One-week Regimen Research Articles

Sinomenine ameliorates bleomycin-induced pulmonary fibrosis by inhibiting the differentiation of fibroblast into myofibroblast

Idiopathic pulmonary fibrosis (IPF) represents a severe interstitial lung disease characterized by limited therapeutic interventions. Recent study has suggested that sinomenine (SIN), an alkaloid derived from the roots of Sinomenium acutum, demonstrates efficacy in interrupting aerobic glycolysis, a predominant metabolic pathway in myofibroblasts. However, its pharmacological potential in the context of pulmonary fibrosis remains inadequately explored. In the present study, we established a bleomycin (BLM)-induced pulmonary fibrosis mouse model and subjected the mice to a one-week regimen of SIN treatment to assess its efficacy. Additionally, a TGF-β1-induced primary lung fibroblast model was employed to investigate the molecular mechanism underlying the effects of SIN. Our observations revealed robust anti-pulmonary fibrosis properties associated with SIN treatment, as evidenced by reduced extracellular matrix deposition, diminished hydroxyproline contents, improved Ashcroft scores, and enhanced lung function parameters. Furthermore, SIN administration significantly impeded TGF-β1-induced fibroblast-to-myofibroblast differentiation. Mechanistically, SIN exerted its beneficial effects by mitigating aerobic glycolysis, achieved through the inhibition of the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (Pfkfb3). Notably, the protective effects of SIN on fibroblasts were reversed upon ectopic overexpression of Pfkfb3. In conclusion, our data underscore the potential of SIN to attenuate fibroblast-to-myofibroblast differentiation by modulating Pfkfb3-associated aerobic glycolysis and SIN emerges as a promising anti-fibrotic agent for pulmonary fibrosis in clinical practice.

Comparing Intradermal (ID) Rabies Vaccination with Conventional IM Regimen on Humoral Response of New Zealand White Rabbits for the Production of Animal-Derived Polyclonal Antibodies.

In developing countries, it is imperative to implement cost-effective strategies for animal humoral response development in the production of antiserum. This study compared the effect of immunization regimens on the humoral immune response of New Zealand White (NZW) rabbits (N = 24) using cell culture rabies vaccine (CCRV) through intradermal (ID) and traditional intramuscular (IM) routes. The rabbits were divided into three experimental groups: (a) IPC-R2 with a two-site one-week regimen; (b) TRC-R3 with a two-site twenty-eight-day regimen; and (c) Alternate-R4 with a four-site one-week regimen. These regimens were then compared to the standard IM schedule of five doses of rabies vaccine administered at days 0, 3, 7, 14, and 28 in control group R-1. The results were evaluated at days 14 and 35 postvaccination using rabies-specific Platelia II™ ELISA kit method. The results showed a better response to the ID regimen than the IM route regarding immunogenicity and volume consumption of the vaccine. The three selected ID regimes showed significantly higher mean titer values than the control IM regimen group R-1 (p < 0.001). The study aims to explore simple immunization strategies to enhance the RV-specific antibody titers for immunization donor animals. This method would produce polyclonal antibodies and strengthen local production of polyclonal antibodies in Pakistan to deal with vaccine and rabies immunoglobulin (RIG) shortage, thus providing effective postexposure prophylaxis (PEP) for better control of rabies in developing countries.

Palliative radiotherapy: a one-week course in advanced head and neck cancer – quality of life outcomes

ObjectivesPalliative radiotherapy regimens for advanced head and neck cancers vary in doses and treatment times. Their quality of life (QoL) implications are not clearly established.MethodsWe randomised patients with advanced, non-metastatic,...

Repeated remote ischaemic preconditioning can prevent acute mountain sickness after rapid ascent to a high altitude

ABSTRACT Background This study assessed the effectiveness of 4 different repeated remote ischaemic preconditioning (RIPC) protocols varying in duration and frequency for preventing acute mountain sickness (AMS) after rapid ascent to high altitude. Methods In a randomized but not blinded design, participants were assigned to receive either of the four RIPC treatments at low altitude (Group A, once daily for 1 week; Group B, twice daily for 1 week; Group C, once daily for 4 weeks; and Group D, twice daily for 4 weeks) or control (no specific sham treatment). Participants were then flown to a high altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. Results A total of 250 participants (50 per group; mean age 38.56 ± 0.76 years) were included. The overall AMS incidence was 26.4%. A total of 20 AMS cases (40%) occurred in the control group, 15 cases (30%) both in the RIPC A and RIPC B groups (RR 1.3; 95%CI 0.8-2.3; χ2 = 1.099; p = 0.29), and 8 cases (16%) both in the RIPC C and D groups (RR 2.5; 95%CI 1.2 - 5.2; χ2 = 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups (F = 6.51, p < 0.001). The scores of gastrointestinal symptoms (F = 7.42, p < 0.001) and dizziness (F = 9.82, p < 0.001) but not headache (F = 0.60, p > 0.05) were lower in the RIPC groups compared to control. The blood oxygen saturation level (SpO2) decreased less in the RIPC B, C and D groups compared to control after arrival at a high altitude (F = 11.42, p < 0.001). The number of RIPC treatments received was moderately correlated with SpO2 (R = 0.38, p < 0.001), and SpO2 was moderately inversely correlated with the LLS (R = –0.48, p < 0.001). Conclusion This study demonstrated that a four-week RIPC intervention but not a one-week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to these results.

