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Background and Aims: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy., Methods: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects., Results: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010)., Conclusions: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT., Trial Registration Number: ChiCTR2300074693., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection., Methods: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13 C-urea breath test was performed to evaluate H. pylori eradication., Results: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups., Conclusion: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions., Trial Registration: ClinicalTrials.gov identifier: NCT05431075., (© 2024 John Wiley & Sons Ltd.)

The present article reviews the literature regarding tetracycline staining of the dentition and its esthetic management. A total of 49 articles were identified in the initial search, and 22 articles met the eligibility criteria of this narrative literature review. Tetracycline staining results from its use in children between the ages of 6 months and 6 years, when tooth crowns are formed; the effects are dependent on the dosage, duration of treatment, stage of tooth mineralization, and activity of the mineralization process. Tooth bleaching is always the first treatment option for low-grade cases of tetracycline staining. Restorative procedures are indicated for severe staining. The article also describes the treatment of severe staining affecting the maxillary anterior dentition of a 48-year-old man who reported the systemic administration of tetracycline during childhood. Direct composite resin laminate veneers were proposed to achieve immediate, highly esthetic restorations. A combination of different resinous materials in different shades was applied to meet the needs of the patient. The use of direct composite resin laminate veneers satisfied the functional and esthetic demands of the patient at a lower cost than ceramic materials., Competing Interests: No conflicts of interest reported.

Background: The optimal dosage of tetracycline remains unclear for Helicobacter pylori eradication. Frequent dosing requirements may decrease patient adherence and increase the incidence of adverse events, potentially reducing treatment efficacy. This study aimed to compare the efficacy of different tetracycline dosages in rescue treatment for H. pylori infection., Methods: A total of 406 patients needing H. pylori rescue treatment were enrolled. Patients were randomized into two groups and received bismuth-containing quadruple therapies as follows: esomeprazole 40 mg twice daily, bismuth 220 mg twice daily, amoxicillin 1000 mg twice daily, and tetracycline 500 mg either three (TET-T group) or four (TET-F group) times daily. At least 6 weeks after treatment completion, a 13 C-urea breath test was performed to evaluate H. pylori eradication., Results: The intention-to-treat (ITT) eradication rates were 91.13% (185/203) and 90.15% (183/203) (p = 0.733), the modified ITT (MITT) eradication rates were 94.87% (185/195) and 95.31% (183/192) (p = 0.841), and the per-protocol (PP) eradication rates were 94.79% (182/192) and 95.21% (179/188) (p = 0.851) in the TET-T group and TET-F group, respectively. The eradication rates for the TET-T group were not inferior to those of the TET-F group in ITT, MITT, and PP analyses. The incidence of adverse effects was significantly lower in the TET-T group than in the TET-F group (23.65% vs. 33.50%, p = 0.028). No significant differences were observed in treatment compliance between the groups., Conclusions: The dose of tetracycline administered three times daily showed comparable efficacy to that administered four times daily, while significantly reducing the incidence of adverse events. The combination of tetracycline and amoxicillin in bismuth-containing quadruple therapy achieved a high eradication rate in H. pylori rescue treatment., (© 2024 John Wiley & Sons Ltd.)

Eph receptor tyrosine kinase EphB1/2 contributes to the development of liver fibrosis, suggesting the rationale that EphB1/2 inhibitors may be effective in liver fibrosis therapy. Since tetracycline antibiotics were recently demonstrated as EphB kinase inhibitors, in present study we investigated their therapeutic potential against liver fibrosis. Our results showed that the tetracycline combination of demeclocycline (D), chlortetracycline (C), and minocycline (M) inhibited the activation of hepatic stellate cells (HSCs) in vitro and alleviated CCl 4 -induced animal model of liver fibrosis in vivo. Mechanistically, DCM combination inhibited EphB1/2 phosphorylation and subsequent activation of the MAPK signaling. Moreover, we found that short-term and low-dose DCM combination treatment decreased tissue inflammation and improved liver fibrosis in mice. Thus, our study indicates that tetracyclines may be repurposed for the treatment of liver fibrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Our aim was to assess, in obese patients undergoing Roux-en Y gastric bypass surgery, the bismuth quadruple therapy (BQT) eradication rates at the first-line Helicobacter pylori (Hp) treatment as proposed by the Maastricht V/Florence consensus in areas with high clarithromycin (CLT) resistance rates-10 days proton pump inhibitor bid and three-in-one single capsule bismuth therapy containing bismuth, metronidazole, and tetracycline, marketed as Pylera four times a day., Methods: This is a single-center prospective study over a 3-year period. Endoscopy and Hp assessment by histology was performed at baseline, and posttreatment Hp status was assessed by C13 urea breath test 4-6 weeks after the end of therapy. Data analysis was performed using the IBM® SPSS® Statistics 28.0 (IBM Corp. 2021, Armonk, NY) using mostly nonparametric comparisons (α = 0.05)., Results: The study cohort consisted of 598 adult obese Hp-positive patients [476, 78.6% female, age 43.2 (± 10.4) years] consecutively scheduled for Hp eradication therapy. Hp was eradicated in 500 patients [83.6.3% (95% CI: 80.4%-86.5%)], and the eradication was independent of gender, age, endoscopic diagnosis, and smoking status (p > 0.05)., Conclusion: Ten days of BQT did achieve Maastricht V/Florence recommended first-line eradication rates (at least 80%) in obese Portuguese patients undergoing Roux-en Y gastric bypass, being by now the most reliable choice for Hp eradication., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Eravacycline is the newest member of the broad-spectrum class of tetracycline antimicrobials. Pancreatitis has been previously associated with the tetracycline class of antibiotics, but, to our knowledge, we believe that this is the first reported case of eravacycline-induced pancreatitis. We describe a 46-year-old male who received eravacycline for treatment of a perirectal abscess. While the patient had slightly elevated lipase levels at baseline post-cardiopulmonary arrest, he developed abdominal pain and a further increase in lipase levels following 10 days of eravacycline, consistent with pancreatitis. Based on the Naranjo adverse drug reaction probability scale, eravacycline was the probable etiology of acute pancreatitis given improvement immediately after discontinuation. Clinicians should be aware of this potential adverse effect of eravacycline and should not initiate eravacycline in those with risk factors for acute pancreatic injury. However, acute pancreatitis should be suspected in all patients complaining of symptoms followed by immediate discontinuation of eravacycline., Competing Interests: Declaration of Competing Interest The author has no financial or other conflicts of interest to disclose., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: The effective regimen is lacking in areas with high antibiotic resistance and tetracycline unavailable. Whether minocycline can replace tetracycline for Helicobacter pylori eradication is unknown. This meta-analysis compared and summarized the efficacy and safety profiles of H. pylori quadruple regimens with and without minocycline., Materials and Methods: We conducted a literature search for regimens including minocycline quadruple therapy for H. pylori eradication and adverse events (AEs). Controls were patients undergoing any other treatment without minocycline. Searches were performed up to July 20, 2023, using PubMed and the Cochrane library., Results: A total of five randomized controlled clinical trials with 2004 patients were included in this meta-analysis. The H. pylori eradication rate of minocycline quadruple therapy was similar with that of control therapy (83.8% vs. 80.6%, OR 1.25, 95% CI [0.99-1.57], I 2  = 0%, p = 0.06) in ITT analysis. When treatment regimens with minocycline were compared only with treatment regimens with tetracycline, no significant difference was found in eradication rate:85.5% vs. 85.5%, OR 1.00, 95% CI 0.67-1.47, p = 1.00. But when treatment regimens with minocycline were compared with treatment regimens without tetracycline, the former was significantly superiority to the latter (82.7% vs. 77.2%; OR, 1.40, 95% CI 1.06-1.87, p = 0.02). The incidence of AEs in the quadruple therapy with minocycline group was similar with the control group (35.9% vs. 38.8%, OR 0.88, 95% CI [0.73-1.06], I 2  = 13%, p = 0.17)., Conclusions: We demonstrated the H. pylori eradication effect of minocycline quadruple therapy, and it might be an optional therapy. The safety of regimens containing minocycline was relatively satisfactory., (© 2023 John Wiley & Sons Ltd.)

