Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix.

OBJECTIVE: High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. METHODS: In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. RESULTS: After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. CONCLUSION: This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

The effects of various therapies on vulvovaginal atrophy and quality of life in gynecological cancer patients: a systematic review.

PURPOSE: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers. METHODS: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science. RESULTS: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed. CONCLUSION: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer.

Efficacy of Palmitoylethanolamide, Epilobium and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III.

OBJECTIVE: The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underlying the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Palmitoylethanolamide, Epilobium and Calendula extract in patients with CP/CPPS III. MATERIALS AND METHODS: From June 2023 to July 2023, we enrolled 45 consecutive patients affected by CP/CPPS type III in three different institution. We included patients aged between 18 and 75 years with symptoms of pelvic pain for 3 months or more before the study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 12 point and diagnosed with NIH category III, according to 4-glass test Meares-Stamey test. Patients were then allocated to receive rectal suppositories of PEA, Epilobium and Calendula, 1 suppository/ die for 1 month. All patients have been tested with standard urinalysis in order to assess urinary leukocytes (U-WBC). The primary endpoint of the study was the reduction of NIHCPSI. The secondary outcomes were the change of peak flow, post-void residual (PVR), IIEF-5, VAS score, PSA and decrease of U-WBC. RESULTS: A total of 45 patients concluded the study protocol. At baseline, the median age of all the patients included in the cohort was 49 years, the median PSA was 2.81 ng/ml, the median NIH-CPSI was 18.55, the median IIEF-5 was 18.27, the median U-WBC was 485.3/mmc, the median VAS score was 6.49, the median PVR was 26.5 ml and the median peak flow was 16.3 ml/s. After 1 month of therapy we observed a statistically significant improvement of NIH-CPSI, U-WBC, PSA, IIEF-5, peak flow, PVR and VAS. CONCLUSIONS: In this observational study, we showed the clinical efficacy of the treatment with PEA, Epilobium and Calendula, 1 suppository/die for 1 month, in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cells in the urine that could imply a reduction of inflammatory cytokines. These results should be confirmed in further studies with greater sample size.

History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report.

BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.

Effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for hemorrhoidal symptoms: a prospective, observational study.

BACKGROUND AND AIMS: A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice. METHODS: Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined. RESULTS: Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated. CONCLUSIONS: The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.

Sertaconazole 300 mg versus clotrimazole 500 mg vaginal suppository for treating pregnant women with acute vaginal candidiasis: a double-blinded, randomized trial.

BACKGROUND: Vaginal candidiasis (VC) commonly affects pregnant women. Traditionally, clotrimazole vaginal tablets (CLO) have been the cornerstone of management. However, sertaconazole ovules (SER) offer a novel topical antimycotic option. This double-blinded, randomized trial evaluated the efficacy of single-dose SER and CLO in treating acute VC during pregnancy. METHODS: From June 2020 to May 2021, this trial recruited pregnant women aged ≥ 18 years with VC symptoms (abnormal vaginal discharge and/or vulvar/vaginal itching) confirmed by microscopy. Participants with ≥ 4 VC episodes in the prior year, immunocompromised status, or imidazole contraindications and those who were absent at the 2-week follow-up were excluded. Participants were randomized to receive either 300 mg SER or 500 mg CLO. Evaluations 2 weeks after the initial medication administration included clinical cure (self-reported resolution of all symptoms), microscopic cure (pseudohyphal absence), patient satisfaction, side effects, and time to clinical cure. Participants with persistent VC received weekly SER doses until delivery. Assessments of recurrence and pregnancy outcomes were done. RESULTS: The analysis included 96 participants (48 per group, mean age 27.4 ± 7.4 years, gestational age at diagnosis 22.9 ± 6.4 weeks). Without statistical significance, SER achieved a higher clinical cure rate (62.5% vs 50%, p = 0.217; a mean difference of 12.5%, 95%CI: -17.5% to 42.5%; and a rate ratio of 1.25, 95%CI: 0.71 to 2.23) and a lower microscopic cure (47.9% vs. 62.5%, p = 0.151; a mean difference of -14.6%, 95%CI: -44.3% to 15.1%; and a rate ratio of 0.77, 95%CI: 0.43 to 1.37). The two groups had comparable times to clinical cure (SER: 3.1 ± 1.8 days, CLO: 3.4 ± 2.7 days; p = 0.848) and substantial satisfaction rates (SER: 66.7%, CLO: 60.4%; p = 0.753). No side effects were reported. Of 60 participants who gave birth at Siriraj Hospital, there were no significant differences in pregnancy outcomes. Repeated SER dosing eradicated symptoms and enhanced the microscopic cure rate. Recurrence was observed in four SER and two CLO participants within 1-2 months. CONCLUSION: In the treatment of acute VC during pregnancy, 300 mg SER and 500 mg CLO exhibited comparable efficacy in terms of clinical and microscopic cure rates, satisfaction, side effects, time to clinical cure, recurrence rates, and pregnancy outcomes. TRIAL REGISTRATION: TCTR20190308004 (registration date March 8, 2019).

