Ileo-sigmoid knotting in a female Ethiopian patient, a case report.

INTRODUCTION: Ileo-sigmoid knotting is a very rare cause of bowel obstruction. The diagnosis can be challenging and may not be suspected pre-operatively. A high index of suspicion, especially in areas of the "sigmoid belt" region, can be helpful. CASE PRESENTATION: A 40-year-old ethnic Amhara female patient presented with symptoms and signs of bowel obstruction. She presented in shock and after resuscitation, laparotomy revealed gangrenous ileum twisted around the sigmoid colon ('ileo-sigmoid knotting'). The gangrenous ileal segment was resected, with end-to-end ileo-ileal anastomosis. The patient had a smooth postoperative course and was discharged on the 4th post-operative day. CONCLUSIONS: Twisting of the ileum around the sigmoid colon is pathognomonic of ileo-sigmoid knotting. Prompt resuscitation and surgical intervention in the shocked patient with an acute abdomen and evidence of intestinal obstruction could be life-saving.

Kinetic mechanistic studies of Cdk5/p25-catalyzed H1P phosphorylation: metal effect and solvent kinetic isotope effect.

Cdk5/p25 is a member of the cyclin-dependent, Ser/Thr kinase family and has been identified as one of the principle Alzheimer's disease-associated kinases that promote the formation of hyperphosphorylated tau, the major component of neurofibrillary tangles. We and others have been developing inhibitors of cdk5/p25 as possible therapeutic agents for Alzheimer's disease (AD). In support of these efforts, we examine the metal effect and solvent kinetic isotope effect on cdk5/p25-catalyzed H1P (a histone H-1-derived peptide) phosphorylation. Here, we report that a second Mg(2+) in addition to the one forming the MgATP complex is required to bind to cdk5/p25 for its catalytic activity. It activates cdk5/p25 by demonstrating an increase in k(cat) and induces a conformational change that favors ATP binding but has no effect on the binding affinity for the H1P peptide substrate. The binding of the second Mg(2+) does not change the binding order of substrates. The reaction follows the same rapid equilibrium random mechanism in the presence or absence of the second Mg(2+) as evidenced by initial velocity analysis and substrate analogue and product inhibition studies. A linear proton inventory with a normal SKIE of 2.0 +/- 0.1 in the presence of the second Mg(2+) was revealed and suggested a single proton transfer in the rate-limiting phosphoryl transfer step. The pH profile revealed a residue with a pK(a) of 6.5 that is most likely the general acid-base catalyst facilitating the proton transfer.