Asymmetric sequential Au(i)/chiral tertiary amine catalysis: an enone-formation/cyanosilylation sequence to synthesize optically active 3-alkenyloxindoles from diazooxindoles.

An unprecedented sequential gold-catalyzed enone-formation and bifunctional tertiary amine mediated asymmetric cyanosilylation reaction is developed, allowing the highly enantioselective synthesis of 3-alkenyloxindoles from diazooxindoles, furans and trimethylsilyl cyanide (TMSCN).

[Microcirculation characters in the elderly septic patients].

OBJECTIVE: To explore the changes of sublingual microcirculation in elderly patients with severe sepsis/septic shock. METHODS: Twenty-three patients with sepsis, 10 patients without sepsis and 10 healthy elderly patients were enrolled. Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. And the 28-day mortality rates of all septic patients were recorded. RESULTS: Compared with the healthy group, all elderly patients had significant sublingual microcirculation dysfunctions. Compared with the severe septic and nonseptic patients, perfused vessel density (PDV) , proportion of perfused vessels (PPV) and microvascular flow index (MFI) of septic shocks were significantly lower. Compared with the severe septic patients, PDV, PPV and MFI instead of lactate and MAP of septic shocks were significantly lower from Day 1 to Day 3. The values of PDV, PPV, MFI and lactate but not MAP of the surviving septic patients were significantly higher than those of the deceased ones. CONCLUSIONS: The elderly patients with septic shock have severe sublingual microcirculatory alterations. And these abnormalities are more marked in septic shock patients. Nonsurvivors showed more severe alterations than survivors. Microcirculatory alterations may be measured to guide the therapy.

Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis.

AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS (1)H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect. METHODS: The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm(3), the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. (1)H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiation- treated pancreatic tumor tissues were compared. RESULTS: Compared with (1)H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the (1)H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased. CONCLUSION: The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.

Asymmetric copper(I)-catalyzed azide-alkyne cycloaddition to quaternary oxindoles.

We report a highly enantioselective Cu(I)-catalyzed azide-alkyne cycloaddition via asymmetric desymmetrization of oxindole-based 1,6-heptadiynes, which furnishes quaternary oxindoles bearing a 1,2,3-triazole-containing moiety with 84-98% ee.

Structured lipid emulsion as nutritional therapy for the elderly patients with severe sepsis.

BACKGROUND: The nutritional support is one of the important therapeutic strategies for the elderly patients with severe sepsis, but there is controversial in choosing a parenteral nutrition formulation. This study was designed to compare the therapeutic effects of structured lipid emulsion, physically mixed medium, and long-chain fat emulsion in the treatment of severe sepsis in elderly patients. METHODS: A total number of 64 elder patients with severe sepsis were enrolled in the study. After a week of enteral nutritional support, the patients were randomly divided into research (structured lipid emulsion as parenteral alimentation) and control groups (physically mixed medium and long-chain fat emulsion as parenteral alimentation). The alterations of plasma albumin, lipid metabolism, and blood glucose level were recorded after parenteral alimentation and were compared between the two groups. RESULTS: The plasma levels of albumin, prealbumin, cholesterol, and triglyceride were decreased in all the patients after one week of enteral nutritional support treatment (t = 7.78, P = 0.000; t = 10.21, P = 0.000; t = 7.99, P = 0.000; and t = 10.99, P = 0.000). Further parenteral alimentation with different lipid emulsions had significant effects on the serum prealbumin and albumin (t = 3.316, P = 0.002; t = 3.200, P = 0.002), whilst had no effects on the blood glucose and triglyceride level (t = 7.78, P = 0.000; t = 4.228, P = 0.000). In addition, the two groups had a significantly different Apache II score, ventilator time, and hospital stay time (t = -2.213, P = 0.031; t = 2.317, P = 0.024; t = 2.514, P = 0.015). CONCLUSIONS: The structured lipid emulsion was safe as parenteral nutrition for elderly patients with severe sepsis. It was demonstrated to be superior to the physically mixed medium and long-chain fat emulsion with respect to the protein synthesis and prognosis.

Role of mitochondrial damage during cardiac apoptosis in septic rats.

BACKGROUND: Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity. RESULTS: Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge. CONCLUSIONS: Septic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.

A highly diastereo- and enantioselective Hg(II)-catalyzed cyclopropanation of diazooxindoles and alkenes.

It is reported for the first time that Hg(II) can catalyze the cyclopropanation of diazo reagents and alkenes, which contributes to the unprecedented highly diastereo- and enantioselective synthesis of spirocyclopropyloxindoles.

Usefulness of heart-type fatty acid-binding protein in patients with severe sepsis.

