Endocrinol Jpn 1985 Oct;32(5):635-43

Effect of excessive ingestion of manganese (Mn) on the mouse thyroid was assessed under the conditions of normal intake of iodide. Female mouse thyroids were enlarged after 7 weeks of administration of 200 mg/l MnCl2 X 4H2O in drinking water; 2.74 +/- 0.25 mg for control (N = 56), and 3.31 +/- 0.28 mg for Mn-treated group (N = 85) (p less than 0.001). In contrast, male mouse thyroids never became goitrous following this treatment. Manganese was goitrogenic to the castrated male mouse, but it had no effect on the testosterone-treated castrated male mouse, indicating the involvement of androgen in goiter formation. Oral administration of Mn did not severely affect blocked T/S of 125I or iodine metabolism in the thyroid. A morphological study, however, revealed that the epithelial cell in the Mn-treated mouse thyroid became flatter than that of the control. The lumens were filed with colloid in Mn-treated female mouse thyroid. The serum levels of thyroxine (T4), but not triiodothyronine (T3), were slightly reduced by Mn. These informations suggest that Mn can be a mild goitrogen for the female mouse and that the etiology of goiter formation can be interpreted by retention of colloid in the lumen.

PMID: 4092670, UI: 86135843

Arch Toxicol 1983 Nov;54(3):243-6

Rats were treated with MnSO4, H2O (1 mg/100 g/day, SC) for a period of 5 weeks. Thyroxine (T4) and triiodothyronine (T3) levels were measured in thyroid by radioimmunoassay. T4, T3 and thyroid-stimulating hormone (TSH) levels were also estimated by radioimmunoassay in serum. Manganese treatment produced no change in thyroid T4 and T3 levels but induced a significant decrease in serum T4, T3 and TSH levels. This decrease can be interpreted as the result of a pituitary alteration which appears to be related to the high accumulation of manganese in the pituitary gland.

 

: Endokrynol Pol 1993;44(1):57-63

[Effect of occupational environment containing manganese on thyroid function].

[Article in Polish]

Misiewicz A, Radwan K, Karmolinski M, Dziewit T, Matysek A

VI Katedra i Klinika Chorob Wewnetrznych Slaskiej AM, Katowicach.

Significantly lower blood serum concentrations of triiodothyronine (T3) and thyroxine (T4) accompanied by a significantly higher concentration of thyrotropin (TSH) have been found in workers exposed to the environmental presence of manganese, iron chromates and other agents as compared to the control group (differing with respect to the environmental exposure to manganese only)

Br J Nutr 1979 Mar;41(2):253-61

Trace nutrients. 2. Manganese in British food.

Wenlock RW, Buss DH, Dixon EJ

1. The amount of manganese in nationally-representative samples of prepared and cooked groups of foods, and in a wide variety of individual foods, was determined by atomic absorption spectroscopy. 2. The average British diet was calculated to provide 4.6 mg Mn/d of which half was derived from tea and other beverages, 30% from cereals, and 15% from vegetables and fruit. Animal products provided little Mn. 3. Individual foods other than tea which were particularly rich in Mn in Britain were unrefined and partially-refined cereals, and some spices and herbs. Some vegetables and fruit, coffee, wine, chocolate and brown sugar also contained significant amounts of Mn.

PMID: 427078, UI: 79145327

Am J Clin Nutr 1983 Dec;38(6):936-42

Tea and coffee as sources of some minerals in the New Zealand diet.

Gillies ME, Birkbeck JA

Daily intakes of tea and coffee of a representative sample of adult New Zealanders (865 men and 1100 women) were calculated from 24-h dietary recalls. The mineral concentrations in tea and coffee samples were determined by atomic absorption spectrometry and used to estimate daily mineral intakes from these beverages. More than 80% consumed tea and about 60% consumed coffee on the day of the recall. The men drank significantly more tea than the women (p less than 0.001), but coffee intakes were similar. The results indicate that for New Zealand adults tea is a very good source of manganese and it also contains appreciable amounts of potassium. Coffee is a better source of potassium than tea, has appreciable amounts of magnesium, and may contribute significantly to manganese intakes in some instances. The amounts of copper, zinc, sodium, calcium, and iron extracted from tea leaves and coffee beans in the brewing processes are too low to be of any nutritional significance but minerals in the water used in their preparation may make a significant contribution to dietary intakes.

PMID: 6650450, UI: 84076931

Burch HB, Barnes S, Nagy EV, Sellitti D, Burman KD, Bahn RS, Lahiri S

Endocrine-Metabolic Service, Kyle Metabolic Unit, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.

