Senna

BACKGROUND: Over-the-counter supplements are commonly used to manage chronic constipation; however, their efficacy remains unclear. We aimed to investigate the effect of food, vitamin or mineral supplements on stool output, gut transit time, symptoms, and quality of life in adults with chronic constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Studies were identified using electronic databases, backward citation, and hand-searching abstracts. RCTs reporting administration of food supplements (e.g., fruit extract supplements), vitamin or mineral supplements in adults with chronic constipation were included. Studies administering whole foods (e.g., fruits) were excluded. Risk of bias (RoB) was assessed with Cochrane RoB 2.0. Relative risks (RR), mean differences (MD), or standardized mean differences (95% confidence intervals [CI]) were calculated using a random-effects model. KEY RESULTS: Eight RCTs (787 participants) were included, investigating kiwifruit (n = 3 RCTs), senna (n = 2), magnesium oxide (n = 2), Ziziphus jujuba (n = 1), and Malva Sylvestris (n = 1) supplements. Kiwifruit supplements did not impact stool frequency (MD 0.24 bowel movements/week [-0.32, 0.80]; p = 0.40) or consistency (MD -0.11 Bristol points [-0.31, 0.09], p = 0.29). Overall, 61% responded to senna and 28% to control; however, this did not reach statistical significance (RR 2.78, [0.93, 8.27]; p = 0.07). Overall, 68% responded to magnesium oxide and 19% to control (RR 3.32 [1.59, 6.92]; p = 0.001). Magnesium oxide improved stool frequency (MD 3.72 bowel movements/week [1.41, 6.03]; p = 0.002) and consistency (MD 1.14 Bristol points [0.48, 1.79]; p = 0.0007). CONCLUSIONS AND INFERENCES: Magnesium oxide supplements are effective at improving cardinal symptoms of chronic constipation. Senna and kiwifruit supplements did not impact symptoms; however, findings were based on a small number of studies. Further research is required to investigate the effect of food supplements (e.g., kiwifruit supplements), as well as their whole food equivalents (e.g., whole kiwifruits) in chronic constipation. © 2023 The Authors. Neurogastroenterology &

2. BMJ Open. 2026 Feb 5;16(2):e104706. doi: 10.1136/bmjopen-2025-104706. Feasibility of a phase 3 partially randomised clinical trial to assess the safety and efficacy of paediatric praziquantel for schistosomiasis treatment in children aged 3 months to 6 years in endemic regions of Brazil: a pil

BACKGROUND: Baricitinib, a Janus kinase inhibitor with an established safety profile across multiple indications, has demonstrated efficacy in the treatment of severe alopecia areata with high maintenance of response during the initial treatment extension period. OBJECTIVES: To evaluate efficacy and safety of baricitinib for adults with severe alopecia areata through 152 weeks of continuous therapy. METHODS: The analysis includes patients from the BRAVE-AA1 and BRAVE-AA2 phase 3, randomized, double-blind, clinical trials: adults with Severity of Alopecia Tool (SALT) scores ≥50 who achieved SALT score ≤20 at week 52 (responders) and were continued on the same dose of baricitinib up to 152 weeks. RESULTS: Among week 52 responders who were continuously treated with baricitinib 4 mg or baricitinib 2 mg, 115 of 129 (89.1%) and 56 of 67 (83.6%), respectively, maintained SALT score ≤20 at week 152. The incidence rate of adverse events of special interest relative to earlier safety reports, remained consistent. LIMITATIONS: The analysis does not include outcomes of patients without SALT score ≤20 response at week 52, who continued therapy post-week 52. CONCLUSIONS: Over 152 weeks, patients stably maintained and extended their regrowth across scalp, eyebrows, and eyelashes with continued baricitinib treatment. There were no new safety signals.

BACKGROUND: Behavioral therapy using electromyography-based biofeedback (BIO) and botulinum toxin type A (BTA) injections are potential treatments for managing awake bruxism (AB) in patients with temporomandibular disorders (TMD). The aim of this study was to compare the effectiveness of BIO and BTA in reducing AB behaviors, pain intensity, and psychosocial distress in individuals with TMD. METHODS: This single-center, single-blind, parallel-group randomized clinical trial enrolled 40 adults with TMD diagnosed with AB. AB was assessed using the Oral Behavior Checklist (OBC) and smartphone-based Ecological Momentary Assessment (EMA). Participants presenting an AB frequency of ≥ 60% were randomly allocated to receive BIO or BTA intervention. Pain intensity was measured by the Characteristic Pain Intensity (CPI) score, and psychosocial status was evaluated using the Patient Health Questionnaires (PHQ-9, PHQ-15) and the Generalized Anxiety Disorder questionnaire (GAD-7). Assessments were conducted at baseline, and at 1-, 3-, and 6-month follow-ups. Statistical analyses included Mann-Whitney U for AB behaviors, Wilcoxon Signed Rank test for within-group comparisons, and the Kruskal-Wallis test followed by the Dwass-Steel-Critchlow-Fligner post hoc test for between-group comparisons. RESULTS: Intra-group comparisons showed a significant reduction in BIO group for sustained teeth contact (BIO: p = 0.004) and EMA-assessed AB global behavior (BIO: p = 0.008). No significant improvements were found in BTA group for the same variables in all follow-ups (p > 0.05). However, no significant differences were found between groups in all follow-ups for OBC and EMA scores (p > 0.05). Similarly, there were no significant differences between groups for CPI (p = 0.39) or psychosocial outcomes (p > 0.05). CONCLUSION: Even though neither intervention improved pain nor psychosocial outcomes, BIO significantly reduced AB behaviors, indicating that BIO may be preferable for controlling AB behaviors in TMD patients. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC), RBR-62cftbp. Registered on January 9, 2024. © 2025. The Author(s).

