Effects of Qing Chang Suppository Powder and its Ingredients on IL-17 Signal Pathway in HT-29 Cells and DSS-induced Mice.

BACKGROUND: Qingchang Suppository, a formula used for more than 30 years in Longhua Hospital, has shown satisfactory clinical effects on Ulcerative Colitis (UC). However, its therapeutic mechanism has not been fully elucidated. PURPOSE: The study aims to investigate the effects of Qingchang Suppository powder (QCSP) and its ingredients by regulating the IL-17A signaling pathway which plays an important role in the development of UC. METHODS: HPLC was used to analyze the main ingredients (Gallic acid, Indigo, Indirubin) in QCSP. HT-29 cells were induced by rhIL-17A and TNF-α, and IL-17A related protein expressions were determined by western blot. BALB/C mice were induced by 4% Dextran Sodium sulfate (DSS). The effects of QCSP and its ingredients were evaluated by measuring weight loss, disease activity index (DAI), colon length, histological analysis. Western blot was used for analysis of IL-17A and MAPK related proteins p-ERK, p-JNK, p-P38. Quantitative reverse transcription polymerase chain reaction (q-PCR) was used to detect the expression of IL-17A, HSP90 and ACT1 in colon tissue. Cytokines such as IL-17A, IL-1ß, IFN-γ and TNF-α were determinated by enzyme-linked immunosorbent assay (ELISA). RESULTS: QCSP had good therapeutic effect on DSS-induced colitis in mice. QCSP significantly relieved weight loss, restored colon length, repaired colon lesions, reduced histological scores and DAI, decreased TNF-α, IL-1ß, IL-17 and IFN-γ contents, significantly suppressed the gene expressions of IL-17A, ACT1 and HSP90, and up-regulated the expressions of tight junction proteins like ZO-1 and Occludin. IL-17A pathway related proteins such as IL-17A, IL-17RA, HSP90, MAPKs, P-iκbα and iNOS were significantly increased in vitro and in vivo. CONCLUSIONS: This paper reveals that QCSP inhibited the IL-17A signaling pathway in HT-29 cells and DSS induced mice, presenting a new mechanism of QCS on treating UC.

Budesonide Suppositories Are Effective and Safe for Treating Acute Ulcerative Proctitis.

BACKGROUND & AIMS: Although proctitis is the most limited form of ulcerative colitis, it causes unpleasant symptoms. Topical mesalamine, the standard treatment, is not always effective. We conducted a randomized phase 2 trial to determine the efficacy and safety of 2 doses of a budesonide suppository vs mesalamine suppositories vs combined budesonide and mesalamine suppositories for proctitis. METHODS: We performed a prospective, double-blind, double-dummy, multicenter trial in 337 patients with active proctitis to compare the efficacies of 4 different suppository treatments. Patients were randomly assigned to groups given 2 mg budesonide suppositories (2 mg BUS; n = 89 patients), 4 mg BUS (n = 79), 1 g mesalamine suppositories (1 g MES; n = 81), or the combination of 2 mg BUS and 1 g MES (n = 88). The study was performed from November 2013 through July 2015 at 36 study sites in Europe and Russia. The primary end point was the time to resolution of clinical symptoms, defined as the first of 3 consecutive days with a score of 0 for rectal bleeding and stool frequency. RESULTS: The mean time to resolution of symptoms in the 4 mg BUS (29.8 days) and combination of 2 mg BUS and 1 g MES (29.3 days) groups resembled that of the standard 1 g MES treatment (29.2 days), but was significantly longer in the 2 mg BUS group (35.5 days). Furthermore, proportions of patients with deep, clinical, and endoscopic remission, as well as mucosal healing, were similar among the 1 g MES, 4 mg BUS, and combination therapy groups, but significantly lower in the group that received 2 mg BUS. No safety signals were observed, and the patients' treatment acceptance was high (67%-85% of patients). CONCLUSIONS: In a multicenter randomized trial, we found that the efficacy and safety of 4 mg BUS in treatment of active proctitis did not differ significantly from those of 1 g MES. Budesonide suppositories offer an alternative therapy to mesalamine for topical treatment of proctitis. Clinicaltrialsregister.eu no: 2012-003362-41.

A randomized clinical trial of the efficacy and safety of terconazole vaginal suppository versus oral fluconazole for treating severe vulvovaginal candidiasis.