Background: To compare the efficacy and tolerability of minocycline vs. tetracycline in bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) rescue treatment., Methods: This study was a multi-center, randomized-controlled, non-inferiority trial. Refractory H. pylori-infected subjects with multiple treatment-failure were randomly (1:1) allocated to receive 14-day therapy with esomeprazole 20 mg b.i.d, bismuth 220 mg b.i.d, plus metronidazole 400 mg q.i.d and minocycline 100 mg b.i.d (minocycline group) or tetracycline 500 mg q.i.d (tetracycline group). Primary outcome was H. pylori eradication rate evaluated by 13 C-urea breath test at least 6 weeks after the end of treatment. Antibiotic resistance was determined using E test method., Results: Three hundred and sixty-eight subjects were randomized. The eradication rates in minocycline group and tetracycline group were 88.0% (162/184, 95% CI 83.3-92.8%) and 88.6% (163/184, 95% CI 83.9-93.2%) in intention-to-treat analysis, 98.0% (149/152, 95% CI 95.8-100%) and 97.4% (150/154, 95% CI 94.9-99.9%) in per-protocol analysis, 93.1% (162/174, 95% CI 89.3-96.9%) and 93.1% (163/175, 95% CI 89.4-96.9%) in modified intention-to-treat analysis. Minocycline, tetracycline and metronidazole resistance rates were 0.7%, 1.4% and 89.6%, respectively. Non-inferiority of minocycline was confirmed (P < 0.025). Metronidazole resistance did not affect the efficacy of either therapy. The two therapies exhibited comparable frequencies of adverse events (55.4% vs. 53.3%); almost half of them were mild. Dizziness was the most common adverse events in the minocycline group., Conclusions: Minocycline can be an alternative for tetracycline in bismuth-containing quadruple therapy for H. pylori empirical rescue treatment, irrespective of metronidazole resistance. However, relatively high incidence of adverse events in both regimens should be emphasized., (© 2023. Japanese Society of Gastroenterology.)

Background: Although highly effective as a component of Helicobacter pylori ( H. pylori ) treatment regimen, tetracycline is associated with a high incidence of medication-related adverse events. Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates., Aim: To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H. pylori infection., Methods: Consecutive patients (10/2020-12/2021) who received tetracycline and furazolidone quadruple therapy for H. pylori infection at Sir Run Run Shaw Hospital were identified. All patients received tetracycline, furazolidone, proton pump inhibitor, and bismuth for 14 d as primary or rescue therapy. Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily., Results: Three hundred and ninety-four patients [mean age = 46.3 ± 13.9, male = 137 (34.8%), and 309 (78.4%) primary therapy] completed tetracycline and furazolidone quadruple therapy for H. pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118 (750 mg twice daily) and 119 (500 mg three times daily). Eradication rates in the modified tetracycline dose group were 92.40% and in the standard groups, eradication rates were 93.20% for 750 mg twice daily group and 92.43% for 500 mg three times daily group, respectively, without statistical difference ( P = 0.959). The incidence of adverse events was lower in the modified tetracycline dose (15.3% vs 32.3% and 29.4%; P = 0.002) compared to the standard dose group., Conclusion: In a real-world experience, modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy, comparable to standard tetracycline dose regimens, with a favorable safety profile., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens., Methods: This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables., Results: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups., Conclusion: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance., Trial Registration: ClinicalTrials.gov, ChiCTR 1900023646., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Tetracyclines are a class of broad-spectrum bacteriostatic antibiotics used to treat many infections, including methicillin-resistant Staphylococcus aureus (MRSA), acne, pelvic inflammatory disease, chlamydial infections, and a host of zoonotic infections. These drugs work by inhibiting protein synthesis in bacterial ribosomes, specifically by disallowing aminoacyl-tRNA molecules from binding to the ribosomal acceptor sites. While rare, tetracycline antibiotics, particularly minocycline and doxycycline, are associated with an increased risk of developing esophageal perforation and pseudotumor cerebri (PTC, or idiopathic intracranial hypertension). Since tetracyclines are a commonly prescribed class of medications, especially in adolescents for acne treatment, it is important for clinicians to appreciate significant side effects that can result in morbidity and mortality. This paper aims to consolidate and to emphasize current research on the association between tetracycline antibiotics and the development of esophageal perforation, and PTC. PTC is a neurological syndrome consisting of increased intracranial pressure, headache, and vision changes without evidence of the contributing source, such as mass lesion, infection, stroke, or malignancy. Esophageal perforation, while rare, can be the result of pill esophagitis. Pill-induced injuries occur when caustic medicinal pills dissolve in the esophagus rather than in the stomach. Most patients experience only self-limited pain (retrosternal burning discomfort, heartburn, dysphagia, or odynophagia), but hemorrhage, stricture, and perforation may occur. Tetracycline use can lead to pill esophagitis. In summary, clinicians should appreciate the potential risks of tetracycline compounds in clinical practice., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Competing Interests: Conflicts of interest Dr Mostaghimi has received consulting fees from Pfizer, hims, Digital Diagnostics, Concert, Lilly, Abbvie, Equillium, Boehringer Ingelheim; equity: hims, Acom, Seebe; licensing/royalties: Pfizer, Concert, Lilly; medical advisory board: hims, digital diagnostics; clinical trials: Lilly, Concert; and editorial: Associate editor, JAMA Dermatology. Dr Semenov is an advisory board member/consultant and has received honoraria from Incyte Corporation, Castle Biosciences, Galderma, and Sanofi outside of the submitted work. Dr Theodosakis, authors Young, Pagan, Yoon, Getachaw, Leung, and Nguyen have no conflicts of interest to declare.

