Biomedical subjects

Na Li

Publications and source records attributed to Na Li.

At least 73 records · Page 4Linked to original sources

PubMed2006

[Effects of valsartan and captopril on expressions and activities of tissue factor and tissue factor pathway inhibitor].

OBJECTIVE: To investigate the effects of ox-LDL, ACEI and ARB on expressions and activities of TF and TFPI in VSMC. METHODS: (1) Rabbit VSMC was cultured by explant-attached method in vitro. (2) The effects of ox-LDL and valsartan on TF and TFPI expressions were analyzed by immunohistochemistry and immunofluorescence. Laser scanning confocal microscopy were applied to analyze the effects of ox-LDL and valsartan on TF expression. The effects of ox-LDL, valsartan and captopril on TF and TFPI antigen expressions were analyzed by ELISA. Chromogenic substrate method was used to determine the effects of ox-LDL, valsartan and captopril on TF activity. The effects of ox-LDL and valsartan on TF mRNA expression were analyzed by RT-PCR. RESULTS: (1) ox-LDL could upregulate TF antigen, activity and TF expression at mRNA level and downregulate TFPI antigen. (2) Valsartan and captopril could reduce TF antigen and activity in VSMC treated by ox-LDL, and valsartan reduce it in a dose-dependent manner. Valsartan could also attenuate TF expression at mRNA level in VSMC treated by ox-LDL. (3) Using ELISA, valsartan and captopril could also enhance TFPI antigen in VSMC treated by ox-LDL. CONCLUSION: Our study showed upregulated TF and downregulated TFPI expression and activity by ox-LDL and these effects could be reversed by ACEI and ARB indicating a new insight on the antiatherosclerotic effects of ACEI and ARB.

Animals↗

PubMed2005

A proteomic investigation into a human gastric cancer cell line BGC823 treated with diallyl trisulfide.

Garlic is generally used as a therapeutic reagent against various diseases worldwide. Although a great effort is made to understand the pharmaceutical mechanisms of garlic and its derivatives, there are many mysteries to be uncovered. Using proteomic means, herein we have systematically studied the responses of protein expression in BGC823 cells, a gastric cancer cell line, induced by diallyl trisulfide (DATS), a major component of garlic derivatives. A total of 41 unique proteins in BGC823 were detected with significant changes in their expression levels corresponding with DATS administration. Of these proteins, five typical ones, glutathione S-transferase-pi (GST-pi), voltage-dependent anion channel-1 (VDAC-1), Annexin I, Galectin and S100A11, were further examined by Western blotting, resulting in coincident data with the proteomic evidence. Moreover quantitative real-time RT-PCR experiments offered dynamic data of mRNA expression, indicating the responses of Annexin I and GST-pi expression within a short period after DATS treatment. Interestingly, approximately 50% of DATS-sensitive proteins (19/41) in BGC823 are tightly associated with apoptotic pathways. These proteomic results presented, therefore, provide additional support to the hypothesis that garlic is a strong inducer of apoptosis in tumor cells.

Allyl Compounds↗

PubMed2005

Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation.

Integrin-mediated adhesion regulates the development and function of a range of tissues; however, little is known about its role in glandular epithelium. To assess the contribution of beta1 integrin, we conditionally deleted its gene in luminal epithelia during different stages of mouse mammary gland development and in cultured primary mammary epithelia. Loss of beta1 integrin in vivo resulted in impaired alveologenesis and lactation. Cultured beta1 integrin-null cells displayed abnormal focal adhesion function and signal transduction and could not form or maintain polarized acini. In vivo, epithelial cells became detached from the extracellular matrix but remained associated with each other and did not undergo overt apoptosis. beta1 integrin-null mammary epithelial cells did not differentiate in response to prolactin stimulation because of defective Stat5 activation. In mice where beta1 integrin was deleted after the initiation of differentiation, fewer defects in alveolar morphology occurred, yet major deficiencies were also observed in milk protein and milk fat production and Stat5 activation, indicating a permissive role for beta1 integrins in prolactin signaling. This study demonstrates that beta1 integrin is critical for the alveolar morphogenesis of a glandular epithelium and for maintenance of its differentiated function. Moreover, it provides genetic evidence for the cooperation between integrin and cytokine signaling pathways.

