Subsalicylate Research Articles

Systematic Review and Meta-Analyses Assessment of the Clinical Efficacy of Bismuth Subsalicylate for Prevention and Treatment of Infectious Diarrhea

BackgroundA large number of studies have evaluated the pharmacology, safety, and/or efficacy of bismuth subsalicylate for the relief of common gastrointestinal symptoms, diarrhea and vomiting due to acute gastroenteritis. In addition, short-term (48 h) medication with bismuth subsalicylate is known to be effective against infectious gastroenteritis such as travelers’ diarrhea.AimsPrevious studies have documented the bacteriostatic/bactericidal effects of bismuth subsalicylate against a variety of pathogenic gastrointestinal bacteria. However, meta-analyses of the clinical efficacy of bismuth subsalicylate for both prevention and treatment of travelers’ diarrhea have not yet been published.MethodsA total of 14 clinical studies (from 1970s to 2007) comprised the core data used in this assessment of efficacy of bismuth subsalicylate against infectious (including travelers’) diarrhea. These studies allowed for statistical meta-analyses regarding prevention (three travelers’ diarrhea studies) and treatment of infectious diarrhea (11 studies [five travelers’ diarrhea]).ResultsThe results show that subjects treated with bismuth subsalicylate for up to 21 days have 3.5 times greater odds of preventing travelers’ diarrhea compared with placebo (95% CI 2.1, 5.9; p < 0.001). In addition, subjects with infectious diarrhea treated with bismuth subsalicylate had 3.7 times greater odds of diarrhea relief (recorded on diaries as subjective symptomatic improvement) compared to those receiving placebo (95% CI 2.1, 6.3; p < 0.001).ConclusionsThis systematic review and meta-analysis suggests that bismuth subsalicylate can be beneficial for those at risk or affected by food and waterborne diarrheal disease such as traveler’s (infectious) diarrhea, and may decrease the risk of inappropriate antibiotic utilization.

Effects of bismuth subsalicylate and encapsulated calcium-ammonium nitrate on enteric methane production, nutrient digestibility, and liver mineral concentration of beef cattle.

Two randomized block designs were performed to evaluate the effects of bismuth subsalicylate (BSS) and encapsulated calcium-ammonium nitrate (eCAN) on enteric methane production, nutrient digestibility, liver mineral concentration, and performance of beef cattle consuming bahiagrass hay (Paspalum notatum; ad libitum) and sugar cane molasses [1.07 kg/d; dry matter basis]. Experiment 1, used 25 crossbred steers [335 ± 46 kg of initial body weight (BW)] with a 2 × 2 + 1 factorial arrangement of treatments for two 20 d periods. Factors were nonprotein nitrogen (NPN) source (350 mg/kg BW of nitrate or 182 mg/kg BW of urea), BSS (0 or 58.4 mg/kg BW), and a negative control (NCTRL; bahiagrass hay and molasses only). Steers were re-randomized for a second period (n = 10/treatment total). Intake, apparent total tract digestibility and enteric methane were evaluated. Experiment 2 used 75 crossbred heifers in 25 pens (3 heifers/pen; 279 ± 57 kg of initial BW), consuming the same diet and treatments as experiment 1, to determine liver mineral concentration and growth performance over 56 d. Orthogonal contrasts were used to evaluate the effects of NPN (NCTRL vs. others), source of NPN (NS; urea vs. eCAN), BSS, and NS × BSS. For experiment 1, no interactions were observed for any variables, nor were there any effects of NPN on total tract digestibility of nutrients, except for crude protein. Digestibility of all nutrients was reduced (P ≤ 0.021) for steers consuming eCAN compared with urea. There was no effect (P > 0.155) of BSS on digestibility of nutrients; however, BSS reduced (P = 0.003) apparent S retention. Enteric CH4 emission (g/kg BW0.75) was decreased (P = 0.051) by 11% with the addition of eCAN compared with urea. For experiment 2, no NS × BSS interactions (P ≥ 0.251) were observed to affect liver mineral concentration; however, the addition of BSS decreased liver concentration of Cu (P = 0.002) while increasing Fe concentration (P = 0.016). There was an NS × BSS interaction (P = 0.048) where heifers consuming eCAN and BSS had lesser final BW compared with heifers consuming urea and BSS. While eCAN may be a viable resource for mitigating enteric CH4 production of forage-fed cattle, the negative effects on digestibility should be considered. Furthermore, BSS, at the amount provided, appears to have no negative effects on digestibility of nutrients in forage-fed cattle; however, there may be deleterious impacts on performance depending upon what nitrogen source is supplied.