Background: Due to general unavailability and common side effects of tetracycline, the clinical application of bismuth quadruple therapy (BQT) is greatly limited. Whether amoxicillin can replace tetracycline in BQT remains unknown. This study aimed to compare the eradication rate, safety and compliance between amoxicillin-containing and tetracycline-containing BQT as a first-line regimen for Helicobacter pylori eradication., Methods: This randomized trial was conducted on 404 naïve patients for H. pylori eradication. The participants were randomly assigned to 14-day amoxicillin-containing (bismuth potassium citrate 110 mg four times/day, esomeprazole 20 mg twice daily, metronidazole 400 mg four times/day and amoxicillin 500 mg four times/day) and tetracycline-containing (tetracycline 500 mg four times/day and the other three drugs used as above) BQT. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4-8 weeks after eradication to evaluate outcome., Results: As for the eradication rates of amoxicillin-containing and tetracycline-containing BQT, the results of both intention-to-treat and per-protocol analyses showed that the difference rate of the lower limit of 95% confidence interval was above -10.0% (intention-to-treat analysis: 81.7% vs. 83.2%, with a rate difference of -1.5% [-6.3% to 9.3%]; per-protocol analysis: 89.0% vs. 91.6%, -2.6% [-4.1% to 9.3%]). The incidence of adverse events in amoxicillin-containing BQT was significantly lower than tetracycline-containing BQT (29.5% vs. 39.7%). Both groups achieved relatively good compliance (92.0% vs. 89.9%)., Conclusion: The eradication efficacy of amoxicillin-containing BQT was non-inferior to tetracycline-containing BQT as a first-line regimen for H. pylori eradication with better safety and similar compliance., (© 2022 John Wiley & Sons Ltd.)

Background: To determine whether the use of a tetracycline-class antibiotic is associated with an increased risk of developing pseudotumor cerebri syndrome (PTCS)., Methods: We identified patients in the University of Utah Health system who were prescribed a tetracycline-class antibiotic and determined what percentage of those individuals were subsequently diagnosed with PTCS secondary to tetracycline use. We compared this calculation to the number of patients with PTCS unrelated to tetracycline use., Results: Between 2007 and 2014, a total of 960 patients in the University system between the ages of 12 and 50 were prescribed a tetracycline antibiotic. Among those, 45 were diagnosed with tetracycline-induced PTCS. We estimate the incidence of tetracycline-induced PTCS to be 63.9 per 100,000 person-years. By comparison, the incidence of idiopathic intracranial hypertension (IIH) is estimated to be less than one per 100,000 person-years (Calculated Risk Ratio = 178)., Conclusions: Although a causative link between tetracycline use and pseudotumor cerebri has yet to be firmly established, our study suggests that the incidence of pseudotumor cerebri among tetracycline users is significantly higher than the incidence of IIH in the general population., Competing Interests: S. F. Passi and D. R. Orme were supported by T35 EY026511 (NEI/NIH) “Medical Student Research Program in Eye Health and Disease”; Principal Investigator Mary Elizabeth Hartnett. FURTHeR is supported by NCRR/ NCATS Grants UL1RR025764 and 3UL1RR025764-02S2, National Center for Clinical and Translational Science 1UL1TR001067, University of Utah Research Foundation, grant 1D1BRH20425 (DHHS), and R01 HS019862 from AHRQ, (DHHS). K. B. Digre, J. E. A. Warner and B. J. Katz are named on a patent or patents related to the treatment of photophobia. B. J. Katz is CEO of Axon Optics, LLC, an internet company that sells eyewear for the treatment of photophobia. B. J. Katz provides expert medical testimony in legal proceedings and some of these proceedings involve the treatment of PTCS. The remaining authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Pomaces of sea buckthorn berry were usually side-products during the processing of juice. Due to a lack of an economical and effective extraction method, it was typically recognized as waste. For the purpose of resource utilization, the mechanochemical-assisted extraction (MCAE) method was applied to develop an ecofriendly extraction method and product with better pharmacology activity. The parameters were investigated through response surface methodology (RSM) design experiments. The processing conditions were optimized as follows: amount of Na 2 CO 3 40%, ball-to-material rate 29:1 g/g, milling speed 410 rpm, milling time 24 min, extraction temperature 25 °C, extraction time 20 min and the solid-to-solution ratio 1:10 g/mL. Under these conditions, the yields of flavonoids from sea buckthorn pomaces were 26.82 ± 0.53 mg/g, which corresponds to an increase of 2 times in comparison with that extracted by the heat reflux extraction method. Meanwhile, the hepatoprotective activity of sea buckthorn pomaces extracts was studied by the liver injury induced by ip injection of tetracycline. Biochemical and histopathological studies showed that biomarkers in serum and liver of nonalcoholic fatty liver disease (NAFLD) mice were significantly ameliorated when sea buckthorn flavonoids extracted by MCAE were used. Altogether, these results demonstrate that, as a green and efficient extraction, MCAE treatment could increase the extraction yield of sea buckthorn flavonoids, meanwhile it could exhibit significant activity of improving liver function. This research provided a new way to use pomaces of sea buckthorn as a functional food. It also has great value on the comprehensive utilization of nature's resources.

Inappropriate use of antibiotics in animal and human plays a role in the emergence and spread of bacteria resistant to antibiotics which threatens human health significantly. Although extensive use of these antibiotics could contribute to the development of drug resistance, information on the knowledge, attitude and practice of antimicrobial resistance and use among animal farm owners/workers in north western Ethiopia is rare. The objective of the present study was to assess knowledge, attitude and practice of animal farm owner/workers towards antibiotic resistance and use in Amhara regional state north western Ethiopia. A cross sectional study was conducted in selected cities of Amhara regional state from January to February, 2020. Data was collected from 91 participants using structured questionnaire and analyzed using SPSSS version 23. The results showed that 96.7% of respondents gave antibiotics to treat their livestock from different sources. Most of the respondents bought their antibiotics from private pharmacies without prescription and the most frequently mentioned antibiotics used to treat animal diseases was tetracycline (76.9%), followed by ampicillin (72.5%). Although, 90.1% of the animal farm owners heard about antibiotics and antibiotic resistance from different sources, they did not know the factors contributing to the transmission of resistant bacteria to humans and the impact of antibiotic resistance on human and animals' health. Using the mean score 4.44 ± 0.15 as the cut-off, half of the animal farm owners/workers had good knowledge about antimicrobial resistance and use. 52.5% of animal farm owners/workers had positive attitudes towards wise antibiotic use and resistance with a mean score of 28.4 ± 0.5. However, 52.75% participants had poor practice with the mean score of practice 4.95 ± 0.17. Better knowledge, positive attitudes and better practices on antibiotic use and resistance were associated with farm owners/workers who engaged in higher education. Although poor awareness on antimicrobial resistance was perceived by 76.9% of respondents as very important factors that contribute to increasing antibiotic resistance, increasing the use of complementary treatments was perceived by the majority of respondents as very important strategies that contribute to reduce antibiotic use and resistance. The current study disclosed that there is low level of awareness among animal farm owners about the correct use of antibiotics and resistance. It is necessary to raise awareness, develop and implement interventions to reduce antimicrobial use and antibiotic resistance in the study area., (© 2021. The Author(s).)