Animals↗

PubMed2005

A novel retinoic acid receptor beta isoform and retinoid resistance in lung carcinogenesis.

BACKGROUND: We previously reported that all-trans-retinoic acid (RA) treatment can prevent in vitro transformation of immortalized human bronchial epithelial (HBE) cells. METHODS: To determine whether methylation inhibits RARbeta expression in HBE cells, we used sodium bisulfite sequencing to compare RARbeta P2 promoter methylation patterns in RA-sensitive (BEAS-2B) and RA-resistant (BEAS-2B-R1) HBE cells. Immunoblotting was used to assess induction of the RARbeta, placental transforming growth factor beta (PTGF-beta), Fos-related antigen 1 (Fra-1), and transglutaminase II (TGase II) proteins by RA following treatment with azacitidine, a DNA demethylating agent. The expression, transcriptional activity, and growth suppressive activity of RARbeta1', a novel RAR isoform, were evaluated in lung cancer cells transfected with RARbeta1', and expression was also studied in paired normal lung tissues and lung tumors. All statistical tests were two-sided. RESULTS: Hypermethylation was observed in the 3' region of the RARbeta P2 promoter of BEAS-2B-R1 but not BEAS-2B cells. Azacitidine treatment of BEAS-2B-R1 cells restored RA-inducible RARbeta2 and PTGF-beta expression but not that of RARbeta1', Fra-1, or TGase II. RARbeta1' expression was repressed in RA-resistant BEAS-2B-R1 cells and in lung cancers, compared with adjacent normal lung tissues. BEAS-2B-R1 cells transiently transfected with RARbeta1' had increased RA-dependent activation of a retinoic acid receptor element (RARE)-containing reporter plasmid compared with vector control (mean = 3.2, 95% confidence interval [CI] = 3.1 to 3.3 versus mean = 1.4, 95% CI = 1.3 to 1.5; P<.001). In H358 lung cancer cells transiently transfected with RARbeta1', RA treatment restored target gene expression compared with that in vector-transfected cells and suppressed cell growth compared with that in untreated cells (4 microM; treated mean = 0.49 versus untreated mean = 1.0, difference = 0.51, 95% CI = 0.35 to 0.67, P = .003; 8 microM: treated mean = 0.50 versus untreated mean = 1.0, difference = 0.50, 95% CI = 0.26 to 0.74, P = .015). CONCLUSION: Restoration of RARbeta1' expression may overcome retinoid resistance in lung carcinogenesis.

Antimetabolites, Antineoplastic↗

PubMed2005

A population association study of angiotensinogen polymorphisms and haplotypes with left ventricular phenotypes.

Several studies have shown an association between single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene and hypertension. Because hypertension is a risk factor for left ventricular (LV) hypertrophy and because evidence from animal models suggests that AGT may play a role in the growth and hypertrophy of the heart, we chose to conduct a population association study examining the relationship of 10 SNPs in the AGT gene with 7 different LV phenotypes measured by echocardiography. Participants (336 whites and 441 blacks) were drawn from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Individuals were genotyped for 10 previously identified SNPs within the AGT gene. SNP genotype results were regressed against continuous LV phenotypes to test associations separately in each race. Using a cutoff of P<0.005 to account for multiple testing, we found 1 SNP (rs943580) significantly associated with transmitral early peak filling velocity (MVE) in the black population. We also used Phase 2.0.2 to reconstruct haplotypes from genotype data. Using the same cutoff of P<0.005, we found no haplotypes to be significantly associated with the LV phenotypes. To better understand the association between rs943580 and MVE, we examined AGT haplotype associations with MVE. The single SNP association was driven by a large group of SNPs in high linkage disequilibrium that includes the promoter SNP rs5051.

Aged↗

PubMed2005

Selectively desulfated heparin inhibits P-selectin-mediated adhesion of human melanoma cells.

Accumulating evidence has suggested that one of the mechanisms by which heparin inhibits metastasis is by blocking the P-selectin-based interaction of platelets with tumor cells. Here we demonstrate that the sulfate groups at C6/N and especially C6, but not C2 and C3, of heparin play a critical role in P-selectin recognition and that 2-O,3-O-desulfated heparin can block P-selectin-mediated A375 human melanoma cell adhesion. Our findings show that chemical modification of heparin, especially 2-O,3-O-desulfation, may result in a therapeutic agent that is anti-metastatic because it blocks unwanted P-selectin-dependent adhesion but that lacks dose-limiting anticoagulant effects.

