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1.  Lead, Mercury, and Arsenic in US- and Indian-Manufactured Ayurvedic Medicines Sold via the Internet 
Context
Lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be present due to the practice of rasa shastra (combining herbs with metals, minerals, and gems). Whether toxic metals are present in both US- and Indian-manufactured Ayurvedic medicines is unknown.
Objectives
To determine the prevalence of Ayurvedic medicines available via the Internet containing detectable lead, mercury, or arsenic and to compare the prevalence of toxic metals in US- vs Indian-manufactured medicines and between rasa shastra and non–rasa shastra medicines.
Design
A search using 5 Internet search engines and the search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda, indicated for oral use, and available for sale. From 673 identified products, 230 Ayurvedic medicines were randomly selected for purchase in August–October 2005. Country of manufacturer/Web site supplier, rasa shastra status, and claims of Good Manufacturing Practices were recorded. Metal concentrations were measured using x-ray fluorescence spectroscopy.
Main Outcome Measures
Prevalence of medicines with detectable toxic metals in the entire sample and stratified by country of manufacture and rasa shastra status.
Results
One hundred ninety-three of the 230 requested medicines were received and analyzed. The prevalence of metal-containing products was 20.7% (95% confidence interval [CI], 15.2%–27.1%). The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%–30.4%) compared with 19.5% (95% CI, 11.3%–30.1%) in Indian products (P=.86). Rasa shastra compared with non–rasa shastra medicines had a greater prevalence of metals (40.6% vs 17.1%; P=.007) and higher median concentrations of lead (11.5 μg/g vs 7.0 μg/g; P=.03) and mercury (20 800 μg/g vs 34.5 μg/g; P=.04). Among the metal-containing products, 95% were sold by US Web sites and 75% claimed Good Manufacturing Practices. All metal-containing products exceeded 1 or more standards for acceptable daily intake of toxic metals.
Conclusion
One-fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain detectable lead, mercury, or arsenic.
doi:10.1001/jama.300.8.915
PMCID: PMC2755247  PMID: 18728265
2.  Predicted metal binding sites for phytoremediation 
Bioinformation  2009;4(2):66-70.
Metal ion binding domains are found in proteins that mediate transport, buffering or detoxification of metal ions. The objective of the study is to design and analyze metal binding motifs against the genes involved in phytoremediation. This is being done on the basis of certain pre-requisite amino-acid residues known to bind metal ions/metal complexes in medicinal and aromatic plants (MAP's). Earlier work on MAP's have shown that heavy metals accumulated by aromatic and medicinal plants do not appear in the essential oil and that some of these species are able to grow in metal contaminated sites. A pattern search against the UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases yielded true positives in each case showing the high specificity of the motifs designed for the ions of nickel, lead, molybdenum, manganese, cadmium, zinc, iron, cobalt and xenobiotic compounds. Motifs were also studied against PDB structures. Results of the study suggested the presence of binding sites on the surface of protein molecules involved. PDB structures of proteins were finally predicted for the binding sites functionality in their respective phytoremediation usage. This was further validated through CASTp server to study its physico-chemical properties. Bioinformatics implications would help in designing strategy for developing transgenic plants with increased metal binding capacity. These metal binding factors can be used to restrict metal update by plants. This helps in reducing the possibility of metal movement into the food chain.
PMCID: PMC2823383  PMID: 20198171
Phytoremediation; medicinal and aromatic plants (MAPs); putative metal binding sites
3.  Effect of mineral-enriched diet and medicinal herbs on Fe, Mn, Zn, and Cu uptake in chicken 
Background
The goal of our study was to evaluate the effects of different medicinal herbs rich in polyphenol (Lemon balm, Sage, St. John's wort and Small-flowered Willowherb) used as dietary supplements on bioaccumulation of some essential metals (Fe, Mn, Zn and Cu) in different chicken meats (liver, legs and breast).