Terconazole is a new, broad-spectrum, triazole antifungal agent. The aim of this study was to compare the efficacy and safety of a 6-day course of a terconazole vaginal suppository (80 mg) with two doses of oral fluconazole (150 mg) for the treatment of severe vulvovaginal candidiasis (SVVC). In this prospective, randomized case-control study, 140 consecutive patients with SVVC were enrolled at the Department of Obstetrics and Gynecology of Peking University Shenzhen Hospital from July 1, 2013, through June 31, 2014. Patients with SVVC, initially at a 1:1 ratio, were randomly assigned to receive treatment with either the terconazole vaginal suppository or oral fluconazole. The patients had follow-up visits at 7-14 days and 30-35 days following the last dose of therapy. The clinical cure rates in the terconazole group and the fluconazole group were, respectively, 81.0% (47/58) and 75.8% (50/66) at follow-up day 7-14 and 60.3% (35/58) and 56.1% (37/66) at day 30-35. The mycological cure rates in the two groups were, respectively, 79.3% (46/58) and 71.2% (47/66) at follow-up day 7-14 and 62.1% (36/58) and 53.0% (35/66) at day 30-35 (P > .05 for all). Local irritation was the primary adverse event associated with terconazole, whereas systemic side effects were associated with fluconazole; however, these effects were minimal. This study demonstrated that a terconazole vaginal suppository (80 mg daily for 6 days) was as effective as two dose of oral fluconazole (150 mg) in the treatment of patients with SVVC; as such, terconazole could be a choice for therapy of this disorder.

A concomitant treatment by CO2-releasing suppositories improves the results of anorectal biofeedback training in patients with dyschezia: results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Dyschezia is a defecatory disorder that places a heavy burden on a patient's quality of life. Biofeedback is the recommended treatment in most cases. OBJECTIVE: The objective of our study was to test whether a CO2-releasing suppository for patients with dyschezia could be effective in improving biofeedback training results. DESIGN: A randomized, double-blind, multicenter, placebo-controlled study was conducted in patients (18-75 years of age) with dyschezia defined according to the modified Rome III criteria. Patients were randomly assigned to either a CO2-releasing suppository or placebo suppository once per day for 21 days. SETTINGS: This was a multicenter trial. PATIENTS: A total of 122 patients were randomly assigned (62 intervention group and 60 placebo group). MAIN OUTCOME MEASURES: The primary end point was the change from day 0 to day 21 in intensity of symptoms on the basis of a self-assessed dyschezia using a visual analog scale (range, 0-100). Analyses were performed using intention-to-treat principles. RESULTS: A greater reduction from baseline to day 21 in symptom visual analog scale score was observed in the intervention group (-41.3 mm) than in the control group (-22.3 mm). Some secondary efficacy parameters improved more in the intervention group, including the percentage of patients who improved ≥50%, symptom intensity over 21 days, stool stains on underwear or pads, and need to practice manual maneuvers to facilitate defecation at day 21. At day 21, rectal sensitivity in the intervention group (31.4 mL) was lower than in the control group (39.1 mL). LIMITATIONS: There was a lower number of patients recruited than planned by the protocol. The sponsor stopped the trial before the inclusion of 306 participants, with no intermediate analysis. In addition, the main analysis conducted on the full analysis set population could have led to a statistical bias. CONCLUSIONS: The results of this multicenter trial demonstrate the added benefits of a CO2-releasing suppository in patients with dyschezia who were treated by anorectal biofeedback training.

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

Randomised clinical trial: study of escalating doses of NRL001 given in rectal suppositories of different weights.

AIMS: The application of α-adrenoceptor agonists can improve faecal incontinence symptoms. The aim of this study was to investigate the pharmacokinetic and systemic effects of NRL001 administered as different strengths in 1 or 2 g suppositories. METHODS: This randomised, double-blind, placebo controlled study included 48 healthy subjects. Group 1 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 5, 7.5 or 10 mg NRL001, or matching placebo. Group 2 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 10, 12.5 or 15 mg NRL001, or matching placebo. Doses were given in an escalating manner with placebo at a random position within the sequence. RESULTS: Tmax was at ~4.5 h post-dose for all NRL001 doses. Median AUC0-tz , AUC0-∞ and Cmax increased with increasing dose for both suppository sizes. The estimate of ratios of geometric means comparing 2 g with 1 g suppository, and regression analysis for dose proportionality, was close to 1 for the variables AUC0-tz , AUC0-∞ and Cmax (P > 0.05). For both suppository sizes, 20-min mean pulse rate was significantly decreased compared with placebo with all doses (P < 0.05). Blood pressure decreased overall. There were 144 adverse events (AEs) and no serious AEs reported during the study. All AEs were mild in severity. CONCLUSIONS: The regression analysis concluded that the doses were dose proportional.

