Redesigning Solvatochromic Probe Laurdan for Imaging Lipid Order Selectively in Cell Plasma Membranes.

Imaging of biological membranes by environmentally sensitive solvatochromic probes, such as Laurdan, provides information about the organization of lipids, their ordering, and their uneven distribution. To address a key drawback of Laurdan linked to its rapid internalization and subsequent labeling of internal membranes, we redesigned it by introducing a membrane anchor group based on negatively charged sulfonate and dodecyl chain. The obtained probe, Pro12A, stains exclusively the outer leaflet of lipid bilayers of liposomes, as evidenced by leaflet-specific fluorescence quenching with a viologen derivative, and shows higher fluorescence brightness than Laurdan. Pro12A also exhibits stronger spectral change between liquid-ordered and liquid-disordered phases in model membranes and distinguishes better lipid domains in giant plasma membrane vesicles (GPMVs) than Laurdan. In live cells, it stains exclusively the cell plasma membranes, in contrast to Laurdan and its carboxylate analogue C-Laurdan. Owing to its outer leaflet binding, Pro12A is much more sensitive to cholesterol extraction than Laurdan, which is redistributed within both plasma membrane leaflets and intracellular membranes. Finally, its operating range in the blue spectral region ensures the absence of crosstalk with a number of orange/red fluorescent proteins and dyes. Thus, Pro12A will enable accurate multicolor imaging of lipid organization of cell plasma membranes in the presence of fluorescently tagged proteins of interest, which will open new opportunities in biomembrane research.

Preventive Beneficial Effect of an Aqueous Extract of Phyllanthus amarus Schum. and Thonn. (Euphorbiaceae) on DOCA-Salt-Induced Hypertension, Cardiac Hypertrophy and Dysfunction, and Endothelial Dysfunction in Rats.

This study investigated the preventive effect of an aqueous extract of the whole plant of Phyllanthus amarus (AEPA) on blood pressure, cardiac, and endothelial function in the deoxycorticosterone acetate (DOCA) salt-induced hypertensive rat model. Male Wistar rats were assigned into 5 groups receiving either vehicle (control and DOCA salt), DOCA salt combined with AEPA at 100 or 300 mg/kg, or AEPA (100 mg/kg) alone for 5 weeks. In addition, DOCA salt-treated rats were allowed free access to water containing 1% NaCl. Systolic blood pressure, left ventricle parameters, vascular reactivity of primary mesenteric artery rings, the vascular level of oxidative stress, and the level of target proteins were determined, using respectively tail-cuff sphygmomanometry, echocardiography, organ chambers, dihydroethidium staining, and immunofluorescence methods. After 5 weeks, AEPA treatments (100 or 300 mg/kg per day) significantly prevented the increase in systolic blood pressure in DOCA salt-treated rats, respectively, by about 24 and 21 mm Hg, improved cardiac diastolic function, and reduced significantly the increased posterior and septum diastolic wall thickness and the left ventricle mass in hypertensive rats. Moreover, the DOCA salt-induced endothelial dysfunction and the blunted nitric oxide- and endothelium-dependent hyperpolarization-mediated relaxations in primary mesenteric artery were improved after the AEPA treatments. AEPA also reduced the level of vascular oxidative stress and the expression level of target proteins (eNOS, COX-2, NADPH oxidase subunit p22) in DOCA salt rats. Altogether, AEPA prevented hypertension, improved cardiac structure and function, and improved endothelial function in DOCA salt rats. Such beneficial effects seem to be related, at least in part, to normalization of the vascular level of oxidative stress.

The acute diuretic effect of an ethanolic fraction of Phyllanthus amarus (Euphorbiaceae) in rats involves prostaglandins.

