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Germanium is considered to be a non-essential element; however, little is still known about its significance for living organisms. It exerts prophylactic and therapeutic effects in the treatment of serious diseases such as cancer, HIV infection, and others. Germanium does not exhibit acute toxicity, but, as it tends to accumulate in various organs and tissues, undesirable and even dangerous side effects have been reported after prolonged and/or high dosage application. In general, inorganic compounds of germanium are more toxic than its organic compounds. Further studies should be performed to elucidate the exact molecular mechanism of germanium action, to determine the safe and effective dose of germanium via curative/mineral waters, and to understand the applications and benefits of using germanium-enriched waters in balneotherapy. The geochemistry of curative (cold CO2-rich, thermal) waters from spas in the Sudetes (Poland) was clarified in terms of components and mineral phases which might govern germanium. Germanium and silicon in thermal (above 20 °C) waters presumably result from the solubility of silicates in crystalline (granites, gneisses) aquifer rocks and might be controlled by neo-formed quartz. The cold CO2-rich waters revealed a significant diversity of aqueous chemistry and relationships of germanium with iron, silicon, or arsenic. Locally, both in sedimentary (sandstones) and metamorphic (gneisses) aquifer rocks, primary (silicates) and/or secondary (oxides) iron-containing minerals likely release germanium into solution. In the CO2-rich waters of the western part of the Kłodzko Region, germanium distinctly correlates with arsenic. It is hypothesized that both elements are co-sourced from crystalline basement and/or migration of substances of post-magmatic origin along deep-seated dislocations related to the seismically active Poříčí-Hronov fault zone. This area was proposed as the most prospective one for finding waters rich in germanium in the Sudetes. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA) is a hard mineral component of mineralized tissues, mainly composed of calcium and phosphate. Due to its bioavailability, HA is potentially used for the repair and regeneration of mineralized tissues. For this purpose, the properties of HA are significantly improved by adding natural and synthetic materials. In this sense, the germanium (Ge) mineral was loaded in HA biomaterial by cold isostatic pressure for the first time and characterization and biocompatibility using bone marrow mesenchymal stem cells (BM-MSCs) were investigated. The addition of Ge at 5% improved the solubility (3.32%), stiffness (18.34 MPa), water holding (31.27%) and biodegradation (21.87%) properties of HA, compared to control. Compared to all composite biomaterials, the drug-releasing behavior of HA-3% Ge was higher at pH 1 and 3 and the maximum drug release was obtained at pH 7 and 9 with HA-5% Ge biomaterials. Among the different mediums tested, the DMEM-medium showed a higher drug release rate, especially at 60 min. HA-Ge biomaterials showed better protein adhesion and apatite layer formation, which ultimately proves the compatibility in BM-MSCs culture. Except for higher concentrations of HA (5 and 10 mg/mL), the different concentrations of Ge and HA and wells coated with 1% of HA-1% Ge had higher BM-MSCs growth than control. All these findings concluded that the fabricated HA biomaterials loaded with Ge could be the potential biomaterial for culturing mammalian cells towards mineralized tissue repair and regeneration.

We examined the effect of various concentrations of HAuCl 4 , AgNO 3 , Na 2 SeO 3 , Na 2 SiO 3 , and GeO 2 on mycelial growth of the soil basidiomycetes Agaricus bisporus and A. arvensis in submerged and solid media. Fungal mycelial extracts and cell-free culture filtrates were able to reduce ions of Au, Ag, Se, Si, and Ge compounds, forming Au 0 , Ag 0 , Se 0 , Si 0 /SiO 2 and Ge 0 /GeO 2 nanoparticles. The physical characteristics of the mycogenic nanoparticles differed depending on the species of Agaricus and the type of extract. Au nanospheres obtained with cell-free culture filtrates were of 2-5 nm diameter in A. bisporus and of 2-10 nm in A. arvensis. Nanoparticles produced by extracts of mycelia were several times larger and highly heterogenous. Ag nanoparticles produced by cell-free culture filtrates were spherical or irregular-shaped and agglomerated, whereas with extracts of mycelia, small homogenous nanospheres of 1-10 nm were formed. Se nanospheres obtained with cell-free culture filtrates were of 100-250 nm diameter in A. bisporus and of 150-550 nm diameter in A. arvensis. The particles synthesized with extracts of mycelia were of 40-140 nm in A. bisporus and of 100-250 nm in A. arvensis. Incubation of Na 2 SiO 3 with cell-free culture filtrates resulted in porous Si nanoparticles of 30-65 nm in A. bisporus and of 50-200 nm in A. arvensis. Ge nanoparticles synthesized by both Agaricus species were mostly spheres of 50-250 nm diameter., (Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Objective: To study the effects of Germanium (Ge) concentration on Ge accumulation and biotransformation of polysaccarified Ge (PG) in Cordyceps militaris., Methods: Solid and liquid culture were used in this study., Results: In the solid culture conditions, when the Ge concentration of medium was 200 mg/L, the sporophore biomass of Cordyceps militaris was the maximum; and when Ge concentration was 300 mg/L,the amount of biotransformation of PG in sporophore was the highest; and when the Ge concentration is 250 mg/L, conversion rate of organic germanium (OG) in sporophore reached the highest value. In the liquid culture conditions, when the Ge concentration was 250 mg/L, the mycelium biomass of Cordyceps militaris was the maximum; and when Ge concentration was 150 mg/L, the amount of organic conversion of PG in mycelium was the most; and conversion rate of OG in mycelium was the highest in media with the Ge concentration of 200 mg/L. This study showed the germanium concentrations in 150 - 300 mg/L was more suitable for Ge accumulation and biotransformation of PG in Cordyceps militaris. In general, the biotransformation capacity to germanium of sporophore was stronger than that of mycelium of Cordyceps militaris., Conclusion: Germanium can significantly affect Ge accumulation and biotransformation of PG in Cordyceps militaris (P < 0.05) at different concentration. This result has practical value for Ge enriched cultivation of fruiting body in Cordyceps militaris.

