Effect Of Bismuth Subsalicylate Research Articles

312 Effects of Bismuth Subsalicylate and Different Sulfate Concentrations on in vitro Ruminal Fermentation Using a Warm-season Perennial Hay Substrate

Abstract A randomized complete block design was used to evaluate the effects of bismuth subsalicylate (BSS) on in vitro ruminal fermentation with differing concentrations of sulfate. In vitro fermentation consisted of 50 mL of a 4:1 buffer:ruminal fluid inoculum and 0.7 g (pre-dehydrated) of substrate [WW-B Dahl bluestem hay (Bothriochloa bladhii)] incubated for 48 h (39oC). Treatments were arranged as a 3 × 4 factorial with concentration of sulfate (0.2, 2.9, or 5.6 g sulfate/L buffer) and BSS (0.0, 0.165, 0.330, or 0.495% substrate DM) as the main factors. In vitro organic matter digestibility (IVOMD), and CH4, H2S, and total gas production (TGP) were measured. Data were analyzed using the MIXED procedure of SAS with the fixed effects of BSS, sulfate, and their interaction. Incubation day (block) was considered a random effect. The average of 2 bottles within day was considered experimental unit. A BSS × sulfate interaction was observed for TGP (P = 0.040) and H2S production (P < 0.001), where BSS had a larger negative impact on TGP and production of H2S with greater concentrations of sulfate. A linear effect (P < 0.001) of sulfate was observed for CH4 production per gram of incubated OM, where CH4 was decreased as sulfate concentration increased. A quadratic effect of sulfate was observed for IVOMD (P = 0.010) and pH (P = 0.009). Production of H2S linearly decreased (P = 0.001) as BSS concentration increased. The addition of BSS to in vitro incubations did not affect (P > 0.10) any other variables measured. Bismuth subsalicylate does not appear to have negative effects on in vitro fermentation parameters while decreasing H2S production; however, elevated concentrations of sulfate in the buffer appears to have negative impacts on fermentation. Further in vivo research is warranted to support BSS supplementation to cattle with high dietary sulfate.

313 Effects of Bismuth Subsalicylate on Ruminal Fermentation of Cattle Consuming a Feedlot Diet

Abstract A replicated 3 × 3 Latin square was used to determine the effects of bismuth subsalicylate on ruminal fermentation parameters of beef cattle consuming a feedlot diet. Six ruminally-cannulated Angus-crossbred steers (n = 3; 573 ± 105 kg BW) and heifers (n = 3; 553 ± 77 kg BW) were assigned 1 of 3 treatments: 1) low sulfur (S = 0.27% diet DM; LSUL); 2) high sulfur (S = 0.38% diet DM; HSUL); and 3) HSUL + 0.33% bismuth subsalicylate in diet DM; (BSS). Cattle were adapted to treatments for 14 d followed by 7 d of collections. Ruminal gas cap samples were collected at 0, 4, 8, and 12 h post-feeding on d 14, and ruminal fluid samples were collected on d 15 every 3 h post-feeding for 24 h. Data were analyzed using the MIXED procedure of SAS. Treatment tended (P = 0.099) to affect H2S concentration where BSS and LSUL were 50 and 61% lesser when compared to HSUL, respectively. A tendency (P = 0.061) was also observed for concentration of NH3-N where HSUL and BSS were lesser than CTRL. There was also a tendency for a treatment effect (P = 0.082) where HSUL had a lower pH than LSUL with BSS being intermediate. Furthermore, treatment tended (P = 0.0712) to affect the concentration of acetate where HSUL was lesser than BSS. No effect of treatment (P ≥ 0.124) was observed on total VFA concentration nor concentrations of butyrate, propionate, or valerate (P ≥ 0.138). Treatment tended (P = 0.084) to affect branched chain VFA concentration where BSS decreased concentrations compared to LSUL. Molar proportions of the major VFA were not impacted by treatment (P ≥ 0.100). In conclusion, BSS appears to decrease H2S production in the rumen without having negative effects on the fermentation profile.