Lipid-Gelucire based rectal delivery of ramipril prodrug exhibits significant lowering of intra-ocular pressure in normotensive rabbit: sustained structural relaxation release kinetics and IVIVC.

Carboxylesterase enzymes convert a prodrug ramipril into the biologically active metabolite ramiprilat. It is prescribed for controlling ocular hypertension after oral administration. High concentrations of carboxylesterase enzymes in rectal and colon tissue can transform ramipril significantly to ramiprilat. Sustained rectal delivery of ramipril has been developed for intra-ocular pressure lowering effect using a normotensive rabbit model. Rectal suppositories have been formulated using a matrix base of HPMC K100-PEG 400-PEG 6000, incorporating varying amounts of Gelucire by the fusion moulding method. The presence of Gelucire in the suppository exhibited sustained structural relaxation-based release kinetics of RM compared to its absence. Intravenous and oral administration of ramipril has decreased IOP in the treated rabbit up to 90 and 360 min, respectively. Treated rabbits with suppositories have revealed decreased IOP for an extended period compared to the above. Formulation containing GEL 3% reduced intra-ocular pressure to 540 min, with the highest area under the decreased IOP curve. Compared to oral, the pharmacodynamic bioavailability of ramipril has been improved significantly using a sustained-release rectal suppository. A rectal suppository for sustained delivery of ramipril could be used to lower IOP significantly.

Effects of pain management using nonsteroidal anti-inflammatory drug suppositories during brachytherapy for cervical cancer: A single-center prospective observational study.

INTRODUCTION: No standardized pain management protocol exists for intracavitary brachytherapy, and various methods of analgesia have been used in different countries and institutions. This study aimed to investigate the effects of pain management during intracavitary brachytherapy using nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen suppositories. METHODS: In this single-center, prospective, observational study, patients undergoing intracavitary brachytherapy for cervical cancer completed a questionnaire survey after each brachytherapy session, which comprised questions regarding pain intensity, satisfaction with analgesia, and desire for effective anesthesia. RESULTS: Data analysis was performed using data from 100 brachytherapy sessions of 27 patients. The median numerical rating scale (NRS; 0-10) score for each intracavitary brachytherapy session was 3-4. The median satisfaction scale score for analgesia (5-point scale, 1-5) for each session was approximately 4. Eight patients (29.6%) answered that they desired anesthesia more effective than suppositories at any session of brachytherapy. A comparison of the high (NRS ≥4) and low (NRS ≤3) NRS groups during the first session revealed that the high NRS group tended to have higher NRS scores and lower satisfaction with analgesia during all sessions. A positive correlation was observed between tumor size and the NRS score during the first brachytherapy session. CONCLUSIONS: The NRS score was approximately 3-4, and satisfaction with analgesia was approximately 4 out of 5 when NSAIDs or acetaminophen suppositories were used as analgesics during intracavitary brachytherapy for cervical cancer. Although the current pain management protocol is clinically acceptable, inadequate analgesia is indicated in approximately 30% of patients.

VagiBIOM Lactobacillus suppository improves vaginal health index in perimenopausal women with bacterial vaginosis: a randomized control trial.