Rice plants accumulate high concentrations of silicon. Silicon has been shown to be involved in plant growth, high yield, and mitigating biotic and abiotic stresses. However, it has been demonstrated that inorganic arsenic is taken up by rice through silicon transporters under anaerobic conditions, thus the ability to efficiently take up silicon may be considered either a positive or a negative trait in rice. Germanium is an analogue of silicon that produces brown lesions in shoots and leaves, and germanium toxicity has been used to identify mutants in silicon and arsenic transport. In this study, two different genetic mapping methods were performed to determine the loci involved in germanium sensitivity in rice. Genetic mapping in the biparental cross of Bala × Azucena (an F6 population) and a genome wide association (GWA) study with 350 accessions from the Rice Diversity Panel 1 were conducted using 15 μM of germanic acid. This identified a number of germanium sensitive loci: some co-localised with previously identified quantitative trait loci (QTL) for tissue silicon or arsenic concentration, none co-localised with Lsi1 or Lsi6, while one single nucleotide polymorphism (SNP) was detected within 200 kb of Lsi2 (these are genes known to transport silicon, whose identity was discovered using germanium toxicity). However, examining candidate genes that are within the genomic region of the loci detected above reveals genes homologous to both Lsi1 and Lsi2, as well as a number of other candidate genes, which are discussed.

Cordyceps sinensis, a traditionally edible and medicinal fungus in China, cannot be artificially solid-cultured. Zinc (Zn), germanium (Ge), and selenium (Se) are the essential trace elements for human body. In this work, C. sinensis SU-01 was cultivated in liquid medium simultaneously containing Zn, Ge, and Se. The bioactive ingredients and in vivo antioxidant activities of Zn, Ge, Se-enriched mycelia (ZGSM) of C. sinensis SU-01 were investigated. Under the determined conditions, the Zn, Ge, and Se contents of ZGSM were 2543.16 ± 158.92, 1873.85 ± 81.82, and 1260.16 ± 107.12 μg/g, respectively. The optimal concentrations of Zn, Ge, and Se had a positive effect on biosynthesis of protein, polysaccharide, cordycepic acid, and amino acids. The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) of mice blood were 3.72 ± 0.15 and 28.74 ± 2.53 % higher than that of control, respectively, and the content of malondialdehyde (MDA) was 41.01 ± 3.66 % lower than that of control.

Rice is a staple food yet is a significant dietary source of inorganic arsenic, a class 1, nonthreshold carcinogen. Establishing the location and speciation of arsenic within the edible rice grain is essential for understanding the risk and for developing effective strategies to reduce grain arsenic concentrations. Conversely, selenium is an essential micronutrient and up to 1 billion people worldwide are selenium-deficient. Several studies have suggested that selenium supplementation can reduce the risk of some cancers, generating substantial interest in biofortifying rice. Knowledge of selenium location and speciation is important, because the anti-cancer effects of selenium depend on its speciation. Germanic acid is an arsenite/silicic acid analogue, and location of germanium may help elucidate the mechanisms of arsenite transport into grain. This review summarises recent discoveries in the location and speciation of arsenic, germanium, and selenium in rice grain using state-of-the-art mass spectrometry and synchrotron techniques, and illustrates both the importance of high-sensitivity and high-resolution techniques and the advantages of combining techniques in an integrated quantitative and spatial approach.

