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Gallium is a remarkably strange, powerful, and very understudied nutrient. There are ample studies listed below showing that a gallium deficiency might be involved in Graves' disease, ophthalmopathy, autoimmune diseases like lupus, osteoporosis, and cancer. When you look at the whole picture of gallium, it looks like a deficiency of gallium is a key part of Graves' and hyperthyroidism. However, at this point, based upon my personal experimentations with gallium, I'm not sure and can't recommend its use.
This study shows that in Graves' hyperthyroidism, gallium uptake by the thyroid, thymus, and tear glands is accelerated. Is this due to a deficiency of gallium and the thyroid and other organs are preferentially accumulating it to correct the deficiency? I'm not sure.
A patient with hyperthyroid Graves' disease presented with ptosis, leading to a workup for myasthenia gravis. An enlarged thymus gland was noted on computed tomography. A scan with gallium-67 citrate showed prominent and diffuse thyroid gland activity as well as prominent lacrimal activity. This finding of thyroid uptake of gallium led to the correct diagnosis of Graves' disease. Such a finding has not been reported previously. The associated thymic, thyroid, and orbital findings in Graves' disease are discussed.
The following study states, "Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma."
Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patients with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake.
The following study shows gallium accumulation in adenomatous goiter. This could be interpreted that gallium is involved in the etiology of the goiter or that the body has sent the gallium to the site as part of a corrective measure.
An elderly woman with a diffusely enlarged goiter and multiple miliary nodular lesions on chest x-ray showed Ga-67 accumulation in the right thyroid lobe. Histologic findings obtained after total thyroidectomy and open lung biopsy revealed papillary carcinoma in the left lobe with pulmonary metastases and adenomatous nodules in the right lobe. This is the first report of Ga-67 accumulation in adenomatous goiter.
The following study sheds more light on gallium's role in building bone. Following gallium administration, increased levels of bone calcium were found. Also gallium accumulates in the active areas of bone formation indicating that it plays an active role in the formation of bone. Another study which indicates a gallium deficiency may be involved in osteoporosis, which we know is a disease which accompanies Graves'.
Gallium, a group IIIa metal, is known to interact with hydroxyapatite as well as the cellular components of bone. In recent studies we have found gallium to be a potent inhibitor of bone resorption that is clinically effective in controlling cancer-related hypercalcemia as well as the accelerated bone resorption associated with bone metastases. To begin to elucidate gallium's mechanism of action we have examined its effects on bone mineral properties. After short-term (14 days) administration to rats, gallium nitrate produced measurable changes in bone mineral properties. Using atomic absorption spectroscopy, low levels of gallium were noted to preferentially accumulate in regions of active bone formation, 0.54 +/- .07 microgram/mg bone in the metaphyses versus 0.21 +/- .03 microgram/mg bone in the diaphyses, P less than 0.001. The bones of treated animals had increased calcium content measured spectrophotometrically. Rats injected with radiolabeled calcium during gallium treatment had greater 45-calcium content compared to control animals. By wide-angle X-ray analyses, larger and/or more perfect hydroxyapatite was observed. The combined effects of gallium on bone cell function and bone mineral may explain its clinical efficacy in blocking accelerated bone resorption.
The following study shows that gallium and zinc are antagonistic minerals which can compete for absorption.