232 Effects of bismuth subsalicylate and encapsulated calcium-ammonium nitrate on beef cattle performance and liver mineral concentration

Abstract The effects of bismuth subsalicylate (BSS) and encapsulated calcium-ammonium nitrate (eCAN) on feedlot beef cattle performance and liver mineral concentration were evaluated. Two hundred Angus steers (BW = 385 ± 27 kg) were used in a randomize complete block design (block = BW) and allocated to 50 pens (4 steers/pen) where treatments were randomly assigned as follows: CTL (urea at 0.70%, 0.28% ruminally available sulfur [RAS]), NIT (eCAN at 2.0%, 0.28% RAS), UBS (urea at 0.70%, BSS at 0.33%, 0.28% RAS), NITBS (eCAN at 2.0%, BSS at 0.33%, 0.28% RAS), and LOW-S (urea at 0.70%, 0.14% RAS). Steers were fed for 171 d and weighed every 35 d. Dry matter intake (DMI) was recorded weekly. Liver biopsies were taken on d -5 and 124 from the same randomly selected animal per pen. The MIXED procedure of SAS was used with the fixed effect of BSS, eCAN, S, BSS × CAN, and the random effect of block. Cattle consuming urea as non-protein nitrogen source (NPNS) had greater final body weight (FBW; P = 0.045) than cattle consuming eCAN. There was a NPNS effect where eCAN reduced DMI (P < 0.001) and average daily gain (ADG; P = 0.041), but did not affect feed efficiency (G:F; P = 0.876). There was a tendency for BSS to reduce DMI (P = 0.095), but not affect ADG (P = 0.436) or G:F (P = 0.876). The effect of S was also observed (P = 0.042) where LOW-S cattle consumed less feed than CTL. A reduction of final liver Cu concentration was observed (P = 0.042) where BSS reduced the concentration of Cu by 58%. Bismuth subsalicylate did not affect cattle performance; however, it might be detrimental to cattle consuming low Cu diets.

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.

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.

Effect of Bismuth Subsalicylate vs Placebo on Use of Antibiotics Among Adult Outpatients With Diarrhea in Pakistan

Many of the 4.5 billion annual episodes of diarrhea are treated unnecessarily with antibiotics; prevalence of antibiotic resistance among diarrheal pathogens is increasing. Knowledge-based antibiotic stewardship interventions typically yield little change in antibiotic use. To compare antibiotic use among adult outpatients with diarrhea given bismuth subsalicylate (BSS) or placebo. This randomized clinical trial took place from April to October 2014. Participants were patients aged 15 to 65 years with acute, nonbloody diarrhea from 22 outpatient clinics in Karachi, Pakistan. Participants were interviewed about symptoms and health care utilization during the 5 days after enrollment. Group assignment was concealed from participants, field staff, and the statistician. Primary analysis occurred from August to September 2015. Participants were randomly assigned (1:1) to receive BSS or placebo for 48 hours or less. Use of systemic antibiotics within 5 days of enrollment. Secondary outcomes included measures of duration and severity of illness. Among eligible patients, 39 declined to participate, 440 enrolled, and 1 enrolled participant was lost to follow-up, for a total of 439 patients included in the analysis. Median (interquartile range) participant age was 32 (23-45) years and 187 (43%) were male. Two hundred twenty patients were randomized to BSS and 220 were randomized to placebo. Overall, 54 participants (12%) used systemic antibiotics (16% in the placebo group and 9% in the BSS group); all antibiotic use followed consultation with a physician. Use of any antibiotic was significantly lower in the BSS group (20 of 220 vs 34 of 219 patients; odds ratio [OR], 0.54; 95% CI, 0.30-0.98), as was use of fluoroquinolones (8 of 220 vs 20 of 219 patients; OR, 0.38; 95% CI, 0.16-0.88). Rates of care seeking and hospitalization were similar between groups and no difference was detected in timing of diarrhea resolution. However, those in the BSS group less commonly received intravenous rehydration (14 of 220 vs 27 of 219 patients; OR, 0.48; 95% CI, 0.25-0.95) and missed less work (median [interquartile range], 0 [0-1] vs 1 [0-1] day; P = .04) during follow-up. This study found less antibiotic use among participants given BSS for acute diarrhea in a setting where antibiotics are commonly used to treat diarrhea. Encouraging health care professionals in such settings to recommend BSS as frontline treatment for adults with diarrhea, and promoting BSS for diarrhea self-management, may reduce antibiotic use and rates of antibiotic resistance globally. ClinicalTrials.gov identifier: NCT02047162.

74 Effects of bismuth subsalicylate and encapsulated calcium-ammonium nitrate on enteric methane production and apparent total-tract nutrient digestibility of beef cattle.

74 Effects of bismuth subsalicylate and encapsulated calcium-ammonium nitrate on enteric methane production and apparent total-tract nutrient digestibility of beef cattle.

113 Effects of Bismuth Subsalicylate and Calcium-Ammonium Nitrate on Liver Mineral Concentration and Performance of Growing Beef Heifers.