• Strategies to reduce arsenic (As) in rice grain, below concentrations that represent a serious human health concern, require that the mechanisms of As accumulation within grain be established. Therefore, retranslocation of As species from flag leaves into filling rice grain was investigated. • Arsenic species were delivered through cut flag leaves during grain fill. Spatial unloading within grains was investigated using synchrotron X-ray fluorescence (SXRF) microtomography. Additionally, the effect of germanic acid (a silicic acid analog) on grain As accumulation in arsenite-treated panicles was examined. • Dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA) were extremely efficiently retranslocated from flag leaves to rice grain; arsenate was poorly retranslocated, and was rapidly reduced to arsenite within flag leaves; arsenite displayed no retranslocation. Within grains, DMA rapidly dispersed while MMA and inorganic As remained close to the entry point. Germanic acid addition did not affect grain As in arsenite-treated panicles. Three-dimensional SXRF microtomography gave further information on arsenite localization in the ovular vascular trace (OVT) of rice grains. • These results demonstrate that inorganic As is poorly remobilized, while organic species are readily remobilized, from leaves to grain. Stem translocation of inorganic As may not rely solely on silicic acid transporters., (© 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.)

The use of germanium (Ge) and the possibility of exposure to trace and ultratrace amounts of this element is increasing. Germanium is widely used in the industrial field as a semiconductor and also as a dietary supplement, an elixir to 'promote health and cure disease' (e.g. cancer and AIDS). More recently, germanium nanoparticles, ranging in size from 60 to 80 nm, have been developed as a potential spleen imaging agent. Like other metal-based nanoparticles used in nanomedicine, Ge nanoparticles may release trace and ultratrace amounts of Ge ions when injected. The metabolic fate and toxicity of these ions still needs to be evaluated. In this study the metabolic fate of a cationic tetravalent Ge species was studied in vivo by injecting rats i.p. with ultratrace amounts of Ge (80 ng kg(-1)) as [(68)Ge]GeCl(4). The cytotoxicity and carcinogenic potential was assessed in vitro using immortalised human skin keratinocytes and mouse fibroblasts (HaCaT and Balb/c 3T3 cell lines, respectively). At 24 h post-exposure Ge was poorly retained in rat tissues (kidney, liver, intestine, femur, spleen and the heart were the organs with the highest Ge concentration). In the blood, Ge was rapidly cleared, being almost equally distributed between plasma and red blood cells. The excretion was mainly via the urine. The hepatic and renal intracellular distribution showed the highest recovery of Ge in the cytosol and the nuclear fractions. Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed that the bulk of Ge was associated with low molecular weight components, representing a 'mobile pool' of the element in the body. However, a significant part of the element was able to interact with biological macromolecules which could be responsible for the presence of Ge in the liver and kidney after 7 days. The in vitro experiments confirmed the low degree of cytotoxicity of GeCl(4) both in HaCaT and Balb/3T3. The latter model was more sensitive to the toxic effects induced by Ge as shown by a colony forming efficiency (CFE) greater than 70% at 700 microm of exposure. At the highest exposure concentration tested (700 microm) GeCl(4) failed to induce morphological neoplastic transformation of the cells, suggesting for the first time that a cationic form of Ge ions has no carcinogenic potential. This supports the results of the only study reported in mice, treated orally long-term to an anionic species of Ge such as sodium germanate (Kanisawa and Schroeder, 1967).

Unlabelled: We quantitatively and qualitatively investigated 2-dimensional (2D) and 3-dimensional (3D) imaging with scan-time reduction in 14 patients with 17 lesions, who had known or suspected head and neck cancer, using a bismuth germanate (BGO) crystal based PET/CT scanner with noise-matched images., Methods: A 2D and 3D acquisition protocol using scan-time reduction on an axial single field of view resulted in a 2D 4-, 3D 4-, 3D 3-, 2D 3-, 2D 2-, and 3D 2-min scan sequence to minimize redistribution and decay bias. Tumor maximum standardized uptake values (SUVmax) and tumor mean standardized uptake values (SUV(mean)) were recorded, and two observers in consensus investigated lesion conspicuity between 2D and 3D paired 4-, 3-, and 2-min noise-matched images., Results: We found some minor advantages quantitatively in favor of 2D scanning, with higher mean SUVmax, and qualitatively in favor of 3D scanning, with lesion conspicuity preference. In our cohort, no great advantage or disadvantage to using either acquisition mode was observed, and all lesions were seen irrespective of acquisition mode and scan time., Conclusion: In head and neck cancer patients, we can recommend a scan-time reduction from 4 to 3 min/bed position in 2D acquisitions with a BGO-based PET/CT scanner, using our imaging protocol and reconstruction defaults.