Anticoagulants↗

PubMed2005

[Expression of RASSF1A mRNA and its relationship with HPV-16 in cervical cancer].

OBJECTIVES: To study the expression of RASSF1A mRNA and its relationship with HPV-16 in cervical cancer. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of RASSF1A mRNA in 56 patients with cervical cancer, 36 patients with CIN and 20 patients with normal cervix. HPV-16 DNA was also examined by PCR in 56 patients with cervical cancer. RESULTS: The rates of loss of RASSF1A mRNA expression were 0% (0/20), 22.2% (8/36) and 50.0% (28/56) in patients with normal cervix, CIN and cervical cancer respectively. The loss rate of RASSF1A mRNA in the cervical tissues at the advanced stages (stages III-IV, 82.4%) was higher than that at the early stages (stages I-II, 35.9%, P < 0.05). RASSF1A mRNA deletion occurred more often in the tissues of squamous cervical cancers (63.3%) than in those of adenocarcinoma (34.6%) (P < 0.05). The loss rate of the poor differentiation group was 70.8%, significantly higher than that of the middle and high differentiation group (37.5%, P < 0.05). The loss of RASSF1A was negatively related with HPV-16 infection in cervical cancers, especially in adenocarcinoma (P < 0.905). CONCLUSION: Loss of RASSF1A may play an important role in tumorgenesis and development of cervical cancer.

Adenocarcinoma↗

PubMed2005

A p53-dominant transcriptional response to cisplatin in testicular germ cell tumor-derived human embryonal carcinoma.

Testicular germ cell cancers remain one of the few solid tumors routinely cured in advanced stages with conventional cisplatin-based chemotherapy. The mechanisms remain largely unknown. Through use of gene-expression array profiling we define immediate transcriptional targets in response to cisplatin in testicular germ cell-derived human embryonal carcinoma cells. We report 46 genes upregulated and five genes repressed by cisplatin. Several of these gene products, including FAS, TRAILR3, PHLDA3, LRDD, and IER3 are previously implicated in the apoptotic death receptor pathway, while others including SESN1, FDXR, PLK3, and DDIT4 are known mediators of reactive oxygen species generation. Approximately 54% of the upregulated genes are established or suspected downstream targets of p53. Specific siRNA to p53 prevents cisplatin-mediated activation of p53 and p53 pathway genes and renders embryonal carcinoma cells relatively resistant to cisplatin cytotoxicity. Interestingly, in p53 knockdown cells nearly the entire set of identified cisplatin targets fail to respond or have a diminished response to cisplatin, suggesting that many are new direct or indirect targets of p53 including GPR87, STK17A, INPP5D, FLJ11259, and EPS8L2. The data indicate that robust transcriptional activation of p53 is linked to the known hypersensitivity of testicular germ cell tumors to chemotherapy. Many of the gene products may participate in the unique curability of this disease.

Antineoplastic Agents↗

PubMed2005

Disparity in osmolarity-induced vascular reactivity.

