Article

Viral Pathogens and Severe Acute Respiratory Syndrome: Oligodynamic Ag+ for Direct Immune Intervention

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Abstract

This retrospective study of silver-based therapeutics briefly reviews their history, and then explores the modern application of charged silver particles, especially as an antiviral agent. The recent outbreak of severe acute respiratory syndrome (SARS) suggests this is timely. Medical literature shows that a variety of viruses have been successfully treated with silver-based drugs. However, 'silver salts' and/or inferior silver preparations lack the bio-availability, active silver content and safety needed to be effective. State-of-the-art, electrolytically produced 'oligodynamic' Ag+, however, offers distinct advantages and versatility of use over older and cruder formulations. Possessing much smaller, subnanometer-sized particles, greater electrical potential and lower concentrations, it is more bio-available than other formulations. Efficacy against the SARS-related coronavirus, for example, may be enhanced when nebulized Ag+ is inhaled. This should achieve swift reduction of viral loads, especially in the early stages. Moreover, there is no known toxicity for Oligodynamic Ag+ in humans. The only known mechanism of resistance also appears to play no role notwithstanding the mutability of the coronavirus. Therefore no functional barrier to the virotoxic effects of oligodynamic Ag+ may be expected regardless of the rapidity or variety of mutations.

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... There are numerous reports that describe antibacterial and antifungal effects of AgNPs [240,241]; however, studies on the antiviral effect of AgNPs are relatively less. For instance, Lv et al. (2014) have shown significant antiviral activity of the AgNPs against an important coronavirus known as transmissible gastroenteritis virus (TGEV) [242], and Rentz Do Comm Cnmo (2003) has found oligodynamic AgNPs potentially effective against SARS virus [243]. Besides, some studies have indicated the antiviral activity of AgNPs against human immunodeficiency virus (HIV) [244,245], herpes simplex virus type-1 (HSV-1) [246], hepatitis B virus (HBV) [247], respiratory syncytial virus (RSV) [248,249], H1N1 influenza A virus [250], monkeypox virus [251], adenovirus [252], and African swine fever virus (ASFV) [253]. ...
... There are numerous reports that describe antibacterial and antifungal effects of AgNPs [240,241]; however, studies on the antiviral effect of AgNPs are relatively less. For instance, Lv et al. (2014) have shown significant antiviral activity of the AgNPs against an important coronavirus known as transmissible gastroenteritis virus (TGEV) [242], and Rentz Do Comm Cnmo (2003) has found oligodynamic AgNPs potentially effective against SARS virus [243]. Besides, some studies have indicated the antiviral activity of AgNPs against human immunodeficiency virus (HIV) [244,245], herpes simplex virus type-1 (HSV-1) [246], hepatitis B virus (HBV) [247], respiratory syncytial virus (RSV) [248,249], H1N1 influenza A virus [250], monkeypox virus [251], adenovirus [252], and African swine fever virus (ASFV) [253]. ...
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Unlike chemical or physical methods of synthesis, biosynthesis/biofabrication of silver nanoparticles (AgNPs) has been recently accentuated due to low-cost, rapid one-step synthesis with controllable size/shape, high stability, effectivity, biocompatibility, and safety. Recent database suggests that the choice of adopting AgNPs biofabrication is rapidly evolving for their usage as promising nanocarriers/targeted drug delivery systems to tackle wide-spectrum atrocious microbial diseases and heterogeneous cancer with higher efficacy and nominal toxicity. However, there is still a dearth of our understanding on the mechanism of action of these biofabricated-AgNPs at the sub-cellular, cellular and organismal level. Phytofabrication of AgNPs has been found to be most preferred one as potential therapeutics/drug delivery systems; however, there is a growing inquisitiveness towards the fabrication of AgNPs using fungi (mycofabrication), bacteria and algae (phycofabrication). This article addresses the recent progress of various biofabricated-AgNPs and their applicability as prospective theranostic systems for cancer and microbial diseases.
... on the bactericidal effect of the FG/Ag; the smaller the particle size, the greater the surface energy and the more biocidal [43]. The enhanced biocidal response of smaller particles may be due to their increased dissolution rate since researchers have reported Ag(I) as the active agent against microbes [44] [45] [46]. ...
Article
A number of researchers have deployed silver (Ag) nanoparticles through a number of techniques on various substrates including carbon, zeolites and polymers for water disinfection applications. However, Ag impregnated on an inorganic fiberglass surface through a simple electroless process was only recently reported for the first time. Fiberglass impregnated with Ag nanoparticles displays superior performance over carbon-based silver support systems but little is known about the factors that affect the architecture of the system, its interfacial properties and its consequent bactericidal activity. In this study, Ag content and particle size on a fiberglass substrate were manipulated by adjusting the AgNO(3) concentration, immersion time, temperature, solution pH and reduction temperature. The reduction chemistry of the Ag-nanoparticle-impregnated fiberglass is described and supported with thermal gravimetric analysis (TGA) and photoelectron spectroscopy (XPS) measurements. The Ag content along with the particle size and particle size distribution were characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS) and x-ray diffraction (XRD). The Ag content on the fiberglass mats ranged from 0.04 to 4.7 wt% Ag/g-fiber with a size distribution of 10-900 nm under standard processing conditions. Inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze the Ag desorption from the fiberglass substrate, while the bactericidal properties were evaluated against Escherichia coli (E. coli).