Selective inhibition of enzymes in the heme biosynthesis pathway with concomitant urinary excretion of heme precursors serve as potentially important biological markers of chemical exposure and cell injury. Intratracheal administration of gallium arsenide particulate suspensions has been shown to result in inhibition of delta-aminolevulinic acid dehydratase (ALAD) in several tissues and increased excretion of the heme precursor aminolevulinic acid (ALA). This study was undertaken to evaluate in vivo the role of gallium alone in ALAD inhibition and increased urinary excretion of ALA. Male CD rats received a single ip injection of Ga2(SO4)3 at doses of 12.5, 25, 50, 100, and 200 mg Ga/kg. A dose-dependent inhibition of ALAD was observed 24 hr later in liver, kidney, and erythrocytes. After injection of 25 mg Ga/kg, maximal inhibition (42 to 49% of control) of ALAD occurred between 6 and 24 hr in liver and kidney with full recovery of activity at 96 hr. In erythrocytes, maximal inhibition (48% of control) occurred between 24 and 48 hr with recovery of activity at 96 hr. Mild to moderate renal proximal tubular necrosis in the pars recta was observed 24 hr after administration of 100 and 200 mg/kg, but no histopathologic changes were evident at lower doses. No consistent changes in urinary excretion of ALA were observed. Lineweaver-Burk analyses of renal and hepatic ALAD activities in the absence and presence of gallium indicated that the inhibition of ALAD by this element is noncompetitive (same Km, decreased Vmax). Gallium was shown to possess an inhibition constant (Ki) of approximately 3 microns for ALAD, similar to the Ki obtained for lead in other studies. Incubation of ALAD in vitro with gallium and lead, an active thiol group inhibitor, resulted in a greater inhibition of the enzyme. Further in vitro studies demonstrated the attenuation of gallium inhibition of hepatic and renal ALAD by zinc, suggesting that the mechanism of gallium action may involve competition for or displacement of zinc from the sulfhydryl group of the enzyme active site. Since ALAD inhibition occurred at doses at which no histopathologic changes were evident, the determination of ALAD activity in various tissues, including blood, may be of potential value as a biomarker of exposure/toxicity to metals such as gallium. The effect of chemical form and route of exposure of gallium and effects of other Group III metals on inhibition of ALAD and excretion of ALA is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
The following study shows that gallium causes the death of tumor cells because it binds to transferrin, thereby preventing iron from being transported to the tumor cells. It is known that lowering iron levels will suppress tumor growth. Bear in mind that the gallium levels used in this type of experiment far exceed what would be a normal physiological dose. One important lesson from this study is that high levels of gallium can suppress iron levels and we know that iron is essential for proper thyroid function. A small amount of gallium may help but a large amount may impede thyroidal health.
Gallium, when bound to transferrin, has been previously shown to cause tumor cell cytotoxicity by preventing cellular uptake of transferrin bound iron in vitro. Patients treated with constant infusion gallium nitrate for carcinoma show a rise in serum iron within 6 hr of the start of treatment. Serum iron returns to baseline by 24 hr post-infusion. Atomic analysis of iron and gallium content of Sephadex G-150 fractions of treatment sera indicate that about an equimolar amount of gallium and iron are associated with transferrin. These gallium and iron concentrations result in inhibition of transferrin mediated iron uptake in vitro, and in vivo allow for > 90% saturation of transferrin with metal. All seven patients who completed two courses of gallium therapy exhibited hypochromic microcytic anemia (mean fall in hemoglobin 3.5 grams %). Evidence for red cell iron depletion was confirmed by an increase (mean 3.3-fold) in zinc protoporphyrin levels. Since transferrin receptor increases on gallium treated iron requiring cells in vitro, we assessed cell surface transferrin receptor on peripheral blood lymphocytes by measuring fluorescent transferrin receptor antibody binding. A population of highly transferrin receptor positive cells peaks at 48 hr into the infusion. DNA analysis as well as double staining indicate the majority of transferrin receptor positive cells are unstimulated B lymphocytes. These studies provide the first documentation that constant infusion gallium treatment results in significant interference with iron metabolism and evidence for tissue iron depletion in vivo. These changes may correlate with therapeutic effects of gallium such as tumor response.
Following is a study showing that gallium inhibits tumor growth in lung cancer. Besides demonstrating that smokers or ex-smokers would be wise to drink green tea, it offers a suggestion that gallium may be an antagonist of cadmium, which is probably the key toxic metal which is responsible for lung cancer.
