Background Oral fluconazole is used to treat vulvovaginal candidiasis during pregnancy. However, there are concerns regarding the pregnancy outcomes following exposure to fluconazole.Objectives To evaluate the pregnancy outcomes associated with exposure to oral fluconazole during the first trimester of pregnancy.Search strategy A systematic literature search was conducted to identify relevant studies published from inception until April 2019.Selection criteria Relevant English-language citations using the terms oral fluconazole and pregnancy in humans.Data collection Two reviewers independently abstracted data and assessed study quality.Main results Oral fluconazole use during the first trimester of pregnancy was marginally associated with an increased risk of congenital malformations (odds ratio [OR] 1.09, 95% CI 0.99-1.2, P = 0.088; n = 6 studies), whereas in the subgroup analysis, this association existed only for high-dose users (>150 mg) (OR 1. 19, 95% CI 1.01-1.4, P = 0.039; n = 2). Exposure to fluconazole also increased the risk of heart malformations (OR 1.31, 95% CI 1.09-1.57, P = 0.003; n = 4), cardiac septal defects (OR 1.3, 95% CI 1.1-1.67, P = 0.047; n = 3), and tetralogy of Fallot (OR 3.39 95% CI 1.71-6.74, P < 0.001; n = 2) in the offspring. In addition, exposure to fluconazole was significantly associated with an increased risk of spontaneous abortion (OR 1.99, 95% CI 1.38-2.88, P < 0.001; n = 3).Conclusions Oral fluconazole use during the first trimester of pregnancy appears to be associated with heart malformations and spontaneous abortion, but a causal link cannot be proven.Tweetable abstract Oral fluconazole during the first trimester of pregnancy may be associated with unfavourable pregnancy outcomes.

Diabetic nephropathy is a major complication facing patients with diabetes mellitus. The renal protective effects of the phosphodiesterase III inhibitor, cilostazol, were investigated in rats with streptozotocin-induced diabetes. Expression of thrombospondin-1 (TSP-1) and transforming growth factor-b (TGF-b) in the kidney was measured by immunohistochemistry and real-time reverse transcription-quantitative polymerase chain reaction analysis in diabetic rats, cilostazol-treated diabetic rats and control rats. Ultrastructural changes in the kidney were also analysed using microscopy. Four weeks after the induction of diabetes, TSP-1 and TGF-b expression was significantly increased in the kidneys of diabetic rats compared with the control and was significantly lower in cilostazol-treated diabetic rats than in the untreated diabetic rats. Microscopy revealed characteristic renal pathology in the diabetic group, which was rarely seen in the cilostazoltreated diabetic rats. In conclusion, this study indicates that cilostazol treatment of diabetic rats effectively prevents pathological kidney changes, possibly via the down-regulation of TSP-1 and TGF-b expression compared with untreated rats.

This study aimed to look at whether a correlation exists between telomerase activity and survival of laryngeal carcinoma patients. Telomerase activity was measured by telomerase repeat amplification protocol in 31 laryngeal carcinomas and adjacent normal tissues, and in 21 vocal cord polyps (controls). Follow-up was for at least 60 months. Telomerase activity in tissues adjacent to laryngeal carcinomas was significantly higher than in the carcinomas which was, in turn, significantly higher than in vocal cord polyps. There was no significant difference between telomerase activity in carcinomas or adjacent tissues and clinicopathological characteristics. Patients with high telomerase activity in carcinoma tissue had significantly shorter survival times than those with low activity, but no significance difference was observed between survival time and telomerase status in adjacent tissues. Linear regression showed significant association between telomerase activity levels in carcinoma tissues and survival time, but this was not observed in adjacent tissues. This study suggests that telomerase activation probably takes place before the cancer phenotype develops and has prognostic significance for survival of patients with laryngeal carcinoma.

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