... Furthermore, Ag 2 O has lower solubility in water compared to that of Na 2 O [51]. The silver ions release profiles (Fig. 6) showed sustained release of silver ions with concentrations range (summarized in Table 2) effective to kill bacteria [52]. Actually, very low concentrations of silver ions are very potent in killing bacterial [53][54][55][56]. ...
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Phosphate and silver-doped phosphate glasses are potential candidates for use as degradable biomaterials and as antibacterial materials as well. The present investigation explores the glass-forming compositions (GFC), physical properties and degradation rates of both phosphate glasses in the P2O5-CaO-Na2O ternary system and silver-phosphate glasses derived from it by introducing Ag2O in replacement of Na2O. The glasses were prepared using the traditional melting-annealing technique applied in glass making industry. Bulk glasses were prepared without using any special precautions or specific conditions (contrary to previous studies) which can prevent crystallization or segregation of silver particles from the melt. A wide glass formation domain with ≥40mol% P2O5 was determined in the ternary P2O5-CaO-Na2O system. However, up on Ag2O addition, the amount of Ag2O that can exist in the glass and remains amorphous was limited to 2mol% as ensured from X-ray diffraction (XRD). The compositions with ≥60mol% P2O5 and 0.5, 1 or 2mol% Ag2O formed transparent and colorless silver phosphate glasses. Whereas, the compositions with ≤55mol% P2O5 did not form glasses and showed immediate partial crystallization and separation of silver particles. Thereafter, the structure of representative glasses was studied by FT-IR and UV-vis absorption spectroscopy. Finally, as silver ions function as antibacterial metal ions, the amounts of silver ions released from silver phosphate glasses were measured by atomic absorption spectrometry (AAS). © 2018 Brazilian Metallurgical, Materials and Mining Association.
... Crude oligodynamic Ag + preparations have a difficult time penetrating these waxy envelopes as discovered by a NASA commissioned study. 30 Picoscalar oligodynamic Ag + hydrosol, which is over 95% bioactive, would not suffer the same handicap as did NASA's 1970 technologically crude Ag + hydrosol preparation. There is an exchange between host cells and the virus of both lipids and proteins. ...
Article
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BACKGROUND: Recently Rentz (2003) published a convincing retrospective, peer-reviewed treatise on a highly advanced, effective and safe virotoxic oligodynamic silver (Ag+) hydrosol, making the case
... Silver is well known for its strong antimicrobial properties. Silver-based biocides, including both ionic silver forms and metallic silver nanoparticles are antimicrobial towards a broad spectrum of Gram-negative and Gram-positive bacteria [24,25], fungi [26,27], and viruses [28,29,30]. Silver ions can inhibit microbial biofilm formation [27] and destabilize the polymeric matrix once the biofilm is formed [31]. ...
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This in vitro study assessed the antimicrobial properties of a novel octasilver salt of Sucrose Octasulfate (IASOS) as well as of an innovative vaginal gel containing IASOS (SilSOS Femme), against bacterial and yeast pathogens isolated from human clinical cases of symptomatic vaginal infections. In BHI and LAPT culture media, different ionic silver concentrations and different pHs were tested. IASOS exerted a strong antimicrobial activity towards all the pathogens tested in both culture media. The results demonstrated that salts and organic compounds present in the culture media influenced IASOS efficacy only to a moderate extent. Whereas comparable MBCs (Minimal Bactericidal Concentrations) were observed for G. vaginalis (10 mg/L Ag+), E. coli and E. aerogenes (25 mg/L Ag+) in both media, higher MBCs were found for S. aureus and S. agalactiae in LAPT cultures (50 mg/L Ag+ versus 25 mg/L Ag+). No minimal concentration totally inhibiting the growth of C. albicans was found. Nevertheless, in both media at the highest ionic silver concentrations (50-200 mg/L Ag+), a significant 34-52% drop in Candida growth was observed. pH differently affected the antimicrobial properties of IASOS against bacteria or yeasts; however, a stronger antimicrobial activity at pH higher than the physiological pH was generally observed. It can be therefore concluded that IASOS exerts a bactericidal action against all the tested bacteria and a clear fungistatic action against C. albicans. The antimicrobial activity of the whole vaginal gel SilSOS Femme further confirmed the antimicrobial activity of IASOS. Overall, our findings support IASOS as a valid active ingredient into a vaginal gel.