The dose of gallium chloride required to inhibit tumor growth after oral and chronic administration depends on the stage of the cancer disease and of the type of metastases. A dose regimen of 800 mg/24 h of gallium chloride will provide serum gallium concentrations greater than or equal to 600 micrograms/l in lung cancer patients with a small and limited disease. A dose of 1,400 mg/24 h is well tolerated in metastatic patients but may not be high enough to reach the desired serum gallium concentrations especially in patients with bone metastases. Radiotherapy and/or a chemotherapy will permit one to increase the serum gallium concentrations and the tumor gallium uptake by reducing the volume of the tumor. After chronic, oral administration of gallium a decrease in RBC Mg is noted. To avoid the Mg deficiency, the treatment must not be interrupted and may perhaps be decreased with care and slowly without resulting in a decrease of the serum gallium concentrations provided the treatment has been prolonged over a sufficient time to enable one to induce intratumor biological modifications and a decrease in the number of the malignant cells. Acute pharmacokinetic data are related to the histologic type of the tumor and may not be used to predict the serum gallium concentrations after chronic administration. The serum gallium concentrations required to inhibit the tumor growth may be higher in small cell lung carcinomas than in nonsmall cell lung carcinomas. Frequent Mg and Ga blood determinations are necessary to manage effective gallium treatment.
The following study indicates that gallium at 96 mgs per kilogram of body weight does not cause adverse effects. Based on this information I took 1/2 mg for my body weight of 100 kgs. I noticed an effect and feel that this is too much. However, it is possible that I was iron-deficient at the time and the negative effect of the gallium was due to a further depletion of iron. If you ever think about taking a gallium supplement, talk to me first.
Reproduction studies were performed with gallium nitrate, an antihypercalcaemic drug that is also used as a chemotherapeutic agent for the treatment of certain malignancies. Male mice were injected subcutaneously with gallium nitrate at doses of 0 (controls), 24, 48 and 96 mg/kg/day every other day for 14 days before mating with untreated females. Fertility and reproductive performance in the gallium nitrate-treated groups did not differ significantly from controls. No significant changes were observed in the relative testes and epididymis weights. Sperm counts in the gallium nitrate-dosed groups were comparable with those in the control group, whereas the percentage of motile cells was similar between treated and untreated animals. Histopathological examination of the testes and epididymis did not reveal any changes at any dose of gallium nitrate. The no-observed-adverse effect level was 96 mg/kg body weight. This dose is about 30 times higher than the current doses of gallium nitrate administered to humans.
The following toxicity study on gallium shows that, "
Galliumnitrate, a drug with antitumor activity, is presently undergoing clinical trials as a chemotherapeutic agent for the treatment of certain malignancies. Since there are very limited published animal toxicity data available, this study was conducted to investigate the potential adverse developmental effects of this drug. Pregnant Swiss mice were administered intraperitoneally gallium nitrate at 12.5, 25, 50, and 100 mg/kg/day on days 6, 8, 10, 12, and 14 of gestation. Monitors for maternal toxicity were body weight, food consumption and clinical signs. At sacrifice (day 18) maternal weight, liver and kidney weights, and gravid uterine weights were measured. Gestational parameters monitored were numbers of total implants, resorptions, postimplantation losses, and dead fetuses. Live fetuses were sexed, weighted, and examined for external, internal and skeletal malformations and variations. Maternal toxicity was noted in all the gallium nitrate-treated groups. Embryo/fetal toxicity was evidenced by a decrease in the number of viable implants, a reduction in fetal weight, and an increase in the number of skeletal variations (12.5, 25, 50 and 100 mg/kg). No significant increase in the incidence of malformations was observed at 12.5, 25, or 50 mg/kg. The no-observable-adverse-effect level (NOAEL) for both maternal and developmental toxicity of gallium nitrate was less than 12.5 mg/kg.
The following study shows that gallium preferentially binds to mucopolysaccharides. These are the proteins which are involved in the retro-ocular fibroblast proliferation found in ophthalmopathy (TED) and in pre-tibial myxedema.