PURPOSE: The purpose of the study was to evaluate the value of heart-type fatty acid-binding protein (hFABP) as a novel clinical biomarker in patients with severe sepsis. METHODS: Serum concentrations of hFABP and traditional cardiac biomarkers including cardiac troponin I, creatine kinase-MB, and B-type natriuretic peptides levels were measured within 6 hours after admission in 93 severe septic patients. The value of hFABP for the diagnosis of sepsis-related myocardial dysfunction (SRMD) and for the prediction of 28-day mortality was evaluated by receiver operating characteristics curve analysis. The prognostic value of elevated hFABP was subsequently confirmed by multivariate Cox proportional hazards analysis and Kaplan-Meier survival analysis. RESULTS: Heart-type fatty acid-binding protein was elevated (≥ 4.5 ng/mL) in 58 (62.4%) patients; patients with elevated hFABP appeared more likely to have SRMD (84.5% vs 31.4%, P < .001) and have higher prevalence of 28-day death (37.9% vs 8.6%, P = .002). Heart-type fatty acid-binding protein offered superior value over conventional biomarkers in both diagnosis of SRMD (area under the curve, 0.767; P < .001) and prediction of 28-day death (area under the curve, 0.805; P < .001). CONCLUSIONS: Serum hFABP is frequently elevated among patients with severe sepsis and appears to be associated with SRMD. Elevated hFABP independently predicts 28-day mortality in severe sepsis.

[An evaluation of stroke volume variation as a predictor of fluid responsiveness in mechanically ventilated elderly patients with severe sepsis].

OBJECTIVE: To evaluate stroke volume variation (SVV) as a predictor of fluid responsiveness in mechanically ventilated (MV) elderly patients with severe sepsis. METHODS: A prospective observation of 31 fluid challenges during fluid resuscitation for treatment of hemodynamic instability in 17 elderly MV patients with severe sepsis was conducted. SVV was measured by pulse indicator continuous cardiac output (PiCCO) system. Fluid responsiveness was defined as the changes in cardiac index (CI) increase after fluid loading (DeltaCI) > or =10%. The changes in hemodynamic parameters and lung water index were observed at the onset of and after fluid therapy. The correlation between DeltaCI and SVV or central venous pressure (CVP) were analyzed. RESULTS: SVV was decreased significantly after fluid loading [(6.6+/-2.1)% vs.(12.1+/-3.7)%, P<0.01], whereas CVP increased significantly [(12.5+/-3.6) mm Hg vs. (8.9+/-4.1) mm Hg, 1 mm Hg=0.133 kPa, P<0.01]. DeltaCI in response to fluid loading were positively correlated to initial values of SVV (r=0.447, P=0.012), but there was no relationship between CVP and DeltaCI (r=-0.082, P=0.674). The areas under the receiver operating characteristic curve (ROC curve) for SVV was 0.672 [95% confidence interval (95%CI) 0.463-0.885] and CVP was 0.336 (95%CI 0.133-0.539), respectively. A SVV value of 11.5% had the sensitivity of 71% and specificity of 67% for prediction of fluid responsiveness. CONCLUSION: Functional hemodynamic parameter SVV can predict fluid responsiveness in elderly MV patients with severe sepsis during fluid resuscitation, it may serve as a useful index for guiding fluid therapy in elderly patients with severe sepsis.

Strong stacking between FH--N hydrogen-bonded foldamers and fullerenes: formation of supramolecular nano networks.

The stacking interactions between FH--N hydrogen-bonded foldamers 1-3, bis-foldamer 4, and tris-foldamer 5 and C(60) and C(70) are described. Compound 4 contains two folded units, which are connected by an isophthalamide linker, whereas 5 has a C(3)-symmetrical discotic structure, in which three folded units are connected by a benzene-1,3,5-tricarboxamide unit. UV/Vis, fluorescence, and NMR experiments have revealed that the foldamers or folded units strongly stack with fullerenes in chloroform. The (apparent) association constants of the respective complexes have been determined by a fluorescence titration method. The strong association is tentatively attributed to intermolecular cooperative fluorophenylpi and solvophobic interactions. A similar but weaker interaction has also been observed between an MeOH--N hydrogen-bonded foldamer and fullerenes. AFM studies have revealed that the surfaces of 3 and 4 show fibrous networks, while the surface of 5 shows particles. In sharp contrast, mixtures of 3 and 4 with C(60) have been shown to generate thinner separated fibrils, whereas a mixture of 5 and C(60) produces honeycomb-like nano networks, for which a columnar cooperative stacking pattern is proposed. The results demonstrate the usefulness of FH--N hydrogen-bonded folded structures in the construction of nanoscaled materials.