BACKGROUND: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia with generally poor prognosis if untreated and no approved treatment options. OBJECTIVE: The aim of this study was to evaluate changes in the molecular signature of FFA lesions after application of delgocitinib cream. Safety, tolerability, and efficacy were also investigated. METHODS: This was a phase 2a, randomized, double-blind, exploratory trial of 20 mg/g delgocitinib cream (2%) versus cream vehicle in patients with FFA. RESULTS: A total of 30 adult females with FFA were randomized to delgocitinib cream (n = 15) or cream vehicle (n = 15). After 12 weeks, expression of the T helper 1-related biomarker CXCL9 was significantly downregulated (-3.10; P < .05), whereas there were nonsignificant reductions in CXCL10 (-2.60; P < .1) and IFN-γ (-1.49; P = .22) in lesions treated with delgocitinib cream but not cream vehicle. Delgocitinib-treated lesions had a small but significant mean improvement in transcriptomic profile (4%; P < .001), whereas lesions treated with cream vehicle worsened (33%). Delgocitinib cream was well-tolerated and associated with improvements in exploratory clinical severity endpoints. LIMITATIONS: Limitations of the trial include small sample size, biomarker analyses only being conducted to week 12, and the exploratory nature of efficacy endpoints. CONCLUSION: Delgocitinib cream resulted in an improvement in the transcriptomic profile of lesions and may have potential as a topical treatment for FFA. This study is registered with NCT05332366.

OBJECTIVES: Inhibition of JAK-mediated signaling pathways leads to hair regrowth and improved quality of life in alopecia areata (AA) but may be associated with potential risks. This study assessed the benefit-risk profile of ritlecitinib, an oral selective JAK3/TEC family kinase inhibitor (JAK3/TEC), from the perspective of adult patients with AA to inform regulatory decisions. METHODS: We combined patient preference data from a discrete choice experiment involving 201 adults with AA in the United States and Europe, efficacy data for ritlecitinib 50 mg once daily and placebo from the ALLEGRO phase 2b/3 trial (NCT03732807) of ritlecitinib efficacy and safety, and safety data from an integrated safety analysis of 4 studies in AA. The discrete choice experiment included 6 treatment attributes: 3 benefits (chance of achieving ≥80% scalp hair coverage, moderate or normal eyebrows, and moderate or normal eyelashes) and 3 risks (3-year risks of serious infections, blood clots, and cancer). Choice probabilities were calculated using the estimated utility function. Weighted net benefit scores were calculated using multicriteria decision analysis. Stochastic multicriteria acceptability analysis assessed the impact of uncertainty and preference heterogeneity on net benefit conclusions. RESULTS: Ritlecitinib 50 mg had a higher weighted net benefit score than placebo with a predicted choice probability of 70.9% (95% CI 61.2%-77.5%), indicating that, on average, patients would likely evaluate benefits to outweigh risks. The probability of positive weighted net benefit based on the stochastic multicriteria acceptability analysis was 78%. CONCLUSIONS: Ritlecitinib 50 mg once daily demonstrated a positive benefit-risk profile compared with placebo in adult patients with AA.

BACKGROUND: Consuming only low-fiber food on the day before the procedure is recommended as standard practice for bowel cleansing in patients using polyethylene glycol (PEG). However, there have been few studies to date investigating the optimal dietary regimen for patients using the more cost-effective Sennoside A+B calcium before colonoscopy. The present study compares the quality of bowel preparation of patients following a clear diet and those following a low-fiber diet on the day before colonoscopy among patients using Sennoside A+B calcium. METHODS: This prospective, randomized, and investigator-blinded study was conducted between November 2023 and February 2024. Included in the study were 150 patients aged 18 years and over with a mean age of 55.6±14 years, with 75 patients assigned to the clear diet group and 75 patients to the low-fiber diet group. The assessment of colonoscopy cleanliness before colonoscopy was conducted using the Boston Bowel Preparation Scale (BBPS). RESULTS: None of the patients experienced intolerance. The mean overall total cleanliness score, measured using the BBPS, was 7.24±2.1, with 7.48 ± 2.1 in the low-fiber diet group and 7.0 ±2.1 in the clear liquid diet group. No significant difference in cleanliness was found between the 2 groups ( P =0.096). CONCLUSION: Patients using cost-effective Senna for bowel cleansing before colonoscopy can safely consume low-fiber foods on the day before the procedure. In the present study, a clear diet offered no benefit over a more comfortable and better-tolerated diet in terms of colon cleanliness.

