland has readily accumulated F and its F/Ca ratio is higher than bone.
... NaF penetrates cell membranes. It can accumulate in organs and tissues (bones, pineal gland) and its effect depends on the dose and time of exposure [2]. Many in vitro and in vivo studies have shown a negative effect of NaF on the functioning of both the male and female reproductive systems [3,4]. ...
... Our experiment revealed that NaF stimulates mRNA expression of gonadotropin hormone receptors (FSHR and LHR) in the chicken embryonic ovary. Previously, Zhou et al. [2,45] found that NaF at higher doses downregulates FSHR and LHR protein expression in female rats. These discrepancies may be explained by the applied NaF dose, animal model, and tissue used in the experiment. ...
... These changes were accompanied by a significant decrease in the FSH receptor protein and the serum concentration of estradiol and progesterone. Another study by this group (Zhou et al. [2]) demonstrated that 6 months exposure of female rats to NaF led to a significant decrease in the concentration of reproductive hormones, with a concomitant reduction of the total number of follicles and inhibition of follicular maturation. These results suggest that fluoride affects the reproductive function not only at the hormone receptor level, but also may affect steroid hormone synthesis and secretion. ...
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Sodium fluoride (NaF), in addition to preventing dental decay may negatively affect the body. The aim of this study was to examine the effect of a 6 h in vitro treatment of gonads isolated from 14-day-old chicken embryos with NaF at doses of 1.7 (D1), 3.5 (D2), 7.1 (D3), and 14.2 mM (D4). The mRNA expression of luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), estrogen receptors (ESR1 and ESR2), progesterone receptor (PGR), and the immunolocalization of progesterone receptors were examined in the tissue. In the ovary, the expression of FSHR and LHR increased following the NaF treatment. In the case of FSHR the highest stimulatory effect was noticed in the D2 group, while the expression of LHR increased in a dose-dependent manner. A gradual increase in ESR1 and PGR mRNA levels was also observed in the ovary following the NaF treatment, but only up to the D3 dose of NaF. The highest ESR2 level was also found in the D3 group. In the testes, the lowest dose of NaF significantly decreased the expression of FSHR, ESR1, ESR2, and PGR. On the other hand, an increase in PGR expression was observed in the D3 group. The expression of LHR in the testes was not affected by the NaF treatment. Immunohistochemical analysis showed that NaF exposure increased progesterone receptor expression in the ovarian cortex, while it decreased its expression in the testes. These results reveal that NaF may disturb the chicken embryonic development and different mechanisms of this toxicant action exist within the females and males.
... It sits outside of the blood-brain barrier, and thus the passage of fluoride is not restricted as it is in other areas of the brain. Its tissue is subject to mineralization, with calcification producing concretions up to several millimeters in diameter [10]. This calcification consists of hydroxyapatite, similar to that of bones or teeth [11][12][13]. ...
... This calcification consists of hydroxyapatite, similar to that of bones or teeth [11][12][13]. It has been found to accumulate high levels of fluoride [10] even from low fluoride consumption due to fluoride's high affinity for hydroxyapatite [12]. This vulnerability could increase the risk of pineal gland fluoride toxicity [13,14]. ...
... This vulnerability could increase the risk of pineal gland fluoride toxicity [13,14]. In older individuals, fluoride measurements in the pineal gland have been shown to be roughly equivalent to those in teeth [10]. ...
... It sits outside of the blood-brain barrier, and thus the passage of fluoride is not restricted as it is in other areas of the brain. Its tissue is subject to mineralization, with calcification producing concretions up to several millimeters in diameter [10]. This calcification consists of hydroxyapatite, similar to that of bones or teeth [11][12][13]. ...
... This calcification consists of hydroxyapatite, similar to that of bones or teeth [11][12][13]. It has been found to accumulate high levels of fluoride [10] even from low fluoride consumption due to fluoride's high affinity for hydroxyapatite [12]. This vulnerability could increase the risk of pineal gland fluoride toxicity [13,14]. ...
... This vulnerability could increase the risk of pineal gland fluoride toxicity [13,14]. In older individuals, fluoride measurements in the pineal gland have been shown to be roughly equivalent to those in teeth [10]. ...
