Biosensitive and antibacterial coatings on metallic material for medical applications.

Metallic materials are commonly used for load-bearing implants and as internal fixation devices. It is customary to use austenitic stainless steel, especially surgical grade type 316L SS as temporary and Ti alloys as permanent implants. However, long-term, poor bonding with bone, corrosion, and release of metal ions, such as chromium and nickel occur. These ions are powerful allergens and carcinogens and their uncontrolled leaching may be avoided by surface coatings. Therefore, bioactive glasses (BGs) became a vital biomedical material, which can form a biologically active phase of hydroxycarbonate apatite on their surface when in contact with physiological fluids. To reduce the high coefficient of friction and the brittle nature of BGs, polymers are normally incorporated to avoid the high-temperature sintering/densification of ceramic-only coatings. For medical application, electrophoretic deposition (EPD) is now used for polymer (organic) and ceramic (inorganic) components at room temperature due to its simplicity, control of coating thickness and uniformity, low cost of equipment, ability to coat substrates of intricate shape and to supply thick films in composite form, high purity of deposits as well as no phase transformation during coating. Although extensive research has been conducted on polymer/inorganic composite coatings, only some studies have reported multifunctional properties, such as biological antibacterial activity, enhanced cell adhesion, controlled drug release ability, and mechanical properties. This review will focus on biodegradable coatings, including zien, chitosan, gelatin, cellulose loaded with antibacterial drugs/metallic ions/natural herbs on biostable substrates (PEEK/PMMA/PCL/PLLA layers), which have the potential of multifunctional coating for metallic implants.

Injectable and Radiopaque Liquid Metal/Calcium Alginate Hydrogels for Endovascular Embolization and Tumor Embolotherapy.

Improved endovascular embolization can contribute to assistant treatment for patients. However, many traditional embolic materials, such as metal microcoils or liquid embolic agents, are associated with limitations of coil migration or recanalization. Herein, as the first trial, an injectable and radiopaque liquid metal/calcium alginate (LM/CA) hydrogel is introduced and fabricated as a candidate for endovascular embolization and tumor embolotherapy through developing LM droplets as radiopaque units into biocompatible calcium alginate cross-linked network. The adoption of LM droplets makes hydrogels radiopaque under X-ray and CT scan, which significantly facilitates the tracking of material location during surgical vascular operation. In addition, in vitro and in vivo experiments prove that such smart hydrogel could convert from liquid to solid rapidly via cross-linking, showing pretty flexible and controllable functions. Benefiting from these properties, the hydrogel can be performed in blood vessels through injection via syringes and then served as an embolic material for endovascular embolization procedures. In vivo experiments demonstrate that such hydrogels can occlude arteries and block blood flow until they ultimately lead to ischemic necrosis of tumors and partial healthy tissues. Overall, the present LM/CA hydrogels are promising to be developed as new generation embolic materials for future tumor embolotherapy.

A New Fire Hazard for MR Imaging Systems: Blankets-Case Report.

In this report, a case of fire in a positron emission tomography (PET)/magnetic resonance (MR) imaging system due to blanket combustion is discussed. Manufacturing companies routinely use copper fibers for blanket fabrication, and these fibers may remain within the blanket hem. By folding a blanket with these copper fibers within an MR imaging system, one can create an electrical current loop with a major risk of local excessive heating, burn injury, and fire. This hazard applies to all MR imaging systems. Hybrid PET/MR imaging systems may be particularly vulnerable to this situation, because blankets are commonly used for fluorodeoxyglucose PET to maintain a normal body temperature and to avoid fluorodeoxyglucose uptake in brown adipose tissue. © RSNA, 2017.

Effect of nutritional supplement on bone marrow-derived mesenchymal stem cells from aplastic anaemia.