BACKGROUND: Phyllanthus amarus (Schum & Thonn), a plant belonging to the family of Euphorbiaceae is used in Ivorian traditional medicine to treat cardiovascular disorders such as hypertension. However, although this plant has been described as a diuretic agent, the underlying mechanism remains unclear. Therefore, the aim of the present study was to investigate the mechanism action of diuretic effects of an ethanolic fraction of Phyllanthus amarus (EFPA) in rats. METHODS: Effects of EFPA on urinary excretion were carried out for doses ranging from 5 to 80 mg/kg given by intraperitoneal injection (i.p.) and compared with that induced by furosemide (5 mg/kg) after 8 h. Thereafter, the diuretic activity of EFPA was also evaluated in the presence of indomethacin (5 mg/kg, i.p.) in order to determine the involvement of prostaglandins, after 24 h. RESULTS: Between 5 and 80 mg/kg, EFPA induced a significant urinary excretion. The profile of urinary excretion showed that after 2 h, the highest dose of 80 mg/kg induced a urinary volumetric excretion (UVE), which was similar to that induced by furosemide. After 24 h, EFPA at 10 mg/kg increased significantly UVE, Na+ (43 mEq) and Cl¯ (97 mEq) urinary excretions without promoting kaliuresis. In rats pretreated with indomethacin, the urinary excretion and the natriuretic response of EFPA were significantly reduced. CONCLUSION: Altogether, this study has shown that EFPA promotes a significant urinary excretion of water and Na+, confirming its diuretic activity. Moreover, the increased diuresis could be attributed, at least in part, to the involvement of prostaglandins.

Assessment of Synthetic Glue for Mesh Attachment in Laparoscopic Sacrocolpopexy: A Prospective Multicenter Pilot Study.

STUDY OBJECTIVE: To assess the anatomic efficacy and safety of synthetic glue to fix prosthetic material in laparoscopic sacrocolpopexy. DESIGN: A 1-year follow-up in a prospective multicenter pilot study between November 2013 and November 2014 (Canadian Task Force Classification II-2). SETTING: An academic urogynecology research hospital. PATIENTS: Seventy consecutive patients with Pelvic Organ Prolapse Quantification stage ≥3 anterior and/or medial prolapse underwent laparoscopic sacrocolpopexy. INTERVENTIONS: All women underwent laparoscopic sacrocolpopexy with the same standardized technique using a synthetic surgical glue to fix anterior and posterior meshes. MEASUREMENTS AND MAIN RESULTS: Patients were followed up at 1 month and 1 year, with anatomic and functional assessment (Pelvic Floor Distress Inventory-20, Pelvic Floor Impact Questionnaire-7, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12). Anatomic success was defined as 1-year Pelvic Organ Prolapse Quantification stage ≤1. Sixty-six patients were included; the mean age was 56.7 ± 1.2 years. The mean operative time was 145 ± 5 minutes. The mean glue fixation time was less than 2 minutes for both anterior and posterior meshes. The 1-year anatomic success rate was 87.5% in the anterior compartment (Ba at -2.3 cm, p < .0001) and 95.3% in the medial compartment (point C at -6.1 cm, p < .0001). There were no intra- or postoperative complications and no cases of mesh exposure; 5 cases of mesh shrinkage (7.8%) were observed at 1 year. The postoperative urinary stress incontinence rate was 29.7% at 1 year. Eight patients (12.1%) underwent revision surgery with transobturator tape. All quality of life scores showed significant improvement (p < .0001) at 1 year. CONCLUSION: Synthetic glue attachment of prosthetic material in laparoscopic sacrocolpopexy proved straightforward, safe, time-saving, and effective at 1 year. Prospective randomized studies will be needed to confirm the long-term benefit.

Potential of Food and Natural Products to Promote Endothelial and Vascular Health.

Endothelial dysfunction is now well established as a pivotal early event in the development of major cardiovascular diseases including hypertension, atherosclerosis, and diabetes. The alteration of the endothelial function is often triggered by an imbalance between the endothelial formation of vasoprotective factors including nitric oxide (NO) and endothelium-dependent hyperpolarization, and an increased level of oxidative stress involving several prooxidant enzymes such as NADPH oxidase and, often also, the appearance of cyclooxygenase-derived vasoconstrictors. Preclinical studies have indicated that polyphenol-rich food and food-derived products such as grape-derived products, black and red berries, green and black teas and cocoa, and omega-3 fatty acids can trigger activating pathways in endothelial cells promoting an increased formation of nitric oxide and endothelium-dependent hyperpolarization. Moreover, intake of such food-derived products has been associated with the prevention and/or the improvement of an established endothelial dysfunction in several experimental models of cardiovascular diseases and in humans with cardiovascular diseases. This review will discuss both experimental and clinical evidences indicating that different types of food and natural products are able to promote endothelial and vascular health, as well as the underlying mechanisms.