BACKGROUND: The specific influence of whole gut transit time (WGTT) on microbiome dynamics and bile acid metabolism remains unclear, despite links between changes in WGTT and certain gastrointestinal disorders. Our investigation aimed to determine the impact of WGTT changes on the composition of the fecal microbiome and bile acid profile. METHODS: Healthy volunteers (n = 18) received loperamide, to decrease bowel movement frequency, and senna, a laxative, each over a 6-day period, in a randomized sequence, with a minimum 16-day interval between each treatment. Stool samples were analyzed for microbiome by shotgun sequencing and bile acid composition determined with high-performance liquid chromatography coupled to tandem mass spectrometry. Sera were examined for markers of bile acid synthesis. KEY RESULTS: Senna or loperamide decreased or increased WGTT, respectively. Treatment altered stool characteristics, bowel movement frequency, and stool weight. The senna-treated group had increased primary and secondary fecal bile acids; serum levels of fibroblast growth factor 19 were significantly reduced. Increasing WGTT with loperamide led to an increase in bile salt hydrolase genes, along with elevated bacterial species richness (p = 0.04). Thirty-six species exhibiting significant differences were identified, several of which have notable implications for gut health. WGTT displayed negative correlations with total primary (particularly chenodeoxycholic acid) and secondary bile acids (ursodeoxycholic acid and glycochenodeoxycholic acid). Treatment-induced changes in microbiome composition and bile acid metabolism reverted back to baseline within 16 days. CONCLUSION: Whole gut transit time changes significantly affect fecal microbiome composition and function, as well as bile acid composition and synthesis in healthy subjects. This consideration is likely to have long-term implications. © 2025 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

BACKGROUND: Etrasimod, an oral, selective sphingosine 1-phosphate 1, 4 and 5 receptor modulator approved for the treatment of ulcerative colitis, has been studied in immune-mediated inflammatory diseases, including alopecia areata (AA). OBJECTIVES: To evaluate the efficacy and safety of etrasimod in adults with moderate to severe AA. METHODS: This Phase 2, randomized, double-blind, placebo-controlled trial included patients (aged ≥18 years) with moderate to severe AA, defined as a Severity of Alopecia Tool (SALT) score of ≥25. Patients were sequentially enrolled into two cohorts. Cohort 1 included patients (SALT score of ≥50) randomized 2:1 to etrasimod 2 mg or placebo. Cohort 2 included patients (SALT score ≥25 to <95) randomized 4:1:2 to etrasimod 3 mg, 2 mg or placebo. Patients completed a 24-week double-blind and 28-week open-label extension period. The primary endpoint was percent change from baseline (%CFB) in SALT score at Week 24. Safety was monitored throughout the trial. RESULTS: Eighty patients were randomized to etrasimod 2 mg (n = 31), 3 mg (n = 25) or placebo (n = 24). At Week 24, least squares mean (SE) percent changes from baseline in SALT score for the etrasimod 2 mg, 3 mg and placebo groups were -13.8 (8.6), -21.4 (6.9) and 0.35 (8.9), respectively. The least squares mean difference (95% CI; P value) in SALT score %CFB of etrasimod 2 mg and 3 mg versus placebo was -14.1 (-38.9 to 10.6; p = 0.2579) and - 21.8 (-44.4 to 0.9; p = 0.0592), respectively; statistical superiority was not achieved. The proportions of patients achieving ≥30%, ≥50% or ≥75% improvement in baseline SALT score at Week 24 were generally numerically higher in etrasimod groups versus placebo. Treatment-emergent adverse events occurred in 67.7%, 80.0% and 78.3% of patients receiving etrasimod 2 mg, 3 mg and placebo, respectively, by Week 24. CONCLUSIONS: Etrasimod did not meet the primary and secondary efficacy endpoints, but efficacy was numerically higher with etrasimod than with placebo. The etrasimod clinical programme for AA has been discontinued. Etrasimod was well tolerated, and its safety profile was consistent with other etrasimod studies to date. TRIAL REGISTRATION: C

