Upon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators ...involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good resolution (M-MΦ) of the inflammatory process. The functional activity of polarized MΦ is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MΦ that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the MΦ secretome involved in the shedding of soluble endoglin. We find that the GM-MΦ secretome contains metalloprotease 12 (MMP-12), a GM-MΦ specific marker that may account for the anti-angiogenic activity of the GM-MΦ secretome. Cell surface endoglin is present in both GM-MΦ and M-MΦ, but soluble endoglin is only detected in GM-MΦ culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MΦ and endothelial cells. These data demonstrate a direct correlation between GM-MΦ polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.
Lessons Learned
The levels of circulating follicle‐stimulating hormone, luteinizing hormone, estriol, estradiol, and estrone remained unchanged after a 12‐week treatment with 0.005% estriol vaginal ...gel in postmenopausal women receiving nonsteroidal aromatase inhibitors for hormone receptor‐positive early breast cancer.
These results support the safety of 0.005% estriol vaginal gel for the treatment of bothering symptoms of vulvovaginal atrophy in breast cancer survivors.
The results provide clinicians with confidence in the use of this product in women who do not experience symptom relief with nonhormonal remedies.
Background
Symptoms of vulvovaginal atrophy associated with treatment with nonsteroidal aromatase inhibitors (NSAIs) negatively impact patients’ quality of life and may affect adherence to NSAIs. Vaginal estrogens effectively improve these symptoms, although their safe use in breast cancer survivors remains unclear.
Methods
Postmenopausal women with hormone receptor‐positive early breast cancer receiving NSAI and moderate‐to‐severe vaginal dryness were randomized to 0.005% estriol vaginal gel or placebo for 12 weeks. Circulating estrogens, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH), were analyzed at baseline and at weeks 1, 3, 8, and 12. The primary safety outcome was the variation in serum FSH from baseline to week 12.
Results
Sixty‐one women (mean age, 59 years) enrolled in the study. Small oscillations were observed in FSH and LH, although they were always maintained within the postmenopausal range. No significant differences were found in the variation of FSH and LH between baseline and week 12 from the physiological variation observed before treatment. Women receiving 0.005% estriol vaginal gel had slightly increased estriol levels at weeks 1 and 3, with a subsequent reduction until normalizing at week 12; estradiol and estrone remained the below limit‐of‐quantitation in almost all samples.
Conclusion
Ultralow‐dose 0.005% estriol vaginal gel did not significantly influence estrogens, FSH, and LH levels in women with breast cancer receiving NSAI. A transient negligible absorption of estriol and a nonsignificant variation of FSH after 12 weeks were observed. These findings provide confidence for the safe use of 0.005% estriol vaginal gel in women with breast cancer with an indication for treatment with vaginal estrogens.
Objective
To evaluate the acceptability, tolerability, and effects on vulvovaginitis symptoms and signs of a non-soap, herbal-based intimate solution (Zelesse®).
Methods
We conducted a prospective, ...observational, multicenter study including adult women with symptoms and signs of vulvovaginitis with various etiologies, including candidiasis, trichomoniasis, bacterial vaginosis, and atrophic and irritative vaginitis. The presence and intensity of signs (edema, erythema, vaginal discharge) and symptoms (pruritus) of vulvovaginitis were evaluated before and after 5–15 days of daily use of Zelesse® alone or as a coadjuvant in antimicrobial therapy. Variables following a normal distribution and categorical variables were analyzed using the Student t-test and chi-square or Fisher’s exact test, respectively.
Results
A total 137 women were enrolled in the study; 87 (63.5%) women received concomitant antimicrobials and 50 (36.5%) used Zelesse® only. Global symptom scores and frequency of patients with vulvovaginitis signs and symptoms, and their mean intensity, decreased after treatment in both patient groups. Vaginal pH and (in the Zelesse®-only group) vaginal flora remained unaltered. The product was safe, well tolerated, and highly accepted by patients.
Conclusions
Zelesse®, the non-soap herbal-based solution in this study, may represent a safe and effective option for symptomatic relief of vulvovaginitis.
Objective
To assess the efficacy, acceptability, and tolerability of a vaginal cream based on plant extracts for treating signs and symptoms of vulvovaginitis (VV) (Zelesse cream®), either as ...monotherapy (non-infectious VV) or adjuvant to antimicrobial therapy (infectious VV).
Methods
This prospective, observational, multicenter study included women who attended outpatient offices for VV. The severity of signs (vaginal discharge, erythema, and edema) and symptoms (pruritus, burning, and dysuria) was assessed before and after 15±5 days of daily treatment with Zelesse cream on a 4-point scale (18-point global score).
Results
The study included 58 women aged 43.0±13.2 years, including 42 who were treated with Zelesse cream only and 16 who used Zelesse cream as adjuvant to antimicrobial therapy. All participants showed significantly reduced scores and absolute prevalence of individual signs and symptoms in both groups. Similarly, the median signs/symptoms decreased by 4.0 and 8.0 points in women using Zelesse only and those using Zelesse plus antimicrobial therapy, respectively. This product was well tolerated and had high acceptability.
Conclusions
Zelesse cream relieves signs and symptoms of VV, either as monotherapy in non-infectious VV or as adjuvant to antimicrobial therapy in infectious VV. Future randomized, placebo-controlled trials with larger sample sizes are warranted.