Aplastic anaemia (AA) is characterised by pancytopenia resulting from a marked reduction in haemopoietic stem cells (HSC). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the bone marrow (BM) microenvironment, including BM-derived mesenchymal stromal cells (BMSC). The purpose of this study was to analyse the biological effect of nutritional supplement (NS), a dietary supplement consisting of thirty-six compounds: amino acids, nucleotides, vitamins and micronutrients on the BMSC of AA rats. The AA rat model was established by irradiating X-ray (2·5 Gy) and intraperitoneal injections of cyclophosphamide (35 mg/kg; Sigma) and chloramphenicol (35 mg/kg; Sigma). Then AA rats were fed with NS in a dose-dependent manner (2266·95, 1511·3, 1057·91 mg/kg d) by intragastric administration. The effect of NS on the BMSC of AA rats was analysed. As compared with AA rats, NS treatment significantly improved these peripheral blood parameters and stimulated the proliferation of total femoral nucleated cells. NS treatment affected proliferative behaviour of BMSC and suppressed BMSC differentiation to adipocytes. Furthermore, NS treatment of AA rats accelerated osteogenic differentiation of BMSC and enhanced bone mineral density. Co-incubation of HSC with mesenchymal stromal cells and serum from AA rats subjected to high-dose NS markedly improved the yield of CD34+cells. Protein microarray analysis revealed that there were eleven differentially expressed proteins in the NS group compared with the AA rat group. The identified specific NS might be implicated in rehabilitation of BMSC in AA rats, suggesting their potential of nutritional support in AA treatment.

Metals Differentially Activate Ovarian Cancer G Protein-Coupled Receptor 1 in Various Species.

Human, mouse, and zebrafish ovarian cancer G protein-coupled receptors (OGR1s) are activated by both metals and extracellular protons. In the present study, we examined whether pig, rat, chicken, and Xenopus OGR1 homologs could sense and be activated by protons and metals. We found that all homologs stimulated serum response element (SRE)-driven promoter activities when they are stimulated by protons. On the other hand, metals differentially activated the homologs. The results using chimeric receptors of human and zebrafish OGR1s indicate that the specificity of the metal-induced activation lies in the extracellular region. These results suggest that protons are an evolutionally conserved agonist of OGR1. However, the types of metals that activated the receptor differed among the homologs.

Preliminary clinical application of integrated 125I seeds stents in the therapy of malignant lower biliary tract obstruction.

PURPOSE: To evaluate the clinical efficacy of percutaneous trans-hepatic integrated 125I seed stents implantation for malignant lower biliary tract obstruction. METHODS: Thirty-two patients with malignant lower biliary obstruction were randomly divided into two groups. One group underwent the therapy with integrated 125I seed stents (Test group, n = 13), and another group received conventional metal stents implantation for treatment (Control group, n = 19). The pre- and post-operative changes in biochemical indices, white blood cell count, IgG level, stent patency, survival time, tumor size and complications were compared between the two groups. RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) was used to evaluate therapeutic effects. The average follow-up time was 12.3 months. RESULTS: The differences between pre- and post-operative (30 days) intragroup biochemical indices had statistically significant difference (P < 0.05), but there were no significant differences (P > 0.05) in leukocyte counts and IgG levels. As to the median time of stent patency and patients' survival, there were significant differences (P < 0.05) between Control and Test groups (3.9 months vs. 8.1 months, 139 days vs. 298 days, respectively). Three months after the operation, the average tumor size was reduced in the Test group, but was increased in the Control group (P < 0.05). There was no significant difference in the incidence of complications between the two groups. The evaluation results using RECIST 1.1 showed that there were statistically significant differences between the two groups in terms of the rates of remission, control, and progression (χ2 = 17.5, P < 0.05). CONCLUSIONS: The study indicates that integrated 125I seed stents are effective in reducing jaundice symptoms, inhibiting tumor growth, improving stent patency and prolonging patient survival, which may serve as a safer and more feasible method in treating malignant lower biliary obstruction with minimal invasiveness.

Characterization and risk of exposure to elements from artisanal gold mining operations in the Bolivian Andes.