INTRODUCTION: No bowel preparation (BP) for colonoscopy achieves optimal efficacy and tolerability. Combining polyethylene glycol plus ascorbic acid (PEG-Asc) with adjuvants has been explored to enhance cleansing efficacy and reduce the required volume. The aim of this study was to evaluate whether adding 0.5 mg linaclotide to 1 L PEG-Asc (1 L-PEG/AL) improves superior cleansing compared with adding 24 mg senna (1 L-PEG/AS), which we previously reported to be noninferior to the standard regimen of 2 L PEG-Asc. METHODS: A multicenter, endoscopist-blinded, randomized controlled trial was conducted at 5 centers in Japan with outpatients scheduled for colonoscopy. The primary outcome was adequate BP, evaluated using the Boston Bowel Preparation Scale. Analyses were stratified based on low-risk and high-risk groups for inadequate BP. RESULTS: Between April 2022 and April 2023, 1,464 patients were randomized to the 1L-PEG/AL (n = 731) or 1L-PEG/AS (n = 733). The 1L-PEG/AL demonstrated higher adequate BP rates (92% vs 86%, P = 0.001) compared with 1L-PEG/AS. Both groups experienced similar adverse events and expressed high willingness for repeat BP (83% vs 81%, P = 0.49). In high-risk patients (n = 892), 1L-PEG/AL had significantly higher adequate BP rates (94% vs 86%, P < 0.001), whereas rates were comparably high in low-risk patients (n = 539) (94% vs 94%, P = 0.66). DISCUSSION: The linaclotide regimen was superior to the senna regimen reagrding BP efficacy without reducing tolerability. It can be a promising new option for BP, especially in patients at a high risk of inadequate BP.

BACKGROUND: This study determines the prognostic value of the luminal-like subtype in patients with hormone receptor-positive breast cancer and explores whether the efficacy of extended anastrozole therapy differs between patients with luminal A-like versus luminal B-like tumours. MATERIALS AND METHODS: The phase III DATA study (NCT00301457) examined the efficacy of 6 versus 3 years of anastrozole in postmenopausal women with early-stage hormone receptor-positive breast cancer who had received 2-3 years of tamoxifen. Patients with available formalin-fixed paraffin-embedded tissue blocks were identified and classified by immunohistochemical luminal-like subtype. Distant recurrence (DR) and breast cancer-specific mortality (BCSM) were compared by luminal-like subtype and treatment arm using competing risk methods. RESULTS: This study included 788 patients: 491 had a luminal A-like tumour and 297 had a luminal B-like tumour. The median follow-up time was 13.1 years. Patients with luminal B-like tumours experienced a higher risk of DR [subdistribution hazard ratio (sHR) 1.44, 95% confidence interval (CI) 1.03-2.01, P = 0.03] and BCSM (sHR 1.68, 95% CI 1.15-2.45, P = 0.008) than patients with luminal A-like tumours. The efficacy of extended anastrozole therapy differed between patients with luminal A-like tumours (DR: sHR 0.51, 95% CI 0.30-0.88, P = 0.02; BCSM: sHR 0.39, 95% CI 0.19-0.82, P = 0.01) and patients with luminal B-like tumours (DR: sHR 2.09, 95% CI 0.96-4.53, P = 0.06; BCSM: sHR 2.36, 95% CI 0.80-7.00, P = 0.12) (P-interaction = 0.03 and P-interaction = 0.06, respectively). CONCLUSION: In patients with hormone receptor-positive breast cancer, the luminal B-like subtype was associated with a significantly worse prognosis when compared with the luminal A-like subtype. Extended anastrozole therapy halved the risk of DR and BCSM in patients with luminal A-like tumours, whereas no effect was seen in patients with luminal B-like tumours.

Cassia angustifolia is a species of plant from the Senna family that has traditionally been used as a laxative in different herbal products and commercial medicines. Even though there are few documented drug-plant interactions, the use of C. angustifolia with different drugs may have additive effects, such as with other laxatives or potassium-depleting diuretics. Its use also increases peristalsis which, may reduce drug absorption. The combination with digoxin has been associated with an increased risk of digoxin toxicity, probably due to an increase in plasma digoxin concentrations and hypokalaemia. We present a case with supratherapeutic trough concentration of tacrolimus, an immunosuppressive agent, and a herbal product in a liver transplant patient after concomitant intake of tacrolimus and a herbal product based on C. angustifolia, suggesting a possible drug-lant interaction through by P-glycoprotein. We observed an increase in the patient's blood concentration 2.8-fold and the area under the curve at steady state 2.1-fold. This interaction could be of clinical relevance, given the dose-dependent side effects of tacrolimus, such as nephrotoxicity, neurotoxicity, hypertension, hyperglycaemia, or electrolyte alterations. © 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

OBJECTIVE: The synergism among extracts of Senna alata, Ricinus communis, and Lannea barteri, and their anti-infective activities were investigated. The data collected for the antimicrobial activity of the extracts combinations were interpreted to be one of the following categories: synergy; indifferent; additive; or antagonistic. The interpretation was made based on the fractional inhibitory concentration index (FICI) results. FICI of ≤ 0.5 indicates synergism, > 0.5 to 1 indicates additive effects, > 1 to ≤ 4 indifference, and > 4 is considered to be antagonism. RESULTS: Compared with the data of the individual extracts, the MIC values of the extract-extract combinations against all strains of the tested microorganisms were significantly lower, ranging from 0.97 to 1.17, 0.97 to 4.69, 0.50 to 1.17, 1.17 to 3.12 and 2.34 to 4.69 mg/mL for Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia and Candida albicans respectively. L. bateri aqueous-S. alata ethanol extracts and S. alata aqueous-R. cummunis ethanol extracts combinations showed a synergy effect against all the test microorganisms. The other combinations exhibited at least one additive effect. Neither antagonism nor indifference activity was observed. This study validates the relevance of combining these plants in treating infections by traditional medicine practitioners. © 2023. The Author(s).