... stability The photocatalyst rings were carefully washed and dried after each cycle. Fig. 2b shows by ICP-MS the Ti-ions leached after each recycling, the values reported in Fig. 2b were far below the allowed limit set by sanitary regulations for the toxicity on mammalian cells, up to one gram TiO 2 /L [23]. Fig. 2c shows the ICP-MS amounts of the Cu-ions leached during the MB-discoloration into the solution. ...
... Inactivation of bacteria by contact with the mats may proceed through an oligodynamic effect due to the very low ppb amounts of Cu involve. [42,43]. This includes: a) Cu-binding of S, N and COOand other electron donor groups of the bacteria cell wall and b) Cu in ppb amounts permeating the cell membrane reaching the cytoplasm and leading to bacterial inactivation [44]. ...
... The adsorption of Cu-NPs on MRSA cell wall has been reported to happen preferentially on the teichoic acid and the peptidoglycan components [62]. For E. coli and MRSA, the bacterial desinfection has been reported to occur on several metals/metal oxides [63][64][65]. ...
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Photocatalytic antibacterial sol-gel coated substrates have been reported to kill bacteria under light or in the dark. These coatings showed non-uniform distribution, poor adhesion to the substrate and short effective lifetime as antibacterial surfaces. These serious limitations to the performance/stability retard the potential application of antibacterial films on a wide range of surfaces in hospital facilities and public places. The write-up reviews the preparation, testing and performance of flexible ultra-thin films prepared by direct current magnetron sputtering (DCMS) at different energies. We also report in this review the recent advancement in the preparation of highly adhesive photocatalytic coatings prepared by up to date sputtering technology: High Power Impulse Magnetron Sputtering (HIPIMS). These latter films demonstrated an accelerated antibacterial capability compared to thicker films prepared by DCMS leading to materials saving. Nanoparticulates of Ti and Cu have been shown during the last decades to possess high oxidative redox potentials leading to bacterial inactivation kinetics in the minute range. In the case of TiO2-CuOx films the kinetics of abatement of Escherichia coli (E. coli) and methicillin resistant Staphylococcus aureus (MRSA), were enhanced under indoor visible light and were perceived to occur within few minutes. Oligodynamic effect was seen to be responsible for bacterial inactivation by the small amount of released material in the dark and/or under light as detected by inductively-coupled plasma mass spectrometry (ICP-MS). The spectral absorbance (detected by Diffuse Reflectance Spectroscopy-DRS) was also seen to slightly shift to the visible region based on the preparation method.
... The oligodynamic effect was discovered in 1893 by the Swiss, Karl Wilhelm von Nägeli, as a toxic effect of heavy metal ions on living cells even in relatively low concentrations [7]. To accelerate the oligodynamic process, Spadaro et al. connected silver to the positive electrode (anode) of a power source and activated the release of Ag + by low intensity direct current (LIDC, 0.02-20 µA) [8]. ...
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Introduction Electrical activation of silver ions, known as oligodynamic iontophoresis, has shown broad-spectrum antimicrobial activities against bacteria, fungi, and viruses. However, it is not clear how the ion delivery manner, which is controlled by the electrical activation, influences the iontophoresis process. This paper focuses on this knowledge gap, aiming to characterize the interactive effects of electric current intensity and activation duration on the antimicrobial efficacy of a silver-based iontophoresis prototype against Gram-positive (S. aureus) and Gram-negative (E. coli) strains respectively. Materials and Methods The modified Kirby–Bauer disc diffusion method was adopted to quantify the antimicrobial efficacy. A linear regression model was established and validated by empirical data. Conclusion This study revealed that the antimicrobial activities of the device was more sensitive to current duration than current intensity, and the marginal antimicrobial efficacy of the device decreased as the current intensity increased. In addition, a sustained release of Ag + had superior antimicrobial efficacy compared to a fast release. These findings will contribute to the performance optimization of silver oligodynamic iontophoresis devices for antimicrobial applications.
... Thus, the role of copper in bacterial inactivation is dual, as the detected copper is found both in the bulk and on the GF-TiO 2 -Cu mat surface. Inactivation of bacteria by contact with the mats may proceed through an oligodynamic effect due to the very low ppb amounts of Cu involve [42,43]. This includes: a) Cu-binding of S, N and COO À and other electron donor groups of the bacteria cell wall and b) Cu in ppb amounts permeating the cell membrane reaching the cytoplasm and leading to bacterial inactivation [44]. ...
