Schistosomiasis prevention option: toxicological evaluation of Vernonia amygdalina on the tissues of Bulinus truncatus at different pH conditions.

Research into, and the use of plant products in the control of vectors of pathogens is being revived and seriously considered as an alternative or complete replacement for the classical synthetic agents. The study was designed to investigate toxicological assessment of the aqueous leaf extract of Vernonia amygdalina on mortality and tissue level damages of the freshwater snail Bulinus truncatus at different pH levels. The effects of the extract on total protein concentration and activities of acetylcholinesterase, acid phosphatase and alkaline phosphatase in the tissues of the snail were assayed using standard methods. Compared to the control (snail group not treated with the extract of V. amygdalina), there were significant (p < 0.05) reductions in the total protein concentrations and acetylcholinesterase activity in the snails' tissues of the treated groups (0.20 mg/L, 0.40 mg/L and 1.00 mg/L) at all the pH conditions (3.5, 7.0 and 10.5). The reverse of this trend followed in the case of acid and alkaline phosphatases' activities. The study provides a substantial possibility of exploiting local indigenous plant resources such as V. amygdalina for control of freshwater snails and monitor water pollution. The study also raised a possibility of the locals living around freshwater bodies prone to trematode borne diseases to reflexively control freshwater snail population by just squeeze-washing their V. amygdalina around the river banks.

The bikini area and bikini line as a location for anterior subcutaneous pelvic fixation: an anatomic and clinical investigation.

Anterior external fixation for pelvic fractures has been the standard for acute stabilization but definitive treatment often leads to pin tract infection, is uncomfortable, and limits patient mobility. We recently developed a subcutaneous anterior pelvic fixator which addresses these issues (INFIX). The objective of this study is to introduce the Bikini Area and Bikini Line as the subcutaneous anatomical location where this apparatus is placed. A study was preformed on eight cadaveric specimens to define the location of the subcutaneous device with respect to anatomic structures. We examined 23 people of various body mass indexes to examine the anterior pelvic anatomy. This was followed by implantation on 42 individuals in whom we reviewed CT scans to assess the location of the implant. We asked these same 42 individuals whether they could sit, stand, and lie on their sides and if they had any discomfort. We measured the dimensions of 26 retrieved rods to approximate the curve of the Bikini Line. Finally in 14 individuals we performed vascular ultrasound to assess the flow in the iliac and femoral vessels with the implant in place in the sitting and standing position. Neurovascular structures are not affected by placing the INFIX device at the Bikini Line, patients are comfortable, mobile and complications are minimized by this procedure. A rod placed on the Bikini Line which connects screws inserted into the anterior inferior iliac spine on each side does not interfere with sitting, standing, or the neurovascular structures.

Prediction of pre-eclampsia by a combination of maternal history, uterine artery Doppler and mean arterial pressure.

OBJECTIVES: To determine the value of combined screening for pre-eclampsia by maternal history, and mid-trimester uterine artery (UtA) Doppler imaging and maternal blood pressure. METHODS: In 3529 singleton pregnancies attending for routine care at 22-24 weeks' gestation we recorded maternal variables, and made UtA Doppler and mean arterial pressure (MAP) measurements. Multiple regression analysis was used to determine the significant predictors of pre-eclampsia, gestational hypertension and small-for-gestational age (SGA) among maternal characteristics, UtA pulsatility index (PI) and MAP. RESULTS: Complete pregnancy outcomes were available in 3359/3529 (95.2%) cases. Pre-eclampsia developed in 101 (3.0%) pregnancies, including 23 (0.7%) in which delivery was before 34 weeks (early pre-eclampsia) and 78 (2.3%) with delivery at 34 weeks or more (late pre-eclampsia); 74 (2.2%) developed gestational hypertension, 366 (10.9%) delivered SGA newborns with no hypertensive disorders, and 2806 (83.8%) were unaffected by pre-eclampsia, gestational hypertension or SGA. Multiple regression analysis demonstrated that maternal characteristics, UtA-PI and MAP provided a significant independent contribution in the prediction of pre-eclampsia, gestational hypertension and SGA. For a false-positive rate of 10%, the estimated detection rates of early and late pre-eclampsia were 100% and 56.4%, respectively. CONCLUSIONS: The combination of maternal demographic characteristics, and UtA Doppler and maternal blood pressure measurements is an effective screening tool for the prediction of pre-eclampsia.

Prediction of pre-eclampsia by uterine artery Doppler imaging: relationship to gestational age at delivery and small-for-gestational age.