Normal male rats were injected with either gallium citrate Ga 67 or sodium sulfate S 35. After 24 h, the stomach, small intestine, pancreas, and muscle were excised and homogenized. After the removal of the nuclear fraction, each of these homogenates was digested with protease. After digestion, the supernatants of the reaction mixtures were applied to a Sephadex-G-100 column. The radioactivity was eluted with buffer solution. The resultant eluates were analyzed for radioactivity and the levels of proteins, uronic acids, and sialic acids. In all four organs, sizable amounts of 67Ga were bound to sulfated acid mucopolysaccharides with molecular masses of about 10,000 daltons and to sulfated acid mucopolysaccharides, a species whose molecular masses exceed 40,000 daltons. In the stomach, large amounts of 67Ga were bound to sulfated acid mucopolysaccharides with molecular masses of about 10,000 daltons. From these results, it is obvious that the main 67Ga-binding substances in these four organs are sulfated acid mucopolysaccharides, and that these acid mucopolysaccharides play the most important role in the concentration of 67Ga in these organs.
The following study shows that the binding location for gallium in tumor cells and inflammatory tissues is the mucopolysaccharide, heparin sulfate. The significance of this is unknown to me at this time but it looks like it may be important in light of the fact of sulfur's important role in thyroid disease.
The role of heparan sulfate (HS) in gallium citrate Ga 67 binding to rat-liver plasma membrane was investigated. HS was found to be the only acid mucopolysaccharide present on the plasma-membrane surface. The extent of 67Ga binding to the plasma membrane reached a plateau 1-2 h after the start of incubation, and binding was higher under alkaline conditions than under acidic conditions. The amount of binding increased in parallel with the protein concentration of the plasma membrane (up to 2 mg per incubation mixture). Solubilizing agents, such as bromelin and 1% Triton X-100 as well as 2 M NaCl and heparin, markedly decreased 67Ga binding, and the decrease in 67Ga binding to the plasma membrane was closely associated with the amount of HS released from the plasma-membrane surface by each solubilizing agent. On the other hand, treatment with HS markedly increased 67Ga binding to about three times the control level. These data provide further support for our previous proposal that HS plays an important role as a receptor for gallium in various tissues, including tumor cells and inflammatory tissues.
The following study shows that gallium is effective in suppressing autoimmune disease. Uveitis is an inflammation of part or all of the uvea, the middle (vascular) tunic of the eye.
Gallium nitrate (GN) has been shown to inhibit T cell-mediated inflammatory disease. The purpose of our study was to test the effect of gallium nitrate (GN) on experimental autoimmune uveitis (EAU). Experimental autoimmune uveitis was induced in male Lewis rats immunized with retinal S-antigen. Rats received subcutaneous injections of GN or saline one day prior to immunization and 1, 4, 7, 10, 13, 16, and 19 days after immunization. Ocular inflammation was graded clinically and histologically by masked observers, and in vitro assays of cell-mediated and humoral immunity were performed. GN significantly inhibited the development of EAU graded clinically (P = 0.001) and histologically (P = 0.002). Treatment with GN also resulted in a small (30-41%) decrease in the lymphocyte responses to retinal S-Antigen and a small (12-37%) reduction in antibody production to S-antigen. These data show that GN suppresses the development of EAU, and inhibits both lymphocyte proliferative responses to antigen and antibody production.
The following study suggests that gallium may inhibit the production of IgG antibodies. These are the antibodies believed to trigger hyperthyroidism in Graves' disease. However, the gallium was combined with arsenic, so the results are difficult to interpret.