The genital prolapse of Australopithecus Lucy?

INTRODUCTION AND HYPOTHESIS: The female bony pelvis has to fulfil opposing functions: it has to be sufficiently closed to support the pelvic viscera in the upright position, while remaining sufficiently open to allow vaginal delivery. We aim to give an evolutionary perspective and the possible evolution of the bony pelvis from Lucy to the modern female with the implications in terms of genital prolapse. METHODS: Thirteen pelvimetric measurements were performed on 178 bony pelves: 1 fossil pelvis from Australopithecus Lucy, 128 female Caucasian modern adult pelves and 49 female Catarrhine pelves (29 gorillas and 20 chimpanzees). RESULTS: Lucy's pelvis shape was the most transversely oval, short and broad, termed platypelloid. Modern female pelves were transversely oval only at the inlet. A protruding ischial spine, fairly small ischial tuberosities and a sacral concavity made Lucy closer to Homo sapiens and less like the great apes. In the last group, pelvic planes were anteroposteriorly oval, except in the gorilla, where the outlet was round or slightly transversely oval. The subpubic angle was narrowest in Lucy, whereas it was greater than 90° in the great apes. CONCLUSIONS: The female pelvis is involved in both visceral support and parturition and represents a compromise. The narrower pelvis of Australopithecus Lucy provided protection against genital prolapse, but resulted in complex obstetrical mechanics. From an evolutionary perspective, the pelvis of Homo sapiens became modified to make parturition easier, but increased the risk of genital prolapse: the ilia became wide open laterally and the sacrum broadened with a shorter distance between the sacroiliac and coxofemoral joints.

Long-term outcome after overlapping anterior anal sphincter repair for fecal incontinence.

PURPOSE: The aim was to assess long-term results and quality of life following anterior anal sphincter repair for anal incontinence. PATIENTS AND METHODS: Twenty-three female patients underwent anterior anal sphincteroplasty over a 10-year period between January 1999 and January 2009 in a gynecological surgery department. Patients were asked to complete pre- and postoperative questionnaires comprising the Jorge and Wexner incontinence score. The secondary objective was to assess pre- and post-sphincteroplasty symptom severity and sexual quality of life. Mean follow-up was 87 months (median, 91.5 months). Kaplan-Meier time-to-event analysis was applied. RESULTS: Mean age was 52 years (±15.2), and mean postoperative Jorge and Wexner score, 7.5/20 (±4.1). Seventeen patients (85 %) declared themselves satisfied by the repair; 12 (60 %) showed good fecal continence. Fecal incontinence had a negative impact on quality of life for 15 % and on sexuality for 50 % of patients. Kaplan-Meier analysis showed 85 % conservation of anal continence correction at 1 year, 74 % at 48 months, 67 % at 60 months, and 48 % at 84 months. CONCLUSIONS: Overlapping anterior anal sphincter repair provided lasting improvement in fecal incontinence, with satisfactory long-term functional results. At 84 months' follow-up, 48 % of patients maintained good fecal continence, with a satisfaction rate of 85 %. Anal sphincteroplasty may be a first-line attitude in young female fecal incontinence patients with a recent sphincter defect following initially undiagnosed obstetric trauma and also restores perineal comfort.

The EGCg-induced redox-sensitive activation of endothelial nitric oxide synthase and relaxation are critically dependent on hydroxyl moieties.