Results
In different type of chicken meats (liver, legs and breast) from chickens fed with diets enriched in minerals and medicinal herbs, beneficial metals (Fe, Mn, Zn and Cu) were analysed by flame atomic absorption spectrometry. Fe is the predominant metal in liver and Zn is the predominant metal in legs and breast chicken meats. The addition of metal salts in the feed influences the accumulations of all metals in the liver, legs and breast chicken meat with specific difference to the type of metal and meat. The greatest influences were observed in legs meat for Fe and Mn. Under the influence of polyphenol-rich medicinal herbs, accumulation of metals in the liver, legs and breast chicken meat presents specific differences for each medicinal herb, to the control group that received a diet supplemented with metal salts only. Great influence on all metal accumulation factors was observed in diet enriched with sage, which had significantly positive effect for all type of chicken meats.
Conclusions
Under the influence of medicinal herbs rich in different type of polyphenol, accumulation of metals in the liver, legs and breast chicken meat presents significant differences from the group that received a diet supplemented only with metal salts. Each medicinal herb from diet had a specific influence on the accumulation of metals and generally moderate or poor correlations were observed between total phenols and accumulation of metals. This may be due to antagonism between metal ions and presence of other chelating agents (amino acids and protein) from feeding diets which can act as competitor for complexation of metals and influence accumulation of metals in chicken meat.
Graphical abstract
doi:10.1186/1752-153X-6-19
PMCID: PMC3337232  PMID: 22429523
Chicken liver; Chicken legs meat; Chicken breast meat; Medicinal herbs; Beneficial metals; Feeding diets; Polyphenol
4.  Clawing Back: Broadening the Notion of Metal Chelators in Medicine 
The traditional notion of chelation therapy is the administration of a chemical agent to remove metals from the body. But formation of a metal-chelate can have biological ramifications that are much broader than metal elimination. Exploring these other possibilities could lead to pharmacological interventions that alter the concentration, distribution, or reactivity of metals in targeted ways for therapeutic benefit. This review highlights recent examples that showcase four general strategies of using principles of metal chelation in medicinal contexts beyond the traditional notion of chelation therapy. These strategies include altering metal biodistribution, inhibiting specific metalloenzymes associated with disease, enhancing the reactivity of a metal complex to promote cytotoxicity, and conversely, passivating the reactivity of metals by site-activated chelation to prevent cytotoxicity.
doi:10.1016/j.cbpa.2012.12.021
PMCID: PMC3634900  PMID: 23332666
5.  Novel Metals and Metal Complexes as Platforms for Cancer Therapy 
Current pharmaceutical design  2010;16(16):1813-1825.
Metals are essential cellular components selected by nature to function in several indispensable biochemical processes for living organisms. Metals are endowed with unique characteristics that include redox activity, variable coordination modes, and reactivity towards organic substrates. Due to their reactivity, metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. For these reasons, coordination complexes, either as drugs or prodrugs, become very attractive probes as potential anticancer agents. The use of metals and their salts for medicinal purposes, from iatrochemistry to modern day, has been present throughout human history. The discovery of cisplatin, cis-[PtII(NH3)2Cl2], was a defining moment which triggered the interest in platinum(II)- and other metal-containing complexes as potential novel anticancer drugs. Other interests in this field address concerns for uptake, toxicity, and resistance to metallodrugs. This review article highlights selected metals that have gained considerable interest in both the development and the treatment of cancer. For example, copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However the use of copper-binding ligands to target tumor copper could provide a novel strategy for cancer selective treatment. The use of nonessential metals as probes to target molecular pathways as anticancer agents is also emphasized. Finally, based on the interface between molecular biology and bioinorganic chemistry the design of coordination complexes for cancer treatment is reviewed and design strategies and mechanisms of action are discussed.
PMCID: PMC3759287  PMID: 20337575
Cancer; metal; zinc; copper; platinum; metal complex; DNA; proteasome
6.  Profile of heavy metals in some medicinal plants from Ghana commonly used as components of herbal formulations 
Pharmacognosy Research  2010;2(1):41-44.