BACKGROUND: Warfarin is underutilised in frail older people because of the fear of bleeding complications. Drug interactions are an independent bleeding risk factor. However, the extent to which potential drug interactions are taken into account at warfarin therapy initiation in frail patients is not known. OBJECTIVE: The objective of this study was to investigate the use of potentially interacting drugs increasing the bleeding risk before and after warfarin initiation in frail and non-frail patients. METHODS: We conducted an observational study including inpatients aged ≥ 60 years initiated on warfarin in a tertiary hospital in Adelaide, South Australia. Frailty status was assessed with the Reported Edmonton Frail Scale. Medication charts were reviewed before and after warfarin initiation. RESULTS: In total, 151 patients (102 non-frail and 49 frail) were included. Before warfarin initiation, the use of clopidogrel and acetaminophen was more common in frail patients compared with non-frail patients (25.5% vs 10.2%, p = 0.0135, 63.8% vs 35.7% p = 0.0014, respectively). The use of non-steroidal anti-inflammatory drugs, 9.2% in non-frail patients and 6.4% in frail patients before warfarin initiation, was completely stopped after warfarin initiation in both groups. The use of antiplatelet drugs decreased from 56.1% in non-frail patients and 66.0 % in frail patients to 12.2% and 14.9%, respectively. Instead, the use of drugs affecting the metabolism of warfarin or vitamin K increased in both groups. No statistically significant difference was seen in the exposure to interacting drugs between study groups after warfarin initiation. Acetaminophen, senna glycosides and cytochrome P450 2C9 inhibiting drugs were the most common interacting drugs at discharge used in 49.0%, 18.4% and 20.4% of non-frail patients and 53.2%, 29.8% and 19.1% of frail patients, respectively. CONCLUSIONS: The overall frequency of potential drug interactions was moderate and frail patients were not exposed to warfarin drug interactions more often than non-frail patients. Further studies in larger study populations are required to verify these results.

One manner in which plant-derived compounds exert their antibiotic potential is the synergism, a positive interaction between two compounds. Studies indicate that the use of plant extracts combined with antimicrobials may promote a significant reduction of the minimum inhibitory concentrations of antibiotics for bacterial strains. This study aimed to evaluate the activity of plant extracts and antibiotics as well as their combination on Staphylococcus aureus. The activity of 15 plant extracts was evaluated using diffusion assay. The minimum inhibitory concentrations (MICs) and the interactions between the extracts and antibiotics as well as compound emodin were evaluated with the checkerboard method. The active extracts were a hexane extract of the leaves of Baccharis dracunculifolia and the ethanol extracts of the leaves of Plectranthus ornatus, Inga edulis, Salvia officinalis and Senna macranthera. The Plectranthus ornatus extract displayed synergism with ampicillin (a β-lactam), kanamycin and gentamicin (aminoglycosides), with 8-fold reductions in the MIC. The same reduction was observed for the extracts of Salvia officinalis and Senna macranthera, which displayed the lowest MIC. Using these combinations resulted in a reduction in the minimum dose required for effective antimicrobial effects, which is interesting because it may decrease both the risk of side effects and the costs of treatment.

The pharmacological profile of DSP-6952, a novel 5-HT4 receptor partial agonist, was investigated to evaluate the potential use for GI disorders, and to compare its effects in some GI dysfunction models with those of clinically efficacious prokinetic agents. DSP-6952 enhanced gastric motility and caused colonic giant migrating contractions (GMCs) associated with defecation in conscious dogs, having ED50 value for inducing GMCs of 1.56 mg/kg. DSP-6952 (3-10 mg/kg, i.g.) significantly enhanced colonic transit rate in guinea pigs; this enhancement was antagonized by SB-207266, a selective 5-HT4 receptor antagonist. DSP-6952 (1-10 mg/kg, p.o.) rapidly increased fecal wet weight without increasing fluid content in mice. Sennoside (30-100 mg/kg, p.o.) also increased fecal wet weight; however, it significantly increased fluid content with diarrhea. DSP-6952 dose-dependently improved clonidine- and morphine-induced delay in whole-gut transit in mice (ED50= 0.429 mg/kg and 0.310 mg/kg, respectively), which represented atonic and spastic constipation models, respectively. In viscerally hypersensitive rats treated with acetic acid, DSP-6952 (10 mg/kg, i.p., 30 mg/kg, p.o., 30 mg/kg, i.c.) and tegaserod (1 mg/kg, i.p.), but not prucalopride (10 mg/kg, i.p.), significantly inhibited the increase in colorectal distension-induced visceromotor response; these findings suggest that DSP-6952 and tegaserod inhibit visceral hypersensitivity in rats. It was concluded that DSP-6952, a novel and orally available 5-HT4 receptor agonist, induced colonic GMCs, enhanced colonic transit, increased defecation without inducing diarrhea, improved drug-induced delay in whole-gut transit, and inhibited visceral hypersensitivity in experimental animals. Therefore, DSP-6952 is expected to become a useful drug for treatment of IBS-C and chronic constipation.