The effects of gallium arsenide (GaAs) exposure on immunocompetence of B6C3F1 female mice were investigated. GaAs was administered as a single intratracheal instillation at doses of 50, 100, and 200 mg/kg. Fourteen days after exposure, various cellular and humoral immune parameters were assessed. GaAs exposure increased spleen cellularity in a dose-dependent manner. However, the percentages of Thy 1.2 positive and Ig positive cells were decreased and that of F4/80 positive cells was increased dose dependently. The IgM and IgG antibody-forming cell response of the spleen to the T-dependent antigen sheep erythrocytes was reduced by 66 and 48%, respectively, at 200 mg/kg. Levels of the serum complement protein, C3, were increased by as much as 16% with no significant change in CH50 levels. The mitogenic response of splenic T cells to Con A and PHA was unaffected by GaAs, but that of B cells to LPS was increased by 52%. The delayed hypersensitivity response to keyhole limpet hemocyanin and mixed lymphocyte response were significantly reduced in a dose-dependent manner by GaAs exposure. Natural killer cell activity against the YAC-1 mouse lymphoma was enhanced in treated mice. Analysis of peritoneal exudate cells (PEC) revealed a dose-dependent decrease in number and a shift in the composition of PECs. The percentage of PEC monocytes increased from 53% of the population to 81%, while the lymphocytes decreased from 46 to 20%. The adherent PEC population demonstrated decreased phagocytosis of covaspheres and increased phagocytosis of chicken erythrocytes (CRBC). GaAs exposure had no effect on host resistance to Plasmodium yoelii or Streptococcus pneumoniae, but dose dependently increased resistance of the mouse to Listeria monocytogenes. Treated mice demonstrated a significantly decreased resistance to the B16F10 melanoma with a sevenfold increase in tumor burden at 200 mg/kg. GaAs affects both humoral and cellular immune parameters in mice and impairs the ability of the immune system to protect against B16F10 tumor challenge.
Gallium (Ga) nitrate, a drug which prevents a variety of experimental autoimmune diseases, was investigated in a murine model of systemic lupus erythematosus (SLE). In one experiment, female MRL/Mp lpr/lpr (MRL/lpr) mice were randomized into 2 groups of 6: 1) vehicle (trisodium citrate) and 2) Ga. Subcutaneous injections began at 3 weeks of age and continued weekly until the mice were euthanized a week after the thirteenth injection. The loading dose of Ga (calculated as elemental Ga) was 45 mg/kg, followed by 15 mg/kg/week. In another experiment (n = 18) with 3 males and 3 females per group, mice received 1) vehicle, 2) Ga x 1 (one 45 mg/kg dose), and 3) Ga x 13. In the experiment with 12 mice, axillary lymph nodes from Ga-treated mice were significantly smaller than those from vehicle-treated mice (91+/-42 and 360+/-358 mg respectively, mean+/-SD), and spleens as well as lymph nodes from the former showed significantly less lymphoid infiltrate. In the experiment with 18 mice, prescapular lymph nodes weighed 312+/-98, 217+/-52, and 42+/-34 mg, and spleens weighed 732+/-492, 409+/-164, and 192+/-93 mg in the groups which received vehicle, Ga x 1, and Ga x 13 respectively. Control mice had significantly more lymphoid infiltrates in the lungs, spleen, and lymph nodes and, unlike Ga x 13 mice, exhibited glomerulitis and renal vasculitis. Within groups, females developed more severe disease than males. The Ga x 13 group had increased percentages of CD4-bearing and CD8-bearing lymphocytes in lymph nodes and increased CD4-bearing lymphocytes in the spleen, with an increased proliferative response to mitogen stimulation in vitro in lymph nodes, although not in the spleen. The Ga x 13 group also gained less weight and developed osteosclerosis. Although preliminary, our findings suggest that clinical trials with Ga in SLE are merited.
The following study shows a significant gallium accumulation in the orbits and parotid glands of a patient with Sjogren's syndrome, a disease which appears related to Graves' disease and which seems to involve disturbances of copper metabolism.
An 8-year-old girl with hypergammaglobulinemia showed an abnormal 67gallium accumulation in the orbits and parotid glands. Although she did not have any subjective siccant complaints, reported typical histopathological and sialographic changes suggesting Sj¨ogren's syndrome (SjS) were observed in the salivary glands. Gallium scintigram might be a valuable and non-invasive diagnostic tool in the diagnosis of children with SjS without sicca symptoms.