Introduction: We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection., Methods: Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed., Results: Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3-7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin)., Discussion: Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

In this work, mesoporous TiO 2 -modified ZnO quantum dots (QDs) were immobilised on a linear low-density polyethylene (LLDPE) polymer using a solution casting method for the photodegradation of tetracycline (TC) antibiotics under fluorescent light irradiation. Various spectroscopic and microscopic techniques were used to investigate the physicochemical properties of the floating hybrid polymer film catalyst (8%-ZT@LLDPE). The highest removal (89.5%) of TC (40 mg/L) was achieved within 90 min at pH 9 due to enhanced water uptake by the LDDPE film and the surface roughness of the hybrid film. The formation of heterojunctions increased the separation of photogenerated electron-hole pairs. The QDs size-dependent quantum confinement effect leads to the displacement of the conduction band potential of ZnO QDs to more negative energy values than TiO 2 . The displacement generates more reactive species with higher oxidation ability. The highly stable film photocatalyst can be separated easily and can be repeatedly used up to 8 cycles without significant loss in the photocatalytic ability. The scavenging test indicates that the main species responsible for the photodegradation was O 2 ● - . The proposed photodegradation mechanism of TC was demonstrated in further detail based on the intermediates detected by LC-time-of-flight/mass spectrometry (LC/TOF-MS).

Encapsulation of probiotic bacteria can enhance their functionality when used in combination with antibiotics for treating intestinal tract infections. The interaction strength of encapsulating shells, however, varies among the encapsulation methods and impacts encapsulation. Here, we compared the protection offered by encapsulating shells with different interaction strengths toward probiotic Bifidobacterium breve against simulated gastric fluid and tetracycline, including protamine-assisted SiO 2 nanoparticle yolk-shell packing (weak interaction across a void), alginate gelation (intermediate interaction due to hydrogen binding), and ZIF-8 mineralization (strong interaction due to coordinate covalent binding). The presence of encapsulating shells was demonstrated using X-ray-photoelectron spectroscopy, particulate microelectrophoresis, and dynamic light scattering. Strong interaction upon ZIF-8 encapsulation caused demonstrable cell wall damage to B. breve and slightly reduced bacterial viability, delaying the growth of encapsulated bacteria. Cell wall damage and reduced viability did not occur upon encapsulation with weakly interacting yolk-shells. Only alginate-hydrogel-based shells yielded protection against simulated gastric acid and tetracycline. Accordingly, only alginate-hydrogel-encapsulated B. breve operated synergistically with tetracycline in killing tetracycline-resistant Escherichia coli adhering to intestinal epithelial layers and maintained surface coverage of transwell membranes by epithelial cell layers and their barrier integrity. This synergy between alginate-hydrogel-encapsulated B. breve and an antibiotic warrants further studies for treating antibiotic-resistant E. coli infections in the gastrointestinal tract.

Purpose: Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this study was to evaluate the pharmacokinetic interaction between tegoprazan and triple-antibiotic therapy containing metronidazole, tetracycline, and bismuth., Methods: An open-label, 2-cohort, randomized, multiple-dose, crossover study was conducted in healthy subjects. In cohort 1, tegoprazan (100 mg/d) was administered orally with or without triple-antibiotic therapy (1500 mg/d metronidazole, 2000 mg/d tetracycline, and 1200 mg/d bismuth) for 7 days in each period. In cohort 2, triple-antibiotic therapy was administered orally with or without tegoprazan for 7 days in each period. Pharmacokinetic blood samples were collected within 24 h after the last dose. Safety assessments were performed., Findings: Eleven cohort 1 subjects and ten cohort 2 subjects were included in the pharmacokinetic analysis. The AUC τ and C max at steady state geometric mean ratios (90% CIs) were 0.78 (0.73-0.83) and 0.75 (0.68-0.82) for tegoprazan; 0.77 (0.68-0.88) and 0.84 (0.72-0.98) for tegoprazan metabolite M1; 1.03 (0.98-1.08) and 1.08 (0.99-1.18) for metronidazole; 0.63 (0.56-0.70) and 0.64 (0.56-0.74) for tetracycline; and 1.55 (0.99-2.44) and 1.38 (0.72-2.66) for bismuth, respectively. All reported adverse events were mild., Implications: Changes in the tegoprazan, tetracycline, and bismuth pharmacokinetic parameters were detected after concurrent administration. These changes were considered mainly due to the pharmacodynamic effect of tegoprazan. The adverse events were predictable and reported as frequent adverse events during triple-antibiotic therapy. There were no significant differences in safety or tolerability between quadruple therapy, including tegoprazan and triple-antibiotic therapy. ClinicalTrials.gov identifier: NCT04066257., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation., Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy., Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line., Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases., Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile., (© 2020 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background: The purpose of this study was to evaluate the long-term patient experience with tetracycline injections for treatment of festoons., Methods: Charts of all patients undergoing tetracycline injection for treatment of lower eyelid festoons at the Cole Eye Institute, Cleveland Clinic, between 2008 and 2018 were identified using billing records. Patients were invited to participate in a questionnaire based on the FACE-Q checklist, a previously validated questionnaire for studying cosmetic procedure outcomes. Data from the questionnaire were summarized with size, mean, and frequency., Results: One hundred two patients who received tetracycline injection during the study period were identified and 61 responses were obtained. The average follow-up time after injection was 3.6 years. Of 61 respondents, 36 (59 percent) noted improvement in their festoons after treatment, and 27 of 33 (82 percent) noted that improvement occurred within 2 months of treatment. Overall, 40 of 60 respondents (67 percent) would consider repeating tetracycline treatment. The most common adverse effects included discomfort (18 percent), swelling (15 percent), and bruising (13 percent). There was no statistically significant difference in questionnaire responses between men and women, except that men were more likely to consider repeated injection (92 percent versus 58 percent; p = 0.005)., Conclusion: Tetracycline injection appears to improve festoons in a majority of patients, with an acceptable side-effect profile, although more data are needed to determine the optimal dose and frequency and to identify possible rare and/or significant side effects.