Objective
To evaluate the efficacy, tolerability and acceptability of Zelesse®, an intimate hygiene wash solution, in the relief of the symptoms and signs of non-specific vulvovaginitis in paediatric ...patients.
Methods
The NINESSE Study was a prospective, observational, multicentre study involving females aged 2–8 years who attended paediatric offices with symptoms suggestive of non-specific vulvovaginitis. They were administered Zelesse® as a single treatment for 15 ± 5 days. Pruritus, burning, dysuria, erythema, leucorrhoea and oedema were evaluated before and after treatment.
Results
A total of 71 paediatric patients were enrolled in the study (mean ± SD age, 4.5 ± 1.9 years). The most significant effects were observed for pruritus and burning, where 98.4% (62 of 63) and 96.9% (63 of 65) of the patients improved after treatment, respectively. Zelesse® demonstrated a beneficial effect on dysuria, erythema, leucorrhoea and oedema. The effects on the symptoms and signs were observed within the first week of treatment; although 44.9% (31 of 69) of patients experienced improvements after 2–3 days. Zelesse® was well accepted and tolerated by most patients. No serious adverse events were reported.
Conclusions
Zelesse® was very effective for the relief of the symptoms and signs of non-specific vulvovaginitis, in particular pruritus, burning and erythema, in females aged 2–8 years.
Phagocytosis and killing of Streptococcus pneumoniae was compared in blood-derived wild-type (WT) and Toll-like receptor 2 (TLR2)-deficient (TLR2superscript -/-) polymorphonuclear leukocytes (PMN). ...Phagocytosis of green fluorescent protein-transformed pneumococci was delayed in TLR2superscript -/- PMN. These cells exhibited also a lower oxidative bactericidal activity against S. pneumoniae than WT PMN, suggesting that TLR2 modulates bacterial clearance in PMN.
This brief report evaluates the early effect of ultra-low dose 0.005% oestriol vaginal gel on dyspareunia in postmenopausal women within the first 2 weeks of treatment. This was a prospective and ...multicentre single-arm pilot study and the effect of the treatment on dyspareunia was evaluated by using a diary. In total 23 women and 150 coitus were studied. 8 coitus were painless in the first week and 42 during the second week (
< .0001). A reduction in pain from the baseline was seen in 116 (77.3%) out of the 150 coitus. 0.005% oestriol vaginal gel produced a rapid and progressive improvement in dyspareunia from the very first days of treatment in postmenopausal women.IMPACT STATEMENT
Local oestrogen therapy has shown efficacy in the treatment of genitourinary syndrome of menopause (GSM) and dyspareunia when used for a duration of greater than 3 weeks.
This study shows that the use of oestriol gel produces clinical effects from the beginning of its use, decreasing dyspareunia in postmenopausal women within just 14 days of daily use.
In cases of dyspareunia in relation to menopause, therapy with local oestrogens, in our case oestriol gel, produces an improvement from the beginning of its use. This information is clinically relevant when evaluating therapeutic options.
How Are the Gifted? Point of View of University Students Rodríguez-Nieto, Maria Concepción; Sánchez-González, Ana Sofía; Sánchez-Miranda, Martha Patricia
Education process: international journal,
2019, Letnik:
8, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The aim of the study was to analyze the conceptions of giftedness of average university students as they influence attitudes and behaviors that positively or negatively influence the emotional, ...academic and social wellbeing of the gifted. The study design was mixed method; the sample was non-probabilistic with 74 participants who answered an open-ended question about the characteristics and behaviors of the gifted. The results showed that conceptions of giftedness are formed by socioemotional characteristics and intellectual characteristics. Some students reported a single category of characteristics, whilst other students showed a combination of components from both categories. The socioemotional characteristics were perceived by some students as negative, whilst others were positive, and some presented a mixture of these two valences. The above-average intelligence was related to the ease, speed and passion for learning and the negative socioemotional characteristics of the gifted.
The aim of this study was to evaluate the efficacy and safety of a new low-concentration estriol formulation (0.005% estriol vaginal gel), providing an ultra low dose of estriol per application (50 ...μg), for the local treatment of postmenopausal vaginal atrophy.
Postmenopausal women with symptoms and signs of vaginal atrophy were enrolled in a prospective, double-blind, placebo-controlled study. Women received either 1 g of vaginal gel containing 50 μg of estriol or placebo gel, daily for 3 weeks and then twice weekly up to 12 weeks. A cytological vaginal study, evaluation of vaginal pH, and assessment of symptoms and signs of vaginal atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded.
A total of 167 women were included (114 received estriol and 53 received placebo). After 12 weeks of therapy, a superiority of estriol compared with placebo gel was shown in the change in maturation value and vaginal pH (P < 0.001 and P < 0.001, respectively). The superiority of estriol was well demonstrated in improvement of vaginal dryness (P = 0.001) and the Global Symptom Score (P = 0.018). Estriol gel proved also superior in the improvement of several of the most outstanding vaginal signs of vaginal atrophy evaluated. After 3 weeks, estriol gel also showed a superiority over the placebo gel in most symptoms and signs evaluated. Treatment-related adverse events were similar among groups.
0.005% Estriol vaginal gel, a new formulation providing an ultra low dose of estriol per application, was shown to be safe and effective in the treatment of postmenopausal vaginal atrophy.
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