The silicic acid uptake kinetics of diatoms were studied to provide a mechanistic explanation for previous work demonstrating both nonsaturable and Michaelis-Menten-type saturable uptake. Using (68)Ge(OH)(4) as a radiotracer for Si(OH)(4), we showed a time-dependent transition from nonsaturable to saturable uptake kinetics in multiple diatom species. In cells grown under silicon (Si)-replete conditions, Si(OH)(4) uptake was initially nonsaturable but became saturable over time. Cells prestarved for Si for 24 h exhibited immediate saturable kinetics. Data suggest nonsaturability was due to surge uptake when intracellular Si pool capacity was high, and saturability occurred when equilibrium was achieved between pool capacity and cell wall silica incorporation. In Thalassiosira pseudonana at low Si(OH)(4) concentrations, uptake followed sigmoidal kinetics, indicating regulation by an allosteric mechanism. Competition of Si(OH)(4) uptake with Ge(OH)(4) suggested uptake at low Si(OH)(4) concentrations was mediated by Si transporters. At high Si(OH)(4), competition experiments and nonsaturability indicated uptake was not carrier mediated and occurred by diffusion. Zinc did not appear to be directly involved in Si(OH)(4) uptake, in contrast to a previous suggestion. A model for Si(OH)(4) uptake in diatoms is presented that proposes two control mechanisms: active transport by Si transporters at low Si(OH)(4) and diffusional transport controlled by the capacity of intracellular pools in relation to cell wall silica incorporation at high Si(OH)(4). The model integrates kinetic and equilibrium components of diatom Si(OH)(4) uptake and consistently explains results in this and previous investigations.

Amide exchange rates were measured for Pyrococcus furiosus (Pf) rubredoxin substituted with either Zn(II), Ga(III), or Ge(IV). Base-catalyzed exchange rate constants increase up to 3000-fold per unit charge for the highly protected amides surrounding the active site metal, yielding apparent residue-specific conformational energy decreases of more than 8 kcal/mol in a comparison of the Zn(II)- and Ge(IV)-substituted proteins. However, the exchange kinetics for many of the other amides of the protein are insensitive to these metal substitutions. These differential rates are inversely correlated with the distance between the amide nitrogen and the metal in the X-ray structure, out to a distance of at least 12 A, consistent with an electrostatic potential-dependent shifting of the amide nitrogen pK. This strongly correlated distance dependence is consistent with a nativelike structure for the exchange-competent conformations. The electric field potential within the interior of the rubredoxin structure gives rise to a change of as much as a million-fold in the rate for the exchange-competent state of the individual amide hydrogens. Nevertheless, the strength of these electrostatic interactions in Pf rubredoxin appears to be comparable to those previously reported within other proteins. As a result, contrary to the conventional analysis of hydrogen exchange data, for exchange processes that occur via nonglobal transitions, the residual conformational structure will often modulate the observed rates. Although this necessarily complicates the estimation of the conformational equilibria of these exchange-competent states, this dependence on residual structure can provide insight into the conformation of these transient states.

The tetracysteine metal coordination site of the rubredoxins from Clostridium pasteurianum (Cp) and Pyrococcus furiosus (Pf) are shown to stably bind the inorganic Ge(IV) ion. This is the first characterized coordination complex of tetravalent germanium with a biological macromolecule. Zn(II), Ga(III) and Ge(IV) substitution yields differential NMR chemical shifts for the 1H and 15N amide resonances throughout much of the protein structure. The differential shifts for the six backbone amides that hydrogen bond to the metal-coordinated sulfurs indicate that the pseudo 2-fold symmetry of the active site is more closely maintained in the hyperthermophile Pf rubredoxin than in its mesophile Cp homolog. These three metal substitutions form an isoelectronic series of small diamagnetic proteins for which reference structures are known to 1A resolution. These series provide a promising system to analyze theoretical predictions of the effects of differential charge distribution on chemical shifts from both proximal and long range interactions.

The biomineralization capacity of the photosynthetic marine diatom Nitzschia frustulum was harnessed to fabricate Si-Ge oxide nanocomposite materials. Germanium was incorporated into the diatom cell by a two-stage cultivation process. In stage 1, the N. frustulum cell suspension was grown up to cell density of 3 x 10(6) cells/mL in 0.35 mM silicic acid within a bubble-column photobioreactor. In stage 2, when all of the soluble silicon was consumed, 0.10 mM Ge(OH)4 or a mixture of 0.020 mM Ge(OH)4 and 0.25 mM Si(OH)4 were added to Si-starved cells. The cells assimilated soluble germanium by a surge uptake mechanism. The cell mass was thermally annealed in air at 800 degrees C for 6 h to oxidize carbonaceous materials. The thermally annealed cell biomass was characterized by TEM-EDS, FT-IR, and XRD. These measurements confirmed the formation nanostructured Ge-Si oxides composed of CaSiO3 and Ca3GeO5.