Galliumis a group IIIa metal that has efficacy in the therapy of malignant disorders such as lymphoma and urothelial tract tumors. Preclinical studies also indicate a role for gallium in autoimmune disorders, suggesting that gallium is able to modulate T-cell immune reactivity. The purpose of this study was to examine the in vitro and in vivo immunomodulatory action of gallium on T-cell function. Since gallium binds to transferrin in vivo, in vitro studies evaluated the effect of transferrin-gallium (Tf-Ga) on human T cells. Tf-Ga inhibited the mitogen-induced proliferative response of peripheral blood mononuclear cells (PBMC) in a dose-dependent fashion. Alloantigen-induced proliferation was also potently suppressed when evaluated in a mixed lymphocyte culture assay. Tf-Ga affected a significant reduction in the density of IL-2 receptors on activated T cells and a slight reduction in the number of CD3+/CD25+ T cells in PHA-stimulated cultures. Neither secretion of interleukin-2 (IL-2) nor the induction of IL-2-stimulated lymphokine-activated killer activity, however, was inhibited by Tf-Ga. Tf-Ga produced significant upregulation of the transferrin receptor (CD71) in T cells as determined by flow cytometric analysis and northern blot assay, but did not affect the percentage of CD3+/ CD71+ T cells after mitogen stimulation. To assess the in vivo effects of gallium on alloreactive T cells, we evaluated the immunosuppressive effect of gallium in a murine model of graft-versus-host disease (GVHD). Administration of gallium significantly prolonged survival in mice undergoing severe GVHD, suggesting that gallium can ameliorate GVH reactivity. Collectively, these data demonstrate that, at clinically achievable concentrations, Tf-Ga potently inhibits T-cell activation and that this immunosuppressive property of gallium may be of adjunctive therapeutic value in the management of disorders characterized by the presence of autoreactive or alloreactive T-cell populations.
The conclusion of the following study is that the mechanism by which gallium accumulates in inflammatory tissue is its binding to the acid mucopolysaccharide present in the tissue.
The present study was undertaken to elucidate the accumulation mechanism of gallium 67 in inflammatory tissue. 67Ga accumulation in inflammatory tissue was observed by macro- and microautoradiogram. Permeability indices were calculated for serum albumin from blood vessels into inflammatory and normal tissue. Neutrophils and macrophages did not play a major role in 67Ga accumulation in the inflammatory tissue because 67Ga could hardly be detected in the sites in which neutrophils were crowded; the accumulation was concentrated in the intercellular space around these cells in the tissue. Permeability indices for inflammatory tissue were much greater than those for normal tissues. It is thought from the present study and previously reported results that 67Ga, together with plasma from permeable blood vessels, readily penetrates the inflammatory tissue and stays there by binding to the acid mucopolysaccharide present in the tissue.
The following study shows that both gallium and iron have a high affinity for the acid mucopolysaccharide heparin sulfate. Also it was shown that high zinc intake caused an increase in the gallium uptake into the liver and a decrease in the iron uptake. Thus high zinc might interfere with the iron binding to heparin sulfate and this increases the availability of heparin sulfate to bind to gallium.
The relationship between 67Ga uptake and iron metabolism was investigated in rat tissues. 67Ga and 59Fe(II) both accumulated in the mitochondrial-lysosomal fraction after being injected. Moreover, they both showed especially high affinity for heparan sulfate (HS) among various acid mucopolysaccharides (AMPS). When iron (ferrous citrate) was injected IV before, simultaneously with, and after 67Ga citrate IV injection, 67Ga uptake was significantly inhibited in normal rat liver in all cases. Elevated 67Ga uptake in the liver of CCl4-treated rats was also lowered to the control level by iron pretreatment. High zinc intake remarkably elevated the 67Ga uptake in rat liver. The contents of iron in the liver and liver AMPS of 0.75% zinc-fed rats were lowered in comparison with those in controls. Thus, the elevation of 67Ga uptake in the liver of zinc-fed rats might be due to the decrease of iron bound to HS.
It was determined from measuring neutral saccharide in the structure that the principal 67Ga-binding acid mucopolysaccharide in liver was keratan sulfate and/or keratan polysulfate. On the other hand, it was clarified from the results of mucopolysaccharase treatment that the main 67Ga-binding acid mucopolysaccharide in liver was not either one of keratan sulfate, heparan sulfate, heparin, chondroitin sulfate A, B and C. Based on the present results, it was deduced that the main 67Ga-binding acid mucopolysaccharide in liver was keratan polysulfate.