The identification of antigenic targets in the retroocular autoimmune response of Graves' ophthalmopathy is likely to increase our understanding of mechanisms underlying this disorder. While a number of putative autoantigens have been identified on the basis of molecular weight or cell of origin, a determination of the significance of these antigens is contingent upon an identification of the amino acid sequence. Our group has previously identified immunoreactive retroocular fibroblast (ROF) proteins recognized by thyrotropin receptor (hTSH-R) antisera (anti-p1), at molecular weights of 95, 71, 41, and 14-25 kDa. In the present study, proteins detected by anti-p1 and visualized by Ponceau staining were isolated and processed for microsequencing. Ponceau staining revealed dense bands at molecular weights of 14 and 23 kDa, and a weak band at 41 kDa. N-terminal sequencing was performed on the prominent band at approximately 23 kDa, showing it to be manganese superoxide dismutase (MnSOD), a mitochondrial enzyme responsible for protection against oxygen free radical-associated cellular damage. Sequence comparison of MnSOD to the hTSH-R peptide, p1, revealed a linear segment of amino acid homology. Preincubation of anti-p1 with p1 blocked immunodetection of the 23 kDa band corresponding to MnSOD, and immunoprecipitation of ROF protein using anti-pi yielded protein recognized by anti-MnSOD. Autoimmunity against human recombinant MnSOD was further assessed by ELISA. Patients with Graves' disease (n = 53) had significantly higher ELISA indices than normal control subjects (n = 29), while patients with Hashimoto's thyroiditis had intermediate values. These results document MnSOD autoantibodies in patients with Graves' disease and suggest that this may result from an immune cross-reactivity between MnSOD and the TSH-receptor.

PMID: 9633023, UI: 98296679

J Am Coll Nutr 1993 Aug;12(4):384-9

The role of trace minerals in osteoporosis.

Saltman PD, Strause LG

Dept. of Biology, University of California San Diego, La Jolla 92093.

Osteoporosis is a multifactorial disease with dimensions of genetics, endocrine function, exercise and nutritional considerations. Of particular considerations are calcium (Ca) status, Vitamin D, fluoride, magnesium and other trace elements. Several trace elements, particularly copper (Cu), manganese (Mn) and zinc (Zn), are essential in bone metabolism as cofactors for specific enzymes. Our investigations regarding the role of Cu, Mn and Zn in bone metabolism include data from studies with animals on Cu- and Mn-deficient diets. We have also demonstrated cellular deficiencies using bone powder implants, as well as fundamental changes in organic matrix constituents. In clinical studies we have demonstrated the efficacy of Ca, Cu, Mn and Zn supplementation on spinal bone mineral density in postmenopausal women. Each of these studies demonstrated the necessity of trace elements for optimal bone matrix development and bone density sustenance.

PMID: 8409100, UI: 94013998

Title

Heavy metal concentrations in blood cells in patients with amyotrophic lateral sclerosis.

Author

Nagata H; Miyata S; Nakamura S; Kameyama M; Katsui Y

Source

J Neurol Sci, 67(2):173-8 1985 Feb

Abstract

Manganese (Mn) and selenium (Se) concentrations in blood cells were measured by neutron activation analysis. Blood was obtained from patients with amyotrophic lateral sclerosis (ALS), patients with other neurological diseases and control subjects. Dried blood cells were activated by neutron irradiation. Mn was determined after chemical separation and Se was determined nondestructively. Mn concentrations in blood cells from ALS patients were significantly lower (P less than 0.01) than those from the other groups. The Mn concentrations were also significantly lower (P less than 0.01) in late than in earlier stages of ALS. Se concentrations in blood cells from ALS patients were significantly higher (P less than 0.01) than those from the other two groups. A generalized abnormal distribution of these metals may play a role in the pathogenesis of this disorder. Bromine, zinc, rubidium, and iron concentrations of erythrocytes were the same in all groups.

Title

Origin of the background sodium current and effects of sodium removal in cultured embryonic cardiac cells.