Article
This study presents the performance of GF-mats loaded with TiO 2 and Cu under solar/visible light leading to bacterial inactivation and pollutant degradation at both solid-air and solid-liquid interfaces. The GF-mats show effective water disinfection, self-cleaning and degradation of an organic pollutant in solution. Cleaning of the GF-mats was found to be a necessary step before grafting TiO 2 and Cu/CuO in amounts of TiO 2 (10%-25% by weight) and Cu (0.03%-0.45% by weight) respectively. A GF-mat consisting of 15.4% TiO 2 and 0.45% Cu led to bacterial disinfection within $30 min under solar irradiation (290-800 nm light) and within $60 min under visible light irradiation (400-800 nm). The oxidative radicals generated on the TiO 2-Cu surface leading to disinfection, self-cleaning and abatement of the pollutant were identified and the diffusion length from the GF-mat was estimated for the most active HO 2 radical. The pH/surface potential changes in solution during the degradation of methylene blue (MB), which was taken as a model pollutant, were followed by means of a microelectrode. A GF-mat loaded with TiO 2 13.1% and Cu 0.03% by weight led to the degradation of a dilute pollutant solution within $100 min. The pollutant degradation was assessed by high performance liquid chromatography (HPLC) by following the decrease of the intensity of its characteristic absorbance peaks. The TiO 2 and Cu eluted from the mat during the degradation of MB were detected by inductively coupled plasma mass-spectrometry (ICP-MS). The surface properties of the mats were investigated by scanning electron microscopy (SEM). Evidence is presented for the redox events on the GF-TiO 2-Cu mats during the self-cleaning reactions by XPS.
... Similarly, nano-encapsulation can also prevent immune-mediated rapid clearance of immuno-dominant peptides, therapeutic antibodies or regulatory RNAs such as siRNA, ssRNA, etc.. Lipid NPs, gold nanorods, VLPs have also found applicability in this aspect [250][251][252][253][254]. Glycoconjugated AuNPs can mimic heparin sulfate proteoglycans which is important for cellular attachment of the viruses and thus prevent viral infections [255]. The inherent virucidal properties of certain metal and metal oxide NPs such as gold, silver and magnesium oxide NPs have also been exploited to control or mitigate some viral infections [256][257][258][259]. Further nanoformulations can cross specialized membranes like bloodbrain-barrier which can be of crucial importance for drug targeting in certain critical applications. ...
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Chapter
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The differential effects produced in culture by silver, platinum, and stainless steel were studied. After 24 h, mouse marrow cultured on silver showed a significant decrease in the percentages of immature granulocytic and erythroid cells, and a significant increase in the percentage of mature granulocytic cells. The effect, which was not observed at 72 h, was unrelated to the equilibrium potential assumed by silver.
Article
To investigate the mechanism of inhibition of silver ions on microorganisms, two strains of bacteria, namely Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), were treated with AgNO3 and studied using combined electron microscopy and X-ray microanalysis. Similar morphological changes occurred in both E. coli and S. aureus cells after Ag⁺ treatment. The cytoplasm membrane detached from the cell wall. A remarkable electron-light region appeared in the center of the cells, which contained condensed deoxyribonucleic acid (DNA) molecules. There are many small electron-dense granules either surrounding the cell wall or depositing inside the cells. The existence of elements of silver and sulfur in the electron-dense granules and cytoplasm detected by X-ray microanalysis suggested the antibacterial mechanism of silver: DNA lost its replication ability and the protein became inactivated after Ag⁺ treatment. The slighter morphological changes of S. aureus compared with E. coli recommended a defense system of S. aureus against the inhibitory effects of Ag⁺ ions. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 52, 662–668, 2000.
Article
An acute progressive pulmonary insufficiency syndrome characterized by hypoxemia, often refractive to conventional intensive oxygen therapy, sometimes complicates recovery from a variety of traumatic and infective illnesses. Patients may survive the critical period and regain lung oxygenation function. Severe cases often die of hypoxemia before oxygenation function is recovered. Six patients demonstrating severe hypoxemia (Pa02 38 to 48 mm Hg) were given continuous intensive care management in a hyperbaric chamber for periods as long as 80 hours. Ventilation with hyperbaric oxygen-nitrogen mixtures produced adequate arterial oxygen levels. Recovery of lung function in live of the six cases eventually permitted them to leave the hyperbaric chamber and maintain satisfactory oxygenation without recurrence of the syndrome although four later died of other nonpulmonary complications. No clinical evidence of OHP induced lung damage could be detected. Retrospectively, a possible association between an altered coagulation state and the period of acute respiratory distress was noted.
Article
Disinfection due to copper or silver ions may result from action at the cell or capsid protein surface or on the nucleic acid of cells or viruses. Metals may alter enzyme structure and function or facilitate hydrolysis or nucleophilic displacement. The means by which cells may reduce the toxic effect of metal ions include: biomethylation, complexation with metallothionen, development of efflux pumps, the binding of metal ions to cell surfaces, and the removal of metal ions by precipitation. The phenomenon of “multiplicity of reactivation” may reduce the effect of a disinfectant on a virus by allowing a clump of partially inactivated viruses to produce a productive infection in a susceptible cell. Conditions which may affect metal ion‐biomolecule interaction include: pH, ionic strength, temperature, dissolved oxygen, presence of interfering substances or light, the chemical form and valency of the metal ion, and the condition of the microorganisms.