Conventional peritoneal dialysis solutions (PDS) are vasoactive. This study was conducted to identify vasoactive components of PDS and to describe quantitatively such vasoactivity. Anesthetized nonheparinized rats were monitored continuously for hemodynamics while the microvasculature of the jejunum was studied with in vivo intravital microscopy. In separate experiments, vascular reactivity of rat endothelium-intact and -denuded aortic rings (2 mm) was studied ex vivo in a standard tissue bath. In both studies, suffusion of the vessels was performed with filter-sterilized isotonic and hypertonic solutions that contained glucose or mannitol as osmotic agents. PDS served as a control (Delflex 2.25%). Hypertonic glucose and mannitol solutions produced a significant vascular reactivity in aortic rings and instantaneous and sustained vascular relaxation at all levels of the intestinal microvasculature. Similarly, lactate that was dissolved in a low-pH isotonic physiologic salt solution produced significant force generation in aortic rings. Whereas isotonic glucose and mannitol solutions had no vasoactivity in aortic rings, isotonic glucose produced a selective, insidious, and time-dependent vasodilation in the intestinal premucosal arterioles (18 +/- 0.2% of baseline), which was not observed in the larger inflow arterioles (100 mum). This isotonic glucose-mediated vascular relaxation can be attenuated by approximately 50% with combined adenosine A(2a) and A(2b) receptor antagonists and completely abolished by adenosine A(1) receptor inhibition. By using two different experimental techniques, this study demonstrates that hyperosmolality and lactate are the major vasoactive components of clinical peritoneal dialysis solutions. The pattern and the magnitude of such reactivity are dependent on vessel size and on the solutes' metabolic activity. Low pH of conventional PDS is not a vasoactive component by itself but renders lactate vasoactive. Energy-dependent transport of glucose into cells mediates vasodilation of small visceral arterioles by an adenosine receptor-mediated mechanism and constitutes a significant fraction of PDS-mediated vascular reactivity in the visceral microvasculature.

Animals↗

PubMed2005

Molecular modeling of the intercalation of porphyrins into alpha-zirconium phosphate.

In this work, n-alkylamines (number of carbon atoms ranging from 3 to 10) were investigated in detail by molecular modeling as spacers for intercalating porphyrins into alpha-zirconium phosphate (alpha-ZrP). Pre-intercalated n-alkylamines can form either a flat monolayer or a canted bilayer in the gallery of alpha-ZrP. Based on the interlayer state and intercalative potential of the two modes in alpha-ZrP, it is suggested that the flat monolayer is a better spacer than the bilayer and that n-propylamine (PA) and n-butylamine (BA) in mobile monolayers are the best spacers among the n-alkylamines studied, as is also found experimentally. The intercalation behavior of TMPyP [5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin] and several other porphyrins was investigated by calculating the intercalative potential. The calculated results showed that the porphyrins were densely packed in a canted monolayer model, and an increase of polarity of the substituent would facilitate the intercalation of the porphyrins.

Alkylation↗

PubMed2005

P-Selectin-mediated acute inflammation can be blocked by chemically modified heparin, RO-heparin.

Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Heparin can bind to P-selectin, and its anti-inflammatory property is mainly due to inhibition of P-selectin. However, the strong anticoagulant activity of heparin limits its clinical use. We prepared periodate-oxidized, borohydride-reduced heparin (RO-heparin) by chemical modification and tested its anticoagulant and anti-inflammatory activities. Activated partial thromboplastin time (aPTT) assays showed that, compared with heparin, RO-heparin had greatly reduced anticoagulant activity. Intravenous administration of this compound led to reduction in the peritoneal infiltration of neutrophils in a mouse acute inflammation model. In vitro cell adhesion experiments demonstrated that the effect of RO-heparin on inflammatory responses was mainly due to inhibiting the interaction of P-selectin with its ligands. These results indicate that RO-heparin may be a safer treatment for inflammation than heparin, especially when selectin is targeted.

Animals↗

PubMed2005

Beta1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli.

Integrin-extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. To study the role of beta1 integrin in the mammary gland, Itgbeta1(flox/flox) mice were crossed with WAPiCre transgenic mice, which led to specific ablation of beta1 integrin in luminal alveolar epithelial cells. In the beta1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell-basement membrane associations. Activity of focal adhesion kinase (FAK) was also decreased in mutant mammary glands. Luminal cell proliferation was strongly inhibited in beta1 integrin mutant glands, which correlated with a specific increase of p21 Cip1 expression. In a p21 Cip1 null background, there was a partial rescue of BrdU incorporation, providing in vivo evidence linking p21 Cip1 to the proliferative defect observed in beta1 integrin mutant glands. A connection between p21 Cip1 and beta1 integrin as well as FAK was also established in primary mammary cells. These results point to the essential role of beta1 integrin signaling in mammary epithelial cell proliferation.

Animals↗

PubMed2005

Ribozyme-catalyzed aminoacylation from CoA thioesters.