Artisanal and small-scale gold mining (ASGM) offers low-skilled workers an opportunity to elevate themselves out of poverty. However, this industry operates with little to no pollution controls and the cost to the environment and human health can be large. The objectives of this study were to measure levels of arsenic (As), manganese (Mn), cobalt (Co), lead (Pb), and mercury (Hg) in the environment and characterize health risks to miners and residents in an area with active ASGM operations. An exposure assessment was conducted at two different mining sites and a nearby village in the Bolivian Anders. The resulting measurements were then used to quantify cancerous and noncancerous health risks to children and adults working at and living near ASGM areas. Soil concentrations of As were well above background levels and showed great variations between the village and mining area. Mercury vapor levels at the two mining sites were approximately 30 times larger than the EPA reference concentration. The risk of developing non-cancerous health effects were primarily due to exposure to As and Hg. The probability of individuals developing cancer was considerably increased with adult miners having a probability of 1.3 out of 100. Cancer potential was driven by exposure to As, with de minimus cancer risk from all other elements. Based on the environmental characterization of elements in soils and Hg vapors, the risk of developing cancerous and non-cancerous health outcomes were above a level of concern based on EPA risk assessment guidance. Personal protective equipment was not worn by workers and Hg amalgam is commonly heated in workers' homes. Better education of the risks of ASGM is needed as well as simple controls to reduce exposure.

Revision total knee arthroplasty due to bone cement and metal hypersensitivity.

INTRODUCTION: Hypersensitivity to implants is a rare complication of total knee arthroplasty (TKA). Metal and, less frequently, bone cement can produce allergic symptomatology that if unresponsive to conservative treatment could lead to revision. MATERIALS AND METHODS: We present the case of a patient with generalized pruritus and metal taste starting during the first postoperative month after TKA. Dermal allergy exams revealed that the patient had hypersensitivity to nickel sulphate and cobalt chloride and bone cement. Conservative treatment with antihistamine medication and corticosteroids failed to control the symptoms. The patient underwent revision TKA with a hypoallergic prosthesis 8 months after the primary procedure. RESULTS: Full disappearance of the symptoms occurred 3 months after revision. The latest follow-up evaluation (3 years post-revision) was unremarkable. CONCLUSIONS: In our opinion, an exhaustive medical history should be obtained from every candidate for total joint replacement and in cases of prior severe allergic reactions to metals, plastics or glues, patch testing of the components of the future prosthesis should be done. When an already implanted prosthesis causes symptoms like pain, edema, pruritus, erythema, limited range of motion and increase in joint's temperature, the possibility of allergy to metals and/or bone cement (in case of cemented prosthesis) should be checked after the exclusion of other reasons like infection. If symptoms cannot be controlled by conservative measures, revision should be decided and carried out with hypoallergic prosthesis.

Evaluation of the impact of multivalent metal ions on the permeation behavior of Dolutegravir sodium.

Interactions between active pharmaceutical ingredients (APIs) and polyvalent cations are an important factor within drug absorption in the gastrointestinal tract. Dolutegravir sodium, as a second-generation integrase stand transfer inhibitor for the treatment of HIV was investigated regarding chelation with Al(3+), Ca(2+), Fe(3+), Mg(2+ )and Zn(2+) ions at three different molar ratios. Furthermore, the influence of drug-ion chelates on the permeability of the drug across two intestinal membrane models was analyzed. For this purpose, Caco-2 monolayer model and Ussing chamber technique utilizing freshly excited rat intestinal mucosa were chosen and a buffer system without additional Mg(2+) and Ca(2+) ions was tested regarding cell detachment. The addition of polyvalent cations in an equal molar ratio to the drug solution decreased the dissolved drug by at least 11%. An increased multivalent cation concentration in a ratio of 1:10 afforded an API drop in the solution of at least 88% with the exception of Mg(2+). In particular, Dolutegravir sodium was chelated with iron ions to nearly 100%. Overall, the higher the amount of metal ions in the solution, the lower was the detected amount of the drug. The permeation experiments across the Caco-2 monolayer and the rat intestinal mucosa pointed out that the addition of AlCl3, CaCl2 and ZnCl2 in a molar ratio of 10:1 to the drug led to significantly decreased drug permeation. According to these results the co-administration of Al(3+), Ca(2+ )or Zn(2+ )as well as of supplementary medications containing these polyvalent ions is in case of oral Dolutegravir delivery not recommended.

[Contact allergic gastritis : Rare manifestation of a metal allergy]. / Kontaktallergische Gastritis : Seltene Manifestation einer Metallallergie.