Article
The effects of imidazole addition on the optical properties and reactivity of colloidal silver particles (40-angstrom diameter) were studied. Absorption spectra of surface-modified silver particles are significantly different from those of the primary silver sol. A decrease and broadening of the surface plasmon absorption band are accompanied with the formation of a distinct long-wavelength absorption band. The interaction of surface atoms with nucleophilic molecules leads to a partial oxidation of surface atoms, while the interior of colloidal particles receives a corresponding negative charge which can be picked up by the electron acceptors. This mechanism explains catalyzed oxidation of surface-modified silver particles in the absence of air by inorganic and organic electron acceptors (Cu2+, nitrobenzene), as well as their high reactivity with oxygen. The Fermi potential of surface-modified silver particles by imidazole seems to lie close to -0.40 V, i.e., close to the standard one-electron transfer potential of nitrobenzene.
Silver accumulation and processing in mouse peritoneal macrophages was studied in vitro by autometallographic visualization of intracellular silver. During the first 24 h of incubation in a medium containing from 5 μM to 20 μM of silver lactate, an inverse relationship between silver concentration in the former and visualizable silver in macrophages was recorded. Later, however, the cells treated with higher silver concentrations accumulated most silver. Cells exposed to silver concentrations above these levels exhibited acute coagulation necrosis and disintegrated within the first 15 min of silver treatment. Macrophages treated with silver lactate concentrations not causing acute cytotoxicity showed no impairment of their phagocytic, migratory or interferon-producing capacities. The significance of autointerference in silver accumulation and processing in macrophages is discussed, and a functional defect in the lysosome/ phagosome system is suggested as a basis for the phenomenon.
Article
Sumario: General principles -- Toxicology -- Theory and rationale of industrial hygiene practice: the work environment, biological responses 3 t. en 10 v. Volume III, Part A y B: 3rd edition Contiene: Volume I, Part A -- Volume I, Part B -- Volume II, Part A -- Volume II, Part B -- Volume II, Part C -- Volume II, Part D -- Volume II, Part E -- Volume II, Part F -- Volume II, Part A -- Volume III, Part B
Article
Silver sulfadiazine, at a concentration of 10 mug/ml, inhibits Herpesvirus hominis types 1 and 2 in vitro. The antiviral effect is directly related to concentration of the drug and duration of exposure.
Article
The infectivities of herpes simplex virus types 1 and 2 were inactivated by silver nitrate at concentrations of 30 μM or less, which did not affect at all the infectivities of hemagglutinating virus of Japan, vesicular stomatitis virus, poliovirus, vaccinia virus, and adenovirus. The inactivated virus retained the capability of adsorbing to the cell, with an adsorption kinetics quite similar to that of intact virus, and of inducing the concanavalin A agglutinability in the infected cells, whereas it lost completely the capability of producing viral antigens and other cytopathic changes.
Article
The inhibitory and bactericidal concentrations of electrically generated silver ions were 10 to 100 times lower than for silver sulfadiazine. Effects on normal mammalian cells were minimal.
Article
Metal-binding proteins are important components of retroviruses such as human immunodeficiency virus (HIV). Therefore, metals could be used as antiviral agents. However, most metals are toxic for humans with the exception of silver which is toxic only to prokaryotic cells and viruses. In addition, HIV infection causes a decrease in body cysteine. We formed a complex of silver and cysteine, named silver-cysteine. Healthy human lymphocytes were incubated with silver-nitrate or silver-cysteine. Negligible cell survival was seen at 50 microM silver-nitrate. However, in presence of 1 mM cysteine, the viability remained unaffected up to 1 mM of silver. Further, silver inhibition of isolated Na,K-ATPase was easily reversed by cysteine. Thus, non-toxic silver-cysteine could be used as an anti-viral and cysteine-replenishing agent.
Article
We report here for the first time that Zn2+ is an effective inhibitor of renin and the protease from HIV-1, two aspartyl proteinases of considerable physiological importance. Inhibition of renin is noncompetitive and is accompanied by binding of 1 mol of Zn2+/mol of enzyme. Depending on the substrate, inhibition of the HIV protease by Zn2+ can be either competitive or noncompetitive, but in neither case is loss of activity due to disruption of the protease dimer. Inhibition of both enzymes is first order with respect to Zn2+ and is rapidly reversed by addition of EDTA. Ki values are strongly pH dependent and optimal in the range of 20 microM at or above pH 7. All of the data in hand suggest that the inhibitory effect of Zn2+ is a consequence of its binding at, or near, the active-site carboxyl groups of these aspartyl proteinases. This inhibition of the viral enzyme may help to explain some of the beneficial effects seen in AIDS patients who have received Zn2+ therapy.