To evaluate the effects of bismuth subsalicylate (BSS) and encapsulated calcium-ammonium nitrate (eCAN) on performance and liver mineral concentration of growing cattle, 75 Bos taurus × Bos indicus heifers (279 ± 57 kg of initial BW; 15.6 ± 4.1 mo of age) were used in an incomplete randomized block design with a 2 × 2 + 1 arrangement of treatments. The experiment consisted of a 28-d adaptation period followed by a 56-d data collection period in which heifers were weighed every 14 d. Heifers were stratified, blocked by weight, and allotted to 25 dormant bahiagrass (Paspalum notatum) pastures where they received 1.07 kg/heifer/d of molasses and ad libitum access to bahiagrass hay. Pastures were randomly assigned to 1 of 5 treatments: NCTRL (no added NPN or BSS), U (urea supplemented at 182 mg/kg of BW), NIT (eCAN supplemented at 350 mg/kg of BW), UB (urea supplemented at 182 mg/kg of BW and BSS supplemented at 58.4 mg/kg of BW) and NITB (eCAN supplemented at 350 mg/kg of BW and BSS supplemented at 58.4 mg/kg of BW). Data were analyzed using the MIXED procedure of SAS with pasture as the experimental unit. Contrasts were used to determine: effect of NCTRL vs. all other treatments (N); source of NPN (NS); effect of BSS (B); and the interaction between NPN source and BSS (B×NS). Final BW was not affected by N (P = 0.470), NS (P = 0.384), or B (P = 0.600); however, there was a B×NS interaction (P = 0.048) where NITB heifers had lesser BW compared with UB heifers. There was no effect of N, NS, B, or B×NS for ADG measured within any time points (P > 0.05). For carcass ultrasound measurements, there was no effect (P > 0.05) of N, NS, or B on LM area; however, a B×NS interaction (P = 0.001) was observed for 12th-rib fat thickness where NITB heifers had less back-fat compared with UB heifers on d 56. Concentration of minerals in the liver was not affected by NS (P > 0.05). No B×NS interactions (P = 0.05) were observed affecting liver mineral concentration; however, the addition of BSS decreased liver concentration of Cu (P = 0.002). In conclusion, the addition of eCAN did not affect performance of growing heifers unless it was provided in combination with BSS, which may decrease growth performance. Furthermore, BSS may negatively affect trace mineral concentrations in the liver.

Effects of bismuth subsalicylate and dietary sulfur level on fermentation by ruminal microbes in continuous culture.

In ruminants, excess dietary sulfur can be associated with a reduction in DM intake, poor feedlot performance and sulfur-associated polioencephalomalacia. Bismuth subsalicylate (BSS) has been shown to decrease hydrogen sulfide in vitro. The objective of this experiment was to evaluate effects of BSS inclusion (0 or 0.5% of diet DM) and dietary sulfur (0.21 or 0.42% of diet DM) on microbial fermentation in continuous culture. Treatments were arranged in a 2 × 2 factorial design. Eight dual-flow continuous culture fermenters were used during 2 consecutive 10-d periods consisting of 7 d for stabilization followed by 3 d of sampling. A pelleted feedlot diet containing 39% dry rolled corn, 32% earlage, 21% wet distillers grains, 3.2% corn silage, 1.5% soybean meal, 0.6% urea and 2.7% mineral premix (DM basis) was provided as substrate for microbes at a rate of 75 g of DM × fermenter–1 × d–1. Effluents from sampling days were composited by fermenter within period, resulting in 4 replicates/treatment. Bismuth subsalicylate inclusion decreased (P < 0.01) true OM digestion, while no effects were observed for NDF and ADF digestion. Total VFA concentrations, molar proportions of acetic, propionic, and branched-chained VFA decreased (P < 0.01) with BSS addition. The ratio of acetic to propionic acid and the molar proportion of butyric acid increased (P < 0.01) with BSS addition. In regard to nitrogen metabolism, BSS increased NH3–N concentration, NH3–N and dietary-N flows (P < 0.01), and decreased non-NH3–N flow, microbial-N flow, CP degradation, and efficiency of microbial protein synthesis (P < 0.01). Inclusion of BSS increased mean, minimum, and maximum fermentation pH (P < 0.01). Amount of dietary sulfur and BSS inclusion influenced flows of amino acids and fatty acids from fermenters. Influences on fatty acid biohydrogenation and amino acid flows demonstrated an overall suppression of microbial fermentation. Results from this experiment indicate that BSS inclusion at 0.5% of diet DM has detrimental effects on in vitro rumen fermentation in continuous culture.