Bacterial vaginosis (BV) can cause vaginal dysbiosis that may influence general vaginal health and pregnancy complications. Balancing vaginal microbiome using Lactobacillus spp. may be a new way to prevent and treat mild BV. We conducted a randomized, double-blind, placebo-controlled pilot study aimed at evaluating the effect of the product VagiBIOM, a multi-Lactobacillus vaginal suppository, on peri- and premenopausal women with BV in restoring vaginal pH and overall vaginal health by resetting the vaginal microbiome composition. Sixty-six peri- and premenopausal women with BV symptoms were randomized with a 2:1 ratio to be treated with VagiBIOM or placebo suppositories. Vaginal pH, VAS itching score, total Nugent score, and vaginal health index (VHI) were measured. Vaginal microbiome changes before and after the treatment were analyzed by 16S rRNA sequencing and bioinformatics analysis. After 4 weeks of intervention with VagiBIOM or a placebo, the mean score for vaginal pH, VAS itching, and total Nugent score was significantly decreased from the baseline. Compared to the baseline scores, the VHI scores improved significantly following 28-day intervention (p < 0.001). Our results revealed two Lactobacillus species, L. hamsteri, and L. helveticus, as indicator species occurring differentially in the VagiBIOM-treated group. Furthermore, the regression and species network analyses revealed significant bacterial associations after VagiBIOM treatment. Lactobacillus hamsteri was positively associated with the Nugent score and negatively associated with vaginal pH. L. iners and L. salivarius were positively and inversely associated with VHI. As is typical, Bacteroides fragilis was positively associated with vaginal pH and negatively associated with the Nugent score. Interestingly, the Lactobacillus spp. diversity improved after VagiBIOM treatment. The VagiBIOM suppository treatment for peri- and premenopausal women with BV significantly relieved vaginal itching by decreasing vaginal pH and Nugent scores and improving the overall VHI after 4 weeks' intervention. This effect was primarily the result of VagiBIOM improving vaginal Lactobacillus diversity.Trial Registration ClinicalTrials.gov registration: NCT05060029, first registration 09/28/2021: Title: A Pilot Study to Evaluate the Efficacy and Safety of Lactobacillus Species Suppositories on Vaginal Health and pH.

Prophylactic application of vaginal lactic acid bacteria against urogenital pathogens and its prospective use in sanitary suppositories / Aplicación profiláctica de bacterias ácido lácticas vaginales contra patógenos urogenitales y su uso prospectivo en supositorios sanitarios

Beneficial and pathogenic microbes coexist in the vaginal canal, where a diminishing population of lactic acid bacteria may cause recurring urogenital infections. Probiotic bacteria Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus vaginalis, and pathogenic microbes Enterococcus faecalis, Enterobacter cloacae, Shigella sp., Staphylococcus epidermidis, and Escherichia fergusonii were isolated from vaginal swabs. Lactobacillus sp. and their probiotic culture free supernatant (PCFS) inhibited the growth of the above-mentioned urogenital pathogens. L. crispatus produced both lactic acid and hydrogen peroxide, exhibiting the best antimicrobial potential against the studied pathogens. Lyophilized L. crispatus had a shelf life of 12 months and the lyophilized PCFS also retained its antibacterial property with a minimum inhibition concentration of 1 μg/μL. Carboxy-methyl cellulose-alginate, a green alternative to super-absorbent polymers, was encapsulated with L. crispatus cells. The probiotic in its encapsulated state retained its viability for 21 days, and the bead showed 30% solvent absorptive capacity. PCFS-laced non-woven fabric displayed antibacterial property with no change in its physicochemical properties. These probiotic and postbiotic formulations have excellent prophylactic potential for urogenital infections. Such formulations can be exploited as additives in sanitary suppositories to enhance vaginal health.(AU)

pH and redox dual response nano-suppository for the treatment of ulcerative colitis.

To improve treatment compliance and reach sustained and controlled drug release in the colon, we developed a hollow mesoporous silica nano-suppository that responded to both pH and redox stimuli. Firstly, we prepared hollow mesoporous silica nanoparticles containing disulfide bonds (HMSN-SS) and loaded them with 5-ASA. Secondly, we modified the surface of HMSN-SS with polydopamine (PDA) and chitosan (CS) and molded the suppository, which we named 5-ASA@HMSN-SS-PDA-CS (5-ASA@HSPC). By administering 5-ASA@HSPC rectally, it acted directly on the affected area. CS helped the nanoparticles adhere to the colon's surface, while PDA dissociates from HMSN-SS due to protonation in the acidic environment of the ulcerative colon. The disulfide bonds were destroyed by the reducing environment of the colon, leading to a stable and slow release of encapsulated 5-ASA from the pores of HMSN. Finally, in vitro release experiments and in vivo pharmacokinetic and pharmacodynamic experiments had demonstrated that 5-ASA@HSPC exhibited a slow and steady action at the colonic site, with an excellent safety profile. This novel approach showed great potential in the treatment of ulcerative colitis.

3D-printed prednisolone phosphate suppositories with tunable dose and rapid release for the treatment of inflammatory bowel disease.