OBJECTIVES: To determine the relationship between pre-eclampsia, small-for-gestational age (SGA) and gestational age at delivery, and the effect of this relationship on the prediction of pre-eclampsia by uterine artery Doppler imaging. METHODS: This was a multicenter prospective Doppler study of the uterine artery at 22-24 weeks of gestation in unselected women with singleton pregnancies. RESULTS: In the 30,639 pregnancies examined, the median uterine artery pulsatility index (PI) was 1.0 and the 95(th) centile was 1.58. In 614 (2%) cases the woman developed pre-eclampsia and in this group there was an inverse significant association between the gestational age at delivery and prevalence of SGA (r = - 0.99, P < 0.0001), and between the gestational at delivery and mean uterine artery PI (r = - 0.51, P < 0.0001) and prevalence of mean uterine artery PI above the 95(th) centile (r = - 0.99, P < 0.0001). The mean uterine artery PI was above the 95(th) centile in 77.2% of women who developed pre-eclampsia requiring delivery before 34 weeks, in 35.9% of those delivering at 34-37 weeks and in 21.9% of those delivering after 37 weeks. The respective percentages were 82.3%, 46.9% and 28.8% for those with pre-eclampsia and SGA, and 43.8%, 21.2% and 8.4% for those with SGA but without pre-eclampsia. CONCLUSIONS: Pre-eclampsia requiring early delivery is more likely to be associated with SGA than less severe pre-eclampsia in women who deliver at term. Doppler ultrasound assessment of the uterine arteries is more effective in identifying pre-eclampsia requiring preterm than term delivery.

Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer.

TRAIL/Apo-2L is a member of the tumor necrosis factor superfamily and has recently been shown to induce apoptosis in cancer cells, but not in normal cells. In nude mice injected with human tumors, TRAIL reduces the size of these tumors without side effects. Akt promotes cell survival and block apoptosis. Some prostate cancer cells express high levels of Akt due to lack of active lipid phosphatase PTEN, a negative regulator of PI-3 kinase pathway, which may be responsible for drug resistance. The objective of this paper is to investigate the intracellular molecules that regulate TRAIL resistance. We have examined caspase-8 activity, BID cleavage, Akt activity, mitochondrial membrane potential (DeltaPsi(m)) and apoptosis in prostate cancer (LNCap, PC-3, PC-3M and DU145) cells treated with or without TRAIL. PC-3, PC-3M and DU145 cells are sensitive to TRAIL, whereas LNCap cells are resistant. LNCap cells express the highest level of constitutively active Akt, which is directly correlated with TRAIL resistance. TRAIL activates caspase-8 in all the cell lines. Downregulation of constitutively active Akt by PI-3 kinase inhibitors (wortmannin and LY-294002), dominant negative Akt or PTEN, renders LNCap cells sensitive to TRAIL. Inhibition of TRAIL sensitivity occurs at the level of BID cleavage. Inhibition of protein synthesis by cycloheximide also causes LNCap cells sensitive to TRAIL. Overexpression of Bcl-2 or Bcl-X(L) inhibits TRAIL-induced DeltaPsi(m) and apoptosis. Overexpression of constitutively active Akt in PC-3M cells (express very low levels of constitutively active Akt) restores TRAIL resistance. These data suggest that elevated Akt activity protects LNCap cells from TRAIL-induced apoptosis, and the PI-3 kinase/Akt pathway may inhibit apoptotic signals by inhibiting processing of BID. Thus, constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer.

Pro-survival function of Akt/protein kinase B in prostate cancer cells. Relationship with TRAIL resistance.

Tumor necrosis factor superfamily member TRAIL/Apo-2L has recently been shown to induce apoptosis in transformed and cancer cells. Some prostate cancer cells express constitutively active Akt/protein kinase B due to a complete loss of lipid phosphatase PTEN gene, a negative regulator of phosphatidylinositol 3-kinase pathway. Constitutively active Akt promotes cellular survival and resistance to chemotherapy and radiation. We have recently noticed that some human prostate cancer cells are resistant to TRAIL. We therefore examined the intracellular mechanisms of cellular resistance to TRAIL. The cell lines expressing the highest level of constitutively active Akt were more resistant to undergo apoptosis by TRAIL than those expressing the lowest level. Down-regulation of constitutively active Akt by phosphatidylinositol 3-kinase inhibitors, wortmannin and LY294002, reversed cellular resistance to TRAIL. Treatment of resistant cells with cycloheximide (a protein synthesis inhibitor) rendered cells sensitive to TRAIL. Transfecting dominant negative Akt decreased Akt activity and increased TRAIL-induced apoptosis in cells with high Akt activity. Conversely, transfecting constitutively active Akt into cells with low Akt activity increased Akt activity and attenuated TRAIL-induced apoptosis. Inhibition of TRAIL sensitivity occurs at the level of BID cleavage, as caspase-8 activity was not affected. Enforced expression of anti-apoptotic protein Bcl-2 or Bcl-X(L) inhibited TRAIL-induced mitochondrial dysfunction and apoptosis. We therefore identify Akt as a constitutively active kinase that promotes survival of prostate cancer cells and demonstrate that modulation of Akt activity, by pharmacological or genetic approaches, alters the cellular responsiveness to TRAIL. Thus, TRAIL in combination with agents that down-regulate Akt activity can be used to treat prostate cancer.