Minimal dose interferon suppository treatment suppresses viral replication with platelet counts and serum albumin levels increased in chronically hepatitis C virus-infected patients: a phase 1b, placebo-controlled, randomized study.

Animal studies have shown that rectally administrated interferon (IFN) is transferred into the lymphatic system via the rectal mucous membrane, suggesting that an IFN suppository could serve as another drug delivery method. We developed an IFN suppository and administered it to patients with chronic hepatitis C to evaluate its efficacy and safety. Twenty-eight patients with chronic hepatitis C participated in the study. The low-dose IFN suppository containing 1,000 international units (IU) of lymphoblastoid IFNα was administered to 14 patients daily for 24 weeks. Others had a placebo dosing. In 13 of the 14 IFN suppository-treated patients, viral load decreased at week 4. The serum hepatitis C virus (HCV) RNA levels (Log IU/mL, mean±standard error) were 5.65±0.18 before the treatment and 5.17±0.27 at week 4 (P=0.01). The 2'-5' oligoadenylate synthetase activity increased, while the CD4/CD8 ratio decreased significantly. Interestingly, platelet counts and serum albumin levels were significantly increased during and after the treatment. No serious adverse events were observed. The low-dose IFN suppository treatment suppressed HCV replication, modifying host immunity, with increased platelet counts and serum albumin levels. The IFN suppository could be considered a new drug delivery method to preserve the quality of life of patients.

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

BACKGROUND: Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. AIM: To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. METHODS: This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. RESULTS: The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). CONCLUSIONS: The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421).

Acceptability of potential rectal microbicide delivery systems for HIV prevention: a randomized crossover trial.

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use.

Clinical trial: marine lipid suppositories as laxatives.

UNLABELLED: Cod-liver oil and other marine products containing polyunsaturated fatty acids have anti-inflammatory, anti-bacterial and anti-viral effects and may be useful in the treatment of various inflammatory and infectious diseases. We developed suppositories and ointment with 30% free fatty acid (FFA) extract from omega-3 fish oil. Our purpose was to evaluate the safety of marine lipid suppositories and ointment in healthy volunteers and to explore the laxative effect of the suppositories. Thirty healthy volunteers were randomized either to a study group administrating 30% FFA suppositories and applying 30% FFA ointment to the perianal region twice per day for two weeks, or to a control group using placebo suppositories and ointment in a double blinded manner. RESULTS: No serious toxic effects or irritation were observed. In the study group 93% felt the urge to defecate after administration of the suppositories as compared to 37% in the control group (P = 0.001). Subsequently 90% in the study group defecated, compared to 33% in the control group (P = 0.001). CONCLUSION: The marine lipid suppositories and ointment were well tolerated with no significant toxic side effects observed during the study period. The suppositories have a distinct laxative effect and we aim to explore this effect in further clinical trials.

Boric acid for recurrent vulvovaginal candidiasis: the clinical evidence.

BACKGROUND: Recurrent vulvovaginal candidiasis (VVC) remains a challenge to manage in clinical practice. Recent epidemiologic studies indicate that non-albicans Candida spp. are more resistant to conventional antifungal treatment with azoles and are considered as causative pathogens of vulvovaginal candidiasis. METHODS: We searched PubMed and Scopus for studies that reported clinical evidence on the intravaginal use of boric acid for vulvovaginal candidiasis. RESULTS: We identified 14 studies (2 randomized clinical trials [RCTs], 9 case series, and 4 case reports) as eligible for inclusion in this review. Boric acid was compared with nystatin, terconazole, flucytosine, itraconazole, clotrimazole, ketoconazole, fluconazole, buconazole, and miconazole; as monotherapy, boric acid was studied in 7 studies. The mycologic cure rates varied from 40% to 100% in patients treated with boric acid; 4 of the 9 included case series reported statistically significant outcomes regarding cure (both mycologic and clinical) rates. None of the included studies reported statistically significant differences in recurrence rates. Regarding the adverse effects caused by boric acid use, vaginal burning sensation (<10% of cases), water discharge during treatment, and vaginal erythema were identified in 7 studies. CONCLUSIONS: Our findings suggest that boric acid is a safe, alternative, economic option for women with recurrent and chronic symptoms of vaginitis when conventional treatment fails because of the involvement of non-albicans Candida spp. or azole-resistant strains.