Purpose: Comparisons between clinical features of tetracycline-induced pseudotumor cerebri (PTC-T) and those of idiopathic intracranial hypertension (IIH) are absent in the literature. We hypothesized that significant clinical differences between these etiologies exist and could be better understood by retrospective analysis., Design: Retrospective cohort study., Methods: We reviewed patients diagnosed with pseudotumor cerebri syndrome (PTCS) at our center and identified those who developed PTC-T after treatment with a tetracycline-class antibiotic and those with IIH. Groups were compared by demographics, body mass index, ophthalmic examination, treatment, clinical course, and visual outcomes., Results: We identified 52 cases of PTC-T and 302 cases of IIH. Obesity rates were significantly different (43.8% for PTC-T vs 79.2% for IIH, P < .001). The mean age at diagnosis was younger for PTC-T (19.8 years vs 28.1 years for IIH, P < .001). Diplopia was more common with PTC-T (40.4% vs 20.1% for IIH, P = .001). The mean illness duration was shorter for PTC-T (18.3 weeks vs 62.9 weeks for IIH, P <.0001). Recurrence rates were significantly different (4.0% for PTC-T vs 16.5% for IIH, P <.001). The frequency of surgical intervention was similar. Vision loss was uncommon but occurred with similar frequency., Conclusion: We identified significant clinical differences but also identified important similarities between the 2 groups. There appear to be nonobese patients who develop PTC-T, discontinue the antibiotic, and never develop PTCS again. There are other patients who develop PTC-T, discontinue the antibiotic, and later develop IIH. We conclude that PTC-T represents a spectrum of disease in susceptible individuals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Oral tetracyclines are the most widely prescribed systemic antibiotic for acne. Synthesis of efficacy and safety of traditional and novel oral tetracyclines is highly informative to clinical practice. We conducted a systematic search of PubMed to identify large interventional and observational studies utilizing oral tetracyclines as an acne treatment. We identified 13 articles meeting inclusion for this review, which represented 226,019 pediatric and adult acne patients. Oral tetracyclines that were included in this systematic review were sarecycline (a novel narrow-spectrum tetracycline), doxycycline, minocycline, and tetracycline. Based on shared and divergent outcome measures, different oral tetracyclines were variably effective against facial acne. Sarecycline also demonstrated efficacy in truncal acne. Members of the oral tetracycline class also differed in their ability to minimize antibiotic resistance and gut dysbiosis. J Drugs Dermatol. 2020;19:11(Suppl):s4-11.

Aim: To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for Helicobacter pylori infection., Methods: This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with H. pylori infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of H. pylori ., Results: In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, P = .37), modified intention-to-treat (96.2% vs. 96%, P > .99), and per-protocol (96.2% vs. 96.9%, P > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies., Conclusion: Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the H. pylori infection in regions with high clarithromycin and metronidazole resistance.

Spatiotemporally regulated targeted gene manipulation is a common way to study the effect of gene variants on phenotypic traits, but the Cre/loxP and Tet-On/Tet-Off systems can affect whole-organism physiology and function due to off-target effects. We highlight some of these adverse effects, including whole-body endocrinology and disturbances in the gut microbiome and in mitochondrial and metabolic function., (© 2020 Wüst et al.)

Background: Bismuth-containing quadruple therapy is widely used as second-line treatment for Helicobacter pylori infection. This prospective study investigated the changes in the annual H. pylori eradication rates of quadruple therapy., Methods: This study included an intention-to-treat (ITT) population of 452 subjects who failed first-line eradication therapy for H. pylori between 2003 and 2018. All subjects received a 14-day course of bismuth-containing quadruple therapy consisting of esomeprazole (40 mg twice daily), metronidazole (500 mg thrice daily), bismuth subcitrate (120 mg four times daily), and tetracycline (500 mg four times daily). Per-protocol (PP) analysis of data was performed in subjects who followed up with strict treatment adherence. Eradication was confirmed based on the results of the 13 C-urea breath test, rapid urease test (CLOtest ® ), and histopathologic evaluation. Compliance and adverse effects were also investigated. A minimal inhibitory concentration test was performed on tissue samples obtained from 103 subjects., Results: The overall eradication rates following ITT and PP analyses were 78.8% (356/452) and 89.5% (314/351), respectively. The annual eradication success rate did not show significant changes (P = .062 [ITT], P = .857 [PP]) over the 15-year study period. Adverse events were reported in 57.3% of the ITT population. The rates of resistance to metronidazole and tetracycline were 44.7% and 18.4%, respectively., Conclusions: Despite high antibiotic resistance rates, no significant reduction in annual eradication rates was observed during the study period., (© 2020 John Wiley & Sons Ltd.)

To evaluate the micro-ecological effects of tetracycline residues on tobacco soil, high-throughput sequencing technology was used to study the effects of the addition of different concentrations (0, 5, 50, and 500 mg·kg -1 ) of tetracycline on the abundance, diversity, and structure of bacterial and fungal communities in the rhizosphere and non-rhizosphere soil of flue-cured tobacco in China. Results showed that the presence of tetracycline had an important but varying effect on soil bacterial and fungal community richness, diversity, and structure. Changes in the diversity indices (Chao index and Shannon index) of soil bacterial and fungal communities showed a similar pattern after the addition of tetracycline; however, a few differences were found in the effects of tetracycline in the rhizosphere and non-rhizosphere soil, suggesting an evident rhizosphere-specific effect. The bacterial community at the phylum level in the rhizosphere closely clustered into one group, which might be the result of tobacco root secretions and rhizodeposition. Tetracycline showed a concentration-dependent effect on the soil bacterial community structure. The soil bacterial community structures observed after treatments with higher concentrations of tetracycline (50 and 500 mg·kg -1 ) were found to be closely related. Moreover, the effects of the treatments with higher concentrations of tetracycline, on the soil bacterial community at the phylum level, were different from those with lower concentrations of tetracycline (5 mg·kg -1 ), and CK treatments. This might have resulted from the induction of increasing selective pressure with increasing antibiotic concentration. Tetracycline continued to affect the soil bacterial community throughout the experiment. Tetracycline was found to have a varying impact on the community structure of soil fungi compared to that of soil bacteria, and the addition of an intermediate concentration of tetracycline (50 mg·kg -1 ) significantly increased the soil fungal diversity in the non-rhizosphere soil. The biological effects of tetracycline on the soil fungal community and the fungal-bacterial interactions, therefore, require further elucidation, warranting further research.

