Biological Characterization and Inhibition of Streptococcus pyogenes ZUH1 Causing Chronic Cystitis by Crocus sativus Methanol Extract, Bee Honey Alone or in Combination with Antibiotics: An In Vitro Study.

Streptococcus pyogenes (S. pyogenes) ZUH1 was isolated and characterized using morphological, cultural and biochemical methods. The results showed that the marker genes (namely spyCEP, ssa, sic, sdaB and speG) indicating group A streptococci (GAS) were detected in the S. pyogenes genome. The results showed that the S. pyogenes strain was inhibited by Crocus sativus methanol extract (CSME), bee honey (BH) and catfish glycoprotein (CFG). The inhibitory activity of these natural agents were compared with standard antibiotics such as Ceftazidime (30 µg/mL), Cefoperazone (75 µg/mL), Cefoxitin (30 µg/mL) and Imipenem (10 µg/mL). There was a synergistic effect between certain antibiotics and CSME. GC-MS and IR analysis of CSME showed different cyclic ketones, aldehydes, esters, alcohols and acids. The main compounds were tetradecanoic acid, safranal and isophorone. Transmission electron microscopy (TEM) images of S. pyogenes cells treated with CSME showed signs of an irregular wrinkled outer surface, fragmentation, adhesion and aggregation of damaged bacterial cells or cellular debris. The marker genes (spyCEP, ssa, sic, sdaB and speG) could be used as a rapid diagnostic tool for GAS. CSME, BH and CFG showed distinctive anti-streptococcal activity either alone or in combinations with antibiotics; their action on S. pyogenes cells was studied by TEM. There was a synergistic effect between antibiotics and Crocus sativus, bee honey, and glycoprotein against S. pyogenes ZUH1. The action of natural agents on the pathogenic cells was shown using TEM.

Intravitreal Sirolimus for the Treatment of Noninfectious Uveitis: Evolution through Preclinical and Clinical Studies.

In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1-3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 µg intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n = 50 and n = 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n = 24 and n = 347, respectively) suggested that 440 µg has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-µg group than in the 44-µg group (22.8% vs. 10.3%; P = 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1-3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 µg intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

[The effectiveness of Uroprofit in women with chronic cystitis].

AIM: To evaluate the effectiveness of the biologically active dietary supplement Uroprofit in the comprehensive management of exacerbations of chronic recurrent cystitis in women. MATERIALS AND METHODS: We examined 40 women with chronic cystitis aged 20-68 years. All patients were allocated to receive either monotherapy with fosfomycin (Monural) (control group, n=20) or combination therapy with fosfomycin and biologically active dietary supplement Uroprofit (study group, n=20). The results were evaluated at 1 and 2 months after treatment initiation. All patients before and after treatment underwent diagnostic work-up including standard laboratory tests, uroflowmetry, cystometry, cystoscopy, and laser Doppler flowmetry to assess microcirculation. RESULTS: The patients of the study group showed faster improvement in clinical manifestations of the disease, laboratory indicators, the dynamics of the endoscopic pattern and had positive changes in the bladder mucosa microcirculation. DISCUSSION: Uroprofit produces an antimicrobial and anti-inflammatory effect, helps normalize urodynamics of the lower urinary tract, improves microcirculation in the bladder wall and reduces the risk of repeated relapses of chronic cystitis. CONCLUSION: Uroprofit could be recommended as a component of the comprehensive management of exacerbations of chronic recurrent cystitis in women and as the means of preventing relapses in disease-free periods.

Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial.

OBJECTIVE: To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious intermediate, posterior, or panuveitis (uveitis). DESIGN: Randomized controlled parallel superiority trial. PARTICIPANTS: Patients with active or recently active uveitis. METHODS: Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (3 countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis. MAIN OUTCOME MEASURES: Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life, ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked. RESULTS: On evaluation of changes from baseline to 24 months among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), the implant and systemic therapy groups had an improvement in visual acuity of +6.0 and +3.2 letters (P = 0.16, 95% confidence interval on difference in improvement between groups, -1.2 to +6.7 letters, positive values favoring implant), an improvement in vision-related quality of life of +11.4 and +6.8 units (P = 0.043), a change in EuroQol-EQ5D health utility of +0.02 and -0.02 (P = 0.060), and residual active uveitis in 12% and 29% (P=0.001), respectively. Over the 24 month period, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio [HR] = 3.3, P < 0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, P < 0.0001), and glaucoma (17%, HR=4.2, P = 0.0008). Patients assigned to systemic therapy had more prescription-requiring infections than patients assigned to implant therapy (0.60 vs 0.36/person-year, P=0.034), without notable long-term consequences; systemic adverse outcomes otherwise were unusual in both groups, with minimal differences between groups. CONCLUSIONS: In each treatment group, mean visual acuity improved over 24 months, with neither approach superior to a degree detectable with the study's power. Therefore, the specific advantages and disadvantages identified should dictate selection between the alternative treatments in consideration of individual patients' particular circumstances. Systemic therapy with aggressive use of corticosteroid-sparing immunosuppression was well tolerated, suggesting that this approach is reasonably safe for local and systemic inflammatory disorders. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.