[Expression of integrin genes in heart of septic rat].

OBJECTIVE: To investigate the expression profile of integrin genes in heart of septic rat and relevant mechanisms responsible for sepsis-induced heart injury. METHODS: Twelve 3-month-old male Wistar rats were randomized to 2 equal groups, sepsis model group (CLP group) undergoing ligation and perforation with needle of the distal caecum so as to establish sepsis model, and sham operation group (Sham group), undergoing sham operation only serve as controls. Twenty-four later the hearts of rats were rapidly excised. After determination of the hemodynamic parameters by using Langendorff apparatus, the isolated hearts were cut into 2 parts vertically to undergo histopathological examination and analysis of the expression of integrin genes by oligonucleotide microarrays respectively. RESULTS: No overt pathological changes were detected in the hearts of septic rats, however, the cardiac output, stroke volume, heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, and maximum rate of left ventricular pressure rise of the CLP group were 29.4+/-3.3 ml/min, 0.12+/-0.01 ml, 256+/-6 bpm, 75.6+/-4.9 mm Hg, 7.5+/-0.3 mm Hg, and 2167+/-159 mm Hg/s respectively, all significantly than those of the Sham group (57.8+/-2.4 ml/min, 0.18+/-0.01 ml, 302+/-12 bpm, 90.0+/-2.7 mmHg, 8.0+/-0.3 mmHg. and 2601+/-34 mmHg/s respectively, all P<0.01). Microarray analysis showed that 20 out of 24 integrin genes were up-regulated by more than 2 times in the septic rat heart, among which the integrin alphaV and beta2 genes were upregulated and the expression of integrin beta1 gene was relatively insufficient. CONCLUSION: Maladjustment in expression of integrin genes is present in the septic rat heart. Up-regulation of integrin alphaV and beta2 genes may accelerate the heart injury mediated by inflammatory mediators, and the relatively insufficient expression of integrin beta1 gene may contribute to cardiac dysfunction.

Dynamic [2]catenanes based on a hydrogen bonding-mediated bis-zinc porphyrin foldamer tweezer: a case study.

This paper describes the self-assembly of a new class of three-component dynamic [2]catenanes, which are driven or stabilized by intramolecular hydrogen bonding, coordination, and electrostatic interaction. One of the component molecules 2, consisting of an aromatic oligoamide spacer and two peripheral zinc porphyrin units, was designed to adopt a folded preorganized conformation, which is stabilized by consecutive intramolecular three-centered hydrogen bonds. Component molecule 3 is a linear secondary ammonium bearing two peripheral pyridine units, which was designed to form a 1:1 complex with 24-crown-8 (5). The 1H NMR and UV-vis experiments in CDCl3-CD3CN (4:1 v/v) revealed that, due to the preorganized U-shaped feature, 2 could efficiently bind 3 through the cooperative zinc-pyridine coordination to generate highly stable 1:1 complex 2.3. Adding 5 to the 1:1 solution of 2 and 3 led to the formation of dynamic three-component [2]catenane 2.3.5 as a result of the threading of 3 through 5. 1H NMR studies indicated that in the 1:1:1 solution (3 mM) [2]catenane 2.3.5 was generated in 55% yield at 25 degrees C. The yield was increased with the reduction of the temperature and [2]catenane could be produced quantitatively in a 1:1:2 solution ([2]=3 mM) at -13 degrees C. Replacing 3 with 1,2-bis(4,4'-bipyridinium)ethane (4) in the three-component solution could also give rise to similar dynamic [2]catenane 2.4.5 albeit in slightly lower yield.

Interaction between tetramethylcucurbit[6]uril and some pyridine derivates.

Interaction between tetramethylcucurbit[6]uril (TMeQ[6], host) with hydrochloride salts of 2-phenylpridine (G1), 2-benzylpyridine (G2), and 4-benzylpyridine (G3) (guests) have been investigated by using 1H NMR spectroscopy and electronic absorption spectroscopy and theoretical calculations. The 1H NMR spectra analysis established an interaction model in which the host selectively included the phenyl moiety of the HCl salt of the above three guests, and formed inclusion complexes with a host-guest ratio of 1:1. Absorption spectrophotometric analysis allowed quantitative measurement of the stability of these host-guest inclusion complexes. Particularly, we have established a competitive interaction in which one host-guest inclusion complex pair is much more stable than another host-guest inclusion complex pair. The stability constants for the three host-guest inclusion complexes of TMeQ[6]-G1, TMeQ[6]-G2, and TMeQ[6]-G3 are approximately 2x10(6), 60.7, and 19.9 mol-1.L, respectively. To understand how subtle differences in the structure of the title guests lead to a significant difference in the stability of the corresponding host-guest inclusion complexes with the TMeQ[6], ab initio theoretical calculations have been performed, not only for the gas phase but also the solution phase (water as solvent) in all cases. The calculation results revealed that when the phenyl moiety of the three pyridine derivate guests was included, the host-guest complexation reached the minimum, and the corresponding energy differences for the formation of the title host-guest inclusion complexes are qualitatively consistent with the experimental results.

