Rare Source of Embolism in a Young Patient: Case Report and Literature Review.

We present a case of a 31-year-old patient, smoker, with no previous medical history, presenting with acute limb ischemia and infarction of the spleen due to peripheral embolism. The source of embolism was thrombi formations in the left ventricular cavity, located in the area of the regional wall motions abnormalities. CT and coronary angiography confirmed the total occlusion of the left anterior descending artery with collateralization.

Synthesis and sequential diastereoselective incorporation of hydroxyl groups into hexahydrofuro[3,2-f]indolizin-7(2H)-one to give mono-, di- and tetra-hydroxyfuroindolizidines.

Dihydrofuro[2,3-f]indolizidinone obtained from biosourced reagents even at multigram-scale was used as an advanced building-block with up to five points of chemical diversification. This resulted in the sequential synthesis of a series of mono-, di- and tetra-hydroxyfuranoindolizidines belonging to a very scarce and elaborate tetrahydrofuran-fused indolizidine family with up to six controlled stereogenic centers. These sequences include, among others, diastereoselective olefin epoxidation, stereoselective epoxide ring opening into tetrahydrofuran trans-diols, their protection as an ester or acetonide, and lactam carbonyl reduction ultimately followed by acetate or acetonide deprotection.

Screening of Phenanthroquinolizidine Alkaloid Derivatives for Inducing Cell Death of L1210 Leukemia Cells with Negative and Positive P-glycoprotein Expression.

We describe the screening of a set of cryptopleurine derivatives, namely thienoquinolizidine derivatives and (epi-)benzo analogs with bioactive phenanthroquinolizidine alkaloids that induce cytotoxic effects in the mouse lymphocytic leukemia cell line L1210. We used three variants of L1210 cells: i) parental cells (S) negative for P-glycoprotein (P-gp) expression; ii) P-glycoprotein positive cells (R), obtained by selection with vincristine; iii) P-glycoprotein positive cells (T), obtained by stable transfection with a human gene encoding P-glycoprotein. We identified the most effective derivative with a median lethal concentration of ≈13 μM in all three L1210 cell variants.

Structure and Mechanism Revision of a Catalyzed Cyclization of Benzaldehyde Bearing Alkyne-Nitrile.

Pt(II)-catalyzed carbocyclization of benzaldehyde containing a keto-nitrile functionality resulted in the formation, respectively, of isochromenes and spiro-lactones instead of fused lactams and spiro-lactams as was previously reported. The reaction mechanism was proposed, and the products were identified by multidimensional NMR, IR, and X-ray analysis. The structure of these new products was also confirmed by their synthesis in an unambiguous manner using practical and short approaches.

Electronic structure, novel synthesis, and O-H...O and C-H...O interactions in two 6-oxopiperidine-2-carboxylic acid derivatives.

Molecules of (S)-6-oxo-1-(thiophen-2-ylmethyl)piperidine-2-carboxylic acid, C11H13NO3S, crystallize as single enantiomers in the space group P21 and the thiophene ring is disordered over two positions, while (S)-6-oxo-1-(thiophen-3-ylmethyl)piperidine-2-carboxylic acid, C11H13NO3S, crystallizes as a single enantiomer in the space group P212121. Their absolute configurations were confirmed by anomalous dispersion effects in diffraction measurements on the crystals. The molecules of each compound are linked by a combination of strong O-H.

(11aS)-1,5,11,11a-Tetra-hydro-1-benzo-thieno[3,2-f]indolizin-3(2H)-one.

The absolute configuration of the title compound, C14H13NOS, was assigned from the synthesis and confirmed by the structure determination. There are two independent mol-ecules in the asymmetric unit. The central six-membered ring of the indolizine moiety adopts an envelope conformation, with the greatest deviations from the mean planes being 0.

(5S,11aS)-5-Hydro-per-oxy-1,5,11,11a-tetra-hydro-[1]benzothieno[3,2-f]indol-izin-3(2H)-one.

The absolute configuration of the title compound, C14H13NO3S, was assigned from the synthesis and confirmed by the structure determination. The central six-membered ring of the indolizine moiety adopts an envelope conformation, with the greatest deviation from the mean plane of the ring being 0.661 (2) Å for the bridgehead C atom.

(8aR,9R)-9-Hy-droxy-7,8,8a,9-tetra-hydro-furo[3,2-f]indolizin-6(4H)-one.

The title compound, C(10)H(11)NO(3), crystallizes with four independent mol-ecules in the asymmetric unit. Their geometries are very similar and corresponding bond distances are almost identical. The central six-membered ring of the indolizine moiety adopts a envelope conformation [the displacement of the flap atom (the C atom opposite the N atom) being 0.

(6S,7S,8S,8aS)-6-Ethyl-3-oxo-1,2,3,5,6,7,8,8a-octa-hydro-indolizine-7,8-diyl diacetate.

In the mol-ecular structure of the title compound, C(14)H(21)NO(5), the six-membered ring of the indolizine moiety adopts a chair conformation. There are two independent mol-ecules in the asymmetric unit. The oxopyrrolidine ring attached to the indolizine ring system is nearly planar, with mean deviations of 0.

(4R,6S,7S,8S,8aS)-6-Ethyl-7,8-dihy-droxy-4-methyl-1,2,3,5,6,7,8,8a-octa-hydro-indolizin-4-ium iodide.

