Acute myocardial infarction therapy using calycosin and tanshinone co-loaded mitochondria targeted lipid-polymer hybrid nano-system: Preparation, characterization, and anti myocardial infarction activity assessment.

BACKGROUND: Acute myocardial infarction (AMI) is one of the most common ischemic heart diseases. However, lack of sufficient drug concentrations in the ischemic heart may led to treatment failure. It is urgent for researchers to engineer novel drug delivery systems to enhance the targeted delivery of cardioprotective agents. OBJECTIVE: The aim of the present study was to investigate the anti-AMI ability of calycosin (CAL) and tanshinone (TAN) co-loaded mitochondria targeted lipid-polymer hybrid nano-system. METHODS: CAL and TAN combined lipid-polymer hybrid nano-systems were prepared and MTP-131 was conjugated with PEG and modified onto the nanoparticles to achieve MTP-CAL/TAN NS. The physicochemical properties of nano-systems were characterized, the AMI therapy ability of the systems was investigated in AMI rats' model. RESULTS: The size of MTP-CAL/TAN NS was 168.7 ±â€¯5.1 nm, with a surface charge of - 21.3 ±â€¯2.3 mV. The area under the curve (AUC) and blood circulation half-life (T1/2) of MTP-CAL/TAN NS was 178.86 ±â€¯6.62 µg·min/mL and 0.47 h, respectively. MTP-CAL/TAN NS exhibited the most significant infarct size reduction effect of 23.9 %. CONCLUSION: MTP-CAL/TAN NS exhibited the highest heart accumulation and best infarct size reduction effect, which could be used as a promising system for efficient treatment of cardiovascular diseases.

Quantitative efficacy of soy isoflavones on menopausal hot flashes.

AIM: This study aimed to quantitate the efficacy of soy isoflavones in the treatment of menopausal hot flashes. METHODS: Model based meta-analysis (MBMA) was used to quantitate the efficacy of soy isoflavones. We conducted a systemic literature search to build a time-effect model for placebo and soy isoflavones in treating menopausal hot flashes. Studies were identified, subjected to inclusion and exclusion criteria, and reviewed. RESULTS: From 55 articles, 16 studies of soy isoflavones met the inclusion criteria, and contained 65 and 66 mean effect values in placebo and soy isoflavone groups, respectively, from about 1710 subjects. Interestingly, the developed model was found to describe adequately the time course of hot flashes reduction after administration of placebo and soy isoflavones. Using this model, we found that the maximal percentage change of hot flashes reduction by soy isoflavones was 25.2% after elimination of the placebo effect, accounting for 57% of the maximum effects of estradiol (Emax-estradiol = 44.9%). However, a time interval of 13.4 weeks was needed for soy isoflavones to achieve half of its maximal effects, much longer than estradiol, which only required 3.09 weeks. These results suggest that treatment intervals of 12 weeks are too short for soy isoflavones, which require at least 48 weeks to achieve 80% of their maximum effects. CONCLUSIONS: Soy isoflavones show slight and slow effects in attenuating menopausal hot flashes compared with estradiol.

Phytoestrogens and endometrial hyperplasia.

(1) Short-term clinical trials have shown that soy phytoestrogens have a slight preventive effect on hot flushes. However, this finding is based on a low level of evidence. (2) A double-blind placebo-controlled trial involving about 300 women and lasting 5 years showed that phytoestrogens were associated with an increase in the incidence of endometrial hyperplasia (3.8% versus 0%). (3) In practice, the risk-benefit ratio of phytoestrogens has not been adequately assessed. Their effect on the endometrium, and the many unknowns concerning the risk of thromboembolism and breast cancer, may offset the modest effect of phytoestrogens on hot flushes.

Psychological assessment of the effects of treatment with phytoestrogens on postmenopausal women: a randomized, double-blind, crossover, placebo-controlled study.

OBJECTIVE: To investigate the effects of soy isoflavones on mood and cognitive function in postmenopausal women. DESIGN: Randomized, double-blind, cross-over, placebo-controlled trial. SETTING: University Hospital, Milan, Italy; A.G.UN.CO. Obstetrics and Gynaecology Centre, Rome, Italy. PATIENT(S): Seventy-eight postmenopausal women. INTERVENTION(S): We administered 60 mg/day isoflavones or placebo for 6 months. After a washout period of 1 month, the patients who had been treated with phytoestrogens received placebo, and those who previously received placebo were administered phytoestrogens (for 6 months). MAIN OUTCOME MEASURE(S): Cognitive performance and mood were assessed by a battery of tests at the end of each treatment period. At the end of the study, the patients were also asked whether they preferred the first or second treatment. RESULT(S): The 17 scores on cognitive performance test and the 6 for mood assessments 6 showed an advantage for the treatment with phytoestrogens. Similarly, of the 8 visual analogue scales used to indicate mood, 7 improved significantly after the treatment with phytoestrogens. Moreover, 49 patients preferred phytoestrogens, 9 placebo, and 18 had no preference. The preference was not related to the order of treatment. CONCLUSION(S): These results suggest that isoflavones may have positive effects on postmenopausal women improving cognitive performance and mood.

Benefits of soy isoflavone therapeutic regimen on menopausal symptoms.

OBJECTIVE: To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100-mg soy isoflavone in postmenopausal women. METHODS: In this double-blind, placebo-controlled study, 80 women were randomly assigned to isoflavone (n = 40) and placebo (n = 40) treatment. The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment. Cardiovascular risk factors were assessed by evaluating plasma lipid levels, body mass index, blood pressure, and glucose levels in the participants. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and 17 beta-estradiol were measured. Transvaginal sonography was performed to quantify endometrial thickness. RESULTS: The data showed a decrease in menopausal symptoms (P <.01, paired t test, two-tailed, between baseline and isoflavone groups, and P <.01, unpaired t test, between placebo and isoflavone groups). Total cholesterol and low-density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group (P <.001, paired t test, two-tailed, between baseline and isoflavone groups, and P <.01, unpaired t test, between placebo and isoflavone groups). The isoflavone treatment appeared to have no effect on blood pressure, plasma glucose, and high-density lipoprotein and triglyceride levels. CONCLUSION: This study suggests that isoflavone 100-mg regime treatment may be a safe and effective alternative therapy for menopausal symptoms and may offer a benefit to the cardiovascular system.

[Long-term assessment of bone loss in patients treated with GnRH agonists]. / Valutazione a lungo termine della perdita calcica ossea nelle pazienti trattate con GnRH Agonisti.

GnRH Analogues therapy of estrogen-dependent gynaecological diseases aims at suppression of physiologic ciclic ovaric function producing a hypogonadotropic condition. The first consequence of GnRH Analogues administration is hypoestrogenism; this condition permits the disease regression but, on the other, it causes a negative impact on bone metabolism particularly for prolonged therapeutic schemes (6 months). This study has evaluated the faculty of bone mass protection combining GnRH Analogues therapy with Ipriflavone that stimulates, both "in vivo" and "in vitro", Osteoblastic cells activity. The result of this study showed a significant bone loss in patients treated with GnRH Analogues only. The Ipriflavone association prevented bone loss.