Bismuth subsalicylate nanoparticles with anaerobic antibacterial activity for dental applications

In recent years, nanomaterials have been used in the medical-dental field as new alternative antimicrobial agents. Bismuth subsalicylate (BSS) has been used as an antimicrobial agent, but the effect of BSS in the form of nanoparticles (BSS-nano) as a potential antimicrobial agent has not been tested, in specific against bacteria responsible for periodontal disease. The aim of this study was to evaluate the antibacterial effect of BSS-nano against oral anaerobic bacteria and to assess the safety of BSS-nano by evaluating their cytotoxicity in human gingival fibroblast (HGF-1) cells. BSS-nano were synthesized by laser ablation and were previously physico-chemically characterized using in vitro assays. The antibacterial activity was measured using the tetrazolium-based XTT assay, and cytotoxicity was determined using lactate dehydrogenase (LDH) and MTS assays in HGF-1 cells. Transmission electron microscopy of HGF-1 exposed to BSS-nano was also performed. BSS-nano was shown to have a primary size of 4–22 nm and a polygonal shape. Among the tested bacterial strains, those with a greater sensitivity to BSS-nano (highest concentration of 21.7 μg ml−1) were A. actinomycetemcomitans, C. gingivalis, and P. gingivalis. BSS-nano at a concentration of 60 μg ml−1 showed low cytotoxicity (6%) in HFG-1 cells and was mainly localized intracellularly in acidic vesicles. Our results indicate that the concentration of BSS-nano used as an effective antibacterial agent does not induce cytotoxicity in mammalian cells; thus, BSS-nano can be applied as an antibacterial agent in dental materials or antiseptic solutions.

563 Effects of bismuth subsalicylate and calcium-ammonium nitrate on ruminal fermentation of beef cattle

A duplicated 5×5 Latin square design 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 cane molasses. Ten ruminally cannulated beef cattle were randomly assigned to 1 of 5 treatments as follows: 3.3 g/kg of BW of molasses (CTRL); CTRL + 182 mg/kg of BW of urea (N0B0); CTRL + 538 mg/kg of BW of eCAN (N1B0); N0B0 + 58.4 mg/kg of BW of BSS (N0B1); and N1B0 + 58.4 mg/kg of BW of BSS (N1B1). With exception of CTRL, all treatments were isonitrogenous. Ruminal fluid and rectal temperature was collected 4× per d 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 d 0 of each period followed by 0 h on d 1, 2, 3, and 14. Repeated measures data were analyzed using the MIXED procedure of SAS with the fixed effects of treatment, time, treatment × time, square, period, and animal within square, and the random effect of animal within treatment. For non-repeated data, the model included the fixed effects of treatment, square, period, and animal within square. Orthogonal contrasts were used to evaluate the effects of NPN, eCAN, BSS, and eCAN × BSS. There was no treatment effect (P>0.05) on concentrations of H2S on d 0, 1, 2, or 14; however, on d 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 eCAN 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 eCAN (P= 0.009) on concentrations of NH3-N, where cattle consuming NPN had lesser concentrations than those consuming eCAN compared to 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. In conclusion, eCAN does not appear to deliver equivalent ruminal fermentation parameters compared to urea, as indicated by reductions in total concentrations of VFA and NH3-N.

1370 Effects of bismuth subsalicylate and calcium-ammonium nitrate on in vitro fermentation of bahiagrass hay with supplemental molasses

1370 Effects of bismuth subsalicylate and calcium-ammonium nitrate on in vitro fermentation of bahiagrass hay with supplemental molasses

Long-term proliferative effects of bismuth subsalicylate are independent of a functional calcium-sensing receptor

Long-term proliferative effects of bismuth subsalicylate are independent of a functional calcium-sensing receptor

Bismuth subsalicylate suppression ofHelicobacter pylori in nonulcer dyspepsia: A double-blind placebo-controlled trial

Gastritis caused by Helicobacter pylori (HP) is common in patients with nonulcer dyspepsia (NUD), but an etiologic relationship between the histologic lesion and clinical symptoms is unproven. HP is inhibited by bismuth subsalicylate (BSS), a traditional remedy for dyspeptic complaints. The aim of this study was to assess the short- and long-term effects of BSS on HP, gastritis, and symptoms in patients with NUD. One hundred twenty-six patients with NUD who were shown to be infected with H. pylori (HP+) were enrolled. There was a two-week placebo run-in period to eliminate placebo responders. Fifty patients remained symptomatic and were randomly assigned to therapy with either BSS liquid or a matching placebo. EGD, biopsy, and clinical evaluations were performed at entry, at week 5 (end of therapy), at week 9 (four weeks after therapy), or at time of symptomatic relapse. Twenty-seven patients received placebo and 23 patients received BSS. BSS suppressed H. pylori in 15/23 patients (65%) and eradicated it in one patient, whereas the placebo had no effect on H. pylori. Gastritis improved during therapy with BSS but relapsed by week 9. There was no significant change in level of dyspeptic symptoms during or after treatment, although one month after the end of treatment, the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured. The study confirms that BSS given for three weeks suppresses but does not usually eradicate H. pylori. Such short-term suppression of H. pylori heals gastritis but does not result in clinical improvement.