The levels of some heavy metals in 27 medicinal plant species from Ghana were studied in order to evaluate their health implications. These plant species, especially those used in the treatment of diseases such as hypertension, diabetes and asthma may require long term usage. The metals were copper, zinc, iron, manganese, nickel and cadmium. Atomic Absorption Spectrophotometry (wet digestion) was used for the analyses, and content of metals per sample was expressed as percent µg/g. Daily total intake of these metals is discussed based on the recommended daily intake of the medicinal plants or their corresponding formulations. From the results of the study zinc, copper and cadmium were present in all the plant species examined. Manganese was present in all species except V. amygdalina. Iron was found in all except five species (82%), whilst nickel was (rather rare) detected in only eight (30%) of the plant species. Significant variations in metal content existed (P<0.05) among the medicinal plant species with respect to the heavy metals evaluated. The concentrations of copper, zinc, cadmium and manganese were within their respective maximum permissible daily levels. However, some species, especially Ocimum canum (8), Clausena anisata and Rauwolfia vomitoria had levels of iron higher than the maximum permissible level of 1000 µg/day and may require care to avoid iron toxicity. The results also highlighted the differences in contents of minerals in Lippia multiflora obtained from different locations in Ghana. The findings generally suggest that the use of these plant species for the management of diseases will not cause heavy metal toxicity and may be beneficial to the users in cases of micronutrient deficiency, as these metals were found to be present in readily bioavailable form.
doi:10.4103/0974-8490.60579
PMCID: PMC3140128  PMID: 21808538
Health implications; heavy metals; herbal formulations; medicinal plant
7.  Proteomic Approaches in Understanding Action Mechanisms of Metal-Based Anticancer Drugs 
Metal-Based Drugs  2008;2008:716329.
Medicinal inorganic chemistry has been stimulating largely by the success of the anticancer drug, cisplatin. Various metal complexes are currently used as therapeutic agents (e.g., Pt, Au, and Ru) in the treatment of malignant diseases, including several types of cancers. Understanding the mechanism of action of these metal-based drugs is for the design of more effective drugs. Proteomic approaches combined with other biochemical methods can provide comprehensive understanding of responses that are involved in metal-based anticancer drugs-induced cell death, including insights into cytotoxic effects of metal-based anticancer drugs, correlation of protein alterations to drug targets, and prediction of drug resistance and toxicity. This information, when coupled with clinical data, can provide rational basses for the future design and modification of present used metal-based anticancer drugs.
doi:10.1155/2008/716329
PMCID: PMC2486358  PMID: 18670610
8.  Therapeutic potentials of metals in ancient India: A review through Charaka Samhita 
The Ayurvedic system of medicine has stood the test of time for four millennia or more. The ancient seers found that drugs of different origin (herbal, metal or animal) in addition to codes of conduct and dietary regulations are suitable tools to maintain health in healthy and eradicating diseases in diseased. Use of metallic preparations in healthcare is a unique feature in this system. Processed metals including Mercury, Gold, Silver, Lead, Zinc, Copper etc. were used very frequently by seers of the Indian tradition in different disease conditions with great authority. It is generally claimed, that these metals are detoxified during the highly complex manufacturing processes described in Ayurvedic, especially Rasashastra texts. Charaka Samhita, one of the scheduled books of Ayurveda also holds ample of references regarding the use of metals for different purposes, which are summarized in the current paper.
doi:10.4103/0975-9476.82523
PMCID: PMC3131772  PMID: 21760689
Ayurveda; Charaka Samhita; lead; mercury; metals
9.  OA01.02. Literary Study on Heavy Metal Poisoning and Ayurveda with Special Reference to Naga Bhasma (Calcined Lead) 
Ancient Science of Life  2012;32(Suppl 1):S2.
Bhasmas are unique Ayurvedic metallic preparations with herbal juices/fruits widely used for treatment of a variety of chronic ailments. The bhasmas are products of classical alchemy, organo-metallic compounds of certain metals and gems in a very fine powdered form, mostly oxides, made in elaborate calcination processes perfected several centuries ago. Recent articles pertaining the alarming level of heavy metals, especially Pb, Hg, and As in Ayurvedic formulations have created a lot of controversy regarding the safety and efficacy of Ayurvedic formulations. It has been reported that lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. An attempt was made to study heavy metal poisoning with special reference to current research on toxicity of Naga bhasma. This study clearly shows that Naga bhasma is not just lead, it's a compound form predominantly crystalline i.e. mixture of PbO Pb3O4. XRD data revealed OH and (CO3) 2 group which contain some other essential elements in minute quantity and didn’t have any toxic effect at LD50 which was 160 times higher to that of Therapeutic Equivalent Dose (TED) (12.5 mg/kg) in acute toxicity study.
