Ruptured Rudimentary Horn Pregnancy Diagnosed by Preoperative Magnetic Resonance Imaging Resulting in Fetal Salvage

Pregnancy in a rudimentary horn is very rare. The rupture of the horn during pregnancy is an obstetric emergency which can be life-threatening for both the mother and fetus. Preoperative diagnosis of such pregnancies can be challenging and they are usually diagnosed intraoperatively. We report a unique case of a 31-year-old multiparous woman who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in January 2013 at 32 gestational weeks with abdominal pain. Ultrasonography was inconclusive. A rudimentary horn pregnancy was subsequently diagnosed via magnetic resonance imaging (MRI). An emergency laparotomy revealed haemoperitoneum and a ruptured rudimentary horn pregnancy. A live baby with an Apgar score of 2 at one minute and 7 at five minutes was delivered. The rudimentary horn with the placenta in situ was excised and a left salpingooophorectomy was performed. The postoperative period was uneventful. The authors recommend MRI as an excellent diagnostic modality to confirm rudimentary horn pregnancies and to expedite appropriate management

A 2D-QSAR and Grid-Independent Molecular Descriptor (GRIND) Analysis of Quinoline-Type Inhibitors of Akt2: Exploration of the Binding Mode in the Pleckstrin Homology (PH) Domain.

Protein kinase B-β (PKBβ/Akt2) is a serine/threonine-specific protein kinase that has emerged as one of the most important regulators of cell growth, differentiation, and division. Upregulation of Akt2 in various human carcinomas, including ovarian, breast, and pancreatic, is a well-known tumorigenesis phenomenon. Early on, the concept of the simultaneous administration of anticancer drugs with inhibitors of Akt2 was advocated to overcome cell proliferation in the chemotherapeutic treatment of cancer. However, clinical studies have not lived up to the high expectations, and several phase II and phase III clinical studies have been terminated prematurely because of severe side effects related to the non-selective isomeric inhibition of Akt2. The notion that the sequence identity of pleckstrin homology (PH) domains within Akt-isoforms is less than 30% might indicate the possibility of the development of selective antagonists against the Akt2 PH domain. Therefore, in this study, various in silico tools were utilized to explore the hypothesis that quinoline-type inhibitors bind in the Akt2 PH domain. A Grid-Independent Molecular Descriptor (GRIND) analysis indicated that two hydrogen bond acceptors, two hydrogen bond donors and one hydrophobic feature at a certain distance from each other were important for the selective inhibition of Akt2. Our docking results delineated the importance of Lys30 as an anchor point for mapping the distances of important amino acid residues in the binding pocket, including Lys14, Glu17, Arg25, Asn53, Asn54 and Arg86. The binding regions identified complement the GRIND-based pharmacophoric features

Two hydrogen bond donor HBD (O-O) hotspot regions at a distance of 15.2–15.6 Å apart within the molecule.

<p>Two hydrogen bond donor HBD (O-O) hotspot regions at a distance of 15.2–15.6 Å apart within the molecule.</p

Selected 3-[1-[[4-(3-phenyl-2-pyridyl)phenyl]methyl]-4-piperidyl]-1H-benzimidazol-2-one analogues used for external validation of 2D-QSAR and GRIND model along with experimental and predicted inhibitory potency (IC₅₀ μM) values.

<p>Selected 3-[1-[[4-(3-phenyl-2-pyridyl)phenyl]methyl]-4-piperidyl]-1H-benzimidazol-2-one analogues used for external validation of 2D-QSAR and GRIND model along with experimental and predicted inhibitory potency (IC₅₀ μM) values.</p

Experimental versus predicted inhibitory potency (log(1/IC₅₀)) values of quinoline type inhibitors of Akt2.

<p>The data points in square and circle represent training and test set compounds respectively.</p

Important hotspots regions for the high inhibitory potency of Akt2 inhibitors.

<p>Red distance line: Representing a distance of 21.2–21.6 Å between two hydrogen bond acceptors HBA1 and HBA2 (blue hotspots) within the molecule. Orange distance line: Representing a distance of 23.6–24.0 Å between hydrophobic HY contours (yellow hotspots) from hydrogen bond acceptor (HBA1) feature. Blue distance line: Representing hydrogen bond donor HBD2 (red hotspots) at a distance of 7.2–7.6 and 16.8–17.2 Å from hydrogen bond acceptor HBA3 and HBA1, respectively.</p

Selected pyrido [2, 3-d]-pyrimidine analogues used for molecular docking along with inhibitory potency (IC₅₀ μM), clogp and LipE values.

<p>Selected pyrido [2, 3-d]-pyrimidine analogues used for molecular docking along with inhibitory potency (IC₅₀ μM), clogp and LipE values.</p

Docking solutions of Akt2 obtained from common scaffold cluster analysis.

<p>(A) Binding conformation of cluster I containing 12/12 docked ligands. (B) Binding conformation of cluster II containing 10/12 docked ligands.</p

Ramachandran plot for Akt2 PH domain homology model.

<p>The plot shows 104 amino acid residues in the favoured region and three amino acid residues in allowed region. None of the amino acid residues lies in disallowed region.</p

Important molecular features along with their mutual distances for inhibitory potency values of quinoline compounds against Akt2.

<p>Important molecular features along with their mutual distances for inhibitory potency values of quinoline compounds against Akt2.</p