By in situ FTIR ATR measurements, the antibody (AB) recognition of human tumor necrosis factor-alpha (TNFalpha) immobilized on the Ge surface of a multiple internal reflection element (MIRE) was investigated. The experiments were performed in aqueous environment in a flow-through cell. After immobilization of TNFalpha on the Ge-MIRE by direct adsorption from aqueous solution, the immobilisate reached stability after about 1 h under flow-through conditions. The remaining sites of the Ge surface were saturated by bovine serum albumin (BSA) in order to prevent unspecific binding of anti-TNFalpha AB which was then added. The obtained FTIR ATR spectra were shown to result exclusively from AB specifically interacting with TNFalpha, since the absence of immunoglobulin binding to BSA adsorbed to the Ge MIRE was verified by a reference experiment. Finally, the stability of all adsorbed protein immobilisates was monitored under flow-through conditions for 10.5 h. The TNFalpha-AB complex showed a decrease of 7.4%, whereas the BSA adsorbate remained stable. IR measurements were performed with polarized light in order to study orientational effects of the immobilized proteins. The dichroic ratios and surface concentrations of all used proteins are available after quantitative analysis of the amide II bands.

Boron (B)-deficient pumpkin (Cucurbita moschata Duchesne) plants exhibit reduced growth, and their tissues are brittle. The leaf cell walls of these plants contain less than one-half the amount of borate cross-linked rhamnogalacturonan II (RG-II) dimer than normal plants. Supplying germanium (Ge), which has been reported to substitute for B, to B-deficient plants does not restore growth or reduce tissue brittleness. Nevertheless, the leaf cell walls of the Ge-treated plants accumulated considerable amounts of Ge. Dimeric RG-II (dRG-II) accounted for between 20% and 35% of the total RG-II in the cell walls of the second to fourth leaves from Ge-treated plants, but only 2% to 7% of the RG-II was cross-linked by germanate (dRG-II-Ge). The ability of RG-II to form a dimer is not reduced by Ge treatment because approximately 95% of the monomeric RG-II generated from the walls of Ge-treated plants is converted to dRG-II-Ge in vitro in the presence of germanium oxide and lead acetate. However, dRG-II-Ge is unstable and is converted to monomeric RG-II when the Ge is removed. Therefore, the content of dRG-II-Ge and dRG-II-B described above may not reflect the actual ratio of these in muro. (10)B-Enriched boric acid and Ge are incorporated into the cell wall within 10 min after their foliar application to B-deficient plants. Foliar application of (10)B but not Ge results in an increase in the proportion of dRG-II in the leaf cell wall. Taken together, our results suggest that Ge does not restore the growth of B-deficient plants.

Unsubstituted aromatic, heterocyclic and perfluoroalkylic sulfonamides possessing the general formula RSO2NH2 act as powerful inhibitors of the zinc enzyme carbonic anhydrase (CA). Unsaturated primary/substituted sulfonamides have never been investigated for their interaction with the enzyme. Here it is shown that such compounds, and more precisely allyl-sulfonamide and trans-styrene sulfonamide possessing the above general formula (with R=CH2=CH-CH2- and C6H5-CH=CH-, respectively) behave as nanomolar inhibitors of the physiologically relevant isozymes CAI and CAII. Some other derivatives of these two leads (incorporating Si(IV), Ge(IV) and B(III) moieties among others) were also synthesized and investigated for their interaction with CA, but showed decreased affinity for both isozymes. The structure-activity relationship for this class of CA inhibitors is discussed. Furthermore, it was observed that allylsulfonyl chloride is a strong CA inactivator, probably by reacting with amino acid residues critical for the catalytic cycle.

Concentrations of selenium (Se), boron (B), and germanium (Ge) were determined in scalp hair of children with Kashin-Beck disease (KBD), in healthy children in KBD-disease endemic areas, and in healthy children in non-KBD areas. Mean Se, B, and Ge concentrations were low in children with KBD; in hair of healthy children in KBD areas, Se levels were normal but B and Ge levels were lower than in KBD-free areas. The hair levels of B and Ge were unaffected by selenium supplementation. It is suggested that B and Ge deficiency may be contributing factors in the etiology of KBD.