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Background Fluoride from dietary and environmental sources may concentrate in calcium-containing regions of the body such as the pineal gland. The pineal gland synthesizes melatonin, a hormone that regulates the sleep-wake cycle. We examined associations between fluoride exposure and sleep outcomes among older adolescents and adults in Canada. Methods We used population-based data from Cycle 3 (2012–2013) of the Canadian Health Measures Survey. Participants were aged 16 to 79 years and 32% lived in communities supplied with fluoridated municipal water. Urinary fluoride concentrations were measured in spot samples and adjusted for specific gravity (UFSG; n = 1303) and water fluoride concentrations were measured in tap water samples among those who reported drinking tap water (n = 1016). We used multinomial and ordered logistic regression analyses (using both unweighted and survey-weighted data) to examine associations of fluoride exposure with self-reported sleep outcomes, including sleep duration, frequency of sleep problems, and daytime sleepiness. Covariates included age, sex, ethnicity, body mass index, chronic health conditions, and household income. Results Median (IQR) UFSG concentration was 0.67 (0.63) mg/L. Median (IQR) water fluoride concentration was 0.58 (0.27) mg/L among participants living in communities supplied with fluoridated municipal water and 0.01 (0.06) mg/L among those living in non-fluoridated communities. A 0.5 mg/L higher water fluoride level was associated with 34% higher relative risk of reporting sleeping less than the recommended duration for age [unweighted: RRR = 1.34, 95% CI: 1.03, 1.73; p = .026]; the relative risk was higher, though less precise, using survey-weighted data [RRR = 1.96, 95% CI: 0.99, 3.87; p = .05]. UFSG was not significantly associated with sleep duration. Water fluoride and UFSG concentration were not significantly associated with frequency of sleep problems or daytime sleepiness. Conclusions Fluoride exposure may contribute to sleeping less than the recommended duration among older adolescents and adults in Canada.
... Кальцинаты могут включать в свой состав белки, нейроамины, отдельные клетки [9] и, как мы видим, на наших препаратах, по-видимому, амилоид. В связи с особенностями кровоснаб-жения шишковидная железа считается уязвимой для образования фторидов кальция и алюмофосфатов [10]. Алюминий, как полагают, участвует в образовании амилоида и, возможно, ответственен за развитие болезни Альцгеймера [11] и диализного амилоидоза [12]. ...
Article
Введение. Шишковидная железа (эпифиз), кровоснабжение которой осуществляется от ветвей а. chorioidea posterior, а отток крови происходит в большую мозговую вену или её приток, может подвергаться локальному амилоидному поражению без вовлечения в процесс больших полушарий, то есть, представлять собой самостоятельный процесс не связанный с болезнью Альцгеймера. Цель исследования - выявление частоты встречаемости локального амилоидоза эпифиза у взрослых людей и изучение его возможной связи с кальцинозом железы. Методика. Проведено патогистологическое исследование шишковидных желез 92 суицидентов и 69 лиц, погибших в результате насильственных действий или различных несчастных случаев (группа сравнения). Всего 37 женщин и 124 мужчины. Средний возраст суицидиентов мужчин - 41,0±13,0, женщин - 57,0±15,0, лиц группы сравнения - 41,0±13,0 и 54,0±13,0 соответственно. Для выявления амилоида и кальцинатов использовали окраску гистопрепаратов конго красным, а также тиофлавином Т. Тяжесть амилоидного поражения и количество кальцинатов в шишковидной железе оценивали в условных баллах. Результаты. При окрашивании образцов конго красным вне зависимости от возраста и причины смерти в 48,5% случаев было выявлено различной тяжести амилоидное поражение шишковидной железы и наличие кальцинатов. Частота встречаемости, тяжесть амилоидного поражения железы и количество кальцинатов не зависели от возраста, пола и причин смерти (анализ различий частот проведен по тесту Колмогорова-Смирнова с поправкой Лиллиефорса). В образцах от суицидентов выявлено зависимое от тяжести амилоидного процесса статистически значимое увеличение массы шишковидной железы по сравнению с массой желез умерших в результате насильственной смерти и несчастных случаев. При отсутствии признаков амилоидного поражения различий в массе эпифизов «суицидентов» и «несуицидентов» не обнаружено. Причиной локального амилоидоза шишковидной железы, возможно является прижизненный гематогенный занос бактерий, который в том числе приводит к образованию кальцинатов. Заключение. Примерно у 50% популяции был выявлен бессимптомный локальный амилоидоз эпифиза; наличие амилоидоза не являлось причиной суицида; в материале от «суицидентов» выявлена