In Situ Production and Deposition of Bismuth Oxide Nanoparticles on Cotton Fabric

In this research, the cotton fabric was modified with bismuth oxide nanoparticles (Bi2O3 NPs) by a simple method. Bismuth oxide nanoparticles were synthesized by chemical reduction of bismuth salt using nitric acid as reducing agent. In situ method was used for synthesis and deposition of bismuth oxide nanoparticles on cotton fabrics. The samples were characterized by X-ray diffraction for evaluation of crystal structure, scanning electron microscopy for presentation of morphology and size, energy-dispersive X-ray spectroscopy for determination of chemical composition, atomic absorption spectroscopy for studding bismuth release, contact angle for explanation of hydrophobic character, and diffuse reflection spectroscopy for ultraviolet (UV) blocking. The antibacterial activity was evaluated by measurement of the reduction of the gram-negative Escherichia coli on modified cotton fabric. Based on the results, modified cotton fabric showed hydrophobic, UV-blocking properties, and antibacterial activity as compared with control cotton fabric, which will have high potential applications in various fields.

Effects of bismuth subsalicylate and encapsulated calcium ammonium nitrate on ruminal fermentation of beef cattle.

A replicated 5 × 5 Latin square design with a 2 × 2 + 1 factorial arrangement of treatments was used to determine the effects of bismuth subsalicylate (BSS) and encapsulated calcium ammonium nitrate (eCAN) on ruminal fermentation of beef cattle consuming bahiagrass hay (Paspalum notatum) and sugarcane molasses. Ten ruminally cannulated steers (n = 8; 461 ± 148 kg of body weight [BW]; average BW ± SD) and heifers (n = 2; 337 ± 74 kg of BW) were randomly assigned to one of five treatments as follows: 1) 2.7 g/kg of BW of molasses (NCTRL), 2) NCTRL + 182 mg/kg of BW of urea (U), 3) U + 58.4 mg/kg of BW of BSS (UB), 4) NCTRL + 538 mg/kg of BW of eCAN (NIT), and 5) NIT + 58.4 mg/kg of BW of BSS (NITB). With the exception of NCTRL, all treatments were isonitrogenous. Beginning on day 14 of each period, ruminal fluid was collected and rectal temperature was recorded 4× per day for 3 d to determine ruminal changes every 2 h from 0 to 22 h post-feeding. Ruminal gas cap samples were collected at 0, 3, 6, 9, and 12 h on day 0 of each period followed by 0 h on days 1, 2, 3, and 14. Microbial N flow was determined using Cr-Ethylenediaminetetraacetic acid, YbCl3, and indigestible neutral detergent fiber for liquid, small particle, and large particle phases, respectively. Data were analyzed using the MIXED procedure of SAS. Orthogonal contrasts were used to evaluate the effects of nonprotein nitrogen (NPN) inclusion, NPN source, BSS, and NPN source × BSS. There was no treatment effect (P > 0.05) on concentrations of H2S on day 0, 1, 2, or 14; however, on day 3, concentrations of H2S were reduced (P = 0.018) when NPN was provided. No effect of treatment (P = 0.864) occurred for ruminal pH. There was an effect of NPN source on total concentrations of VFA (P = 0.011), where a 6% reduction occurred when eCAN was provided. There were effects of NPN (P = 0.001) and NPN source (P = 0.009) on the concentration of NH3-N, where cattle consuming NPN had a greater concentration than those not consuming NPN, and eCAN reduced the concentration compared with urea. Total concentrations of VFA and NH3-N were not affected (P > 0.05) by BSS. There was an effect of BSS (P = 0.009) on rectal temperature, where cattle not consuming BSS had greater temperatures than those receiving BSS. No differences for NPN, NPN source, nor BSS (P > 0.05) were observed for microbial N flow. In conclusion, eCAN does not appear to deliver equivalent ruminal fermentation parameters compared with urea, and BSS has limited effects on fermentation.