Many antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. The purpose of this systematic review was to determine the evidence behind alcohol warnings issued for many common antimicrobials. The search was conducted from inception of each database to 2018 using PubMed, Medline via Ovid, and Embase. It included studies that involved interactions, effects on efficacy, and toxicity/adverse drug reactions (ADR) due to concomitant alcohol consumption and antimicrobials. All interactions were considered in terms of three components: (i) alteration in pharmacokinetics/pharmacodynamics (PK/PD) of antimicrobials and/or alcohol, (ii) change in antimicrobial efficacy, and (iii) development of toxicity/ADR. Available data support that oral penicillins, cefdinir, cefpodoxime, fluoroquinolones, azithromycin, tetracycline, nitrofurantoin, secnidazole, tinidazole, and fluconazole can be safely used with concomitant alcohol consumption. Data are equivocal for trimethoprim-sulfamethoxazole. Erythromycin may have reduced efficacy with alcohol consumption, and doxycycline may have reduced efficacy in chronic alcoholism. Alcohol low in tyramine may be consumed with oxazolidinones. The disulfiram-like reaction, though classically associated with metronidazole, occurs with uncertain frequency and with varied severity. Cephalosporins with a methylthiotetrazole (MTT) side chain or a methylthiodioxotriazine (MTDT) ring, ketoconazole, and griseofulvin have an increased risk of a disulfiram-like reaction. Alcohol and antimicrobial interactions are often lacking evidence. This review questions common beliefs due to poor, often conflicting data and identifies important knowledge gaps., (Copyright © 2020 American Society for Microbiology.)

Background: Although antibiotic-induced hepatotoxicity is recoverable with mild impairment, and some cases were reported to cause morbidity. However, an adjuvant is essential in reducing such incidences., Objective: The aim of this study is to evaluate the protective effect of ascorbic acid on antibiotic induced liver toxicity using liver slices., Method: Fresh liver slices were incubated with different concentrations of sulfamethoxazole tetracycline and clavulanic acid along with ascorbic acid (200μg/ml) for 2 hours. The liver homogenate was assessed for markers like ALT, AST, MDA and CAT levels. Cytotoxicity assessment was performed using MTT assay., Results: Incubating liver slices with all three antibiotics shows elevated levels of aminotransferases, MDA and CAT enzyme when compared to the control groups which indicates the level of hepatotoxicity. In the presence of ascorbic acid, the elevated levels of TBARS, ALT and AST were significantly reduced which showcases the protective effect of ascorbic acid. The percentage survival of cell was also shown to have improved while accessed using cell viability assay., Conclusion: Obtained data suggests that consuming vitamin C or vitamin C containing food like citrus fruits or green leafy vegetables equivalent to 3g/day during antibiotic treatment, perhaps put down the risk of liver toxicity to a greater extent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The study reports the phenolic composition of propolis from Bangladesh and its ameliorative effects against tetracycline-induced hepatonephrotoxicity in rats. Male Wistar Albino rats (n = 18) were randomly divided into three following groups: (1) normal control, (2) tetracycline-treatment (200 mg kg -1  rat -1 ), and (3) tetracycline (200 mg kg -1  rat -1 ) + propolis (100 mg kg -1  rat -1 ) treatments. The ethanolic extract of propolis contained major phenolic acids as well as a flavonoid, rutin. Oral exposure to tetracycline caused severe hepatic and renal damage as indicated by significant alterations in liver marker enzymes in rat serum: bilirubin and protein concentrations, lipid profile, and markers of kidney function when compared with controls. The observed biochemical perturbations were accompanied by histopathological changes. Co-administration with propolis extract, however, prevented the changes in biochemical parameters, as revealed by maintenance of cell membrane integrity and regulation of lipid profile and the conservation of the histoarchitecture. PRACTICAL APPLICATIONS: Propolis is a resinous honeybee product which is becoming increasingly popular due to its potential contributions to human health. The phenolic compounds identified in propolis from Bangladesh were effective against tetracycline-induced hepatic and renal toxicity. Propolis may be a promising natural product in reducing the effects of chronic liver and kidney damage., (© 2019 Wiley Periodicals, Inc.)

Introduction and Objectives: quadruple therapy with bismuth is recommended as a first line treatment for Helicobacter pylori (H. pylori) infection. The aim of this study was to evaluate the compliance, adverse effects and effectiveness of this treatment with the new galenic three-in-one capsule formulation containing bismuth subcitrate, metronidazole and tetracycline (Pylera®)., Methods: a prospective, non-controlled, single center observational study was performed in a cohort of 200 consecutive patients with an untreated H. pylori infection; 58% were female. The subjects were treated for ten days with Pylera® of three capsules four times daily with meals and a proton pump inhibitor taken before breakfast and dinner. The Pylera® capsule contains 140 mg of bismuth subcitrate, 125 mg of metronidazole and 125 mg of tetracycline. The compliance and adverse effects of the treatment were evaluated via telephone contact and via an interview during the clinical revision. Eradication of infection was controlled for at least four weeks after treatment termination via the urea breath test, the stool antigen test with monoclonal antibodies or by histology., Results: treatment compliance was observed in 96% (192/200) of the patients. Only 28.5% (57/200) of the patients experienced adverse effects, which led to abandoning the treatment in only seven subjects. Severe adverse effects developed in only one case due to Clostridium difficile infection. The effectiveness based on intention to treat was 91.5% (183/200, 95% CI: 87.1-96.8) and per protocol was 95.2% (182/191, 95% CI: 90.9-98.9)., Conclusions: in our experience, Pylera® is an effective and safe treatment that should be considered as a first line therapeutic option for the eradication of H. pylori infection.

Drug-induced liver injury (DILI) is a major concern in clinical studies as well as in postmarketing surveillance. It is necessary to establish an animal model of DILI for thorough investigation of mechanisms of DILI and searching for protective medications. This article reviews the current status and future perspective on establishment of DILI models based on different hepatotoxic drugs, as well as the underlying mechanisms of liver function damage induced by specific medicine. Therefore, information from this article can help researchers make a suitable selection of animal models for further study.