Several rich sources of polyphenols stimulate the endothelial formation of nitric oxide (NO), a potent vasoprotecting factor, via the redox-sensitive activation of the PI3-kinase/Akt pathway leading to the phosphorylation of endothelial NO synthase (eNOS). The present study examined the molecular mechanism underlying the stimulatory effect of epicatechins on eNOS. NO-mediated relaxation was assessed using porcine coronary artery rings in the presence of indomethacin, and charybdotoxin plus apamin, inhibitors of cyclooxygenases and EDHF-mediated responses, respectively. The phosphorylation level of Akt and eNOS was assessed in cultured coronary artery endothelial cells by Western blot, and ROS formation using dihydroethidine. (-)-Epigallocatechin-3-O-gallate (EGCg) caused endothelium-dependent relaxations in coronary artery rings and the phosphorylation of Akt and eNOS in endothelial cells. These responses were inhibited by membrane-permeant analogues of superoxide dismutase and catalase, whereas native superoxide dismutase, catalase and inhibitors of major enzymatic sources of reactive oxygen species including NADPH oxidase, xanthine oxidase, cytochrome P450 and the mitochondrial respiration chain were without effect. The EGCg derivative with all hydroxyl functions methylated induced neither relaxations nor the intracellular formation of ROS, whereas both responses were observed when the hydroxyl functions on the gallate moiety were present. In conclusion, EGCg causes endothelium-dependent NO-mediated relaxations of coronary artery rings through the Akt-dependent activation of eNOS in endothelial cells. This response is initiated by the intracellular formation of superoxide anions and hydrogen peroxide, and is critically dependent on the gallate moiety and on the presence of hydroxyl functions possibly through intracellular auto-oxidation.

Structure elucidation of new acacic acid-type saponins from Albizia coriaria.

Three new acacic acid derivatives, named coriariosides C, D, and E (1-3) were isolated from the roots of Albizia coriaria. Their structures were elucidated on the basis of extensive 1D- and 2D-NMR studies and mass spectrometry as 3-O-[ß-D-xylopyranosyl-(1 → 2)-ß-D-fucopyranosyl-(1 → 6)-2-(acetamido)-2-deoxy-ß-D-glucopyranosyl]-21-O-{(2E,6S)-6-O-{4-O-[(2E,6S)-2,6-dimethyl- 6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-ß-D-quinovopyranosyl}-2,6-dimethylocta-2,7-dienoyl}acacic acid 28-O-ß-D-xylopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (1), 3-O-{ß-D-fucopyranosyl-(1 → 6)-[ß-D-glucopyranosyl-(1 → 2)]-ß-D-glucopyranosyl}-21-O-{(2E,6S)-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-ß-D-quinovopyranosyl}-2,6-dimethylocta-2,7-dienoyl}acacic acid 28-O-α-L-rhamno pyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (2), and 3-O-[ß-D-fucopyranosyl-(1 → 6)-ß-D-glucopyranosyl]-21-O-{(2E,6S)-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl)-ß-D-quinovopyranosyl]octa-2,7-dienoyl}acacic acid 28-O-ß-D-glucopyranosyl ester (3).

Technical trick to limit excess skin ("dog-ears") at the ends of a mastectomy scar.

The unsightly excess skin located at the two ends of the scar of a mastectomy ("dog-ears"), beyond the aesthetic discomfort that they generate, can be responsible for functional impediments. These commonly occur when closing oval or circular defects. These skin excesses require then complementary resections by an incision at their base, at the cost of an extension of the original scar, sometimes during a second surgical operation. We describe a simple technique that can help to improve the cosmetic results and limit this scar ransom.

Outpatient vaginal surgery for pelvic organ prolapse: a prospective feasibility study.

BACKGROUND: In the light of recent progress in pelvic organ prolapse surgery, the modalities of hospital admission need reconsidering. This work aims to assess success rate of outpatient (ambulatory) vaginal mesh surgery for genital prolapse. METHODS: A prospective observational study was conducted between January 2015 and July 2017, including all patients presenting with POP-Q stage ≥3 anterior and/or apical prolapse. RESULTS: Sixty-nine of the 89 eligible patients were treated on an ambulatory basis (group A); 20 required overnight admission (group B): i.e., ambulatory success rate, 77.5%. Mean operative time was 44.9±2.5 min in group A and 62±6.5 min in group B. Reasons for ineligibility for ambulatory management comprised organizational issues at home (10.5%) and excessive home-to-hospital distance (5.7%). The postoperative urinary retention rate was 4.5%. Rates for successful cystocele correction (POP-Q <2) at 2 months were similar in the two groups: 94.2% in group A and 94.4% in group B (P=ns). Mean satisfaction score was 8.6±0.3/10. CONCLUSIONS: Outpatient anterior vaginal mesh surgery for prolapse is safe and effective. The current medical-economic context favors ambulatory management. Patient selection, prior information and continuity of care seem primordial.