PMCID: PMC3800896
10.  The Contents of Heavy Metals (Cd, Cr, As, Pb, Ni, and Sn) in the Selected Commercial Yam Powder Products in South Korea 
Yam (Dioscorea) has long been used as foods and folk medicine with the approved positive effects for health promotion. Although consumption of yam products is increasing for health promotion, reports for the metal contamination in commercial yam powder products to protect the consumers are lacking. In this study, we aimed to assess whether the commercial yam powder products were heavy metal contaminated or not using the yam products from six commercial products from various places in South Korea. The contents of heavy metals (Cd, Cr, As, Pb, Ni, and Sn) in yam powder products were measured and compared to national and international food standard levels. Also, the metal contamination was monitored during the food manufacturing steps. The study results showed that the contents of heavy metals (Cd, Cr, As, and Pb) in yam powder products are similar to those in national ‘roots and tubers’ as well as in various crops. In comparison to three international standard levels (EU, Codex and Korea), Cd content in yam powder products was lower but Pb content was 5 times higher. Also, Pb, Ni, and Sn may have the potential to be contaminated during food manufacturing steps. In conclusion, the level of heavy metals (Cd, Cr, As, Ni, and Sn) except Pb is considered relatively safe on comparison to national and international food standard levels.
doi:10.3746/pnf.2013.18.4.249
PMCID: PMC3925214  PMID: 24551826
Dioscorea; yam; heavy metals (Cd, Cr, As, Pb, Ni, and Sn); food safety
11.  Standard manufacturing procedure of Rajata Bhasma 
Ayu  2011;32(4):566-571.
Rasa Shastra is a branch of Ayurveda which deals with the processing of minerals and metals having therapeutic importance. Rajata comes under the group of metals having high therapeutic value. Minerals and metals are mostly used in the form of Bhasma. During the medieval period Rasacharyas extensively worked and developed a number of processing methods for a single drug. They all are standard manufacturing procedures (SMP) which ensure the quality, safety, efficacy and reproducibility of the product. Earlier Ayurvedic physicians were producing medicines by themselves according to their need. Now a day, due to commercialization of Ayurvedic medicines and ignorance of classical methods, quality of drugs has deteriorated. Presently, the demand of Ayurvedic drugs in the global market is increasing day by day. Hence it is the need of time to develop SMP for Ayurvedic products for global acceptability. This paper aims at providing SMP for the manufacture of Rajata Bhasma and also attempts to study the effect of Shodhana process on Rajata. Rajata was obtained from the local market of Varanasi. Rajata Bhasma was prepared and it was observed that during the preparation of Rajata Bhasma, use of Muffle Furnace instead of conventional Puta is more advantageous due to better temperature control. Use of mercury and sulphur together acts as best medium in the preparation of Rajata Bhasma.
doi:10.4103/0974-8520.96135
PMCID: PMC3361937  PMID: 22661856
Bhavana; Marana; Rajata; Rajata sindura; Shodhana
12.  Clinical Delivery of Therapeutic Agents Based on Metals 
Metal-Based Drugs  1997;4(3):133-135.
Metals have been used in clinical practice for hundreds of years and for a variety of indications. Although potent agents whose activity may be adapted by manipulation of their chemistry and that of associated ligands, their use has been limited by toxic effects. There is now a burgeoning series of delivery technologies available which may be adapted to the administration of metal based drugs. Together with greater understanding of metal chemistry and their mechanisms of action in disease processes, there is an opportunity to increase the use of metals in medicine by targeting their action more effectively to the therapeutic site and/or protecting the body from toxic effects.
doi:10.1155/MBD.1997.133
PMCID: PMC2365056  PMID: 18475783
13.  Redox activation of metal-based prodrugs as a strategy for drug delivery 
Advanced drug delivery reviews  2012;64(11):993-1004.