зависимость влажной массы железы от тяжести амилоидного поражения Introduction. The pineal gland is supplied with blood by branches of the posterior choroidal artery, and the blood drains into the great cerebral vein or its tributaries. This gland may undergo local amyloid damage without involving the large hemispheres. Thus, this damage is an independent process not related to Alzheimer’s disease. The aim of the study was to determine the incidence of local amyloidosis in pineal glands of adults and to study a possible connection of amyloidosis with calcification of the gland. Methods. This pathohistological study was performed in 92 suicides and 69 victims of murders and accidents (the comparison group), a total of 37 women and 124 men. The mean age of male and female suicides was 41.0±13.0 and 57.0±15.0 yrs, respectively, and the mean age of men and women in the comparison group was 41.0±13.0 and 54.0±13.0 yrs, respectively. Amyloid lesion and calcinates were detected with Congo red and thioflavin T staining. Severity of the amyloid lesion and the number of calcinates in the pineal gland were scored conventionally. Differences in findings were analyzed using the Kolmogorov-Smirnov test with Lilliefors significance correction. Results. Congo red staining revealed pineal amyloid lesions of varying severity and the presence of calcinates in 48.5% of cases, regardless of the age, gender or the cause of death. The incidence and severity of amyloid lesions and the number of calcinates in the pineal gland did not depend on the age, gender or the cause of death. However, in suicides, the pineal gland weight was significantly increased (154.0±89.0 mg (D 64.0÷298.0, p=0.0143) compared to the weight of pineal glands from victims of accidents and murders (104.0±34.0 mg (D 51.0÷198.0)). This increase depended on the severity of the amyloid process. In the absence of amyloid lesions, there were no differences in pineal gland weights between suicides and non-suicides. Local amyloidosis of the pineal gland is possibly caused by hematogenic flux of bacteria, which also leads to the formation of calcinates. Conclusions. Approximately 50% of the population had asymptomatic, local amyloidosis of the pineal gland. The presence of amyloidosis was not the cause of suicide. In suicides, the wet weight of the pineal gland depended on the severity of amyloid lesion.
... Studies have demonstrated that fluoride accumulates primarily in the bone and teeth [10]. High levels of fluoride are also known to accumulate in the calcified regions of the pineal gland [11]. High levels of fluoride in pineal glands have been reported to interfere with melatonin production [12] and hence affect the sleep-wake cycle [13]. ...
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Background: Excessive fluoride consumption affects reproductive and child health. We examined the association between levels of fluoride in drinking water and birth weight, in the National Health and Nutrition Examination Survey 2013–2016, after adjusting for known risk factors Low Birth Weight (LBW) including age, smoking, and socio-demographic variables including education, food security, health care access, and health status. Methods: The study included 7147 and 6858 women with complete birth weight and water fluoride data, respectively. Linear regression models evaluated the association between water fluoride and birth weight across racial/ethnic groups. The odds of delivering an LBW infant (<2500 g) compared to an infant weighing ≥ 2500 g, as well as the odds of delivering a Very Low Birth Weight (VLBW, <1500 g) infant compared to an LBW infant were explored in separate logistic regression models. Results: Women with LBW infants were exposed to significantly higher levels of water fluoride compared to those with normal birth weight infants. Our findings suggest a significant association between excess water fluoride exposure (>0.7 ppm) and LBW weight in Hispanic women, independent of established LBW risk factors. In logistic regression models, Hispanic women exposed to increased levels of water fluoride were 1.5 times more likely to give birth to an LBW infant and 3.5 more likely to give birth to a VLBW infant. Conclusion: Taken together, these findings can inform public health education strategies that highlight water fluoride as a potential risk factor during pregnancy in Hispanic women. More research is needed to confirm these findings.
... However, recently fluoride was designated as one of the developmental neurotoxicants as more adverse effects of fluoride are revealed [3]. Although besides the developmental neurotoxicants, fluoride is also known to affect the pineal gland [4] and thyroid gland [5] and there is even some evidence between bone disease and fluoride exposure [6]. ...