Article
The three series of experiments conducted on 139 adult wistar rats it was found, that two-hour stay of the animals in barochamber under the pressure of 3 atmospheres reduces considerably the percentage of mortality rate and decelerates the development of arterial hypoxemia in rats with an experimental model of acute respiratory distress syndrome (ARDS) reproduced by intrapleural injection of oleic acid (0.27 ml/100 g). Stalle in comparison with the control (I) series elevation of corticosterone in the animal blood II and III series (conduction of HBO correspondingly in 4 and 12 hours from the beginning of the process) is considered as the manifestation of one of the most important mechanism of organism adaptation to the development of acute hypoxia in ARDS.
Silver accumulation and processing in mouse peritoneal macrophages was studied in vitro by autometallographic visualization of intracellular silver. During the first 24 h of incubation in a medium containing from 5 microM to 20 microM of silver lactate, an inverse relationship between silver concentration in the former and visualizable silver in macrophages was recorded. Later, however, the cells treated with higher silver concentrations accumulated most silver. Cells exposed to silver concentrations above these levels exhibited acute coagulation necrosis and disintegrated within the first 15 min of silver treatment. Macrophages treated with silver lactate concentrations not causing acute cytotoxicity showed no impairment of their phagocytic, migratory or interferon-producing capacities. The significance of autointerference in silver accumulation and processing in macrophages is discussed, and a functional defect in the lysosome/phagosome system is suggested as a basis for the phenomenon.
Article
Two commercial substances, Certisil and Micropur, containing microbicidal silver compounds and destinated for decontamination as well as preservation of water were examined for virus inactivating activity against ECBO-, influenza A, Newcastle Disease, pseudorabies and vaccinia viruses in drinking water. In the recommended concentration as well as higher concentrated the lability of the viruses was increased by the silver compounds. This activity which cannot be designated as a true virucidal effect was clearly evident in the case of ECBO and vaccinia viruses, moderate on influenza and pseudorabies viruses but insignificant on Newcastle disease virus. Two combined silver compounds, Certisil-Combina and Sanosil, each containing an immediate microbicidal part besides silver differed in their antiviral activity. The chlorine separating part of Certisil-Combina didn't cause an improvement or acceleration of the destabilizing effect on viruses compared to the pure silver compound, while the hydrogen peroxide part of Sanosil led to a better and continuing inactivating influence on the viruses which were merely reduced in infectivity by 99,9% within one day. Only in the case of evident or suspected contamination of water reservoirs by viruses the addition of a combined silver drug with oxygen separating part seems to be useful.
Article
The addition of silver sulfadiazine to cultures of varicella zoster virus resulted in inactivation of the viral infectivity. At a concentration of 10 micrograms/ml or higher the virus was inactivated after thirty minutes exposure at 37 degrees C. Forty-two patients with herpes zoster were treated topically with 1 percent silver sulfadiazine cream applied four times a day. All patients experienced complete drying of vesicles, marked reduction erythema and edema, and striking elimination of pain and burning sensation within twenty-four to seventy-two hours. The sooner the treatment began after the onset of symptoms, the more dramatic was the response. Postherpetic neuralgia was either mild or did not occur. Signs of local, systemic, or laboratory-documented toxicity were not observed.
Article
Herpes simplex virus (HSV) types 1 and 2 (two strains each) were inactivated at different rates in vitro by 40 μM AgNO3. The inactivation of HSV type 1 strains was virtually complete in 10 to 15 min, whereas almost half of the infectivity of HSV type 2 strains survived this exposure. One strain of type 1 inoculated into rabbit eyes was almost completely inactivated by 1% AgNO3 solution dropped into the eye 20 min later, so that there was markedly reduced viral replication and less corneal herpetic disease. One strain of HSV type 2 in the rabbit eye was not effectively inactivated by 1% AgNO3. From these results, it seems likely that AgNO3 instillation into the eyes of a newborn who has passed through a birth canal infected with HSV might prevent eye infection with HSV type 1 but not with type 2. The greater resistance of HSV type 2 strains to chemical inactivation in vitro and in vivo may be of medical concern.
The antiviral chemotherapeutic action of silver sulfadiazine (AgSD) was studied in tissue culture and the ocular infection model. Among viruses affecting the eyes, herpes simplex (HSV) and vesicular stomatitis viruses (VSV) were found to be susceptible to direct inactivation by this compound. At 1 μg/ml it suppressed HSV growth in tissue culture. No corneal opacity caused by contact toxicity to AgSD occurred following a one week course of treatment. The virulence of the strains of the infecting agent was the most important factor in assessing the efficacy of AgSD. In the rabbit eye, infection by Pseudomonas aeruginosa was suppressed also by similar applications of AgSD.