Progressive systemic sclerosis (PSS) is a generalized disorder characterized by fibrosis of many organs including the lung parenchyma. Unlike most other interstitial disorders, traditional concepts of the interstitial lung disease associated with PSS have held it to be a "pure fibrotic disorder without a significant inflammatory component. To directly evaluate whether an active alveolitis is associated with this disorder, patients with chronic interstitial lung disease and PSS were studied by open lung biopsy, gallium-67 scanning, and bronchoalveolar lavage. Histologic evaluation of the biopsies demonstrated that the interstitial fibrosis of PSS is clearly associated with the presence of macrophages, lymphocytes, and polymorphonuclear leukocytes, both in the interstitium and on the alveolar epithelial surface. Gallium-67 scans were positive in 77% of the patients, showing diffuse, primarily lower zone uptake, suggestive of active inflammation. Consistent with the histologic findings, bronchoalveolar lavage studies demonstrated a mild increase in the proportions of neutrophils and eosinophils with occasional increased numbers of lymphocytes. Importantly, alveolar macrophages from patients with PSS showed increased release of fibronectin and alveolar-macrophage-derived growth factor, mediators that together stimulate lung fibroblasts to proliferate, thus suggesting at least one mechanism modulating the lung fibrosis of these patients. Thus, evidence from several different points of view together demonstrates that the interstitial lung disease associated with PSS is associated with chronic inflammation in the local milieu, leading to the hypothesis that the inflammation plays some role in the derangements to the alveolar structures that characterize this disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
The following study suggests that a gallium deficiency might be involved in Alzheimer's disease and Down syndrome. High aluminum is found in the brain in these diseases and since aluminum is directly above gallium in the Periodic Table, this suggests that a gallium deficiency allows the aluminum to accumulate. Another interpretation is that excessive iron binds to the transferrin depriving gallium from being transported by transferrin. This resultant lack of gallium allows aluminum to build up in the cells. Perhaps the disturbance starts with a copper deficiency which allows the iron to build up and occupy a dominate share of the transferrin binding sites.
Lancet1990 Mar 31;335(8692):747-50
Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminum in brain.
Farrar G, Altmann P, Welch S, Wychrij O, Ghose B, Lejeune J, Corbett J, Prasher V, Blair JA
Division of Biology, University of Aston, Birmingham, UK.
The plasma distribution of gallium (as an analogue of aluminium) was investigated in patients with Alzheimer disease, Down syndrome, or stroke dementia, in subjects on haemodialysis for chronic renal failure, and in healthy controls. Gallium-transferrin binding was significantly lower in the Alzheimer (mean [SEM] 7.9 [1.1]%) and Down syndrome groups (6.9 [0.7]%) than in the controls (17.1 [1.6]%), whereas stroke dementia and haemodialysis patients had normal binding. There were no differences among the groups in plasma citrate concentration. The plasma transferrin concentration was slightly lower in the Alzheimer and Down syndrome groups than in the controls, but even lower in stroke dementia patients (1.74 [0.14] g/l vs 2.98 [0.18] g/l in controls). Transferrin iron saturation was higher in the Alzheimer (58.9%) and Down syndrome groups (81.6%) than in the controls (39.0%) or stroke dementia patients (33.4%). This deficiency of gallium/aluminium binding would leave more unbound aluminium which could move readily into the brain, where it has neurotoxic effects.
The following is an interesting hypothesis that there is a connection between the metals found to make good semiconductors for computers and the metals which are found to have anti-tumor activity. I like the idea. Very thought provoking.
Med Hypotheses1988 Aug;26(4):239-49
Carcinogenesis as the result of the deficiency of some essential trace elements.
Department of Biochemistry, Silesian University, Katowice, Poland.