Established medicines are often not tailored to the needs of the pediatric population, causing difficulties with administration or dosing. Three-dimensional (3D) printing technology allows novel approaches for compounding of personalized medicine, as is exemplified in this study for the automated compounding of rectal preparations for children. We investigated the material requirements to print prednisolone phosphate-loaded suppositories with tunable dose and rapid drug release for the treatment of inflammatory bowel diseases. Three formulations containing 4 % w/w prednisolone sodium phosphate (PSP) and different amounts of hydroxypropyl cellulose (HPC) and mannitol as excipients were printed as suppositories with a fused deposition modeling (FDM) 3D-printer. Dissolution studies showed that the PSP release rate was increased when higher weight fractions of mannitol were added as a pore former, with 90 % drug release within 30 min for mannitol 48 % w/w. We further printed suppositories with 48 % mannitol with different infill densities and dimensions to tune the dose. Our findings demonstrated that 3D-printed suppositories with PSP doses ranging from 6 to 30 mg could be compounded without notably affecting the dissolution kinetics, ensuring equivalent therapeutic efficacies for different doses.

Prophylactic application of vaginal lactic acid bacteria against urogenital pathogens and its prospective use in sanitary suppositories.

Beneficial and pathogenic microbes coexist in the vaginal canal, where a diminishing population of lactic acid bacteria may cause recurring urogenital infections. Probiotic bacteria Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus vaginalis, and pathogenic microbes Enterococcus faecalis, Enterobacter cloacae, Shigella sp., Staphylococcus epidermidis, and Escherichia fergusonii were isolated from vaginal swabs. Lactobacillus sp. and their probiotic culture free supernatant (PCFS) inhibited the growth of the above-mentioned urogenital pathogens. L. crispatus produced both lactic acid and hydrogen peroxide, exhibiting the best antimicrobial potential against the studied pathogens. Lyophilized L. crispatus had a shelf life of 12 months and the lyophilized PCFS also retained its antibacterial property with a minimum inhibition concentration of 1 µg/µL. Carboxy-methyl cellulose-alginate, a green alternative to super-absorbent polymers, was encapsulated with L. crispatus cells. The probiotic in its encapsulated state retained its viability for 21 days, and the bead showed 30% solvent absorptive capacity. PCFS-laced non-woven fabric displayed antibacterial property with no change in its physicochemical properties. These probiotic and postbiotic formulations have excellent prophylactic potential for urogenital infections. Such formulations can be exploited as additives in sanitary suppositories to enhance vaginal health.

A phase I study of intra-anal artesunate (suppositories) to treat anal high-grade squamous intraepithelial lesions.

BACKGROUND: Ablation or surgical excision is the typical treatment of anal high-grade squamous intraepithelial lesions (HSIL). Recurrences are common due to the persistence of underlying human papillomavirus (HPV) infection. Additional well-tolerated and effective non-surgical options for HPV-associated anal disease are needed. METHODS: This 3+3 dose escalation Phase I clinical trial evaluated the safety and tolerability of artesunate suppositories in the treatment of patients with biopsy-proven HSIL. RESULTS: The maximal tolerated dose was 400 mg, administered in 3 cycles. All adverse events associated with the use 200- and 400-mg artesunate suppositories were Grade 1. At the 600-mg dose, patients experienced clinically significant nausea. CONCLUSION: Artesunate suppositories are a safe treatment option for anal HSIL.

[Onto-phylogenetic prerequisites for development of chronic cystitis in women].

INTRODUCTION: Urinary tract infections (UTIs) are among the most common bacterial infections. At the request "cystitis", there are 12,067 publications in the RSCI system (e.library) as of 10/08/2023 and 16,332 articles were screened in the Pubmed. This is evidence that the problem of cystitis is far from being resolved. MATERIAL AND METHODS: A total of 425 patients with bacterial vaginosis and 77 women with chronic recurrent cystitis were included in the study. In all patients, the vaginal biocenosis was assessed through molecular genetic testing. The examination included filling out the Russian version of the Acute Cystitis Symptom Score (ACSS), urinalysis, and urine culture. In addition, local microcirculation was measured using laser Doppler flowmetry (LDF). After examination, patients were prescribed basic therapy and randomly assigned to one of three groups. In a control group (n=17), only basic therapy, consisting of fosfomycin 3.0 once at night + furagin 100 mg after meals 3 times a day for 5 days was prescribed. In the main group 1, 29 women received basic therapy plus Superlymph suppositories 10 units 2 times a day vaginally for 10 days. In the main group 2, 31 patients received basic therapy plus suppositories Superlymph 10 units (rectally in the morning) and Acylact Duo (vaginally in the evening) for 10 days. RESULTS: Among 425 patients with bacterial vaginosis, 78 (18.3%) complained of various urinary disorders, but only 21 women (4.9% of those with vaginal dysbiosis and 26.9% with dysuria) had a diagnosis of cystitis. In all cases, it was an exacerbation of a chronic disease. Among 77 patients with chronic cystitis, normal vaginal flora was initially present in 32 patients (41.6%), and bacterial vaginosis was found in 45 (58.4%) cases. After therapy, positive results were noted in patients of all groups. Complete eradication of the pathogen occurred in 15 women (88.2%) who received only basic therapy; in the main groups 1 and 2, uropathogens were not detected in 27 (93.1%) and 28 (90.3%) cases, respectively. In the control group, the proportion of patients with normal vaginal flora remained virtually unchanged (41.2% [n=7] vs. 47.1% [n=8]). In the main group 1, the proportion of patients with normal vaginal flora almost doubled: from 41.4% (n=12) to 79.3% (n=23). In main group 2, restoration of vaginal flora was noted in 87.1% of cases. CONCLUSION: According to our data, only 4.9% of patients with bacterial vaginosis were diagnosed with chronic cystitis, however, 58.4% of patients with chronic cystitis had vaginal dysbiosis. The use of a complex of antimicrobial peptides and cytokines has significantly increased the bidirectional effect of therapy. Suppositories Superlymph in a combination with vaginal use of Acylact Duo allow to obtain the best results.

