Safety and efficacy of pimecrolimus versus vehicle for the treatment of atopic dermatitis in adults and paediatric population: a systematic review and meta-analysis.

Atopic dermatitis remains a widespread problem affecting various populations globally. While numerous treatment options have been employed, pimecrolimus remains a potent and viable option. Recently, there has been increasing interest in comparing the safety and efficacy of pimecrolimus with its vehicle. Methods: The authors conducted a comprehensive search of several databases, including PubMed, COCHRANE, MEDLINE, and Cochrane Central, from inception to May 2022, using a wide search strategy with Boolean operators. The authors also employed backward snowballing to identify any studies missed in the initial search. The authors included randomized controlled trials in our meta-analysis and extracted data from the identified studies. The authors used Review Manager (RevMan) Version 5.4 to analyze the data, selecting a random-effects model due to observed differences in study populations and settings. The authors considered a P-value of 0.05 or lower to be statistically significant. Results: The authors initially identified 211 studies, of which 13 randomized controlled trials involving 4180 participants were selected for analysis. Our pooled analysis revealed that pimecrolimus 1% was more effective at reducing the severity of atopic dermatitis than its vehicles. However, no significant difference was observed in adverse effects between pimecrolimus and vehicle, except for pyrexia, nasopharyngitis, and headache, which were increased with pimecrolimus. Conclusion: Our meta-analysis showed that pimecrolimus 1% is more effective than vehicle, although the safety profile remains inconclusive. Pimecrolimus reduced the Investigator's Global Assessment score, Eczema Area and Severity Index score, and severity of pruritus when compared to its vehicle, indicating a higher efficacy profile. This is one of the first meta-analyses to assess the efficacy and safety profile of pimecrolimus 1% against a vehicle and may assist physicians in making informed decisions.

Spironolactone reversed hepato-ovarian triglyceride accumulation caused by letrozole-induced polycystic ovarian syndrome: tissue uric acid-a familiar foe.

Polycystic ovarian syndrome (PCOS) is a complex endocrine disease among women of reproductive age and is one of the main causes of infertility. Non-alcoholic fatty liver disease (NAFLD), the most prominent chronic liver disease in adults, is characterized by excess hepatic triglyceride (TG) accumulation. PCOS women have increased risk of NAFLD and uric acid has been documented to have a positive correlation with subclinical tissue damage and might be the link in the cystic. Spironolactone (SPL) is a mineralocorticoid receptor (MR) blocker that has been in wide clinical use for some decades. In this research, we investigated the effects of SPL on ovarian and hepatic tissue damage in experimental PCOS rats induced by letrozole (LET). A total of eighteen adult female Wistar rats were used for this study and the animals divided into 3 groups are treated with vehicle, LET (1 mg/kg), and LET+SPL (SPL; 0.25 mg/kg), p.o. once daily respectively for 21 uninterrupted days. Results showed that LET treatment induced features of PCOS characterized by increased plasma testosterone (T) and luteinizing hormone (LH) together with increased body weight. Abnormal ovarian and hepatic histomorphological changes were also observed with elevated uric acid (UA) and TG accumulation in both tissues respectively. Treatment with SPL however attenuated the elevated testosterone in the LET-induced PCOS model accompanied with a reversal in the observed ovarian and hepatic UA, TG accumulation, and altered histomorphological changes. Taken together, spironolactone reversed the PCOS-induced ovarian and hepatic tissue damage by suppressing tissue UA and TG accumulation.

Very low dose spironolactone protects experimentally-induced polycystic ovarian syndrome from insulin-resistant metabolic disturbances by suppressing elevated circulating testosterone.

Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women of reproductive age and hyperandrogenism is a prominent feature of PCOS resulting in infertility and increased risk of developing metabolic disorders including insulin resistance (IR), abdominal adiposity, glucose intolerance and cardiovascular diseases. Spironolactone (SPL), a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. In this study, we investigated the effects of SPL on IR and metabolic disturbances in letrozole-induced PCOS rats. Eighteen adults female Wistar rats were randomly divided into 3 groups and treated with vehicle, letrozole (LET; 1 mg/kg) and LET + SPL (SPL; 0.25 mg/kg), p.o. once daily for 21 consecutive days. Results showed that LET treatment induced PCOS characterised by elevated plasma testosterone and luteinizing hormone (LH) accompanied with increased body weight and visceral adiposity, IR, glucose intolerance, dyslipidemia and altered histomorphological ovaries. Treatment with SPL however attenuated the elevated testosterone in LET-induced PCOS model accompanied with a reversal in all the observed alterations. Taken together, analysis of the physical, biochemical and histological evidences shows that the protective effect of this very low dose spironolactone may be through its anti-androgenic mechanism.