Background: Long-term oral ingestion of germanium dioxide (GeO2) causes progressive renal failure derived from tubulointerstitial nephropathy in humans and animals. The characteristic of GeO2-induced nephropathy is the renal tissue injury persisting for a long time, even after cessation of GeO2 ingestion. However, a treatment that can suppress the long-lasting renal tissue injury has not yet been established., Methods: Using the methods of immunohistochemistry and reverse transcription-polymerase chain reaction, we examined the expression of ED1-positive cells (macrophages/monocytes), transforming growth factor (TGF)-beta1 mRNA and protein and collagen type IV mRNA and protein in the kidneys of rats with GeO2-induced nephropathy. Concomitantly, the effects of L-arginine treatment on their expression was explored in the kidneys of rats with GeO2-induced nephropathy., Results: Chronic administration of GeO2 caused tubulointerstitial nephropathy characterized by leukocyte invasion into the enlarged tubulointerstitial space in rats. The expression of ED1-positive cells, TGF-beta1 protein and collagen type IV protein was markedly increased in the tubulointerstitium of the renal cortex from rats with GeO2-induced nephropathy. Similarly, TGF-beta1 and collagen type IV mRNA were significantly enhanced in the renal cortex of rats with GeO2-induced nephropathy. A small number of tubulointerstitial cells expressing TGF-beta1 protein were also observed in the renal cortex of rats with GeO2-induced nephropathy. However, L-arginine treatment led to a parallel decrease in the expression of ED1-positive cells, TGF-beta1 mRNA and collagen type IV mRNA and protein in rats with GeO2-induced nephropathy., Conclusions: In general, collagen synthesis is driven by TGF-beta1 in the fibrotic process associated with a variety of renal disorders. TGF-beta1 is secreted by TGF-beta1 producing cells such as macrophages, fibroblasts and myofibroblasts. Thus, the present study indicates that the expression of collagen type IV may be mediated by TGF-beta1 released from invading macrophages and, to a lesser extent, released from tubulointerstitial cells, presumably fibroblasts and/or myofibroblasts in GeO2-induced nephropathy. L-Arginine treatment inhibits collagen type IV synthesis possibly by suppressing macrophage invasion and the resultant TGF-beta1 expression in this nephropathy. L-Arginine treatment may be beneficial in the prevention of tubulointerstitial fibrosis, which is considered to be the terminal stage of GeO2-induced nephropathy.

The metalloid germanium has found widespread application in electronics, nuclear sciences and in medicine. General toxicity of germanium is low, except for the tetrahydride germane, and few observations on toxicity of germanium in man exist. Germanium is not carcinogenic and even appears to inhibit cancer development and, in the form of the organic germanium compound, spirogermanium, to destroy cancer cells. Germanium compounds have no mutagenic activity and may, under certain conditions, inhibit the mutagenic activity of other substances. High doses of germanium may result in an increased embryonic resorption, but possible malformations have been reported only after administration of dimethyl germanium oxide to pregnant animals. Germanium may thus be considered an element of rather low risk to man.

The surfaces of bioactive Ca-P ceramics immediately change when exposed to proteinaceous solutions. The dissolution behavior and protein interactions of these bioactive materials at the bone/implant interface need to be investigated to understand their material-cellular interactions fully. In this study, FT-IR/ATR techniques were used to study the in situ phosphate release kinetics of Ca-P coatings. The net loss of phosphate molecules from coatings was slower in saline solutions compared with alpha-MEM solutions. Coatings exposed to alpha-MEM solutions containing fibronectin released phosphate molecules slower than coatings exposed to alpha-MEM solutions containing albumin. Conformational changes in fibronectin and albumin adsorbed onto Ca-P and uncoated germanium surfaces were also investigated using FT-IR/ATR spectroscopy. Analysis of changes in the amide I bands indicated that there was a greater loss of beta-sheet structure in adsorbed fibronectin on Ca-P coatings when compared with bare germanium surfaces. Although albumin did change its structure upon adsorption on both Ca-P and germanium, unlike fibronectin, adsorbed albumin structure was similar on Ca-P coatings and germanium. Furthermore, with time the conformation of adsorbed fibronectin and albumin appeared to be very stable on Ca-P coatings, whereas albumin adsorbed to germanium exhibited an increase in ratio of alpha-helix to beta-turn.

Silicon (Si) is an essential trace element normally present in brain and cerebrospinal fluid, although the mechanism by which it enters and distributes in brain is largely unknown. Due to the short radioactive half-life of 31Si (156 min) we have investigated the use of 68Germanium (68-Ge, half-life 282 days) as a possible marker for Si transport in rat brain over longer periods than are possible with 31Si. Adult male anaesthetised rats were given a bolus of 68Ge I.V. and arterial blood samples taken during experiments that lasted between 5 min and 3 days. At termination, the brain was removed and analysed for radioactivity as were the plasma samples. Data were analyzed by Graphical Analysis which showed that the blood-brain barrier permeability to 68Ge (Kin approximately 10(-4) ml/min/g) is similar to that for many non protein-bound electrolytes in plasma and that 68Ge fluxes across cerebral capillaries are bidirectional. The autoradiographic distribution of 68Ge in brain was homogenous. Our results are in agreement with those of previous studies using 31Si or 68Ge, which suggest 68Ge may be a useful marker for Si when investigating the role of this element in conditions such as neurodegenerative diseases.

The possibility of deriving normal biological values for some rare metals is investigated. The metals under study are gallium, germanium, indium, niobium and tellurium, i.e. a group of metals with increasing utilization in the electronics industry. So far some data are unavailable for some of the elements, e.g. daily intake, oral absorption and half-life time for gallium, and body burden for gallium and germanium. Reliable values of blood concentration are available only for gallium, niobium and tellurium. The problem related to a proposed urinary biological limit value for tellurium is also discussed.