Dlaczego nie należy przerywać terapii inhibitorami pompy protonowej i antybiotykami stosowanymi w eradykacji Helicobacter pylori w czasie pandemii COVID-19?

Helicobacter pylori infection is one of the most widespread infectious diseases in the world, but its prevalence varies depending on geographical region and economic and social condition. The percent of infected adult persons in Poland is 67, among younger population under 18 years being as high as about 32%. This infection in some number of the concerned persons can be associated with chronic gastritis, peptic gastric and duodenal ulcers, gastric mucosa-associated lymphoid tissue lymphoma (MALT) and gastric cancer. Extra-gastric manifestation of H. pylori infection are iron deficiency anemia, idiopathic thrombocytopenic purpura and significant B12 deficiency. According to the Maastricht V/Florence Consensus Report considering H. pylori infection a contagious disease that requires treatment in each case, indications for diagnostic evaluation to detect its presence are established, and then to its eradication. The treatment of H. pylori infection is complex and based on the combination of the following groups of medicines: proton pump inhibitors (PPI), antibiotics and anti-microbial nitroimidazoles and bismuth salts and probiotics. Currently, the main challenge in the field of H. pylori infection is antibiotic resistance, which influences the efficacy of eradication regiments. According to Maastricht V/Florence Consensus, in Poland where H. pylori resistance to clarithromycin is more than 15%, quadruple therapy with bismuth, PPI, tetracycline and metronidazole/tinidazole for 10–14 days should be used as first-line treatment. Triple therapy with fluoroquinolone is recommended as second-line treatment. After two unsuccessful attempts to eradicate, bacterial cultures should be should be performed to asses antibiotic sensitivity of the H. pylori strain. There are no reasons in front of pandaemia of COVID-19 to delay eradication of H. pylori infection, when the urgent indications: peptic ulcer complicated with haemorrhage, MALT lymphoma or early gastric cancer exists.

Electrochemical Investigations of L-Cysteine Interactions with Bismuth Ions

The interaction of L-cysteine with various bismuth compounds, namely, bismuth(III) salicylate, bismuth(III) citrate, and bismuth(III) nitrate, was studied at pH 1.0 (0.100 M HNO3 and 0.100 M HCl) and pH 7.4 MOPS buffer by cyclic voltammetry at glassy carbon and boron-doped diamond electrodes. Using details of the voltammetric behavior, it was determined that Bi3+ and L-cysteine (Cys) form a soluble complex at both pH 1.0 and pH 7.4. In addition, the reduction of the bismuth-cysteine complex to bismuth metal results in subsequent bismuth stripping. UV-VIS spectroscopy revealed that Bi3+ and L-Cysteine form a 1:2 Bi3+: Cys complex in pH 7.4 MOPS buffer.

SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts.

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. SARS-coronavirus-2 (SARS-CoV-2), the causative pathogen of COVID-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals.Electronic supplementary materialThe online version of this article (10.1007/s12250-020-00242-1) contains supplementary material, which is available to authorized users.

