Uterine fibroids : from observational epidemiology to clinical management

According to this systematic review of epidemiological studies, fibroid prevalence varied widely, with no consistent association across studies between observed estimates and country, methodology, and population. Fibroid incidence was higher in black than in white women independently of other risk factors, suggesting a racial predisposition. A genetic influence was confirmed also by the association with a positive family history. The association with age and menopausal status maybe interpreted in terms of varying degrees of oestrogen exposure, which could explain also the association with food additives and soybean consumption. Along this line, the "anti-oestrogenic" effect of smoking was observed only in women with low BMI. Association were observed also with reproductive factors (parity and time since last birth) and oral/injectable contraceptives

Antioxidant and Anti-Inflammatory Activities of Flavanones from Glycyrrhiza glabra L. (licorice) Leaf Phytocomplexes: Identification of Licoflavanone as a Modulator of NF-kB/MAPK Pathway

Inflammation represents an adaptive response generated by injuries or harmful stimuli. Natural remedies represent an interesting alternative to traditional therapies, involving several biochemical pathways. Besides, the valorization of agrochemical wastes nowadays seems to be a feasible way to reduce the health spending and improve the accessibility at bioactive natural compounds. In this context, the chemical composition of three Glycyrrhiza glabra L. (licorice) leaf extracts, obtained through maceration or ultrasound-assisted method (fresh and dried leaves) was investigated. A guided fractionation obtained three main components: pinocembrin, glabranin and licoflavanone. All the extracts showed similar antioxidant properties, evaluated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) or 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Diammonium Salt (ABTS) assay, while, among the isolated compounds, licoflavanone exhibited the best antioxidant activity. The anti-inflammatory activity of the extracts and the purified compounds was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Extract C and licoflavanone showed a good anti-inflammatory activity without affecting cell viability, as they decreased nitrite levels even when used at 12.5 μg/mL (p < 0.005) and 50 μM concentration (p < 0.001), respectively. Interestingly, licoflavanone markedly decreased pro-inflammatory cytokines and cyclooxygenase 2/inducible nitric oxide synthase (COX-2/iNOS) expression levels (p < 0.001). A modulation of nuclear factor kappa B/mitogen-activated protein kinases (NF-kB/MAPK) pathway underlay such behavior, highlighting the potential of this natural compound as a new scaffold in anti-inflammatory drug research

exploring the relationship between endometriomas and infertility

Several clinical and epidemiological studies demonstrated an association between endometriosis and infertility. A role in the genesis of infertility may be played by endometriomas, which may interfere with ovulation or damage ovarian tissue. Unlike peritoneal implants, the availability of an accurate noninvasive sonographic diagnosis facilitates the investigation of endometrioma associated infertility. The laparoscopic excision of an endometrioma relieves the ovary from the damage caused by the cyst itself, which may be progressive over time, but at the same time is associated with a detrimental effect on ovarian reserve and with high rates of postoperative endometrioma recurrence. Therefore, the management of endometrioma-related infertility should not be based upon surgery alone, but upon a combination of surgery, with a refinement of the operating technique, long-term oral contraceptive, in vitro fertilization and oocyte cryopreservation

5-(carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ROS levels and mitochondrial dysfunction in breast and cervical cancer

Oxazolidinones are antibiotics that inhibit protein synthesis by binding the 50S ribosomal subunit. Recently, numerous worldwide researches focused on their properties and possible involvement in cancer therapy have been conducted. Here, we evaluated in vitro the antiproliferative activity of some 5-(carbamoylmethylene)-oxazolidin-2-ones on MCF-7 and HeLa cells. The tested compounds displayed a wide range of cytotoxicity on these cancer cell lines, measured by MTT assay, exhibiting no cytotoxicity on non-tumorigenic MCF-10A cells. Among the nine tested derivatives, four displayed a good anticancer potential. Remarkably, OI compound showed IC50 values of 17.66 and 31.10 µM for MCF-7 and HeLa cancer cells, respectively. Furthermore, we assessed OI effect on the cell cycle by FACS analysis, highlighting a G1 phase arrest after 72 h, supported by a low expression level of Cyclin D1 protein. Moreover, mitochondrial membrane potential was reduced after OI treatment driven by high levels of ROS. These findings demonstrate that OI treatment can inhibit MCF-7 and HeLa cell proliferation and induce apoptosis by caspase-9 activation and cytochrome c release in the cytosol. Hence, 5-(carbamoylmethylene)-oxazolidin-2-ones have a promising anticancer activity, in particular, OI derivative could represent a good candidate for in vivo further studies and potential clinical use

a genomics based approach identifies a thioviridamide like compound with selective anticancer activity

Thioviridamide is a structurally novel ribosomally synthesized and post-translational modified peptide (RiPP) produced by Streptomyces olivoviridis NA005001. It is characterized by a structure that features a series of thioamide groups and possesses potent antiproliferative activity in cancer cell lines. Its unusual structure allied to its promise as an anticancer compound led us to investigate the diversity of thioviridamide-like pathways across sequenced bacterial genomes. We have isolated and characterized three diverse members of this family of natural products. This characterization is supported by transformation-associated recombination cloning and heterologous expression of one of these compounds, thiostreptamide S4. Our work provides an insight into the diversity of this rare class of compound and indicates that the unusual N-terminus of thioviridamide is not introduced biosynthetically but is instead introduced during acetone extraction. A detailed analysis of the biological activity of one of th..