Rectal artesunate suppositories for the pre-referral treatment of suspected severe malaria.

In this Policy Forum article, James A. Watson and colleagues discuss recent guidelines relating to pre-referral treatment of suspected severe malaria with rectal artesunate suppositories in remote areas.

Can vaginal lactobacillus suppositories help reduce urinary tract infections?

INTRODUCTION AND HYPOTHESIS: Recurrent urinary tract infections (rUTIs) are a burden to patients and the health care economy. Vaginal probiotics and supplements have gained significant attention in mainstream media and lay press as a non-antibiotic alternative. We performed a systematic review to determine whether vaginal probiotics are an effective means of prophylaxis for rUTI. METHODS: A PubMed/MEDLINE article search was performed from inception to August 2022 for prospective, in vivo use of vaginal suppositories for the prevention of rUTIs. Search terms included: vaginal probiotic suppository (34 results), vaginal probiotic randomized (184 results), vaginal probiotic prevention (441 results), vaginal probiotic UTI (21 results), and vaginal probiotic urinary tract infection (91 results). A total of 771 article titles and abstracts were screened. RESULTS: A total of 8 articles fit the inclusion criteria and were reviewed and summarized. Four were randomized controlled trials, with 3 of the studies having a placebo arm. Three were prospective cohort studies, and 1 was a single arm, open label trial. Five of the 7 articles that specifically evaluated for rUTI reduction with vaginal suppositories did find a decreased incidence with probiotic use; however, only 2 had statistically significant results. Both of these were studies of Lactobacillus crispatus and were not randomized. Three studies demonstrated the efficacy and safety of Lactobacillus as a vaginal suppository. CONCLUSION: Current data support the use of vaginal suppositories containing Lactobacillus as a safe, non-antibiotic measure, but actual reduction of rUTI in susceptible women remains inconclusive. The appropriate dosing and duration of therapy remain unknown.

Mesalazine hollow suppositories based on 3D printing for treatment of ulcerative colitis.

Mesalazine (MSZ) suppositories are a first-line medication for the localized treatment of ulcerative colitis (UC). However, the frequent defecation of patients with UC influences the retention of the suppository in the rectum and multiple doses have to be applied. Here, a mesalazine hollow suppository (MHS) is developed using three-dimensional (3D) printing. The MHS is composed of an inner supporting spring and an outer MSZ-loaded curved hollow shell. Springs were prepared using fused deposition modeling (FDM) 3D printing with thermoplastic urethane filaments, followed by splitting. The optimal parameters, including elasticity, filament diameter, spring inner diameter, and filament distance, were screened. The shell was prepared by FDM 3D printing utilizing MSZ, polyvinyl alcohol, and polyethylene glycol, which were assembled with springs to obtain FDM 3D-printed MHS (F-MHS); if 3D-printed metal molding was used in preparing shell, mold-formed MHS (M-MHS) was obtained. The F-MHS exhibited faster MSZ release than the M-MHS; therefore, the molding method is preferable. The inserted M-MHS was retained in the rat rectum for 5 h without affecting defecation. M-MHS alleviated tissue damage of UC rats and reduced inflammation with low levels of myeloperoxidase and proinflammatory cytokines. Personalized MHS is a promising medication for the localized treatment of UC.