[Influence of glutamine and growth hormone intensified nutrition support on immunomodulation in critically ill elderly patients].

OBJECTIVE: To evaluate the impacts of glutamine (Gln) and recombinant human growth hormone (rhGH) intensified nutrition support on critically ill elderly patients. METHODS: Ninety critically ill aged patients were included in a prospective, randomized and controlled clinical study, and randomly divided into three groups: group A (standard nutrition support), group B (standard nutrition support+10% Gln 100 ml/d), group C (standard nutrition support+ Gln 100 ml/d+rhGH 10 U/d). Before treatment and then 7 and 14 days after treatment, blood samples were collected for analysis of serum proteins including albumin (ALB), pre-albumin (PAB), C-reactive protein (CRP), immunoglobulin G (IgG). Meanwhile, the variables including T-cell subsets, CD14 human leukocyte antigen (locus) DR (CD14 HLA-DR), and total lymphocytes were measured. The changes in acute physiology and chronic health evaluation II (APACHE II) and multiple organ dysfunction syndrome (MODS) scores, the durations of intensive care unit (ICU) stay and mechanical ventilation, and 28-day survival rate were recorded. RESULTS: Comparing with group A and B, the levels of serum ALB, PAB and IgG were significantly elevated in group C. The T-cell subsets, CD14 HLA-DR and the number of total lymphocytes were markedly higher in group C (P<0.01), and the APACHE II and MODS scores were decreased significantly in group C (P<0.05 or P<0.01). The levels of serum CRP were lowered significantly in group C (P<0.01). There were no significant differences in the durations of ICU stay, mechanical ventilation and 28-day survival rate among three groups (all P>0.05). CONCLUSION: Gln and rhGH intensified nutrition support can improve nutritional condition and immune function, downregulate the inflammatory response in the critically ill elderly patients.

Synthesis and characterization of pentaerythritol-derived oligoglycol and their application to catalytic Wittig-type reactions.

Several pentaerythritol-derived oligoglycols 1 with free hydroxyl groups are readily prepared by a convergent approach. Quantitative (13)C NMR proves to be an efficient tool for the characterization of oligoglycols. The corresponding telluride of oligoglycol 17 is synthesized and used as a good catalyst for Wittig-type reactions in preparing both disubstituted and trisubstituted olefins in good to high yields.

Role of planar chirality of S,N- and P,N-ferrocene ligands in palladium-catalyzed allylic substitutions.

Palladium-catalyzed asymmetric allylic substitutions using thioether and phosphino derivatives of ferrocenyloxazoline as ligands have been investigated with a focus on studying the role of planar chirality. In allylic alkylation, up to 98% ee and 95% ee were achieved with S,N- and P,N-ligands, respectively. In allylic amination, 97% ee was realized with P,N-ligands in the presence of TBAF. Several palladium allylic complexes were characterized by X-ray diffraction and/or solution NMR. Thioether derivatives of ferrocenyloxazolines with only planar chirality showed lower enantioselectivity in the allylic alkylation except 5c because of the formation of a new chirality on sulfur atom during the coordination of sulfur with palladium. On the other hand, in the planar chiral P,N-ligands without central chirality, (Sp)-11a-c there was no such disturbance and comparatively higher enantioselectivity in both palladium-catalyzed allylic alkylation and amination was provided.

Wittig-type olefination catalyzed by PEG-telluride.

Soluble poly(ethylene glycol) (PEG)-supported telluride 2 was designed and synthesized for catalytic Wittig-type reactions. It was found that the catalytic loading could be reduced from 20 to 2 mol % by the introduction of PEG (even to 0.5 mol % when some telluride salts were used as the catalyst). Under the catalytic reaction conditions, a wide variety of aldehydes with different structures could react with bromoacetate to afford beta-substituted or alpha,beta-disubstituted unsaturated esters in high yields with excellent E-stereoselectivity. The modified process, by using sodium bisulfite instead of triphenyl phosphite, represented a very simple product isolation procedure. The roles of PEG for promoting the ylide formation and stabilizing the catalytic species were disclosed. The mechanism was also studied.