The ominous association between severe endometriosis, in-vitro fertilisation, and placenta praevia : Raising awareness, limiting risks, informing women

Endometriosis is associated with several adverse pregnancy outcomes.(1) The most severe maternal complications are spontaneous haemoperitoneum in the second half of pregnancy and placenta praevia.(1) Spontaneous haemoperitoneum, mostly associated with endometriosis infiltrating the broad and uterosacral ligaments and the Douglas pouch, is a potentially fatal but rare event. Placenta praevia is more common,(1-3) and it is important to define its incidence, the association with different lesion types, the impact of additional risk factors, the potential obstetrical consequences, and the information that women should receive

Surgery versus hormonal therapy for deep endometriosis : is it a choice of the physician?

Deep endometriosis, occurring approximately in 1% of women of reproductive age, represents the most severe form of endometriosis. It causes severe pain in the vast majority of affected women and it can affect the bowel and the urinary tract. Hormonal treatment of deep endometriosis with progestins, such as norethindrone acetate or dienogest, or estroprogestins is effective in relieving pain in more than 90% of women at one year follow up. Progestins and estroprogestins can be safely administered in the long-term, may be not expensive and are usually well tolerated. Therefore, they should represent the first-line treatment of deep endometriosis associated pain in women not seeking natural conception. However, hormonal treatment is ineffective or not tolerated in about 30% of women, the most common side effects being erratic bleeding, weight gain, decreased libido and headache. Surgical excision of deep endometriosis is mandatory in presence of symptomatic bowel stenosis, ureteral stenosis with secondary hydronephrosis, and when hormonal treatments fail. Surgical treatment is similarly effective as compared to hormonal treatment in relieving dismenorhea, dyspareunia and dyschezia at one year follow up in more than 90% of women with deep endometriosis. Surgical removal of the nodules may require resection of the bowel, ureter or bladder, with possible severe complications such as rectovaginal or ureterovaginal fistula and anastomotic leakage. A thorough counsel with the patient is necessary in order to pursue a therapeutic plan centered not on the endometriotic lesions, but on the patient's symptoms, priorities and expectations

Advances in the medical management of bowel endometriosis

Endometriosis infiltrating the bowel can be treated medically in accurately selected women not seeking conception and without overt obstructive symptomatology. When the rectosigmoid junction is involved, the probabilities of intestinal symptoms relief, undergoing surgery after treatment failure, and developing bowel obstruction during hormonal treatment are around 70%, 10%, and 1-2%, respectively. When the lesion infiltrates exclusively the mid-rectum, thus in cases of true rectovaginal endometriosis, the probabilities of intestinal symptoms relief and undergoing surgery are about 80% and 3%, respectively. Endometriotic obstructions of the rectal ampulla have not been reported. A rectosigmoidoscopy or colonoscopy should be performed systematically before starting medical therapies, also to rule out malignant tumours arising from the intestinal mucosa. Progestogens are safe, generally effective, well-tolerated, inexpensive, and should be considered as first-line medications for bowel endometriosis. Independently of symptom relief, intestinal lesions should be checked periodically to exclude nodule progression during hormonal treatment

Medical treatment of endometriosis-related pain

Available medical treatments for symptomatic endometriosis act by inhibiting ovulation, reducing serum oestradiol levels, and suppressing uterine blood flows. To this aim, several drugs can be used, with a similar magnitude of effect, in term of pain relief, independently of the mechanism of action. Conversely, safety, tolerability, and cost differ. Medications for endometriosis can be categorised into low-cost drugs, including OCs and most progestogens, and high cost drugs, including dienogest and GnRH agonists. As the individual response to different drugs is variable, a stepwise approach is suggested, starting with OCs or low-cost progestogens, and stepping up to high-cost drugs only in case of inefficacy or intolerance. Oral contraceptives may be used in women with dysmenorrhoea as their main complaint, and when only superficial peritoneal implants or ovarian endometriomas < 5 cm are present, while progestogens should be preferred in women with severe deep dyspareunia and when infiltrating lesions are identified