The title compound, C(11)H(22)NO(2) (+)·I(-), is a chiral mol-ecule with five stereogenic centres. The absolute configuration was assigned from the synthesis and confirmed by the structure determination. The central six-membered ring of the indolizine system adopts a chair conformation, with two atoms displaced by -0.

(8aRS)-8,8a-Dihydro-furo[3,2-f]indolizine-6,9(4H,7H)-dione.

The title compound, C(10)H(9)NO(3), is a chiral mol-ecule with one stereogenic carbon atom, but which crystallizes as a racemate in the centrosymmetric space group P2(1)/n. The central six-membered ring of the indolizine moiety adopts a definite envelope conformation, while the conformation of the oxopyrrolidine ring is close to that of a flat-envelope with a maximum deviation of 0.352 (1) Å for the flap atom.

(6S,7S,8S,8aS)-6-Ethyl-7,8-dihy-droxy-1,5,6,7,8,8a-hexa-hydro-indolizin-3(2H)-one monohydrate.

The absolute configuration of the title compound, C(10)H(17)NO(3)·H(2)O, was assigned from the synthesis. In the mol-ecular structure, the central six-membered ring of the indolizine moiety adopts a chair conformation, with two atoms displaced by -0.578 (2) and 0.

Protective head-cooling during cardiac arrest and cardiopulmonary resuscitation: the original animal studies.

Prolonged standard cardiopulmonary resuscitation (CPR) does not reliably sustain brain viability during cardiac arrest. Pre-hospital adjuncts to standard CPR are needed in order to improve outcomes. A preliminary dog study demonstrated that surface cooling of the head during arrest and CPR can achieve protective levels of brain hypothermia (30°C) within 10 minutes.

(7R,8S,8aS)-8-Hydr-oxy-7-phenyl-perhydro-indolizin-3-one.

In the title compound, C(14)H(17)NO(2), the six-membered ring of the indolizine system adopts a chair conformation. In the crystal, mol-ecules form chains parallel to the b axis via inter-molecular O-H⋯O hydrogen bonds. The absolute mol-ecular configuration was assigned from the synthesis.

(8aS)-7,8,8a,9-Tetra-hydro-thieno[3,2-f]indolizin-6(4H)-one.

In the mol-ecular structure of the title compound, C(10)H(11)NOS, the central six-membered ring of the indolizine unit adopts an envelope conformation, the maximum deviations from the mean plane of the ring being 0.533 (2) Å. The fused thieno ring is nearly coplanar [mean deviation = 0.

(11R,11aS)-11-Hydr-oxy-1,5,11,11a-tetra-hydro-1-benzothieno[2,3-f]indolizin-3(2H)-one.

The absolute configuration of the title compound, C(14)H(13)NO(2)S, was assigned from the synthesis and confirmed by the structure determination. The central six-membered ring of the indolizine system adopts an envelope conformation, the greatest deviation from the mean plane of the ring being 0.459 (2) Å for the N atom.

Small volume resuscitation with tempol is detrimental during uncontrolled hemorrhagic shock in rats.

Background: In a previous study, titration of a hypertonic saline (HTS) solution during severe uncontrolled hemorrhagic shock (UHS) failed to reduce mortality. In a separate study, a novel antioxidant, polynitroxylated albumin (PNA) plus tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), infused during shock increased long-term survival. We hypothesized that combining potent antioxidants with a hypertonic solution during UHS would preserve the logistical advantage of small volume resuscitation and improve survival.

Suspended animation for delayed resuscitation.

'Suspended animation for delayed resuscitation' is a new concept for attempting resuscitation from cardiac arrest of patients who currently (totally or temporarily) cannot be resuscitated, such as traumatic exsanguination cardiac arrest. Suspended animation means preservation of the viability of brain and organism during cardiac arrest, until restoration of stable spontaneous circulation or prolonged artificial circulation is possible. Suspended animation for exsanguination cardiac arrest of trauma victims would have to be induced within the critical first 5 min after the start of cardiac arrest no-flow, to buy time for transport and resuscitative surgery (hemostasis) performed during no-flow.

Critical time window for intra-arrest cooling with cold saline flush in a dog model of cardiopulmonary resuscitation.

Background: Mild hypothermia improves outcome when induced after cardiac arrest in humans. Recent studies in both dogs and mice suggest that induction of mild hypothermia during cardiopulmonary resuscitation (CPR) greatly enhances its efficacy. In this study, we evaluate the time window for the beneficial effect of intra-arrest cooling in the setting of prolonged CPR in a clinically relevant large-animal model.

Titrated hypertonic/hyperoncotic solution for hypotensive fluid resuscitation during uncontrolled hemorrhagic shock in rats.

Background: In volume- or pressure-controlled hemorrhagic shock (HS) a bolus intravenous infusion of hypertonic/hyperoncotic solution (HHS) proved beneficial compared to isotonic crystalloid solutions. During uncontrolled HS in animals, however, HHS by bolus increased blood pressure unpredictably, and increased blood loss and mortality. We hypothesized that a titrated i.

Suspended animation can allow survival without brain damage after traumatic exsanguination cardiac arrest of 60 minutes in dogs.

Background: We have previously shown in dogs that exsanguination cardiac arrest of up to 120 minutes without trauma under profound hypothermia induced by aortic flush (suspended animation) can be survived without neurologic deficit. In the present study, the effects of major trauma (laparotomy, thoracotomy) are explored. This study is designed to better mimic the clinical scenario of an exsanguinating trauma victim, for whom suspended animation may buy time for resuscitative surgery and delayed resuscitation.