This review provides an overview of metal-based anticancer drugs and drug candidates. In particular, we focus on metal complexes that can be activated in the reducing environment of cancer cells, thus serving as prodrugs. There are many reports of Pt and Ru complexes as redox-activatable drug candidates, but other d-block elements with variable oxidation states have a similar potential to serve as prodrugs in this manner. In this context are compounds based on Fe, Co, or Cu chemistry, which are also covered. A trend in the field of medicinal inorganic chemistry has been toward molecularly targeted, metal-based drugs obtained by functionalizing complexes with biologically active ligands. Another recent activity is the use of nanomaterials for drug delivery, exploiting passive targeting of tumors with nanosized constructs made from Au, Fe, carbon, or organic polymers. Although complexes of all of the above mentioned metals will be described, this review focuses primarily on Pt compounds, including constructs containing nanomaterials.
doi:10.1016/j.addr.2012.01.007
PMCID: PMC3342443  PMID: 22289471
Prodrugs; Pt anticancer drugs; Ru anticancer drugs; activation by reduction; medicinal inorganic chemistry; nanocarriers
14.  Heavy Metal and Pesticide Content in Commonly Prescribed Individual Raw Chinese Herbal Medicines 
The Science of the total environment  2011;409(20):4297-4305.
Heavy metal and pesticide contamination has previously been reported in Chinese Herbal Medicines (CHMs), in some cases at potentially toxic levels. This study was conducted to determine general patterns and toxicological significance of heavy metal and pesticide contamination in a broad sample of raw CHMs. Three-hundred-thirty-four samples representing 126 species of CHMs were collected throughout China and examined for arsenic, cadmium, chromium, lead, and mercury. Of the total, 294 samples representing 112 species were also tested for 162 pesticides. At least 1 metal was detected in all 334 samples (100%) and 115 samples (34%) had detectable levels of all metals. Forty-two different pesticides were detected in 108 samples (36.7%), with 1 to 9 pesticides per sample. Contaminant levels were compared to toxicological reference values in the context of different exposure scenarios. According to a likely scenario of CHM consumption, only 3 samples (1%) with heavy metals and 14 samples (5%) with pesticides were found with concentrations that could contribute to elevated background levels of contaminant exposure. According to the most conservative scenario of CHM consumption, 231 samples (69%) with heavy metals and 81 samples (28%) with pesticides had contaminants that could contribute to elevated levels of exposure. Wild collected plants had higher contaminant levels than cultivated samples. Cadmium, chromium, lead, and chlorpyrifos contamination showed weak correlations with geographic location. Based on our assumptions of the likely mode of consumption of raw CHMs, the vast majority (95%) of the 334 samples in this study contained levels of heavy metals or pesticides that would be of negligible concern. However, given the number of samples with detectable contaminants and the range between the more likely and more conservative scenarios of contaminant exposure, more research and monitoring of heavy metals (especially cadmium and chromium) and pesticide residues (especially chlorpyrifos) in raw CHMs are advised.
doi:10.1016/j.scitotenv.2011.07.032
PMCID: PMC3163780  PMID: 21824641
Traditional Chinese Medicine (TCM); heavy metals; pesticide residues; herbal products; exposure assessment
15.  8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications 
Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalance is the leading cause for many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. 8-Hydroxyquinoline (8HQ) is a small planar molecule with a lipophilic effect and a metal chelating ability. As a result, 8HQ and its derivatives hold medicinal properties such as antineurodegenerative, anticancer, antioxidant, antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed together with their mechanisms of actions and structure–activity relationships.
Video abstract
doi:10.2147/DDDT.S49763
PMCID: PMC3793592  PMID: 24115839
metal binding compound; antineurodegenerative; anticancer; antidiabetic; multifunctional actions; structure-activity relationships
16.  Investigation of heavy metals in frequently utilized medicinal plants collected from environmentally diverse locations of north western India 
SpringerPlus  2013;2:676.