Only a few cases of contact allergic gastritis in patients with nickel allergy have been reported in the literature. We report a case of probable contact-allergic gastritis in a 46-year-old woman. Clinical examination revealed lichenoid mucosal lesions of the gums adjacent to a bridge and crowns that had been implanted several weeks previously. Since implantation, the patient suffered from gastrointestinal complaints including stomach pain. Gastroscopy and histological investigation of stomach biopsies showed eosinophilic gastritis. Patch testing done under the diagnosis of contact allergic stomatitis showed positive reactions to gold sodium thiosulphate, manganese (II) chloride, nickel (II) sulphate, palladium chloride, vanadium (III) chloride, zirconium (IV) chloride, and fragrances. The crowns and the bridge contained gold, palladium, and zirconium, hence they were replaced by titan-based dentition. Shortly after replacing the artificial dentition, all gastrointestinal symptoms resolved spontaneously without further treatment. Delayed-type allergy to components in the artificial dentition seem to have caused the gastritis.

Development and application of a dosimetry model (ExDoM2) for calculating internal dose of specific particle-bound metals in the human body.

The objective of the current study was to develop a dosimetry model (ExDoM2) for calculating internal dose of specific particle-bound metals (As, Pb, Cd, Cr and Mn) in the human body. The ExDoM2 is a revised version of a respiratory tract model (ExDoM) incorporating a new particle clearance mechanism in the respiratory tract model and a Physiologically-Based PharmacoKinetic (PBPK) model. The revised respiratory tract model was used to calculate the deposition, clearance and retention of particles in the human respiratory tract and the mass transferred to the oesophagus (gastrointestinal tract) and blood. The PBPK module was used to analyze the distribution of metals (As, Pb, Cd, Cr and Mn) from the blood circulation system to other organs or tissues like liver, kidneys, heart, brain, muscle and bone. The model was applied to calculate the internal human dose for an adult Caucasian male exposed to particulate mass matter (PM), PMPb, PMCd, PMMn and PMCr in an urban area (Athens, Greece). The analysis showed that at the end of the exposure (one day exposure scenario) to PMPb, the major accumulation occurs in the bone, blood and muscle, whereas as regards PMCd the major accumulation occurs in the other tissues, like kidney and liver. In addition, for PMMn, the major accumulation occurs in the other tissues and lungs, whereas as regards PMCr the major accumulation occurs in the gastrointestinal (GI) tract and lungs. Therefore, ExDoM2 is an important feature in studying deposition of particles in the human body.

Partitioning of Dietary Metal Intake--A Metal Dietary Exposure Screening Tool.

Detection of heavy metals at trace or higher levels in foods and food ingredients is not unexpected given the widespread unavoidable presence of several metals in nature, coupled with advancement in analytical methods and lowering limits of detection. To assist risk managers with a rapid risk assessment when facing these situations, a metal dietary exposure screening tool (MDEST) was developed. The tool uses food intake rates based on the National Health and Nutrition Examination Survey 2005-2010 consumption data for the U.S. population two+ years and up and for infants age six months to

Decolorization of Reactive Black-5 by Shewanella sp. in the Presence of Metal Ions and Salts.

In this study, effect of various metal ions and salts on biodecolorization of Reactive black-5, azoreductase activity, and growth of Shewanella sp. strain IFN4 was evaluated. Among the tested metals, Cr²âº, Pb(²âº, Ni²âº, Fe²âº, and Mn²âº did not inhibit the biodecolorization of reactive black-5, azoreductase activity and bacterial growth. Three metals (Cu²âº, Zn²âº, and Co²âº) delayed the decolorization process without completely inhibiting the reaction and also suppressed the bacterial growth. However, no dye decolorization was observed in the presence of Cd²âº (10 mg L⁻¹). Furthermore, bacterium decolorized the dye at high concentration (15 mg L⁻¹) of mixed metal ions. Strain IFN4 was also able to decolorize the dye at 50 g NaCl L⁻¹ and 60 g Na2SO4 L⁻¹. NaCl was found to be more inhibitory to bacterial growth than Na2SO4and the reverse was observed for azoreductase activity. These findings suggest that strain IFN4 could be used in designing a bioreactor for the treatment of textile effluent.

Association between prenatal exposure to metals and neonatal morbidity.