136. Gen Dent. 2018 Jan-Feb;66(1):74-78. The effect of EDTA on the antibacterial activity of sodium hypochlorite. Senna RA, Spohr AR, Gastmann AH, Pappen FG, Lima RKP, Morgental RD. The combination of ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite (NaOCl) has been suggested as an irrigant for root canal therapy. However, the chemical interaction between these agents is a complex subject that is not completely understood. The aim of this study was to evaluate the interference of an EDTA chelating agent in the antibacterial ability of NaOCl, while also considering variations in methodology. Various concentrations of NaOCl and EDTA solutions were prepared from 6% and 17% solutions, respectively. The antibacterial potential of pure solutions and their combinations was assessed using a direct contact test against Enterococcus faecalis. In the first experiment, NaOCl and EDTA solutions were mixed 5 minutes before the addition of the E faecalis bacterial suspension. In the second experiment, both solutions were simultaneously put in contact with the bacterial suspension. Data were submitted to a Spearman correlation coefficient and chi-square test. Results indicated that growth of E faecalis was significantly dependent on the solution-mixing method. In the first experiment, high concentrations (17% and 8.5%) of EDTA prevented the complete killing of E faecalis by 6% NaOCl at all experimental timepoints. In the second experiment, all concentrations of NaOCl were able to eliminate E faecalis, even in the presence of EDTA. In conclusion, when NaOCl and EDTA were added simultaneously to a bacterial suspension without premixing, NaOCl was able to exert its full bactericidal action.

Rhubarb is one of the most well-known herbal medicines that constitute daiokanzoto (DKT), which is clinically effective for constipation. Sennoside A is transformed into an active metabolite, rheinanthrone, by intestinal bacteria. Sennoside A in rhubarb showed significantly accelerated metabolic activity in intestinal bacteria in comparison with sennoside A alone. In this study, we investigated the influence of rhubarb constituents on the metabolism and purgative activity of sennoside A. The 20% MeOH-eluted fraction separated by MCI-gel CHP-20P column chromatography from the water extract of rhubarb showed sennoside A metabolic activity similar to that of rhubarb extract. The 20% MeOH elute was further purified and rhein 8-O-β-D-glucopyranoside (RG) was isolated. The metabolic activity of sennoside A was significantly accelerated by increasing the level of RG. Moreover, rhein, emodin and aloe-emodin also accelerated sennoside A metabolism. The purgative activity of sennoside A was significantly accelerated when RG or rhein was concomitantly given with sennoside A in a dose-dependent manner. These results suggest that anthraquinones contribute to the purgative action of sennoside A in rhubarb. Therefore, it is assumed that the influence of anthraquinones on the fate of rheinanthrone transformed from sennoside A may promote the purgative action of sennoside A.

AIMS: Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity. METHODS AND RESULTS: This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94). CONCLUSION: The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.

139. Lancet. 2008 Mar 1;371(9614):784. doi: 10.1016/S0140-6736(08)60347-5. Near-fatal bleeding, senna, and the opposite of lettuce. Kittisupamongkol W(1), Nilaratanakul V, Kulwichit W. Author information: (1)Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. DOI: 10.1016/S0140-6736(08)60347-5 PMID: 18313506 [Indexed for MEDLINE]

Herbal medication in the United States is a popular form of therapy. This paper provides an overview of the utilization of herbal supplements with particular emphasis on possible interactions with oral health drugs and oral manifestations. Herbal supplements are regulated by the Dietary Supplement Health and Education Act (DSHEA), which limits their regulation by the U.S Food and Drug Administration (FDA). A number of studies indicate that there is a progressive increase in the utilization of herbal supplements. The majority of consumers of these products are white, middle-aged women who have some college education. Many of the consumers use pharmaceutical drugs concurrently, but most do not inform their health-care providers about their use of herbal supplements. Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being 1) bromelain, cayenne, chamomile, feverfew, dong quai, eleuthro/Seberian ginseng, garlic, ginkgo, ginger, ginseng and licorice interacting with aspirin; 2) aloe latex, ephedra, ginseng, rhubarb, cascara sagrada, licorice, and senna interacting with corticosteriods; 3) kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs; and 4) herbs acting on the gastrointestinal system, altering the absorption of several orally administered drugs. Further, the use of some herbal supplements has been reported to be associated with oral manifestations, including aphthous ulcers, lip and tongue irritation, and swelling with feverfew; gingival bleeding with feverfew and ginkgo; tongue numbness with echinacea; xerostomia with St. John's wort; oral and lingual dyskinesia with kava; and salivation with yohimbe. These potential effects of herbal supplements in conjunction with factors related to regulation restrictions suggest that the use of these products may be associated with various adverse reactions that can affect oral health and treatment. Dental hygienists should inform themselves about herbal supplements in order to offer appropriate oral health care to individuals who take these substances.