The increasing prevalence of environmental pollution, especially soil contamination with heavy metals has led to their uptake in the human food chains through plant parts. Accumulation and magnification of heavy metals in human tissues through consumption of herbal remedies can cause hazardous impacts on health. Therefore, chemical profiling of nine heavy metals (Mn, Cr, Pb, Fe, Cd, Co, Zn, Ni and Hg) was undertaken in stem and leaf samples of ten medicinal plants (Acacia nilotica, Bacopa monnieri, Commiphora wightii, Ficus religiosa, Glycyrrhiza glabra, Hemidesmus indicus, Salvadora oleoides, Terminalia bellirica, Terminalia chebula and Withania somnifera) collected from environmentally diverse regions of Haryana and Rajasthan states in North-Western India. Concentration of all heavy metals, except Cr, was within permissible limits in the tested stem and leaf samples. Leaf samples had consistently more Cr compared to respective stem samples with highest concentration in leaf samples of Bacopa monnieri (13.19 ± 0.0480 ppm) and stem samples of Withania somnifera (4.93 ± 0.0185 ppm) both collected from Bahadurgarh (heavy industrial area), Haryana. This amount was beyond the permissible limit of 2.0 ppm defined by WHO for raw herbal material. Other two most perilous metals Pb (2.64 ± 0.0260) and Cd (0.04 ± 0.0274) were also recorded in Bahadurgarh region, although below permissible limits. Concentration of Hg remained below detectable levels in all the leaf and stem samples tested. These results suggested that cultivation of medicinal plants and other dietary herbs should be curtailed near environmentally polluted especially industrial areas for avoidance of health hazards.
doi:10.1186/2193-1801-2-676
PMCID: PMC3877414  PMID: 24386622
AAS; Heavy metals; Herbal plants; Soil pollution; Toxicity
17.  Effect of Cadmium on Growth, Bacoside A, and Bacopaside I of Bacopa monnieri (L.), a Memory Enhancing Herb 
The Scientific World Journal  2014;2014:824586.
Bacopa monnieri (L.) is an important medicinal plant mainly known as a memory enhancing herb. It is important to see the effect of metal pollution on its active constituents. In this context, efforts have been made to observe the effect of Cd on the triterpenoid saponins bacoside A and bacopaside I in this plant. The influence of the metal on growth parameters like protein, chlorophyll content, and biomass has also been observed. It is interesting to note that the bacoside A and bacopaside I gradually increased by the Cd treatment up to 10 μM and then decreased at higher concentrations, that is, 50 and 100 μM, but the concentration of these components was more in all the treated plants as compared to control. On the contrary, protein, chlorophyll content, and biomass decreased with the increase in metal concentration and exposure duration due to metal toxicity.
doi:10.1155/2014/824586
PMCID: PMC3928858  PMID: 24672380
18.  Phytosynthesis of nanoparticles: concept, controversy and application 
Nanoscale Research Letters  2014;9(1):229.
Nanotechnology is an exciting and powerful discipline of science; the altered properties of which have offered many new and profitable products and applications. Agriculture, food and medicine sector industries have been investing more in nanotechnology research. Plants or their extracts provide a biological synthesis route of several metallic nanoparticles which is more eco-friendly and allows a controlled synthesis with well-defined size and shape. The rapid drug delivery in the presence of a carrier is a recent development to treat patients with nanoparticles of certain metals. The engineered nanoparticles are more useful in increasing the crop production, although this issue is still in infancy. This is simply due to the unprecedented and unforeseen health hazard and environmental concern. The well-known metal ions such as zinc, iron and copper are essential constituents of several enzymes found in the human system even though the indiscriminate use of similar other metal nanoparticle in food and medicine without clinical trial is not advisable. This review is intended to describe the novel phytosynthesis of metal and metal oxide nanoparticles with regard to their shape, size, structure and diverse application in almost all fields of medicine, agriculture and technology. We have also emphasized the concept and controversial mechanism of green synthesis of nanoparticles.
doi:10.1186/1556-276X-9-229
PMCID: PMC4031915  PMID: 24910577
Metal; Metal oxide; Carbon nanomaterials; Green synthesis; Agriculture; Medicine
19.  Chelating Agents and the Regulation of Metal Ions 
Metal-Based Drugs  1994;1(2-3):87-106.