Author

Mead RH; Clusin WT

Source

Circ Res, 55(1):67-77 1984 Jul

Abstract

Cardiac automaticity is partly due to a diastolic sodium current. Possible mediators of this include tetrodotoxin-sensitive "fast channels, cesium-sensitive time-dependent pacemaker current channels, calcium-gated nonspecific channels, and electrogenic sodium-calcium exchange. We have studied the effects of abrupt sodium removal on membrane current and conductance in voltage-clamped chick embryonic myocardial cell aggregates, in the presence of various sodium flux inhibitors. Total replacement of sodium by lithium, Tris, or tetraethylammonium ions in aggregates clamped in the pacemaker range caused a brief outward current followed by a sustained net inward current. The outward current reached a peak value of 1.1 +/- 0.5 microA/cm2 at a mean latency of 5.4 +/- 1.2 sec. (n = 6; V = -70.5 +/- 8.9 mV; Tris). Conductance often decreased during the outward current. The inward current developed exponentially (t = 19 +/- 5 sec) and reached a steady state value of -1.6 +/- 0.4 microA/cm2. This current was reversed by depolarization (mean reversal potential = -13 +/- 13 mV), and was accompanied by increased conductance and spontaneous mechanical activity. Neither of the sodium-removal currents was affected by 20 microM tetrodotoxin. Cesium (up to 20 mM) had no effect on the late inward current or the mechanical activity, but decreased the early outward current by 80 +/- 12%. Manganese (25 mM), which blocks sodium-calcium exchange, abolished the late inward current and the mechanical activity. Manganese also reduced the early outward current by 27 +/- 10%. Manganese and cesium together blocked all the effects of sodium removal. We conclude that removal of extracellular sodium interrupts a cesium-sensitive "background current, that may be related to the time-dependent pacemaker current, If. Sodium removal also causes gradual activation of a nonspecific conductance, which can ultimately depolarize the cells, and which may be gated by cytoplasmic calcium.

 

 

: FEBS Lett 1997 Oct 13;416(1):69-71

Induction of manganese superoxide dismutase by thyroid stimulating hormone in rat thyroid cells.

Nishida S, Nakano T, Kimoto S, Kusunoki T, Suzuki K, Taniguchi N, Murata K, Tomura TT

Department of Biochemistry and Oncology, Kinki University School of Medicine, Osakasayama, Osaka, Japan. nishida@med.kindai.ac.jp

Alterations in the superoxide dismutase (SOD) content of thyroid tissues occurring in association with thyroid dysfunction have been reported. In this study, the Mn-SOD content was found to increase in thyroid tissues of rats administered thyroid stimulating hormone (TSH) and in thyrocytes cultured in medium supplemented with TSH. Furthermore, in the thyroid glands of rats whose serum TSH level was elevated by inhibiting the synthesis of T3 and T4 by 6-methyl-2-thiouracil, the Mn-SOD increased as the TSH concentration increased. In the cultured thyrocytes, the increase in Mn-SOD induced by TSH was inhibited by the C-kinase inhibitor H7. These findings suggest the induction of Mn-SOD by TSH in thyroid cells and point to a role of C-kinase in this process, thereby indicating that a close relationship exists between the serum TSH level and the change in Mn-SOD content in thyrocytes with thyroid dysfunction.

 

Acta Endocrinol (Copenh) 1993 Dec;129(6):573-8

t

Localization of Cu/Zn and Mn superoxide dismutase in various thyroid disorders.

Iwase K, Nagasaka A, Kato K, Ohtani S, Tsujimura T, Inagaki A, Jimbo S, Nakai A, Masunaga R, Hamada M, et al

Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan.

The intracellular localization of Cu/Zn- and Mn-superoxide dismutase (SOD), which catalyze the dismutation of superoxide radicals (O2-) to O2 and H2O2, was studied in the thyroid tissue of various thyroid disorders by an immunohistochemical technique. The concentrations of both SODs in those tissues were measured also by a sandwich enzyme immunoassay technique. Copper/zinc-SOD in thyroid tissues were identified by immunocytochemical staining in most cases of papillary carcinoma and in some cases of other thyroid disorders. In normal follicular cells this enzyme is localized in the perinuclear cytoplasm, whereas in thyroid tumor or hyperplastic follicular cells it exists homogeneously in cytoplasm. Manganese-SOD stained strongly in papillary carcinoma and papillary-growing cells in the thyroid tissue of adenoma and Graves' disease. The concentrations of Cu/Zn-and Mn-SOD in thyroid tumor tissues and hyperplastic follicular disorders were significantly higher than those in normal thyroid tissue when they were compared as a function of protein or deoxyribonucleic acid contents. The ratio of Mn-SOD to Cu/Zn-SOD was significantly higher only in papillary carcinoma, except for other thyroid disorders as compared with that in the normal thyroid. In conclusion, SOD seems to be related to cell proliferation and differentiation in the thyroid follicular cell because Cu/Zn-SOD changes its localization in tumor and hyperplastic follicular cells and because the Mn-SOD concentration is increased in papillary carcinoma or papillary-growing cells.

 

 

J Toxicol Clin Toxicol 1999;37(2):293-307

Manganese.