Lichen planopilaris (LPP) is a primary cicatricial alopecia suggested to be associated with various comorbid medical conditions, including autoimmune, endocrine, and metabolic disorders. However, there is conflicting data regarding these associations. This study quantitatively evaluated the prevalence and odds of comorbidities among patients with LPP. PubMed/MEDLINE, EMBASE, Cochrane Library, and Web of Science were searched from inception to December 25, 2023, to include observational studies reporting prevalent/incident cases of at least one comorbidity in LPP patients. The study adhered to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Risk-of-bias assessment was performed using the Newcastle-Ottawa scale. Random-effect models were utilized to analyze available data. Of the 2535 studies screened, 59 studies were included for meta-analysis, comprising 15,178 LPP patients and 64,735,181 non-LPP controls. Among LPP patients, comorbidities with the highest risk (odds ratio, OR [95% confidence interval, Cl]; prevalence) compared with non-LPP controls and data available from more than one study included lichen planus (15.78 [1.79-139.30]; 6.5%), psoriasis (3.55 [1.10-11.51]; 4.3%), rosacea (3.15 [2.25-4.40]; 10.4%), melanoma (3.11 [1.41-6.87]; 2.3%), systemic lupus erythematosus (3.06 [2.29-4.09]; 1.8%), cutaneous squamous cell carcinoma (3.04 [1.64-5.66]; 4.8%), vitiligo (2.89 [1.60-5.24]; 2.0%), coronary artery disease (1.66 [1.46-1.88]; 7.6%), rheumatoid arthritis (1.50 [1.22-1.84]; 3.5%), hypothyroidism (1.48 [1.12-1.96]; 17.8%), thyroiditis (1.26 [1.08-1.48]; 3.9%), and iron deficiency anemia (1.18 [1.05-1.33]; 9.1%). LPP is significantly associated with autoimmune disorders, thyroid diseases, and skin cancer. Further investigation is required to elucidate the underlying pathogenesis and establish appropriate screening criteria. © 2025 the International Society of Dermatology.

Comment in J Am Acad Dermatol. 2024 Jan;90(1):39. doi: 10.1016/j.jaad.2023.05.025.

143. Int J Dermatol. 2023 Sep;62(9):e473-e474. doi: 10.1111/ijd.16660. Epub 2023 Apr 10. Adverse effects of hydroxychloroquine use in patients with cicatricial alopecia: A systematic review. Ezemma O(1), Devjani S(1), Jothishankar B(2), Kelley KJ(1), Senna MM(1)(2). Author information: (1)Department of Dermatology, Lahey Hospital & Medical Center, Burlington, MA, USA. (2)Department of Dermatology, Harvard Medical School, Boston, MA, USA. DOI: 10.1111/ijd.16660 PMID: 37036025 [Indexed for MEDLINE]

BACKGROUND: Approximately 30% to 40% of alopecia areata (AA) patients have atopic dermatitis. Studies suggest that antihistamines and dupilumab may be effective treatments; however, the potential benefit of these therapies as either adjunct or monotherapy has yet to be elucidated. OBJECTIVE: To evaluate the use of antihistamines and dupilumab in the treatment of AA. METHODS: A literature search was conducted in August 2021 according to PRISMA guidelines. Inclusion criteria were articles describing the use of antihistamines or dupilumab for AA or those discussing AA development as an adverse event of these therapies. RESULTS: Forty-two articles with 395 patients describe the use of antihistamines or dupilumab in AA. The most common antihistamine regimens were oxatomide 30 mg twice a day, fexofenadine 60 or 120 mg/day, and ebastine 10 mg/day; and the majority of cases reported significant hair regrowth, decreased pruritus, and erythema. Studies on the use of dupilumab for AA demonstrated remarkable hair growth in some patients (n=23), no change in others (n=3), and no new hair loss in a patient with resolved alopecia universalis (AU) (n=1). In contrast, dupilumab therapy for AD has been implicated as a cause of AA (n=21), drug-induced alopecia (n=2), and AA-like psoriasis (n=1). CONCLUSION: Current literature is promising for the use of antihistamines as adjunct treatments for AA, while monotherapy needs to be further explored. The role of dupilumab in AA treatment and/or development also requires further research.J Drugs Dermatol. 2022;21(10):1070-1083. doi:10.36849/JDD.6553.