Up to about the early 1980s it was perhaps still possible to summarize in a review of a moderate length the development of the medicinal applications of chelation chemistry and the exploitation of such chemistry in regulating the metal ion concentrations in the body. However, in the last few years there has a great surge in the development of chelation chemistry and its usage in medicine and related areas of life sciences research. It is no longer the case that such a review primarily concentrates upon the use of chelating agents in removing toxic metals from the body but it must now cover the use of chelating agents in the imaging procedures nuclear medicine and magnetic resonance imaging (MRI), the use of chelating agents in unravelling the biochemistry of reactive oxidative species (ROS) and the control and measurement of intracellular calcium ions. It is in the recent applications that there have been the greatest developments over the last ten years.
doi:10.1155/MBD.1994.87
PMCID: PMC2364881  PMID: 18476223
20.  Detection of Carbonaceous Material in Naga Bhasma 
Traditional medicines have maintained their popularity in all regions of the developing world and are being adopted increasingly by people worldwide. Indian traditional system of medicine Ayurveda make use of unique metallic-herbal preparations (called Bhasma) which involves different processing steps including repeated steps of calcination of metal in the presence of natural precursor (herbal juices, decoctions, and powders, etc). It has been recently established that Bhasma contains nano/sub-micron size particles and different nutrient elements. However, the role and the end product of the raw materials, especially the herbal parts, used during the synthesis of the drug (Bhasma) is one of the important but unanswered problems in such medicinal preparations. Present work on Naga Bhasma is an attempt to understand the role of natural precursors in detail. Our results on infrared, Raman and X-ray photoelectron spectroscopy along with thermal measurements identify the presence of carbonaceous material (hydrogenated amorphous carbon) in the drug along with other compounds. In addition, this work also suggests the science and mechanism behind such complex preparations which could help in standardization of such medicines.
doi:10.4103/0250-474X.103858
PMCID: PMC3546339  PMID: 23326003
Bhasma; carbonaceous material; nanostructure; traditional medicines
21.  ‘New Trends for Metal Complexes with Anticancer Activity’ 
Summary
Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selected delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in ‘metals in medicine’.
doi:10.1016/j.cbpa.2007.11.013
PMCID: PMC2923029  PMID: 18155674
22.  Metal Analysis in Citrus Sinensis Fruit Peel and Psidium Guajava Leaf 
Toxicology International  2011;18(2):163-167.
The determination of metal traces is very important because they are involved in biological cycles and indicate high toxicity. The objective of the present study is to measure the levels of heavy metals and mineral ions in medicinally important plant species, Citrus sinensis and Psidium guajava. This study investigates the accumulation of Copper (Cu), Zinc (Zn), Cadmium (Cd), Aluminum (Al), Mercury (Hg), Arsenic (As), Selenium (Se) and inorganic minerals like Calcium (Ca) and Magnesium (Mg) in C. sinensis (sweet orange) fruit peel and P. guajava (guava) leaf, to measure the levels of heavy metal contamination. Dried powdered samples of the plants were digested using wet digestion method and elemental determination was done by atomic absorption spectrophotometer. Results are expressed as mean ± standard deviation and analysed by student's ‘t’ test. Values are considered significant at P < 0.05. The results were compared with suitable safety standards and the levels of Cu, Zn, Cd, Mg and Ca in C. sinensis fruit peel and P. guajava leaves were within the acceptable limits for human consumption. The order of concentration of elements in both the samples showed the following trend: Mg > Ca > Al > Zn > Cu > Cd > Hg = As = Se. The content of Hg, As and Se in C. sinensis fruit peel and P. guajava leaves was significantly low and below detection limit. The content of toxic metals in tested plant samples was found to be low when compared with the limits prescribed by various authorities (World Health Organization, WHO; International Centre for Materials Research, ICMR; American Public Health Association, APHA). The content of Hg, As and Se in C. sinensis fruit peel and P. guajava leaves was not detectable and met the appropriate safety standards. In conclusion, the tested plant parts taken in the present study were found to be safe.
doi:10.4103/0971-6580.84271
PMCID: PMC3183626  PMID: 21976824
Atomic absorption spectrophotometer; Citrus sinensis; heavy metals; Psidium guajava
23.  Specific DNA structural attributes modulate platinum anticancer drug site selection and cross-link generation 
Nucleic Acids Research  2011;39(18):8200-8212.