Barceloux DG

dgbarcelou@aol.com

Manganese is a very hard, brittle metal, which is used to increase the strength of steel alloys. Absorption from the gastrointestinal tract occurs in the divalent and tetravalent forms. Permanganates, which are strong oxidizing agents, have a +7 valence. The principal organomanganese compound is the anti-knock additive, methylcyclopentadienyl manganese tricarbonyl. Manganese is a ubiquitous constituent of the environment comprising about 0.1% of the earth's crust. For the general population, food is the most important source of manganese with daily intake ranging from 2-9 mg Mn. Combustion of gasoline containing methylcyclopentadienyl manganese tricarbonyl releases submicron particles of Mn3O4 that are potentially respirable. Biomagnification of manganese in the food chain probably does not occur. The lungs and gastrointestinal tract absorb some manganese, but the relative amounts absorbed from each site are not known. Homeostatic mechanisms limit the absorption of manganese from the gastrointestinal tract. Elimination of manganese occurs primarily by excretion into the bile. Animal studies indicate that manganese is an essential co-factor for enzymes, such as hexokinase, superoxide dismutase, and xanthine oxidase. However, no case of manganese deficiency in humans has been identified. Manganism is a central nervous system disease first described in the 1800s following exposure to high concentrations of manganese oxides. Manganese madness was the term used to describe the initial psychiatric syndrome (compulsive behavior, emotional lability, hallucinations). More commonly, these workers developed a Parkinson's-like syndrome. Currently, the risks of exposure to low concentrations of manganese in the industrial and in the environmental settings (e.g., methylcyclopentadienyl manganese tricarbonyl in gasoline) are being evaluated with regards to the development of subclinical neuropsychological changes. The American Conference of Governmental and Industrial Hygienists recently lowered the TLV-TWA for manganese compounds and inorganic manganese compounds to 0.2 mg Mn/m3.

 

 

 

Subj: MANGANESE AND NOREPI
Date: 10/19/00 6:31:04 PM Pacific Standard Time
From: BU 007
To: BU 007

Subj: Re: Rigidity
Date: 10/19/00 8:05:33 AM Pacific Daylight Time
From: docv@COX-INTERNET.COM (kirk vestal)
Sender: WILSONS-LIST@LISTSERV.ACSU.BUFFALO.EDU (Wilson's Disease Discussion Group)
Reply-to: WILSONS-LIST@LISTSERV.ACSU.BUFFALO.EDU (Wilson's Disease Discussion Group)
To: WILSONS-LIST@LISTSERV.ACSU.BUFFALO.EDU

mn and mo may be antaganists to cu in someone without wilsons disease. they would be lethal if used solely for treatment in someone with wd in about 6 months to a year! mo is required in 3 enzymes. mo inhibits copper containing enzymes and ceruloplasmin which is a carrier of cu normally. wd people need all the normal copper containing enzymes and ceruloplasmin possible to prevent damage like oxidation causing arthritis, kidney damage, liver damage, basal ganglia damage, etc. the trouble in wd is free cu in the blood getting absorbed at various sites causing damage thru mostly oxidation of surrounding molecules and the lack of normal cu containing enzymes like superoxide dismutase which helps stop oxidative damage. manganese, atomic number 25, is different from magnesium, atomic number 12. i cant find where mn may have an antagonistic effect on cu? mn is required for at least 12 or 15 processes. it is essential to all higher forms of life above a bacteria as it is used in ATP production, an energy metabolite. too much mn or chronic mn poisoning has been described. this occurs in miners, foundry workers, welders, drug manufacturers, potters, glass, ceramic, varnish workers, and food additive workers. the symptoms are schizophrenia and parkinsons like! it is thought mn is required for norepinephrine synthesis and hence, dopamine synthesis. mn intoxication has also been found in chronic liver falure victims. i got this data from Tietz textbook of clinical chemistry 1999 edition. tietz is more authoritative and safer to rely upon than some natural foods book. drv

 

 

Compr Psychiatry 1991 May-Jun;32(3):229-37

Abnormalities in hair trace elements as indicators of aberrant behavior.

Gottschalk LA, Rebello T, Buchsbaum MS, Tucker HG, Hodges EL.

Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine 92717.

There are long-standing viewpoints that impulsive and violent behavior may stem from brain dysfunction or damage secondary to head injury, disease, or toxic chemical substances. This research has aimed to examine the relationship between potentially toxic metals and aberrant behavior, especially violent activity, through the nonintrusive technique of hair analysis for trace elements. In an initial study, phase I, it was not possible to replicate findings of others who reported high levels of lead, cadmium, and copper in violent offenders. However, high levels of manganese were found in prison versus control groups. In phase II, the possibility of artifactual results arising from prison cooking utensils was controlled for by sampling early after incarceration. Phase III was included to substantiate the initial post hoc findings in an additional jail population. In both latter phases, significantly elevated manganese levels were found in the hair of violent versus nonviolent subjects (P less than .0001). A review of the effects of manganese at deficient and toxic levels does not provide a simple answer as to why manganese levels are elevated in the hair of individuals who have been incarcerated for violent behavior. Our study does not implicate the prison environment or soaps and shampoos used in California prisons. Other factors, such as alcohol, dietary, or psychosocial factors, might influence manganese levels in hair, or any of these factors might function in combination with mild manganese toxicity to contribute to aberrant behavior.