Germanium is an inert metal with no known biological function in prokaryotic or eukaryotic organisms. Its toxicity is low compared to that of silver. Germanium is accumulated in certain bacterial strains by either energy-independent passive binding or an energy-dependent mechanism. Little is known about the molecular aspects of silver resistance, toxicity, and accumulation in bacterial strains. This is surprising because silver has been used as an antimicrobial agent in the medical field for centuries. It is likely that silver ions are excluded (resulting in decreased silver accumulation) from certain bacterial strains or immobilized intracellularly to prevent toxic effects from being exerted. These mechanisms of silver resistance have not been fully elucidated. This review examines the toxicity and accumulation of germanium and silver in selected microbial species. In addition, resistance mechanisms to these biologically nonessential metals is discussed, with more emphasis placed on silver-resistant bacteria due to the knowledge available.

Germanium dioxide is found to increase the frequencies of the genetical transformation in Bacillus subtilis 30-40 fold. The increased frequency of transformation was registered in Sil- mutant in contrast to Sil+ strain having the decreased one. Bacillus megatherium strain KU-2 and Bacillus oligonitrophilus KU-1 were isolated from soil. These strains possess better ability to utilize the orthoclase and biotite. Germanium dioxide did not induce the transformation frequencies increase in these strains. Sil mutant of Bacillus oligonitrophilus demonstrated no competence to transformation.

The dose dependency of germanium dioxide(GeO2)-induced nephrotoxicity was investigated experimentally in rat groups orally treated with high (150 mg/kg/day), moderate (75 mg/kg/day), or low (37.5 mg/kg/day) doses of GeO2, and in an untreated group. Renal dysfunction, indicated by the increase of blood urea nitrogen and the decrease of creatinine clearance, and systemic toxicity by weight loss, anemia, and hypoproteinemia were more apparent in rats treated with higher dose of GeO2. Urinalysis including daily urinary protein excretion did not reveal any abnormalities in any of the groups. Urinary excretion and renal-tissue content of Ge were significantly elevated in the group of the higher dose of GeO2. Light microscopically, vacuolar degeneration and depositions of granules positive for periodic acid-Schiff in distal tubules were predominant in the higher-dose group of GeO2. The present study demonstrates that GeO2-induced nephrotoxicity develops dose dependently.

Acute renal failure (ARF) or renal dysfunction (RD) associated with germanium-induced nephrotoxicity has been reported in 18 patients since 1982. In 2 of these cases the patients died of acute renal and cardiogenic failure. In 17 of 18 cases biopsies showed vacuolar degeneration in renal tubular epithelial cells in the absence of glomerular changes, without proteinuria or hematuria. Accumulated elemental Ge intake in 17 patients over a period of 4 to 36 months ranged between 16 and 328 g, or more than 100 to 2000 times the average estimated dietary intake of Ge for man (1.5 mg/d; range 0.40 to 3.40 mg/d). The biological half-life of Ge is 4.5 days for kidneys, the highest retention level of any organ. The mean concentration of Ge in healthy adult kidneys is 9.0 mg/kg wet weight. In 3 patients studied with Ge-induced RD or ARF, urinary Ge excretion was 9, 15, and 60 ng/mL, compared to greater than 5 ng/mL in healthy controls, and remained elevated even 12 months after discontinuing supplemental Ge intake. The mechanism for Ge-induced nephrotoxicity remains unknown, although the suspected cause is the inorganic Ge salts, such as germanium dioxide. Sufficient evidence for a role of organogermanium compounds, such as carboxyethyl germanium sesquioxide or citrate-lactate germanate, in Ge-induced nephrotoxicity remains lacking. The recent introduction of over-the-counter Ge "nutritional" supplements in some countries increases the risk of additional cases of Ge-induced nephrotoxicity, especially if appreciable levels of inorganic Ge salts are present and consumed for long periods (greater than 3 months) at levels above the average daily estimated dietary intake for Ge.(ABSTRACT TRUNCATED AT 250 WORDS)

The species-specific, genetically determined silica frustule of diatoms provides an excellent eukaryotic model for understanding the process of biomineralization and how it is regulated. An effort is made to define molecular events and biochemical constituents in silicon mineralization and to correlate these events with those aspects of silica frustule morphogenesis which have been reported in the published work. A sequential series of steps of silicic acid interaction with the cell is proposed which might be expected for silicon metabolism leading to cell wall formation. A model is put forward that provides for a conceptual framework for continued studies in this area, and provides testable hypotheses which should lead to a greater understanding of biomineralization processes in general and silicification in particular.