Article
This chapter discusses antimicrobial activity and action of silver. Silver and its compounds have long been used, in one form or another, as antimicrobial agents. The silver compound of major therapeutic interest at the present time is silver sulphadiazine. Many in healthcare know that other silver compounds are still in use. It is worth stating that the treatment of ophthalmia neonatorum was revolutionized by the instillation of silver derivatives into the eyes of new-born sufferers. Several factors influence the antimicrobial activity of silver salts. Silver has a marked tendency to adsorb to surfaces and bactericidal activity is reduced in the presence of phosphates, chlorides, sulphides and hard water. Activity is increased as the temperature is raised and is pH-dependent, increasing with increasing pH. Sodium thioglycollate has been recommended as a suitable neutralizing agent for use in bactericidal testing although other SH compounds also fulfil this role. Silver, one of the native metals and second only to gold in its stability amongst the metals of antiquity, has provided several therapeutic agents which have been employed since the beginning of recorded history. These agents range from the metal itself, its salts and complexes with proteins and other macromolecules to the latest, silver sulphadiazine (AgSD).
Article
In a survey of a number of heavy metal ions for effects on the oxidative metabolism (respiratory burst) of human polymorphonuclear leukocytes (neutrophils) we have found that mercury(II) and silver ions in micromolar concentration significantly increase the production of superoxide anions in cells, initiated by formyl-methionyl-leucylphenylalanine (fMLP). The stimulation of radical formation induced by a certain ion concentration varied considerably in cells isolated from different blood donors, from a moderate increase to a very large (up to 400% of control values). When the soluble stimulator phorbol myristate acetate (PMA) or the particulate stimulator Zymosan were used to initiate the cell respiratory burst, no additional stimulating effects by the metal ions on superoxide anion formation were observed. This fact might indicate that the effect of the metal ions on the fMLP-dependent initiation of cell activity is a mechanism coupled to the interaction between the chemotactic peptide and its corresponding receptor molecules on the cell surface. By increasing the concentration of silver ions during pre-incubation of resting neutrophils, a spontaneous activation of the cells could be recorded at a concentration exceeding 5 microM. However, the silver ion concentration at which such spontaneous initiation of the respiratory burst occurred varied significantly between blood samples from different donors with a concentration range of 5 to 15 microM. This effect could not be shown for mercuric ions due to the toxicity of the metal above 5 microM. Blood samples from some donors contained neutrophils that could be activated by either mercuric- or silver ions at concentration as low at 1 microM. The spontaneous activation of neutrophils with elevated concentrations of silver ions is kinetically similar to the PMA-induced. The onset of superoxide anion formation is preceded by a lag period whose length varies in time with the concentration of agent applied to the cells. It is a known fact that once the neutrophils have been activated with fMLP it is not possible to reactivate the cells by a second supplementation of fMLP. However, after cessation of the fMLP-induced activation, addition of PMA or silver ions gives rise to renewed production of superoxide anions. We propose two different mechanisms of action of silver ions on oxidative metabolism of neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Twenty-five HIV-infected patients underwent hyperbaric oxygen therapy to determine the treatment's effectiveness in relieving the debilitating fatigue associated with HIV/AIDS and its effect on immunologic function. Patients were treated with 100% oxygen at two atmospheres of absolute pressure three times per week for two months, then two times per week on an ongoing basis. Laboratory markers were assessed monthly. All patients experienced relief of debilitating fatigue within one month of hyperbaric oxygen therapy. It was concluded that hyperbaric oxygen therapy is an effective adjunctive treatment in the medical management of HIV/AIDS. Laboratory markers, clinical significance, nursing implications, and cost-effectiveness of hyperbaric oxygen therapy are discussed.
Article
The susceptibility of Escherichia coli B to the antibacterial activity of silver ions was measured in terms of the initial inhibitory concentration, complete inhibitory concentration, postagent effect for bacteriostatic susceptibility, minimum bactericidal concentration, maximum tolerant concentration, and log killing time for bactericidal activity. At a concentration of 9.45 microM and an inoculum size of 10(4-5) CFU ml-1, silver caused growth delay of E. coli; at a concentration of 18.90 microM, silver completely inhibited bacterial growth. Prolonged postagent effects ranged between 1.5 and 12 h at 0.75 x the initial inhibitory concentration, 1.0 x the initial inhibitory concentration, and 1.5 x the initial inhibitory concentration of the silver ion. One log-unit of viable bacterial population size was lost every 30 min at the minimum bactericidal concentration of the silver ion. Silver tolerance was determined as 20 times the initial inhibitory concentration with 48 h of exposure. This study presents an evaluative model as a reference for the quantitative analysis of the susceptibility of bacteria to silver ions.