An association between prenatal exposure to (semi-)metals and of neonatal morbidity was assessed by introducing an oxidative stress as a possible intermediate step. An oxidative stress was measured by cell proliferation (CP) ratio in umbilical cord blood cells. Urine samples of 18 out of 58 enrolled women (31%) were positive for (semi-)metals; 25.9% of women were positive for aluminum (Al). The CP ratio was higher (1) in subjects with Al, (2) in mothers to newborns diagnosed as small-for-gestational age (p value = .052), (3) neonates that weighed less (p value = .079), and (4) in women who experienced repeated abortions (p value = .049). Our findings suggest the possibility of metal-induced oxidative stress.

The new nitinol conformable self-expandable metal stents for malignant colonic obstruction: a pilot experience as bridge to surgery treatment.

INTRODUCTION: Self-expandable metal stents (SEMS) are a nonsurgical option for treatment of malignant colorectal obstruction also as a bridge to surgery approach. The new nitinol conformable stent has improved clinical outcomes in these kinds of patients. We report a pilot experience with nitinol conformable SEMS placement as bridge to surgery treatment in patients with colorectal obstruction. MATERIALS AND METHODS: Between April and August 2012, we collected data on colonic nitinol conformable SEMS placement in a cohort of consecutive symptomatic patients, with malignant colorectal obstruction, who were treated as a bridge to surgery. Technical success, clinical success, and adverse events were recorded. RESULTS: Ten patients (7 male (70%)), with a mean age of 69.2±10.1, were evaluated. The mean length of the stenosis was 3.6±0.6 cm. Five patients (50%) were treated on an emergency basis. The median time from stent placement to surgery was 16 days (interquartile range 7-21). Technical and clinical success was achieved in all patients with a significant early improvement of symptoms. No adverse events due to the SEMS placement were observed. CONCLUSION: This pilot study confirmed the important role of nitinol conformable SEMS as a bridge to surgery option in the treatment of symptomatic malignant colorectal obstruction.

Strategic feeding of ammonium and metal ions for enhanced GLA-rich lipid accumulation in Cunninghamella bainieri 2A1.

Strategic feeding of ammonium and metal ions (Mg(2+), Mn(2+), Fe(3+), Cu(2+), Ca(2+), Co(2+), and Zn(2+)) for enhanced GLA-rich lipid accumulation in C. bainieri 2A1 was established. When cultivated in nitrogen-limited medium, the fungus produced up to 30% lipid (g/g biomass) with 12.9% (g/g lipid) GLA. However, the accumulation of lipid stopped at 48 hours of cultivation although glucose was abundant. This event occurred in parallel to the diminishing activity of malic enzyme (ME), fatty acid synthase (FAS), and ATP citrate lyase (ACL) as well as the depletion of metal ions in the medium. Reinstatement of the enzymes activities was achieved by feeding of ammonium tartrate, but no increment in the lipid content was observed. However, increment in lipid content from 32% to 50% (g/g biomass) with 13.2% GLA was achieved when simultaneous feeding of ammonium, glucose, and metal ions was carried out. This showed that the cessation of lipid accumulation was caused by diminishing activities of the enzymes as well as depletion of the metal ions in the medium. Therefore, strategic feeding of ammonium and metal ions successfully reinstated enzymes activities and enhanced GLA-rich lipid accumulation in C. bainieri 2A1.

Light-triggered eradication of Acinetobacter baumannii by means of NO delivery from a porous material with an entrapped metal nitrosyl.