Prevention of Diarrhea Caused by Enterotoxigenic Escherichia coli: Lessons Learned with Volunteers

The effectiveness of bismuth subsalicylate in the prevention and treatment of diarrhea induced in volunteers by a single strain of enterotoxigenic Escherichia coli and a standard inoculum size was evaluated. Bismuth subsalicylate (500 mg in a solid dosage form) was administered 8 hours and 2 hours before and 2 hours and 4 hours after the E. coli challenge; treatment was continued four times a day for three additional days. Volunteers experiencing diarrhea were re-randomized to receive placebo or bismuth subsalicylate (300 mg every 30 minutes, for a total of 2.4 g of bismuth subsalicylate, in eight doses). Diarrhea occurred in nine (56%) of the 16 volunteers receiving placebo and in two (13%) of the 15 volunteers receiving bismuth subsalicylate (P less than .03). In vitro studies revealed that bismuth subsalicylate and its components each were bactericidal at concentrations possibly attained during the clinical trial. The effect of the dosage form (solid vs. liquid), the relation of drug administration to meals, and how these variables might greatly influence the effectiveness of bismuth subsalicylate prophylaxis for travelers' diarrhea were considered.

Effect of Bismuth Subsalicylate on Chronic Diarrhea in Childhood: A Preliminary Report

Stools collected from 39 infants and children with chronic nonspecific diarrhea and from 10 age-matched controls were examined for bile acid content with use of gas-liquid chromatography. Values were correlated with stool color. Mean concentration of bile acids in green stools (7.7 +/- 1.52 mg/g dry weight) was significantly higher than that in brown stools (3.76 +/- 0.7 mg/g dry weight) and in control stools (1.42 +/- 0.35 mg/g dry weight). In patients with green diarrhea, treatments with cholestyramine and bismuth subsalicylate (Pepto-Bismol) were equally effective in decreasing stool frequency, with the latter being more effective in decreasing water content. Patients with brown stools had an insignificant response to therapy.

Effect of Bismuth Subsalicylate on Fecal Microflora

Several studies have documented the efficacy of bismuth subsalicylate (BSS) for the prophylaxis and treatment of bacterial diarrhea. It is not known what effect, if any, BSS has on the normal bowel flora. We quantitated the fecal flora in healthy volunteers before and after they took BSS. In the first group, 8 ounces of BSS was given on two successive days. In the second group, a standard oral intestinal lavage preparation (GoLYTELY) was used to clean the colon and then 8 ounces of BSS was given during a 4-hour period. There were no changes in total microbial counts or in counts of individual groups such as enteric bacteria, Pseudomonas, Staphylococcus, Bacteroides, or Clostridium difficile. On day 2 the yeast counts rose 2.4 log10 colony-forming units/g in the group taking 16 ounces of BSS but did not increase in the group taking 8 ounces of BSS plus GoLYTELY. The counts returned to pretreatment levels by day 7. These results show that a 1- or 2-day course of BSS, even with an oral intestinal lavage preparation, did not have significant effects on the normal microbial populations in the fecal microflora.

Effect of Bismuth Subsalicylate on Clostridium difficile Colitis in Hamsters

The therapeutic effect of bismuth subsalicylate (BSS, Pepto-Bismol) in Clostridium difficile colitis was studied in golden Syrian hamsters. C. difficile was fed to the hamsters by orogastric intubation 2-3 days after their arrival. Clindamycin (1.5 mg per animal) was given intraperitoneally 4 days later. Twenty-four hours after challenge with clindamycin, animals were given BSS at dosages of 5, 10, and 15 mg twice daily for 5 days by orogastric intubation. Controls included untreated animals and those given 5 mg of vancomycin once daily by intubation. Delay in the time of death was observed in all BSS-treated animals and was statistically significant on days 4-6 in those receiving 15 mg twice daily. Vancomycin produced a greater delay in death than did BSS. Our study suggests that BSS at a dosage of 15 mg twice daily has some therapeutic effect on C. difficile colitis in hamsters.