Electrochemical Investigations of L-Cysteine Interactions with Bismuth Ions

The use of bismuth compounds as medicinal treatments has prompted the electrochemical investigation of bismuth(III) salicylate, bismuth(III) citrate and bismuth(III) nitrate with L-cysteine in 0.1M HNO3 and 0.1M HCl using cyclic and square wave voltammetry. This level of acidity is meant to approximate the proton levels in gastric fluids. Platinum and gold electrodes were not used in order to avoid the reduction of protons to hydrogen gas at these high proton levels. At boron-doped diamond (BDD) and glassy carbon (GC) electrodes, significant voltammetric changes were observed upon incremental additions of L-cysteine even at pH 1.00. For example, additions of L-cysteine to bismuth(III) salicylate in 0.1M HNO3 at GC caused the Bi(III) reduction process to became narrower with an initial negative potential shift. Upon further additions of L-cysteine, the reduction curve displayed a positive potential shift and became even narrower as the complex exhibited faster electron transfer than the original Bi(III) species. A positive peak potential shift of the corresponding bismuth stripping peaks was also observed upon L-cysteine additions. These results show that L-cysteine, even in its most protonated state, is capable of acting as a complexing agent for Bi(III) species at pH 1.00. The results for other Bi(III) compounds under similar conditions are also planned for presentation.

Coincidence of Nicolau Syndrome and Rhabdomyolysis after Intramuscular Benzathine Penicillin Injection: A Case Report

Nicolau syndrome (NS) is a rare but well-known complication of intramuscular Benzathine Penicillin (BP) injection, manifesting by symptoms of livedoid discoloration of the skin, edema, as well as classical clinical features of myalgia, muscle weakness and pigmenturia immediately after intramuscular. NS or embolia cutis medicamentosa was first described in 1925 by Nicolau and Freudenthal following intramuscular injection of bismuth salt for the treatment of syphilis. Since then, a few cases have been reported both in adult and children.

Primary Pure Duodenal Squamous Cell Carcinoma

A 68-year-old woman presented with 3 months of bloating and epigastric discomfort with intermittent black stools while taking bismuth subsalicylate during multiple international trips and 1 week of fatigue and dyspnea on exertion without weight loss, fevers, or chills. A colonoscopy 5 years earlier had found a subcentimeter sigmoid hyperplastic polyp. Bloodwork showed hemoglobin of 4.8 g/dL and mean corpuscular volume of 79 fL. Endoscopy found an oozing, 5-cm fungating nonobstructing mass with 4 cm of surrounding ulceration in the third part of the duodenum (Figure A).

Pink Prescribing: Bismuth Subsalicylate; History, Actions, Risks, and Future Use.

Recently, there seems to be more creative advertising regarding bismuth subsalicylate (BSS) for lots of gastrointestinal issues. I have found during medication reconciliation that some patients overuse and believe use of BSS products is without risks. From an advertising perspective, there seem to be many happy persons consuming BSS with no mention of restrictions or safety recommendations. What are the risks associated with its use? How effective is BSS? What about drug interactions?

Characterization of New Lead-free Ballistic Modifiers and Phthalate-free Plasticizers in Propellants

This paper describes the synthesis and characterization of a copper-based ballistic modifier, copper subsalicylate (monobasic copper salicylate), and its performance in green-type propellants. New lead-free ballistic modifiers and phthalatefree plasticizers with reduced toxicity, less harmful to the environment, have been employed to replace their traditional additives in green-type double-base propellant preparations. The characterization of the chemical compound was performed by FTIR, TGA-DSC, and WAXS, indicating that copper subsalicylate was obtained. The results of the characterization of propellant compositions showed that copper subsalicylate, in combination with a bismuth salt, could be a substitute for the traditional lead-based ballistic modifier producing green-type propellants without reducing ballistic performance.

IR spectroscopic study of Bismuth(III) salts with tartaric acid

Bismuth(III) salts with L(+)-tartaric acid were obtained by precipitation from mineral acid solutions. Two samples of bismuth(III) salts: [Bi(C4H4O6)(C4H5O6)].3H2O of a previously known crystal structure and amorphous BiC4H3O6·H2O used as an active component of antibacterial preparations were examined by using the methods of X-ray diffraction, IR spectroscopy, differential thermal analysis (DTA) in combination with chemical analysis of solid phases. IR spectroscopy is shown to be sufficiently informative to establish compositions of non-crystalline bismuth salts.