Heavy metal compounds have toxic and medicinal potential through capacity to form strong specific bonds with macromolecules, and the interaction of platinum drugs at the major groove nitrogen atom of guanine bases primarily underlies their therapeutic activity. By crystallographic analysis of transition metal–and in particular platinum compound–DNA site selectivity in the nucleosome core, we establish that steric accessibility, which is controlled by specific structural parameters of the double helix, modulates initial guanine–metal bond formation. Moreover, DNA conformational features can be linked to both similarities and distinctions in platinum drug adduct formation between the naked and nucleosomal DNA states. Notably, structures that facilitate initial platinum–guanine bond formation can oppose cross-link generation, rationalizing the occurrence of long-lived therapeutically ineffective monofunctional adducts. These findings illuminate DNA structure-dependent reactivity and provide a novel framework for understanding metal–double helix interactions, which should facilitate the development of improved chromatin-targeting medicinal agents.
doi:10.1093/nar/gkr491
PMCID: PMC3185412  PMID: 21724603
24.  Chloroform Extract of Rasagenthi Mezhugu, a Siddha Formulation, as an Evidence-Based Complementary and Alternative Medicine for HPV-Positive Cervical Cancers 
Rasagenthi Mezhugu (RGM) is a herbomineral formulation in the Siddha system of traditional medicine and is prescribed in the southern parts of India as a remedy for all kinds of cancers. However, scientific evidence for its therapeutic efficacy in cervical cancer is lacking, and it contains heavy metals. To overcome these limitations, RGM was extracted, and the fractions were tested on HPV-positive cervical cancer cells, ME-180 and SiHa. The extracts, free from the toxic heavy metals, affected the viability of both the cells. The chloroform fraction (cRGM) induced DNA damage and apoptosis. Mitochondria-mediated apoptosis was indicated. Though both the cells responded to the treatment, ME-180 was more responsive. Thus, this study brings up scientific evidence for the efficacy of RGM against the HPV-mediated cervical cancer cells and, if the toxic heavy metals are the limitation in its use, cRGM would be a suitable candidate as evidence-based complementary and alternative medicine for HPV-positive cervical cancers.
doi:10.1155/2012/136527
PMCID: PMC3205714  PMID: 22114617
25.  Comparison of Metallic Foreign-Body Removal between Dynamic Ultrasound and Static Radiography in a Pigs' Feet Model 
Introduction
We compared the immediate cosmetic outcome of metallic foreign-body removal by emergency medicine (EM) residents with ultrasound guidance and conventional radiography.
Methods
This single-blinded, randomized, crossover study evaluated the ability of EM residents to remove metallic pins embedded in pigs' feet. Before the experiment, we embedded 1.5-cm metallic pins into numbered pigs' feet. We randomly assigned 14 EM residents to use either ultrasound or radiography to help remove the foreign body. Residents had minimal ultrasound experience. After a brief lecture, we provided residents with a scalpel, laceration kit, a bedside portable ultrasound machine, nipple markers, paper clips, a dedicated radiograph technician, and radiograph machine 20 feet away. After removal, 3 board-certified emergency physicians, who were blinded to the study group, evaluated the soft-tissue model by using a standardized form. They recorded incision length and cosmetic appearance on the Visual Analog Scale.
Results
In total, 28 foreign bodies were removed. No significant difference in the time of removal (P = 0.12), cosmetic appearance (P = 0.96), or incision length (P = 0.76) was found.
Conclusion
This study showed no difference between bedside ultrasound and radiography in assisting EM residents with metallic foreign-body removal from soft tissue. No significant difference was found in removal time or cosmetic outcome when comparing ultrasound with radiography.
doi:10.5811/westjem.2010.6.1885
PMCID: PMC3236155  PMID: 22224139

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