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Caffeine and theobromine are members of the xanthine family. Coffee and soft drinks contain caffeine, whereas, in cacao, theobromine is the main ingredient. The mineral contents of the tooth which sucked the caffeine-containing dam’s milk were decreased. To determine if caffeine would affect enamel, dams were fed with a caffeine and pups were killed and first and second molars were extracted. Enamel was exposed to the acid solution and dissolved minerals from the enamel were measured. Calcium, phosphorus and magnesium from the first molars of the caffeine group were significantly dissolved. To determine why minerals were released, enamel was separated. The crystallite size of the enamel from the caffeine group showed decreased. If the pups with the same dietary regimen, but given a cariogenic diet, the caffeine group should show a higher incidence of dental caries. The caffeine group revealed higher caries scores. An in vitro experiment to grow apatite crystals was conducted, adding the various members of the xanthine. Theobromine produced larger crystal sizes than caffeine. Theobromine was added to the maternal diet. Dissolution experiments revealed that these minerals were far less dissolved. Comparative studies of the various parameters between theobromine and fluoride were conducted. Theobromine was superior to fluoride in every aspect.
... 475 Fluoride has been reported to readily accumulate in the human pineal gland and could affect pineal metabolism, in a similar way as it impacts the metabolism of other calcified tissues. 476 In female gerbils, exposure to fluoride was suggested to have a role in accelerated sexual maturation. A fluoride-free diet was observed to stimulate pineal growth in aged male rats. ...
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A general scheme of analysis for the investigation of minute calcification is presented. After low temperature ashing, the samples are subjected to chemical, structural and morphological study, using atomic absorption spectrometry, infrared spectrometry, X-ray diffraction and scanning electron microscopy. Details about the calcification of the human pineal gland are given. The content of trace elements is very high, but within the limits found in other biological apatites. It is concluded that calcification of the pineal is a more general occurence than has been realized.
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Recently published bone fluoride values from Iowa are very high compared to earlier reports, suggesting an increase in fluoride intake. Reanalysis of the Iowa specimens shows levels one-fourth those reported by the Iowa laboratory indicating an error in the original report. Seventeen bone specimens, collected from long-term residents of Rochester, New York, drinking 1 ppm F- water, had a mean value of 2085 +/- 270 ppm F- on an ashed-weight basis. This value is not significantly different from that predicted by the data of Zipkin et al. in 1958. These data, therefore, do not support the contention that there has been an increase in fluoride intake.
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Mild acid-base disturbances were induced in rats for 30 days. These disturbances did not affect % ash of maxillary incisors or % P of the developing enamel from mandibular incisors. Total fluoride intake (food and water) among groups drinking fluoride-free water was constant. Nevertheless, average plasma and developing enamel fluroide concentrations were highest in the acidotic group and lowest in the alkalotic group. Among groups drinking water containing 50 ppm fluoride, total fluoride intake was highest by the alkalotic group and lowest by the acidotic group. Plasma and enamel fluoride concentrations, however, were highest in the acidotic group. It is concluded that plasma and developing enamel fluoride levels can be independent of, or inversely related to, fluoride intake.
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Untreated, decalcified and trypsinized acervuli from human pineal bodies were studied with the scanning and transmission electron microscope as well as by electron probe microanalysis. The mulberry-like acervuli are composed of a various number of spherical lobes (135-800 mum) between which clustered groups of globuli (4--14 mum in diameter) are observed. The acervular lobes are very probably formed by an aggregation of these globuli. Small round particles 125--500 A in diameter are observed on the surface of the pineal concretions. These are not influenced by either decalcification or trypsin treatment. The acervular mineral corresponds morphologically to hydroxyapatite. The electron probe microanalysis reveals the existence of calcium and phosphorus as main components of the acervuli. Small quantities of magnesium and strontium were also detected.