Deuterium oxide affected all types of transport processes of ions in rice seedlings. The processes of the active transport of Rb+, the passive diffusion of Ca2+, and the preferential and specific absorption of Ge by the seedlings in D2O solutions, were suppressively distorted by D2O. The suppressive effect on the translocation of all ions studied and the absorption of Rb+, was greater with higher concentrations of D2O. However, clear-cut relations of the effect of increasing D2O concentrations on the ion transport were not obtained. The extent of the replacement of H2O by D2O in the plant appeared to affect the movement of ions in the plant.

In the presence of germanium (Ge) the needle-shaped silica spicules of the freshwater sponge Ephydatia m ulleri are very short and thin and possess bulbs with large spines. SEM-coupled X-ray analyses confirm the incorporation of Ge into the silica. A small number of bulbs are susceptible to erosion by HNO3 and hypochlorite and although the chemical basis of such erosion is presently unknown it suggests the presence of an organic matrix within the bulbs and/or an incomplete polymerization of the silica. Addition of Ge to control media in which silicification is newly initiated increases the incidence of erosion and results in centrally located eroded areas of the silica and discontinuities in its deposition. Removal of Ge from such newly forming structures results in a partial recovery of normal morphology (spine development and thickening of the silica) but only in the central region surrounding the bulbs. Both results establish the presence of a central, active region for silicification and further support the view that there is a distal spreading, away from this center, of transported forms of silica. Secondary centers may also be present. The newly assembled organic core of control structures is associated with tubular elements possibly derived from the surrounding membrane. In such newly silicifying structures the spicule tips contain oriented material in the form of "rays." Both of these new observations increase the likelihood of the presence of an organic matrix within the silica.

Acute renal failure developed in a patient accompanied by systemic manifestations such as myopathy and skin rash. The patient, a middle aged house wife, had been taking 600 mg of germanium (Ge) preparation daily for 18 months as an elixir. The main component of the preparation was GeO2 and some organic compound was also present. Histological study of the kidney post mortem showed foamy cell transformation of glomerular epithelia, degeneration of tubular epithelia with red blood cell casts and urate crystals, and a mild proliferation of mesangial matrix. Analysis of the tissue content of Ge, prompted by her history, revealed an increased accumulation of the metal. As compared to a non-user died of liver cirrhosis, the concentration of the metal was higher particularly in the spleen (183X), thyroid gland (175X), psoas muscle (93X), jejunum (76X), and renal cortex (69X). So far, neither accumulation of Ge in humal tissue nor systemic toxicity of the Ge in human has been reported. The relevance of massive accumulation of Ge to the renal failure as well as to other systemic manifestations the patient presented remains to be clarified.

The NADPH- and oxygen-dependent microsomal metabolism of the di-, tri- and tetra-ethyl-substituted derivatives of germanium, tin and lead was shown to give rise to ethylene as a major product and ethane as a minor product. These reactions were shown to be catalysed by the liver microsomal cytochrome P-450-dependent mono-oxygenase. Since formation of ethane and ethylene was differentially inhibited by anaerobiosis, the results suggest that at least a large portion of the ethane produced may be derived by a reductive mechanism. Triethyltin bromide in both the absence and presence of NADPH was shown to convert cytochrome P-450 into cytochrome P-420 and to affect the function of the mono-oxygenase in vitro. Tetraethyltin caused the NADPH- and time-dependent formation of cytochrome P-420, suggesting that tetraethyltin is converted into triethyltin salts in significant concentrations. The order of potency in formation of cytochrome P-420 was closely paralleled by the ability of the tin derivatives to induce microsomal lipid peroxidation in vitro.

Uptake of Si and Ge (chemical analogue of Si) in rat tissues was compared to establish their subcellular localization and determine if Ge could be used to trace Si in situ. 31Si and 68Ge were found in tissues and in cell organelles after injection of 31Si (OH) 4 or 68Ge (OH) 4. Accumulation of 31Si and 68Ge in the tissues increased for 30 minutes, declined rapidly about 30 minutes and then was gradually but steadily depleted. Simultaneous double labelling with 31Si and 68Ge produced concomitant accumulation and release of both isotopes. After a single IP injection, some 68Ge remained in the spleen and kidney for up to 20 days. The 31Si and 68Ge concentration in the tissues and cell organelles increased linearly with the amount administered (31Si, 10-4 to 10-2 g/kg body wt and 68Ge, 10-9 to 10-3 g/kg body wt). Thus, substitution of 68Ge for 31Si can extend the limit of detection of Si by at least 5 orders of magnitude. Both 31Si and 68Ge were water extractable (47%-74% and 38%-89%, respectively) from liver cell organelles; 45%-81% 31Si and 66%-90% 68Ge were extractable in 10% TCA, while only 10%-59% of either isotope were extractable in organic solvents (acetone, chloroform, ethanol). A small percentage of Si may be bound or polymerized.