Sodium pancratistatin 3,4-o-cyclic phosphate, a water-soluble synthetic derivative of pancratistatin, is highly effective in a human colon tumor model

Sodium pancratistatin 3,4- O-cyclic phosphate ( 2) is a novel water-soluble synthetic derivative of pancratistatin ( 1), a natural alkaloid constituent of Amaryllidaceae plants, that exhibits good cytostatic and antineoplastic activity but is highly insoluble. Unlike most other natural alkaloids it does not act by binding to tubulin, and its mechanism of action has yet to be fully elucidated. Here the efficacy of 2 in a human colon adenocarcinoma model, DLD-1, and some understanding of its mode of action are investigated. Agreeing with previous studies, low cytotoxicity in vitro was seen for 2 with IC 50's of 253 and 19.7 microM for 1 and 96 h exposures, respectively. However in vivo the compound caused statistically significant tumor growth delays ( p < 0.01) at its maximum tolerated dose, and significant vascular shutdown and tumor necrosis were observed. Like 1, the compound appeared to have an unconventional mechanism of action with no effect on microtubule structure, yet causing a G 2/M block, while it was seen to disrupt mitochondrial function. The mechanism of action of 1 and 2 appears to be similar. Thus compound 2, being considerably more soluble than 1, has good potential as an anticancer agent, and further investigation is warranted.     

Down syndrome biochemical markers and screening for preeclampsia at first and second trimester: correlation with the week of onset and the severity

OBJECTIVES: To estimate the combined screening performance of first and early second trimester prenatal serum markers for Down syndrome, in screening for the development of preeclampsia, and analyze the correlation among marker levels, week of onset, and severity of the disease. METHODS: A retrospective cohort study was carried out on 32 women with preeclampsia and 3044 controls. Serum samples from these pregnancies were assayed for pregnancy-associated plasma protein-A (PAPP-A), alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotrophin (hCG), and inhibin-A. A likelihood ratio and the odds of being affected given a positive result (OAPR) of various combinations of markers were calculated and receiver operating characteristic (ROC) curves analysis was performed. RESULTS: In the pregnancies that subsequently developed preeclampsia, first trimester PAPP-A concentration was significantly lower and concentrations of early second trimester inhibin-A and hCG significantly elevated. Levels of early second trimester uE3 and AFP were not significantly altered. We also found that inhibin-A correlates with both onset of the disease and the severity. CONCLUSION: Down syndrome biochemical markers levels are altered in those patients who subsequently developed preeclampsia and may be a useful screening test for preeclampsia. Inhibin-A is the most predictive marker and correlates with the severity of subsequent preeclampsia and inversely with the week of occurrence of preeclampsia.     

Foetal and neonatal ovarian cysts: a 5-year experience

Background Abdominal cystic formations in newborns are relatively common and often diagnostic suspicion arises in this regard even before birth as a result of ultrasound scans carried out during pregnancy. The aim of this study is to highlight the problems posed by the prenatal diagnosis of abdominal cysts in order to outline the most appropriate therapeutic approach in case of suspected ovarian cysts. Materials and methods Between January 2003 and January 2007, 57 women were enrolled in this study for a prenatal ultrasound (US) that revealed the presence of an echo-rare or echo-free area in the foetal abdomen. After birth all babies underwent blood tests and abdominal US scans in order to confirm or identify the nature of the cyst. If abdominal US could not show the nature of the cystic formation, magnetic resonance imaging with sedation was performed. When the radiological tests were not useful to identify the nature of the cysts and surgery was then necessary, surgical procedures were performed with laparoscopy. Results Ultrasounds were useful to identify the diameter of the cysts but not all their origins; also MRI confirmed the morphology and volume of the cysts, but could not give further details about their origin. Discussion Abdominal ultrasound and finally laparoscopy used to treat and remove the cysts were useful to monitor all simple abdominal cysts. MRI seemed not to be useful for the treatment of this condition, especially in the pediatric age when mild sedation is required.     

Deep dyspareunia: causes, treatments, and results

PURPOSE OF REVIEW: We critically review the causes and treatments of deep dyspareunia. RECENT FINDINGS: Endometriosis, pelvic congestion syndrome, and interstitial cystitis have been associated with deep dyspareunia. Although medical therapies may improve deep dyspareunia in women with endometriosis, laparoscopic excision of deep endometriotic lesions has been demonstrated to improve not only deep dyspareunia but also the quality of sex life. Deep dyspareunia related to the presence of pelvic congestion syndrome should be treated by pelvic vein embolization. Intravesical therapy may be effective in treating deep dyspareunia in women with interstitial cystitis. It remains unclear whether uterine myomas and adenomyosis are causes of deep dyspareunia. SUMMARY: Treatment of deep dyspareunia should be mainly directed to causative factors; however, clinicians should keep in mind that secondary sexual dysfunction can arise from organic pelvic pathology.     

Atherosclerosis in women with endometriosis

OBJECTIVE: This study aims to determine whether women with endometriosis have greater subclinical atherosclerosis than the general population. STUDY DESIGN: This case-control study included 66 women with endometriosis and 66 controls matched for age and body mass index. All subjects were >or=35 years old. Exclusion criteria were obesity, diabetes, hypertension, hyperlipidemia, renal or metabolic diseases. Before laparoscopy, all patients underwent a measurement of intima-media thickness (IMT) and distensibility coefficient (DC) on the common carotid artery. In addition, blood samples were taken to determine the levels of lipids, fibrinogen, C-reactive protein, homocysteine, fasting glycemia, antithrombin III, plasminogen, protein C, protein S, and activated protein C resistance. RESULTS: All the biochemical parameters evaluated had similar levels in the two study groups. IMT was similar in women with endometriosis and in controls both on left (p=0.330) and right (p=0.648) carotid artery. Similarly, no significant difference was observed in the DC between women with endometriosis and controls both on left (p=0.539) and right (p=0.178) carotid artery. No significant difference was observed in IMT and DC between women with mild and severe endometriosis. CONCLUSION: Women with endometriosis do not have more subclinical atherosclerosis than the general population.