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The most recent report on fluoride concentrations ([F]) in human bone was published over a decade ago. Such data are of interest in the context of changing patterns in systemic fluoride exposure. In the study reported here, bone samples were collected from 24 human subjects who underwent orthopedic surgery. Medical histories and the best possible life-time systemic fluoride exposure information were obtained from each subject. Bone samples were assayed for fluoride concentration using the acid diffusion, ion selective electrode method. For ash from whole bone, the lowest value was 378 ppm in a 16-year-old subject, and the highest value was 3,708 ppm in a 79-year-old person. Fluoride concentrations in bone were significantly correlated with age (r = .62). The regression line intercept at birth was 442 ppm, and the slope was 22 ppm per year. When measured separately, trabecular bone ash fluoride concentrations were significantly higher than the corresponding cortical bone values. Trabecular and cortical bone samples from rats' drinking water containing 75 ppm F were assayed for F. The mean trabecular bone fluoride concentration was significantly higher than the mean cortical bone concentration. There was close agreement between F assay results using a modification of the acid diffusion method and the method originally reported by Singer and Armstrong. The human bone ash [F] values reported in this study are similar to those reported from other North American subjects over the last three decades. These findings are of interest in the context of evidence indicating increased systemic fluoride exposure in the United States population.(ABSTRACT TRUNCATED AT 250 WORDS)
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Calcium content and pineal concretions were studied in young (2-3 months) and old (28 months) Wistar rats. Samples, deep-frozen by liquid propane isopentane and freeze-dried were analysed by means of X-ray microanalysis in a scanning electron microscope. Total semi-quantitative measurements revealed that pineals of old rats showed a marked increase of calcium compared with the pineals of young rats. It is thus suggested that a calcium-rich environment is responsible for the growth of pineal concretions, which only appear in old rats. Pineal calcifications in rats could thus be an indicator of aging and/or of a degenerating state.
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Acervuli and fragments of pineal gland obtained from 33 subjects of both sexes and age ranging from 1 to 87 years, (30 autopsy and 3 biopsy specimens) were analyzed by light microscopy, transmission and scanning electron microscopy, X-ray diffraction and X-ray energy dispersive microanalysis. It was found that primary mineralization occurs in an organic matrix formed by pinealocytes and that hydroxyapatite also takes place in mineral deposition. From our analysis, the formation of acervuli appears to be age and sex independent and can be possibly related to the secretory activity of the gland.
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Age-related changes of human pineal gland were studied morphologically on 168 autopsy cases. Pineal weight in the formalin-fixed condition was 99 +/- 56 mg in males (n = 88, mean age 78 years) and 91 +/- 41 mg in females (n = 80, mean age 79 years), which showed no sexual difference (P = 0.290). There was no correlation between pineal weight and age of the patient (r = 0.0678, P = 0.191, n = 168). The pineal volume calculated as a spheroid was directly proportional to the weight (r = 0.904, n = 167, P = 0.000). A significant correlation existed between pineal weight and the degree of calcification (r = 0.231, P = 0.002, n = 156). The density of the pineals decreased with age (r = -0.164, P = 0.017, n = 167). The degree of calcification and cyst formation did not increase with age, but the grade of cyst formation was related to the pineal volume (P = 0.0002). Some pineals of the patients over 90 years old showed no calcification and appeared indistinguishable from the ones of the younger subjects. The weight and volume of the pineals of the patients with hypertension was appreciably greater than those of the non-hypertensive patients. These results indicate that human pineals do not necessarily degenerate progressively after involution.
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In order to demonstrate fine localization of Ca2+ in the superficial pineal gland of Meriones unguiculatus, the pyroantimonate technique was employed. Control experiments were performed with EGTA and analysis of obtained reaction product using an energy-dispersive x-ray microanalysis. Precipitates of calcium antimonate were formed almost exclusively in swollen clear pinealocytes, in and along their cell membranes, over their nuclei, in mitochondria, the Golgi apparatus, endoplasmic and integrade reticulums. acervuli, in vesicles surrounding synaptic bars, cytoplasmic matrix, and flocculent extracellular material. It has been concluded that the swollen pinealocytes represent a degenerative cell form probably occurring by impairment of plasmalemmal Ca2+-ATPase's ability to eliminate Ca2+ ion from the cell, with consecutive increase of calcium in the cytoplasmic matrix, followed by increase of intramitochondrial Ca2+ concentration, gradual arrest of mitochondrial function, depolymerization of cytoskeletal microtubuli, loss of the cell form, and cell death. Decrease of function of pinealocyte plasmalemma seems to be related to aging.