Red Wine Extract Disrupts Th17 Lymphocyte Differentiation in a Colorectal Cancer Context.

SCOPE: Scope: It is well established that immune response and inflammation promote tumoral progression. Immune cells communicate through direct contact or through cytokine secretion, and it is the pro-inflammatory status that will tip the balance toward tumor progression or anti-tumor immunity. It is demonstrated here that a red wine extract (RWE) can decrease inflammation through its action on the inflammasome complex. This study determines whether an RWE could impact other key actors of inflammation, including T helper 17 (Th17) immune cells in particular. METHODS AND RESULTS: Methods and results: Using an RWE containing 4.16 g of polyphenols/liter of wine, it is shown that RWE decreases colorectal cancer cells in vitro and induces a reduction in colorectal tumor growth associated with a decrease in tumor-infiltrating lymphocytes in vivo. The process of T-lymphocyte differentiation in Th17 cells is altered by RWE, as revealed by the decrease in the expression of key actors controlling this process, such as signal transducer and activator of transcription 3 and retinoid acid-related orphan receptor γt. This disruption is associated with an inhibition of inflammatory interleukin 17 secretion. CONCLUSION: The data highlights the major involvement of Th17 immune cells in the biological effects of an RWE.

Quality of life after laparoscopic removal of Essure® sterilization devices.

OBJECTIVES: To assess changes in quality of life after laparoscopic removal of Essure® sterilization devices (Bayer AG, Leverkusen, Germany). STUDY DESIGN: In this prospective observational study in an academic research hospital, 80 women with new or worsening symptoms since placement of Essure® sterilization devices undergoing subsequent surgical removal were included. Laparoscopic removal of Essure® devices and salpingectomy with or without cornual excision were performed. Concomitant uterine procedures could be associated where indicated for gynaecological complaints. Comparison using the T student test for coupled series was done in this before-and-after study. RESULTS: Health related quality of life (HRQL) was the primary outcome measured by the Short Form 12 (SF-12) questionnaire and a global 10 cm visual analogue scale (VAS). Secondary outcomes included assessment of pain, using continuous (VAS) and ordinal scales (Modified McGill Pain Questionnaire), menstrual bleeding (pictorial blood loss assessment chart (PBAC) score) and surgical feasibility and safety. There was a significant improvement in quality of life in both mental and physical health aspects of the SF-12 (34.02 (+/-1.19) vs. 49.61 (+/-1.42, P < .0001) and 36.55 (+/-0.99) vs. 43.32 (+/-1.18, P < .0001 respectively) as well as global VAS assessment (+2.91 (SD +/-0.27)) at the end of the first post-operative month. These improvements were maintained at three and six months. Mean pain decreased at one month following surgery compared to baseline (VAS 3.6 (+/-0.36) to 1.4 (+/-0.25), P < .0001 and McGill pain score 18.70 (+/-1.88) to 4.73 (+/-0.90), P < .0001). Improvements of a similar magnitude were observed when analysis was restricted to the 47 women without concomitant uterine surgery. No significant changes in bleeding were seen following of Essure® device removal. Planned procedures were all successfully completed. CONCLUSION: Laparoscopic removal of Essure® devices in symptomatic women is technically successful and associated with short and medium-term improvement in quality of life as well as reduction in pelvic pain.

Opportunistic Salpingectomy at the Time of Benign Laparoscopic Hysterectomy: Assessment of Possible Complications and Histopathological p53-Signatures.