"Energetic" biological trace elements [gallium (III), germanium (IV), silicon (silica), arsenic (V) and selenium (IV)] occurring in DNA of eukaryotic cells may improve the semiconductor properties of DNA and may influence the mechanisms that control genetic expression at the electronic level. Their roles are postulated as follows: (i) to maintain the level and direction of free sliding electrons in DNA, (ii) to modulate the electron conductivity and hole conductivity of DNA. This specific electronic nature of DNA take the form of magnetic pigeonholes in which an electric pulse is (0), or is not (1) stored as an area of local magnetisation. These types of conductivity occurring in different parts of DNA of different cells could participate in the switch on and switch off of genetic information in gene expression. This model may help to elucidate the mechanism of action of these naturally occurring antitumor agents and may help in understanding the role of trace elements in charge transport of DNA and in carcinogenesis.
Following is an interesting study showing an increase accumulation of gallium in the lungs of patients with AIDS. Is a gallium deficiency involved in AIDS?
J Nucl Med1987 Dec;28(12):1915-9
Gallium scanning in lymphoid interstitial pneumonitis of children with AIDS.
Schiff RG, Kabat L, Kamani N
Department of Radiology, Schneider Children's Hospital, New Hyde Park, New York.
Lymphoid interstitial pneumonitis (LIP) is a frequent pulmonary complication in the child with the acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. We report the gallium scan findings in two children with AIDS and LIP. Gallium scintigraphy in both children demonstrated increased radionuclide concentration throughout the lungs, a pattern indistinguishable scintigraphically from that of Pneumocystis carinii pneumonia (PCP). This should alert nuclear medicine practitioners and referring physicians to another cause of diffusely increased gallium uptake in the lungs of patients with AIDS.
Another study indicating that intense gallium uptake by the thyroid is a characteristic of hyperthyroidism.
Gallium-avid painless thyroiditis in a patient with AIDS.
Achong DM, Snow KJ
Department of Radiology, New England Medical Center, Boston, Massachusetts 02111.
Intense thyroidal Ga-67 accumulation was seen in a man with AIDS imaged for suspected Pneumocystis carinii pneumonia. Concurrent Tc-99m pertechnetate thyroid scanning demonstrated absent trapping, helping establish the diagnosis of painless thyroiditis. Occult hyperthyroidism, and not pulmonary infection, may have been responsible for the patient's original presenting symptoms.
Another study linking uptake of gallium with thymus disease.
Thymic hyperplasia associated with Hodgkin disease and thyrotoxicosis.
Pendlebury SC, Boyages S, Koutts J, Boyages J
Joint Lymphoma Clinic, Westmead Hospital, New South Wales, Australia.
A 19-year-old woman had a residual gallium-sequestering mediastinal mass after treatment for Hodgkin disease. Coincidentally, she also had hyperthyroidism. The initial concern was that the mass was residual Hodgkin disease. Thymic hyperplasia has been described in association with both these conditions. The mass disappeared after treatment of her hyperthyroidism.
Cancer Chemother Rep1975 May-Jun;59(3):599-610
Another study showing the power of gallium to suppress cancer. If you ever get cancer, think of gallium first. Meanwhile drink green tea.
Studies on the antitumor activity of gallium nitrate (NSC-15200) and other group IIIa metal salts.
Adamson RH, Canellos GP, Sieber SM
Several group IIIa metal salts, eg, aluminum nitrate, gallium nitrate, indium nitrate, and thallium chloride, have been evaluated for in vivo toxicity in mice and rats, for cytotoxicity in tumor cells in vitro, and for activity against a broad spectrum of experimental rodent tumors. The position of these agents in the periodical table roughly parallels their toxicity, the LD50s decreasing with increasing atomic weights. This parallel also exists with regard to in vitro cytotoxicity to Walker 256 carcinosarcoma cells. Although all of the metal salts had activity against the ascites Walker 256 carcinosarcoma, they were ineffective in ascites leukemias, plasma cell tumors, or Ehrlich carcinoma. Gallium nitrate was particularly active against solid tumors transplanted subcutaneously, suppressing the growth of six of eight tumors more than 90%. Because of its demonstrated antitumor activity in rodents and its uptake and concentration by various animal and human tumors, gallium nitrate has potential usefulness in the treatment of solid tumors in man and has been entered into a phase I study at the National Cancer Institute.