Article
This paper demonstrates that there are many examples in the literature of contradictory data concerning reactive oxygen intermediates (ROIs), responsible for producing cellular oxidative stress (OS), and their enhancement or diminution of viral replication. Nevertheless, ROIs repeatedly have been shown to be virucidal against enveloped-viruses, like the human immunodeficiency virus (HIV). Hyperbaric oxygen therapy (HBOT) increases the production of ROIs throughout the body, leaving no safe harbor for the virus to hide outside the genome. This technique already has been tried on acquired immune deficiency syndrome (AIDS) patients, with exciting results. Historically, the biggest setback to demonstrating HBO's antiviral effects has been the investigator's folly of studying non-enveloped viruses or failing to initiate ROI production. ROIs specifically attack areas of unsaturation occurring in the polyunsaturated fatty acids of cell membranes and viral envelopes. Moreover, it consistently has been shown that a peroxidized viral envelope breaches, and a breached viral envelope causes viral disintegration.
Article
To investigate the mechanism of inhibition of silver ions on microorganisms, two strains of bacteria, namely Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), were treated with AgNO(3) and studied using combined electron microscopy and X-ray microanalysis. Similar morphological changes occurred in both E. coli and S. aureus cells after Ag(+) treatment. The cytoplasm membrane detached from the cell wall. A remarkable electron-light region appeared in the center of the cells, which contained condensed deoxyribonucleic acid (DNA) molecules. There are many small electron-dense granules either surrounding the cell wall or depositing inside the cells. The existence of elements of silver and sulfur in the electron-dense granules and cytoplasm detected by X-ray microanalysis suggested the antibacterial mechanism of silver: DNA lost its replication ability and the protein became inactivated after Ag(+) treatment. The slighter morphological changes of S. aureus compared with E. coli recommended a defense system of S. aureus against the inhibitory effects of Ag(+) ions.
Article
Novel therapies for the next decade include hyperbaric oxygen, nitric oxide, and extracorporeal membrane oxygenation. Hyperbaric oxygen delivers oxygen at a pressure greater than one atmosphere and has been used in diseases ranging from decompression sickness to carbon monoxide poisoning. Inhaled nitric oxide, a potent vasodilator, has been used in the acute respiratory distress syndrome and for the diagnosis and treatment of pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) has been used to provide cardiopulmonary bypass support, particularly in the pediatric and neonatal population.
Article
The basic mechanisms behind the pharmacologic effects of hyperbaric oxygen therapy are not clear. Reactive oxygen metabolites are generally associated with the adverse reactions to hyperbaric oxygen exposure but they are also believed to be involved in the antibacterial effects of this therapy. The possibility that reactive oxygen metabolites are responsible for some of the other reported beneficial effects of hyperbaric oxygen therapy has not been investigated. This hypothesis paper briefly reviews the literature suggesting that the pharmacologic actions underlying some of the beneficial effects of hyperbaric oxygen therapy may be caused by superoxide and/or hydrogen peroxide. Elucidation of the pharmacologic mechanisms is fundamental in order to fully exploit the therapeutic potential of hyperbaric oxygen and we incite experimental research to be done within this area.
Article
The immunomodulatory effect of hyperbaric oxygen, involving altered cytokine release by macrophages, is well described. Importantly, however, it is not known what the relative contribution is of the hyperbaric environment of the cells vs. increased oxygen tension on these hyperbaric oxygen-dependent effects. We compared, therefore, cytokine release by murine macrophages under hyperbaric oxygen, hyperpressure of normal air and normobaric conditions. We observed that hyperbaric oxygen enhanced cytokine release of both unstimulated as well as lipopolysaccharide (LPS)-challenged macrophages. Hyperpressure of normal air, however, enhanced LPS-induced cytokine production but did not elicit cytokine release in unstimulated macrophages. To further investigate the molecular details underlying the effects of hyperbaric oxygen, we investigated the effect of the p42/p44 mitogen-activated protein (MAP) kinase inhibitor PD98059 and the p38 MAP kinase inhibitor SB203580. Neither inhibitor, however, had a significant effect on the modulatory effects of hyperbaric oxygen on cytokine release. We concluded that the immunomodulatory effect of hyperbaric oxygen contains a component for which hyperpressure is sufficient and a component that apart from hyperpressure also requires hyperoxygenation.
Ag1 Concentration Determination of Argentyn 23
  • X Zhu
Zhu X. Ag 1 Concentration Determination of Argentyn 23. Miami: Department of Marine Biology, University of Miami, 2003.
Biocidal effects of silver. Contract NAS 9-9300 Final Technical Report
  • D O Cliver
  • W K Foell
  • J M Goepfert
Cliver DO, Sarles WB, Foell WK, Goepfert JM. Biocidal effects of silver. Contract NAS 9-9300 Final Technical Report, University of Wisconsin, Accession Number N70 23888, NASA CR Number CR-108338, February 1970, 29.