Background: This systematic review assesses effects of paternal exposure to dermatologic medications by using the former US Food and Drug Administration (FDA) pregnancy categories as a benchmark., Objective: To assess whether systemic dermatologic medications can cause infertility and teratogenicity when taken by men., Methods: Categories D and X dermatologic medications were identified; a systematic review of the literature and reviews of the FDA Adverse Events Reporting System and prescribing information were performed to identify the effects of these medications on male fertility and teratogenicity. A secondary search was performed to assess for other systemic dermatologic medications causing teratogenicity or infertility following paternal exposure., Results: A total of 13 medications met the inclusion criteria. Of 1,032 studies identified, 19 were included after a systematic review of the literature. Studies evaluating medication effects with paternal exposure were identified for 10 of the 13 evaluated medications, and evidence of a negative effect was identified for 6 medications., Limitations: We did not encounter any studies for 3 medications that met the inclusion criteria. Information submitted to the FDA Adverse Events Reporting System may not reflect the incidence of side effects., Conclusions: Many former pregnancy category D and X systemic dermatologic medications also have effects on male fertility. More research and better-quality studies are required in this area, particularly studies assessing potential teratogenicity., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Microbial symbiosis is essential for the normal development and growth of hosts. Past attention has mostly been paid to its effects on plants and vertebrates. The effects of environmental pressures such as antibiotics on the microbiome of soil fauna remain largely elusive. We used bacterial 16S rRNA gene high-throughput sequencing to examine the response of microbiome of soil invertebrate Enchytraeus crypticus to oral tetracycline exposure. After two-week exposure, tetracycline-free oat was used as food to monitor the restoration of E. crypticus microbiome. The results showed that Proteobacteria, Actinobacteria and Planctomycetes were the three dominant phyla in all samples, Rhizobiaceae and Kaistia were the most abundant family and genus in all samples, respectively. After 14 days tetracycline exposure, Planctomycetes declined dramatically from 33.05% to 3.28% (P = 0.016), but Actinobacteria elevated substantially from 2.47% to 23.65% (P = 0.004). The alpha-diversity of microbial community increased significantly after tetracycline exposure compared to the control (P = 0.014). Terminating tetracycline exposure led to the recovery of E. crypticus microbiome back to the background level within 14 days. Our results suggest that while tetracycline can disturb the microbiome in E. crypticus significantly, the effects of the antibiotic on E. crypticus microbiome may not be permanent but reversibly diminish after stopping exposure for a period of time. The results may contribute to extending our understanding of the effect of antibiotics on microbiome of soil invertebrates. CAPSULE: The microbiome of E. crypticus exposed to tetracycline is perturbed and reversibly restored after terminating the exposure., (Copyright © 2018. Published by Elsevier B.V.)

Background: Bismuth quadruple therapy is the treatment of choice for the first-line therapy of Helicobacter pylori infection in areas of high clarithromycin resistance. Currently, the impact of the promising treatment on gut microbiota remains unclear., Aim: To investigate the short-term and long-term impacts of bismuth quadruple therapy on gut microbiota., Methods: Adult patients with H. pylori-related gastritis were treated with 14-day bismuth quadruple therapy. Fecal samples were collected before treatment at week 2, week 8, and week 48. Nucleic acid extraction from fecal samples was performed. The V3-V4 region of the bacterial 16S rRNA gene was amplified by polymerase chain reaction and sequenced with the MiSeq followed by data analysis using Qiime pipeline., Results: Eleven patients received complete follow-up. Before treatment, the most abundant phyla were Firmicutes (45.3%), Bacteroidetes (24.3%), Proteobacteria (9.9%), and Actinobacteria (5.0%). At the end of bismuth therapy, the relative abundances of Bacteroidetes and Actinobacteria decreased to 0.5% (P < .001) and 1.3% (P = .038), respectively. Additionally, the relative abundance of Verrucomicrobia also decreased from 3.2% to 1.11E-3% (P = .034). In contrast, the relative abundances of Proteobacteria and Cyanobacteria increased (P < .001 and P = .003, respectively). At week 8, the relative abundances of all phyla restored to the levels at baseline. The relative abundances of all phyla at week 48 also did not significantly differ from those at baseline. During eradication therapy, 6 patients (55%) reported at least 1 adverse event. The relative abundance of phylum Proteobacteria in patients with adverse effects was more than that in patients without adverse effects (68.7% ± 8.8% vs 43.4% ± 25.5%; P = .048)., Conclusions: Bismuth quadruple therapy for H. pylori eradication can lead to short-term dysbiosis of gut microbiota. The increase in Proteobacteria in gut microbiota may attribute to the development of adverse effects during bismuth quadruple therapy., (© 2018 John Wiley & Sons Ltd.)

Background: Clinical trials have shown a good efficacy of the "three-in-one" formulation of bismuth quadruple therapy (BQT) for Helicobacter (H.) pylori eradication. We aimed to assess the efficacy and safety of the three-in-one BQT in clinical practice, and investigate the effect of probiotic supplementation, in Italy., Materials and Methods: A retrospective database, multicentre observational study was conducted in seven Italian Hospitals. Consecutive H. pylori-positive patients who received the three-in-one BQT for 10 days were included in the analysis. H. pylori eradication was assessed by histology, 13 C-urea breath test, or stool antigen test. Compliance and adverse events were evaluated by interview., Results: A total of 376 patients were included in the intention-to-treat (ITT) and 352 in the per protocol (PP) analyses. One hundred and ninety-three subjects received probiotics supplementation. Overall, eradication rates were 90.2% (95% Confidence Interval (CI):86.7-93.0) in ITT and 94.6% (95% CI: 91.7-96.7) in PP analyses. The compliance was good (≥90% of treatment taken) in 94.9% of patients. The proportion of patients with a good compliance was not different with and without probiotics supplementation (94.8% vs 95.1%). Eradication rates were equally high for first-line (91.4%), second-line (87.5%), and third-line treatments (91.7%) in the ITT analysis (P = .48). Adverse events were reported by 32.4% of patients, but only 6.1% of patients discontinued treatment., Conclusions: The three-in-one BQT is highly effective and well tolerated for H. pylori eradication in daily clinical practice. Probiotics supplementation fails to improve compliance., (© 2018 John Wiley & Sons Ltd.)