A photoactive manganese nitrosyl, namely [Mn(PaPy(3))(NO)](ClO(4)) ({Mn-NO}), has been loaded into the columnar pores of an MCM-41 host. Strong interaction between the polar nitrosyl and the -OH groups on the host wall leads to excellent entrapment of the NO donor within the porous host. With the aluminosilicate-based host (Al-MCM-41), the loading is further enhanced due to electrostatic interaction of the cationic species with the aluminum sites. The extent of loading has been determined via analytical techniques including N(2) adsorption/desorption isometry. Powder X-ray diffraction studies on the loaded materials afford patterns typical of an ordered mesoporous silicate consisting of a hexagonal array of unidimensional channels (with slight loss of crystallinity). Elemental mapping of the loaded particles confirms the incorporation of {Mn-NO} into the porous MCM-41 structure and attests to the homogeneity of the guest molecule distribution throughout individual particles. When suspensions of the loaded materials in saline solution are exposed to low-power (10-100 mW) visible light, rapid release of NO is observed. With continuous exposure, a steady release of 50-80 µM of NO is attained with 5 mg of material/mL buffer within 5 min, and the NO flux is maintained for a period of ~60 min. Rapid bursts of 5-10 µM NO are noted with short light pulses. Loss of either the nitrosyl or its photoproduct(s) from these materials in biological media is minimal over long periods of time. The NO release profiles suggest potential use of these powdery biocompatible materials as NO donors where the delivery of NO (a strong antibiotic) could be controlled via the exposure of light. Such prediction has been confirmed with the successful eradication of both drug-susceptible and drug-resistant Acinetobacter baumannii in a soft-tissue infection model through light-triggered NO delivery.

In situ activation of therapeutics through bioorthogonal catalysis.

Bioorthogonal chemistry refers to any chemical reactions that can occur inside of living systems without interfering with native biochemical processes, which has become a promising strategy for modulating biological processes. The development of synthetic metal-based catalysts to perform bioorthogonal reactions has significantly expanded the toolkit of bioorthogonal chemistry for medicinal chemistry and synthetic biology. A wide range of homogeneous and heterogeneous transition metal catalysts (TMCs) have been reported, mediating different transformations such as cycloaddition reactions, as well as bond forming and cleaving reactions. However, the direct application of 'naked' TMCs in complex biological media poses numerous challenges, including poor water solubility, toxicity and catalyst deactivation. Incorporating TMCs into nanomaterials to create bioorthogonal nanocatalysts can solubilize and stabilize catalyst molecules, with the decoration of the nanocatalysts used to provide spatiotemporal control of catalysis. This review presents an overview of the advances in the creation of bioorthogonal nanocatalysts, highlighting different choice of nano-scaffolds, and the therapeutic and diagnostic applications.

A single luminescence center ultra-broadband near-infrared LiScGeO4:Cr phosphor for biological tissue penetration.

In this work, in order to meet the application of near-infrared phosphor-converted light emitting diodes (pc-LEDs), an ultra-broadband emission phosphor, LiScGeO4:Cr, was synthesized. Its FWHM reaches 335 nm, and its emission spectrum ranges from 800 nm to 1650 nm, which almost covers the entire near-infrared second window (NIR-II). The broadband emission is thought to be caused by the 4T2 → 4A2 transition of the Cr3+ ion. This transition occurs due to the olivine structure of the crystal, which causes the Cr3+ ions to inhabit a low-symmetric crystal field, and the crystal field strength is very weak. NIR pc-LEDs were fabricated by combining a 460 nm blue LED with this phosphor, which penetrates 4 cm thick beef. The results indicate that there may be a potential application for this phosphor in the field of biological tissue penetration and non-destructive testing.

Evidence-Based Recommendations for an Optimal Prenatal Supplement for Women in the U.S., Part Two: Minerals.

The levels of many essential minerals decrease during pregnancy if un-supplemented, including calcium, iron, magnesium, selenium, zinc, and possibly chromium and iodine. Sub-optimal intake of minerals from preconception through pregnancy increases the risk of many pregnancy complications and infant health problems. In the U.S., dietary intake of minerals is often below the Recommended Dietary Allowance (RDA), especially for iodine and magnesium, and 28% of women develop iron deficiency anemia during their third trimester. The goal of this paper is to propose evidence-based recommendations for the optimal level of prenatal supplementation for each mineral for most women in the United States. Overall, the evidence suggests that optimal mineral supplementation can significantly reduce a wide range of pregnancy complications (including anemia, gestational hypertension, gestational diabetes, hyperthyroidism, miscarriage, and pre-eclampsia) and infant health problems (including anemia, asthma/wheeze, autism, cerebral palsy, hypothyroidism, intellectual disability, low birth weight, neural tube defects, preterm birth, rickets, and wheeze). An evaluation of 180 commercial prenatal supplements found that they varied widely in mineral content, often contained only a subset of essential minerals, and the levels were often below our recommendations. Therefore, there is a need to establish recommendations on the optimal level of mineral supplementation during pregnancy.