INTRODUCTION: The aim of this study is to assess the prevalence of tubal histopathological abnormalities (serous tubal intraepithelial carcinoma STIC and p53 signatures) and the prevalence of perioperative and postoperative complications related to opportunistic laparoscopic salpingectomy in a low risk population. MATERIALS AND METHODS: In this observational prospective cohort, prophylactic bilateral salpingectomy during benign laparoscopic hysterectomy was systematically performed in 100 consecutive women. Peri- and postoperative complications were registered. Duration of salpingectomy and post-salpingectomy blood loss were also measured. Histopathological and immunohistochemical analysis with anti-p53 antibody were performed on the whole fallopian tubes according to a specific and validated protocol. RESULTS: Laparoscopic salpingectomy was always possible without any peri- or postoperative complication attributable to the salpingectomy itself. The mean duration was 428 seconds (354 - 596) and the blood loss was 9 cm 3 (2 - 15). Using histopathological and immunohistochemical assessment with anti-p53 antibody on 199 fallopian tubes (99 bilateral salpingectomies and one unilateral salpingectomy because of previous salpingectomy for ectopic pregnancy), there was a prevalence of 5.52% (11/199) of p53 signatures. No STIC were observed and no associated cancer. CONCLUSIONS: Laparoscopic salpingectomy is both feasible and innocuous during benign hysterectomy. Meticulous histopathologic examination of the tubes may reveal specific abnormalities.

Study of Potential Anti-Inflammatory Effects of Red Wine Extract and Resveratrol through a Modulation of Interleukin-1-Beta in Macrophages.

Inflammation has been described as an initiator event of major diseases with significant impacts in terms of public health including in cardiovascular disease, autoimmune disorders, eye diseases, age-related diseases, and the occurrence of cancers. A preventive action to reduce the key processes leading to inflammation could be an advantageous approach to reducing these associated pathologies. Many studies have reported the value of polyphenols such as resveratrol in counteracting pro-inflammatory cytokines. We have previously shown the potential of red wine extract (RWE) and the value of its qualitative and quantitative polyphenolic composition to prevent the carcinogenesis process. In this study, we addressed a new effect of RWE in inflammation through a modulation of IL-1ß secretion and the NLRP3 inflammasome pathway. NLRP3 inflammasome requires two signals, priming to increase the synthesis of NLRP3 and pro-IL-1ß proteins and activation, which activates NLRP3. Inflammasome formation is triggered by a range of substances such as lipopolysaccharide (LPS). Using two different macrophages, one of which does not express the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which is essential to form active inflammasome complexes that produce IL-1ß, we show that RWE decreases IL-1 ß secretion and gene expression whatever line is used. Moreover, this strong reduction of pro-inflammatory IL-1ß is associated with a decrease of NLRP3 and, in J774A, ASC protein expression, which depends on the choice of activator ATP or nigericin.

Dynamic real-time in vivo confocal laser endomicroscopy of the fallopian tube during laparoscopy in the prevention of ovarian cancer.

OBJECTIVES: Recently it has been postulated that most ovarian cancers have a tubal origin. The identification of preinvasive tubal lesions would be of great interest in the early diagnosis of ovarian cancer. Optical biopsy has been developed and validated in the detection of precancerous lesions (such as Barrett's oesophagus). The first objective of this study was to assess the feasibility of optical biopsy in the study of fallopian tubes during laparoscopy. The second objective was to describe the images in benign premalignant and malignant tubes with a histopathological and immunohistochemical (p53 and Ki67 expressions) correlation. STUDY DESIGN: In this prospective study, 40 patients undergoing laparoscopic salpingectomy for benign conditions (benign hysterectomy), prophylactic conditions (BRCA mutation) or in case of pelvic cancers were included after obtaining informed and signed consent prior to surgery. The optical biopsy was performed on the fimbria of each tube in and ex vivo. A correlation was made with the histopathological and immunohistochemical analysis. RESULTS: The feasibility of optical biopsy was always confirmed during laparoscopy. The optical biopsy iconography revealed different images in benign tubal epithelium (well-defined black and grey structure), in adenomatoid tumour (tortuous architectural organization), in STIC precancerous lesion (enlarged, irregular and pleomorphic cells, dilated and distorted vessels) and in tubal metastasis of high grade serous ovarian cancer (dark neoplastic cells irregular in size and shape) CONCLUSIONS: Optical biopsy may be the first emerging mini-invasive technology that could detect tubal lesions and may be considered as a promising tool in the early detection of ovarian cancer.