Aim: To evaluate the efficacy and tolerability of tetracycline vs. high-dose amoxicillin in bismuth-based quadruple therapy for Helicobacter pylori(H. pylori) eradication., Methods: This randomized, open-label clinical trial included 228 patients with H.pylori infection and duodenal ulcer without a history of H.pylori treatment. Patients were randomly divided into two groups. The amoxicillin group received metronidazole 500mg, bismuth subcitrate 240mg, and amoxicillin 1000mg, all three times a day, plus omeprazole 20 mg twice a day, for 14 days. The tetracycline group received metronidazole 500mg three times a day; bismuth subcitrate240mg and tetracycline HCl 500mg, both four times a day; and omeprazole 20 mg twice a day, for 14 days. Evaluation for compliance and drug-relatedadverse effects were evaluated at the end of two weeks. Eight weeks after the end of treatment, the rate of H.pylori eradication was assessed by the C13urease breath test., Results: There were no significant demographic differences between the two groups. Eradication rate was higher with the amoxicillin-containing regimen than the tetracycline-containing regimen: 105/110 (95.51%; 95% confidence interval, 91.5%-99.3%) vs. 88/105 (83.8%; 95%CI, 76.7%-90.8%) by per-protocol analysis (p = 0.005) and 92.9% (95%CI, 88.1%-97.6%) vs. 76.5% (95%CI, 68.7%-84.2%) by intention-to-treat analysis (ITT, p = 0.001). Adverse effects were significant higher in the tetracycline groupthan in the amoxicillin group (65.2% vs. 43.4%; p = 0.001)., Conclusion: Bismuth-based quadruple therapy including high-dose amoxicillin and metronidazole achieved an acceptable rate of H.pylori infection eradication with good tolerance in patients with duodenal ulcer. This regimen can overcome treatment resistance in areas with high prevalence of metronidazole and clarithromycin resistance., Trial Registration: The Thai Clinical Trial Registry (TCTR) 20170623004., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the clinical effectiveness of cold-light whitening technique on tetracycline pigmentation teeth and aged extrinsic stain teeth., Methods: One hundred and fifty-two cases bleached by cold-light whitening technique were included in this study. The patients' teeth were divided into 3 groups: aged extrinsic stain teeth, mild tetracycline pigmentation teeth and moderate tetracycline pigmentation teeth. Visual determination of shade and Olympus crystaleye spectrophotometer were used to measure the tooth discoloration after bleaching. SPSS17.0 software package was used for statistical analysis., Results: Visual determination showed that the efficiency of aged extrinsic stain teeth was significantly higher than that of mild and moderate tetracycline teeth group (P<0.05). Colorimetric method showed that the △E of moderate tetracycline teeth was significantly lower than aged extrinsic teeth and mild tetracycline teeth (P<0.05) . The △E of cervix changed more significantly than that of central and incisal edge in both mild and moderate tetracycline teeth group (P<0.05)., Conclusions: The effect of cold-light whitening technique on aged extrinsic stain teeth is better than that of the tetracycline pigmentation teeth. Cold-light whitening technique can improve pigmentation of tetracycline teeth cervix．.

Aim: The aim of this study was to critically assess all available evidence suggesting an association between antibiotic exposure and new onset of inflammatory bowel disease (IBD)., Materials and Methods: This systematic review was conducted according to the PRISMA statement and eligible studies were identified through search of PubMed, Embase and the Cochrane Library. Data on patient demographics, antibiotic exposure and confounding factors were analyzed. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of eligible studies., Results: A total of 15 observational studies (10 case control and five cohort) including 8748 patients diagnosed with IBD were systematically reviewed. Antibiotic exposure was mostly associated with Crohn's disease but not with ulcerative colitis. In particular, penicillin's, cephalosporins, metronidazole and fluoroquinolones were most commonly associated with the onset of Crohn's disease. The impact of tetracycline-family antibiotics on the pathogenesis of IBD was not clear., Conclusion: There may be an association between antibiotic exposure and the development of IBD; especially Crohn's disease. Even though, clinicians should be cautious when prescribing certain antibiotic regimens to patients with a strong family history of IBD, it should be emphasized that available data are not granular enough to reach any definitive conclusions.

Background: Mycoplasma pneumoniae strains with resistance to macrolides have been spreading worldwide. Here, we aimed to clarify which antimicrobial agent is a better treatment for patients with M. pneumoniae pneumonia in a setting with large epidemics of macrolide resistance., Methods: Adult patients hospitalized with laboratory-confirmed M. pneumoniae pneumonia from 2010 to 2013 were identified from the Japanese Diagnosis Procedure Combination national database. Drug switching, length of stay (LOS), 30-day mortality, and total costs for patients who underwent macrolide, quinolone, and tetracycline therapy were compared using propensity score analyses., Results: Eligible patients (N = 1650) from 602 hospitals were divided into the macrolide group (n = 508), quinolone group (n = 569), or tetracycline group (n = 573). We found that 52.8%, 21.8%, and 38.6% of patients in the macrolide, quinolone, and tetracycline groups, respectively, had to switch drugs (P < .0001). There was no significant difference in the LOS and the 30-day mortality rates among these 3 groups. Cost was highest in the quinolone group (P = .0062). The propensity score-matched pairs (n = 487×2) generated from the quinolone and tetracycline groups also showed a lower proportion of patients who require switches in the quinolone group than in the tetracycline group (21.2% vs 39.6%, P < .0001) but not in the LOS, mortality, and cost., Conclusions: There were no significant differences in the LOS and mortality among any antimycoplasmal drugs as initial treatment for hospitalized M. pneumoniae pneumonia patients despite the lower switching rate in the quinolone group., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Aims: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice., Methods: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy. All patients received a rescue quadruple therapy with Pylera (3 capsules four times daily) and esomeprazole 20 mg (1 tablet twice daily) for 10 days. H. pylori eradication was assessed by using Urea Breath Test 4-6 weeks following therapy ending. H. pylori eradication rates, compliance, and side-effects were calculated., Results: A total of 208 patients in the 9 participating centres were enrolled. Overall, 180 patients were successfully cured from the infection, accounting for 86.5% (95% CI 81.9-91.2) and 92.3% (95% CI 88.6-96.1) eradication rates at intention-to-treat analysis and at per protocol analysis, respectively. Cure rates were similar across patients who failed one to three previous therapy attempts, but the success rate fell to 67% after 4 or more therapy failures. Compliance to therapy was good in 198 (95.2%) patients, whilst in 7 (5.3%) cases the therapy was interrupted within 5 days due to side effects. A total of 97 (46.6%) patients complained of at least one side effect; nausea, diarrhea and vomiting were the most frequently reported., Conclusions: Our study found that this bismuth-based quadruple therapy is highly effective as second-line and rescue therapy for H. pylori eradication in clinical practice.

Objective: To evaluate the efficacy and safety of a quadruple regimen (BMTO) of the "3-in-1 capsule" (containing bismuth subcitrate potassium, metronidazole and tetracycline) plus omeprazole in naïve and previously treated patients diagnosed with Helicobacter pylori (H. pylori) infection in the clinical setting in Seville (Spain)., Methods: This is a prospective study carried out on consecutive patients with a confirmed H. pylori infection and upper gastrointestinal symptoms. After providing their informed consent, the patients were treated for ten days with a 3-in-1 capsule containing bismuth subcitrate potassium (140 mg), metronidazole (125 mg) and tetracycline (125 mg: Pylera®), three capsules four times daily, plus omeprazole (20 or 40 mg) twice daily. Eradication of infection was determined by a negative urea breath test at least 28 days after the end of treatment., Results: A total of 58 consecutive patients were enrolled into this study, two of whom withdrew early due to vomiting on days three and five, respectively. In this cohort, 17 patients (29.3%) had a prior history of medication to treat H. pylori. In the intent-to-treat population, eradication was achieved in 97.6% (40/41) and 82.4% (14/17) of cases in patients treated with BMTO as a first-line or rescue therapy, respectively. At least one adverse event was reported by 28 (48%) patients, mostly mild effects (86%)., Conclusion: A ten day treatment with BMTO is an effective and safe strategy to combat confirmed H. pylori infection in patients.