Bismuth subsalicylate, a low-toxicity catalyst for the ring-opening polymerization (ROP) of l-lactide (l-LA) with aliphatic diol initiators: synthesis, characterization, and mechanism of initiation.

The ring-opening polymerization (ROP) of l-lactide (l-LA) was induced by the catalytic action of bismuth subsalicylate (BiSS) using linear aliphatic diols [HO(CH2)nOH, where n = 2, 3, 4, 5, 6, and 8] as initiators and chain transfer agents. The theoretical and experimental degree of polymerization (DP) in all samples of α,ω-hydroxy telechelic poly(l-lactide) (HOPLLAOH) had a good agreement in all samples, an effect attributed to the interaction of BiSS with HO(CH2)nOH inducing a transfer reaction. HOPLLAOH was synthesized and characterized by a range of analytical techniques, confirming the insertion of methylene groups from the initiator into the main chain of the polyester. The glass-transition temperature (Tg) of HOPLLAOH was found to be proportional to the number of methylene groups present in the diol. Various parameters regarding the ROP of l-LA were studied, such as temperature, time of reaction, amount of catalyst, and the nature of the diols. A kinetic study of the reaction allowed the determination of the rate constants (k) and activation energy (Ea). A mechanism of initiation is proposed based on a computational study using density functional theory (DFT), evidencing the role of the alkyl diol as an initiator, producing an alkoxide (Bi–OROH). This species then acts as a nucleophile, attacking the carbonyl group, inducing its insertion, and ultimately completing the ring-opening of l-LA.

Oxygen Plasma/Bismuth Modified Inkjet Printed Graphene Electrode for the Sensitive Simultaneous Detection of Lead and Cadmium

In this work, a simple procedure for the preparation of an inkjet printed disposable graphene electrode is reported. Commercial graphene ink was printed on a kapton substrate and the resulting electrode was 30 min treated by oxygen plasma, then modified by a bismuth salt. The as prepared electrode was characterized by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), laser scanning microscopy (LSM) and scanning electron microscopy (SEM) coupled to energy-dispersive X-ray spectroscopy (EDX). The sensing properties of the characterized electrodes were then investigated using cyclic voltammetry and Electrochemical Impedance Spectroscopy (EIS). Afterwards, these electrodes were exploited in a comparative way for the electroanalysis of Cadmium(II) and Lead(II) ions. An increase in the electrode sensitivity due to its modification and to the presence of bismuth was observed. Some preliminary experiments based on stripping square wave voltammetry highlighted the interest of using the proposed disposable inkjet printed electrodes for the electrochemical detection of heavy metals in tap water.

A short route to access oxaspiro[n,3,3]propellanes.

Novel access to oxaspiro[n,3,3]propellanes has been developed from bicyclic lactones directly prepared by a photochemical hydroxymethylation or alternatively by a three-step sequence. Thanks to the presence of additional hydroxy- and propargylic groups, a second cyclization catalyzed by silver or bismuth salts, led to the propellane structure which was finally transformed into spiranic derivatives by a Simmons-Smith reaction or condensation with α-ketoesters.

