Maternal and perinatal outcome in obstetric cholestasis- a prospective observational study

Background: The objective of this study was to study the maternal and perinatal outcome of pregnancy complicated by obstetric cholestasis.Methods: This prospective observational study included 80 cases, diagnosed as obstetric cholestasis on the basis of symptoms of persistent pruritus (generalized or localized), biochemical evidence of altered liver function test and excluding other liver and skin disorder. Medical treatment and active management (fetal surveillance and termination of pregnancy at 37-38 weeks) were offered to all. Maternal and perinatal outcome were studied.Results: Incidence of obstetric cholestasis was 1.9%. Majority of women (55%) were primigravida and recurrence rate was 61.1% among multiparous women. Pruritus (generalized) was the cardinal symptoms in 90% patients and mostly (88.7%) presented and diagnosed after 28 weeks i.e. in third trimester. A total of 43.7%women had caesarean section (CS) which was quite high incidence. Most common pregnancy complications included preterm labor (25%), post-partum haemorrhage (13.75%) and preterm premature rupture of membrane (11.25%). Perinatal outcome revealed meconium aspiration (20%), preterm birth (30%), low birth weight (35%), fetal distress (18.75%) and intrauterine fetal death (2.5%). 43.75% neonates required NICU (Neonatal intensive care unit) admission. Serum transaminase levels tended to be higher in patients with poor perinatal outcome such as still birth, fetal distress and meconium stained amniotic fluid. LFT (liver function test) returned to normal in 95% of women and 100% women became symptom free after 6 weeks postpartum.Conclusions: Obstetric cholestasis has an adverse effect on the fetal outcome and hence early diagnosis with careful clinical examination and biochemical testing is essential. Serum abnormality in liver function test (transaminases) tended to be higher in women with poor perinatal outcome

Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease:Study protocol for a randomised controlled trial (ELAD study)

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer's disease compared to those who are receiving placebo. Methods/design: ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer's dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer's Disease Assessment Scale - Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Cooperative Study - Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Discussion: Alzheimer's disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer's treatment. Trial registration: ClinicalTrials.gov, NCT01843075. Registration 30 April 2013

The biflavonoids, amentoflavone degrades calf thymus DNA in the presence of copper ions

Previous reports from this laboratory have shown that flavonoids including apigenin are capable of inducing oxidative DNA cleavage in the presence of copper ions. In the present report, we have examined the ability of amentoflavone, a biflavonoid which is a dimer of apigenin, to catalyze the degradation of DNA. Amentoflavone was found to degrade calf thymus DNA in the presence of Cu(II) at a rate almost twice that of apigenin. Amentoflavone was also shown to reduce Cu(II) to Cu(I) and to generate hydroxyl radicals in the presence of copper ions. In the presence of Cu(II), the absorption spectrum of amentoflavone undergoes a shift and a quenching effect indicating that the biflavonoid is capable of binding to copper ions. Amentoflavone and apigenin were isolated from Cycas rumphii and Trifolium alexandrinum, respectively. The results are discussed in relation to the putative chemopreventive mechanism of amentoflavone