Chronic constipation is a common gastrointestinal condition, and most individuals self-treat with multiple over-the-counter (OTC) laxatives prior to consulting a health care provider. This brief report is a synopsis of an updated systematic review the authors conducted of published data on the efficacy and safety of OTC treatments to provide evidence-based recommendations. After applying the selection criteria, 41 randomized controlled clinical trials of ≥ 4-week duration were identified and analyzed. Standardized definitions of constipation were applied across these studies; however, definitions for stool frequency and consistency varied. Overall, the short- and long-term efficacy of polyethylene glycol-based preparations and senna were supported by good (grade A) evidence suggesting their use as first-line laxatives. Modest evidence (grade B) supported the use of other agents including the stimulants bisacodyl and sodium picosulfate, fiber, fruit-based laxatives, and magnesium oxide. Additional evidence from rigorously designed studies is needed to support the use of other options for chronic constipation. The OTC products studied were generally well tolerated with common adverse effects being abdominal pain, cramping, bloating, diarrhea, and nausea.

The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is uncertain. We conducted a systematic review and meta-analysis to synthesize data on whether using a senna bowel preparation regimen enhances the bowel cleanliness. We searched Web of Science Core Collection, MEDLINE, PubMed, Embase, Cochrane Library, and Scopus databases (from the inception to August 2021). The primary efficacy outcome was bowel cleanliness. Secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria (3,343 patients. Overall, we found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% confidence interval]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (odds ratio [95% confidence interval]: 1.66 [1.08, 2.54], p = .02) and compliance (odds ratio [95% confidence interval]: 3.05 [1.42, 6.55], p = .004). The senna regimen yielded a significantly greater proportion of no nausea (odds ratio [95% confidence interval]: 1.84 [1.45, 2.32]) and vomiting (odds ratio [95% confidence interval]: 1.65 [0.81, 3.35]). Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.

This systematic review addressed the implant success rate after mandible reconstruction with vascularized fibula bone graft. Therefore, preferred reporting items for systematic review and meta-analysis guidelines were used to perform the systematic review, and the search included following databases: PubMed, Lilacs, Google Scholar, Open Gray, Science Direct and Cochrane. A search of medical subject headings (MeSH) and related terms (fibula) OR (vascularized) OR (microvascularized) AND (implant) OR (rehabilitation) OR (osseointegrated) AND (mandible) OR (jaw) OR (maxillofacial), without any language or time restrictions until October 2017 was carried out. The eligible studies primarily consisted of clinical cohorts designed to evaluate the feasibility of mandible reconstruction using vascularized fibula bone grafts and implant-supported rehabilitations, with a minimum observation period of 12 months. After screening, 13 eligible cohort studies for this review were selected (3 retrospective and 10 prospective). Of 285 vascularized fibular reconstructions, only 6 failures were reported with a success rate of approximately 98% after a mean follow-up period of 40 months. In total, 910 implants were placed in vascularized fibular grafts with a success rate of 92.6% (range, 82%-100%) after 40 months. Also, similar success rates for primary (95%; range, 93%-100%) and secondary (91%; range, 83%-100%) implant surgeries have been demonstrated. Considering risk factors, implant survival in irradiated patients was usually lower (76%; range, 38%-88%) than nonirradiated patients (90%; range, 83%-94%); however, it was significantly different in only 1 study. Alcohol and tobacco use has shown no significant association with implant failure in any study. Hence, implant placement in vascularized fibula bone graft presented similar success rates relative to native mandible bone rehabilitations.

BACKGROUND: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. METHODS: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. RESULTS: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. CONCLUSION: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most f

BACKGROUND: Although rare, anaphylaxis during pregnancy implies a risk to both mothers and newborns. OBJECTIVE: This systematic review is intended to identify key issues in the diagnosis and management of this condition to support prevention strategies and decrease the risk for death related to anaphylaxis during pregnancy. METHODS: We searched MEDLINE, Cochrane, LILACS, SciELO, and Science Direct databases for manuscripts concerning the term "anaphylaxis during pregnancy," without language restrictions. We screened studies, extracted data, and assessed the risk for bias independently in duplicate. RESULTS: We selected 12 articles. Frequency of anaphylaxis during maternity was estimated to be 1.5 to 3.8 per 100,000 pregnancies. Only one study provided anaphylaxis mortality data in pregnant women; the rate of anaphylaxis-related maternal mortality was estimated at 0.05/100,000 live births. No standard definition of anaphylaxis severity has been used. A total of 49% to 74% of anaphylaxis cases were described during caesarean section. Beta-lactam antibiotics (58%), latex (25%), and anesthetic agents (17%) were the main causes. In 17% of reports, causative agents were proven by allergy testing. Moreover, 72% of articles proposed the same management and treatment for a clinical episode of anaphylaxis during pregnancy as for nonpregnant patients, and the use of epinephrine in the patient's care during anaphylaxis in pregnancy. CONCLUSIONS: Few studies address anaphylaxis during pregnancy. Most have been produced by nonallergy specialists. Collaboration among different specialists involved in the care of pregnant women should be established to support preventive strategies and reduce avoidable deaths.