Alternative Bi precursor effects on the structural, optical, morphological and photocatalytic properties of BiOI nanostructures

BiOI nanostructures were synthetized through a hydrothermal process using either bismuth acetate or subsalicylate as Bi precursor. Regardless of the used Bi source, the same crystalline structure of BiOI was obtained; nevertheless, the nature of the Bi precursor had an evident impact in the color appearance of the obtained sample. Another notable difference was observed in the resulting morphology, where ∼1.6 μm flower- and dandelion-like shapes were obtained for acetate and subsalicylate, respectively; both structures assembled by around 30 nm thick nanoflakes with rounded and straight edge, respectively. UV–vis diffuse reflectance shows an energy gap around 1.8 eV. Raman spectroscopy confirms also the tetragonal phase of BiOI. The photocatalytic activity was evaluated through degradation of methyl orange dye using visible and UV light sources, comparing results with P25 TiO2. Both BiOI nanostructures presented an improvement of photocatalytic activity when irradiated with visible light, having the best photoactivity the sample synthetized with bismuth acetate.

Controlled synthesis of Bi2O2C4H2O4 hierarchical micro-spheres by solution-phase methods

This paper presents the results of the preparation of bismuth (III) oxofumarate (BiO)2C4H2O4 hierarchical micro-spheres from solutions of bismuth salts. Precipitation of (BiO)2C4H2O4 occurred from aqueous solutions of fumaric acid C4H4O4. The solubility of the obtained samples was studied in inorganic solvents. Strong electrolytes were used to show solubility over a wide pH range. Solubility in a weak electrolyte NH4OH was also considered. The phase composition of (BiO)2C4H2O4 in the samples was established by X-ray diffraction, thermogravimetric and chemical analyzes. Analysis of the size and morphology of the resulting particles was carried out by using methods of scanning electron microscopy and low-angle laser light scattering.

Bi3TaO7 film: a promising photoelectrode for photoelectrochemical water splitting.

Most of the transition metal bismuth salts have excellent visible absorption range and carrier transport properties due to their unique structure capable of orbits and s-p bonds. As one of the transition metal bismuth salts, Bi3TaO7 is firstly directly prepared on fluorine-doped SnO2 transparent conductive glass (FTO) as a photoanode for photoelectrochemical (PEC) water oxidation via a simple hydrothermal method using a special precursor solution. The growth mechanism of the Bi3TaO7 film is investigated in detail. Besides, the Bi3TaO7 photoanode exhibits a wide visible light response range with an optical band gap of 2.88 eV, which is useful for its PEC properties. Bi3TaO7 achieves an excellent PEC performance by tuning the calcination temperature, producing a photocurrent density of 23.0 μA cm-2 at 1.23 V vs. RHE and showing excellent stability that decays by only 2% after illumination for 6000 s. The above results indicate that Bi3TaO7 has broad application prospects in the field of PEC water oxidation.

Colitis microscópica, un diagnóstico en aumento

Actualmente, la colitis microscópica agrupa tres subgrupos de patologías, las clásicas son la colitis linfocítica (CL) y la colitis colagenosa (CC), que histológicamente se distinguen por la presencia o ausencia de engrosamiento subepitelial; el tercer subgrupo corresponde a la colitis microscópica incompleta (CMI), que incluye a pacientes que no cumplen los criterios clásicos de colitis microscópica, pero que presentan cambios histológicos similares. Aunque se considera una enfermedad con baja prevalencia e incidencia, los estudios presentados en los últimos años evidencian un incremento leve de esta patología. Se han mencionado como factores causales los inmunológicos e infecciosos y se ha relacionado con el consumo de algunos medicamentos y de cigarrillo. Clínicamente se caracteriza por la presencia de diarrea acuosa crónica, que en algunos pacientes puede cursar con períodos de estreñimiento. Los tres subgrupos presentan manifestaciones clínicas similares, por lo que su diagnóstico generalmente es histológico. La colonoscopia con toma de biopsias es el pilar diagnóstico y se debe complementar con hemograma, examen parasitológico, estudios inmunológicos (anticuerpos antinucleares, IgG) y de función tiroidea. El tratamiento se basa en la suspensión de medicamentos relacionados, cambios en los hábitos alimenticios y en el uso de medicamentos, como los esteroides, subsalicilato de bismuto, 5-ASA y colestiramina. En la gran mayoría de los pacientes, la mejoría se logra con un bajo porcentaje de recidivas.