Efficacy of Triple Therapy of Vonoprazan, Amoxicillin, and Sitafloxacin as the Third-Line Regimen for Helicobacter pylori Eradication in Japan

Introduction: In Japan, the increase in bacterial resistance to clarithromycin caused a decline in the eradication rate of first-line therapy. Although second-line therapy using metronidazole has higher eradication rate until now, increase of the number of patients who receive H. pylori eradication therapy resulting in the increase of patients who failed to respond to both first- and second-line therapy. Triple therapy of PPI, amoxicillin (AMOX) and sitafloxacin (STFX) has been shown as a preferable third-line therapy. Vonoprazan (VPZ), a novel oral potassium-competitive acid blocker, has higher acid-inhibitory effects comparing with PPIs. The aim of this study was to investigate the efficacy of the triple therapy of VPZ, AMOX and STFX for the treatment of H. pylori infection in patients who failed both first- and second-line therapy. Methods: 49 H. pylori-positive patients who had failed both first-line therapy (PPI or VPZ + AMOX + clarithromycin) and second-line therapy (PPI or VPZ + AMOX + metronidazole) were enrolled into the study. Prior to the third-line therapy, patients underwent endoscopy to obtain H. pylori strains to test the susceptibility to antibiotics if they agreed. VPZ (20 mg bid), AMOX (750 mg bid) and STFX (100 mg bid) were administered for 1 week and the result was tested by one of 13C-UBT or stool antigen test 6-10 week after finishing the treatment. Results: One patient did not hope third-line therapy after she was told about the low susceptibility to STFX. No major adverse effects were seen and all the 48 patients completed the one-week regimen. The eradication rate of PCAB-AMOX-STFX was 85.7% (42/49; 95% CI, 75.9-95.5%) by intention-to-treat analysis and 87.5% (42/48; 78.4-96.9%) by per protocol analysis. H. pylori was isolated from 19 patients before starting the triple therapy of PCAB, AMOX and STFX. Eradication was unsuccessful in one of two patients whose strains had low sensitivity to AMOX (MIC 0.25≤ mg/mL) and three patients whose strains showed STFX MICs of 0.5≤ mg/mL. In contrast, eradication therapy was successful in 13 patients infected with strains which were sensitive to both AMOX and STFX. Conclusion: Triple therapy of VPZ, AMOX and STFX would be an effective third-line H. pylori eradication therapy in Japan. Bacterial low susceptibility to AMOX and STFX would be a major cause of the treatment failure.

Rescue Therapy Using a Rifabutin-Based Regimen is Effective for Cure ofHelicobacter pyloriInfection

To evaluate the efficacy of rescue therapy using rifabutin, amoxicillin and a proton pump inhibitor (PPI) in the eradication of Helicobacter pylori in patients who have failed at least one course of PPI-based triple therapy. The present study was a single-centre case series of 16 consecutive patients who had received at least one course of standard eradication therapy. Pretreatment evaluation included endoscopy with biopsies for histology and culture for H pylori infection. Treatment consisted of a one-week regimen containing a PPI twice daily, amoxicillin (A) 1 g twice daily and rifabutin (R) 300 mg once daily (PPI-AR). Post-treatment evaluation consisted of a repeat endoscopy with biopsy for histology and culture, or a validated urea breath test at least four weeks after treatment was completed. Pretreatment antibiotic susceptibility to metronidazole, clarithromycin and A was evaluated using a validated epsilometer test. Of the 16 patients, four had previously received one course of triple therapy, 10 had received two courses and two had received more than two courses. The overall success rate of PPI-AR was 63% (10 of 16). Resistance to A was 0% (0 of 13), metronidazole 77% (10 of 13), clarithromycin 70% (seven of 10), and both metronidazole and clarithromycin 60% (six of 10). There was no correlation between resistance patterns and cure rate. An R-containing regimen such as PPI-AR is a viable option as rescue therapy for H pylori infection.

Furazolidone-based, metronidazole-based, or a combination regimen for eradication of Helicobacter pylori in peptic ulcer disease.