Anti-mitotic properties of resveratrol analog (Z)-3,5,4'-trimethoxystilbene.

(Z)-3,5,4'-Trimethoxystilbene is a natural polyphenol present in five different plants, Virola cuspidata, Virola elongata, Centipeda minima, Schoenus nigricans and Rheum undulatum. This molecule was prepared in a three-step sequence in good overall yield. The isomerisation from the (E)- to (Z)-isomer is performed using UV irradiation. Biological investigations were conducted on a human colon cancer cell line (Caco-2) with anti-mitotic activities. Growth was completely arrested at an added 0.4 microM level of (Z)-3,5,4'-trimethoxystilbene. This agent is 100-fold more active than resveratrol or (E)-3,5,4'-trihydroxystilbene, and the mechanism of this process involves an inhibition of tubulin polymerisation in a dose dependent manner.

Croton lobatus, an African medicinal plant: spectroscopic and chemical elucidation of its many constituents.

The chemical constituents of the African medicinal plant Croton lobatus were elucidated and characterised using 1D and 2D-NMR analysis and the application of the technique of High Resolution Electron Ionization Mass Spectrometry (HREIMS) and High Resolution Mass Spectrometry (HRMS). The novel triglyceride lobaceride or 3-((6Z,9Z)dodeca-6,9-dienoyloxy)-2-octanoyloxypropyl (6Z,9Z)dodeca-6,9-dienoate, along with ten compounds were isolated from the stems and leaves of Croton lobatus.

Does ultrasonic advanced energy reduce lymphocele incidence in laparoscopic para-aortic lymphadenectomy?

OBJECTIVE: To evaluate the use of ultrasonic advanced energy in reducing the occurrence of symptomatic lymphocele and its related complications in laparoscopic extra-peritoneal para-aortic lymphadenectomy in patients with gynecological cancer. STUDY DESIGN: A retrospective cohort study of consecutive patients in a tertiary referral center identified 2 groups of patients, undergoing laparoscopic extra-peritoneal para-aortic lymphadenectomy with or without the use of ultrasonic advanced energy. Surgery time, hospital stay, number of retrieved nodes and lymphocele requiring treatment were studied. Results were also compared between trained and trainee surgeons. RESULTS: 163 patients were scheduled for laparoscopic extra-peritoneal para-aortic lymphadenectomy: 81 treated using bipolar energy (control group: group 1) between August 1999 and January 2005, and 82 treated using ultrasonic advanced energy (study group: group 2) between July 2010 and March 2014. The main indication (90% in group 1, 61% in group 2) was advanced cervical carcinoma (stage IB2 and above). Ultrasonic advanced energy significantly decreased operative time (p=0.001) and intra-operative bleeding (p=0.01) and increased the number of para-aortic nodes retrieved (p=0.02). There was no significant difference in hospital stay or lymphocele requiring treatment (8.6% in group 1, 8.5% in group 2: p=0.98). For senior than for junior surgeons, surgery time was shorter but not significantly (p=0.80) and postoperative lymphocele rates were identical. CONCLUSION: Ultrasonic advanced energy may provide benefit in laparoscopic para-aortic lymphadenectomy, facilitating surgical ergonomics, but did not decrease post-surgery lymphocele.

[Prophylactic salpingectomy or salpingo-oophorectomy as an ovarian cancer prevention?]. / Salpingectomie prophylactique ou annexectomie prophylactique dans la prévention du cancer de l'ovaire ?

A recent hypothesis has stated that many ovarian cancers (especially high-grade serous histotype) could arise from the distal part of the fallopian tube. On one hand we know that risk-reducing salpingo-oophorectomy is the most effective prevention for ovarian cancer among BRCA mutation carriers. On the other, oophorectomy increases the relative risk for cardiovascular, osteoporotic psychosexual and cognitive dysfunctions in premenopausal women. This raises the question whether bilateral salpingectomy could be an effective strategy in the prevention of ovarian cancer in case of hereditary predisposition and in the general population. Here we discuss origin of ovarian cancer in the light of the latest molecular studies and the relative risks and benefits of a strategy of exclusive salpingectomy in comparison with the classical adnexectomy.