Furazolidone has been effective against Helicobacter pylori in Iran, with no resistance, but with intolerable side effects in the second week. One-week regimens have not been useful here. We compared the efficacy and side effect profiles of three anti-H. pylori regimens. Patients with peptic ulcer disease and positive H. pylori infection were randomly allocated into three groups. The patients in group A received omeprazole 20 mg + amoxicillin 1g + metronidazole 500 mg, and bismuth subcitrate 240 mg twice daily each, for two weeks; the patients in group B received the same regimen but metronidazole was replaced by furazolidone 200 mg twice daily; and the patients in group C received regimen B for the first week and regimen A for the second week. H. pylori eradication was verified with 13C-urea breath test at the tenth week. Three hundred and fourteen patients were enrolled; 107, 104, and 103 patients in groups A-C, respectively but 278 patients completed the study. Seven, three, and six patients discontinued their medication in groups A-C, respectively. Fever, dizziness, and weakness were more common in group B than group C (P < 0.05). Vomiting, pruritus, and rash were more common in group C than group A (P < 0.05). Per-protocol eradication rates were 83.1%, 95.2%, and 95.3% in groups A-C, respectively (P = 0.005, groups A and C). Intention to treat eradication rates were 74.5%, 87.0%, and 86.6% in groups A-C, respectively (P = 0.02, groups A and C). One-week furazolidone followed by one-week metronidazole regimen is as efficient as two-week furazolidone regimen but with fewer side effects. Furazolidone-based regimens are superior to metronidazole-based ones for H. pylori eradication in Iran.

Efficacy of one-day quadruple therapy for H pylori infection in Chinese patients

To compare the efficacies of one-day quadruple therapy and seven-day triple therapy in Chinese patients. Sixty consecutive patients with nonulcer dyspepsia and confirmed H pylori infection were randomized to receive either omeprazole 40 mg, amoxycillin 1 g, and furazolidone 100 mg, all twice a day for 7 d or omeprazole 20 mg (at breakfast and dinner), amoxicillin 1 g, furazolidone 200 mg, and colloidal bismuth subcitrate 220 mg four times for only one day. H pylori status was determined before and at least 5 weeks after therapy by endoscopy with antral and corpus biopsies for rapid urease test and histology. H pylori eradication was successful in 66.67% (20/30) patients in the 7-d group and in 36.67% (11/30) patients in the 1-d group (P = 0.037). Side effects were induced by the treatment in 13.3% (4/30) patients of each group, but these were all self-limiting, short-lasting, and did not require any specific treatment. The one-day quadruple therapy is less effective than the one-week regimen in curing H pylori infection in Chinese patients.

Sources of variation of Helicobacter pylori treatment success in adults worldwide: a meta-analysis.

A vast number of Helicobacter pylori treatment trials have been conducted. Regimens may vary in efficacy in different patient populations. We identified sources of treatment effect variation from 618 treatment groups using weighted cross-classified multi-level meta-regression models. Summary effect estimates were calculated within groups that lacked identified heterogeneity. Overall, treatment was less successful with shorter treatment duration and dual drug (versus triple or quadruple drug) therapies. For nitroimidazole-based regimens, treatment was less successful in populations with frequent childhood H. pylori infection or metronidazole resistance and more successful in northeastern Asia. Non-nitroimidazole treatments of longer duration and those from less recent reports were most successful. Some one-week regimens--(nitroimidazole/ tetracycline/bismuth, ranitidine bismuth citrate/amoxicillin/clarithromycin, and clarithromycin/amoxicillin/proton pump inhibitor) were highly successful in northeastern Asia regardless of metronidazole resistance. The most successful regimen in populations with both a high prevalence of metrondiazole resistance and frequent infection in children (metronidazole/furazolidone/amoxicillin) eliminated fewer than 70% of infections. More effective treatments are needed for most populations of the world where H. pylori infection in children and drug resistance are common. Current treatment guidelines do not coincide with the best treatment regimens identified in this meta-analysis.

Helicobacter pylori eradication therapy: Three different one-week regimen comparisons

Helicobacter pylori eradication therapy: Three different one-week regimen comparisons

Metronidazole resistance reduces efficacy of triple therapy and leads to secondary clarithromycin resistance.

There has been a significant increase in the prevalence of H. pylori resistance to metronidazole in recent years, while clarithromycin resistance is still relatively rare. In this study we assessed: (1) the effect of primary H. pylori resistance to metronidazole and clarithromycin on the clinical efficacy of a one-week regimen consisting of omeprazole, metronidazole, and clarithromycin; and (2) the rate of acquisition of secondary antimicrobial resistance after treatment failure. Eighty-seven patients with duodenal ulceration or nonulcer dyspepsia were included in the study. The primary metronidazole and clarithromycin resistance rates were 35.6% and 3.4%, respectively (all three pretreatment clarithromycin resistant strains had concurrent metronidazole resistance). H. pylori was eradicated in 81.6% of patients. The eradication rate for fully sensitive isolates was 98.2% (55/56) but was significantly reduced to 57.1% (16/28) for isolates that were resistant to metronidazole alone and 0% (0/3) in cases of dual resistance (P < 0.001). Secondary resistance to clarithromycin was acquired in 58.3% of cases of treatment failure. In areas of high prevalence of primary metronidazole resistance, this is a significant cause of treatment failure with this triple therapy regimen. This leads to the selection of strains with dual resistance that are difficult to eradicate and may contribute to an increase in the prevalence of clarithromycin resistance. In such areas an alternative first-line treatment should be prescribed.