Coenzyme A (CoA) thioesters play essential roles in modern metabolism. To demonstrate plausible biochemical functions of thioesters in the RNA world, we have isolated a new class of ribozymes (ACT) that catalyze self-aminoacylation from a number of CoA thioesters with catalytic efficiencies ranging from 7000 to 24 000 M(-1) x min(-1). Active thioester substrates are required to contain both a free alpha-amino group in the acyl moiety and a CoA as the thiol component. We hypothesize ribozyme-based aminoacylation systems using aminoacyl thioesters of CoA as the ancestors of modern aminoacyl tRNA synthetases. On the basis of our previous results [Huang et al. (2000) Biochemistry 39, 15548-15555; Coleman and Huang (2002) Chem. Biol. 9, 1227-1236], an extensive RNA-catalyzed "metabolic pathway" involving CoA and its thioesters is proposed. Complex contemporary metabolic systems could have evolved from the proposed ribozyme pathways.

3' Untranslated Regions↗

PubMed2005

Novel cyanine-AMP conjugates for efficient 5' RNA fluorescent labeling by one-step transcription and replacement of [gamma-32P]ATP in RNA structural investigation.

Two novel fluorescent cyanine-AMP conjugates, F550/570 and F650/670, have been synthesized to serve as transcription initiators under the T7 phi2.5 promoter. Efficient fluorophore labeling of 5' RNA is achieved in a single transcription step by including F550/570 and F650/670 in the transcription solution. The current work makes fluorescently labeled RNA readily available for broad applications in biochemistry, molecular biology, structural biology and biomedicine. In particular, site-specifically fluorophore-labeled large RNAs prepared by the current method may be used to investigate RNA structure, folding and mechanism by various fluorescence techniques. In addition, F550/570 and F650/670 may replace [gamma-32P]ATP to prepare 5' labeled RNA for RNA structural and functional investigation, thereby eliminating the need for the unstable and radio-hazardous [gamma-32P]ATP.

Adenosine Monophosphate↗

PubMed2005

The Genomes of Oryza sativa: a history of duplications.

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.

Base Sequence↗

PubMed2005

OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia.

The cellular and subcellular localization and mechanism of transport of the heteromeric organic solute transporter (OST) OSTalpha-OSTbeta was examined in human and rodent epithelia. The two subunits of the transporter were expressed together in human small intestine, kidney, and liver, tissues that also express the apical sodium-dependent bile acid uptake transporter ASBT (SLC10A2). Indirect immunofluorescence microscopy localized OSTalpha and OSTbeta to the basolateral membrane of mouse, rat, and human ileal enterocytes, renal proximal tubular cells, and cholangiocytes. Transport in OSTalpha-OSTbeta-expressing Xenopus laevis oocytes was unaffected by depletion of intracellular adenosine triphosphate, or by changes in transmembrane Na(+), K(+), H(+), or Cl(-) concentration gradients. However, the oocytes demonstrated robust substrate efflux and trans-stimulation, indicating that transport occurs by facilitated diffusion. Madin Darby canine kidney cells coexpressing mouse Ostalpha and Ostbeta exhibited enhanced apical to basolateral transport of the major glycine and taurine conjugated bile acid species. In conclusion, the selective localization of OSTalpha and OSTbeta to the basolateral plasma membrane of epithelial cells responsible for bile acid and sterol reabsorption, the substrate selectivity of the transporter, and the facilitated diffusion transport mode collectively indicate that OSTalpha-OSTbeta is a key basolateral transporter for the reabsorption of these important steroid-derived molecules.

Amino Acid Sequence↗

PubMed2005

Gene expression differences in mice divergently selected for methamphetamine sensitivity.

In an effort to identify genes that may be important for drug-abuse liability, we mapped behavioral quantitative trait loci (bQTL) for sensitivity to the locomotor stimulant effect of methamphetamine (MA) using two mouse lines that were selectively bred for high MA-induced activity (HMACT) or low MA-induced activity (LMACT). We then examined gene expression differences between these lines in the nucleus accumbens, using 20 U74Av2 Affymetrix microarrays and quantitative polymerase chain reaction (qPCR). Expression differences were detected for several genes, including Casein Kinase 1 Epsilon (Csnkle), glutamate receptor, ionotropic, AMPA1 (GluR1), GABA B1 receptor (Gabbr1), and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (Darpp-32). We used the www.WebQTL.org database to identify QTL that regulate the expression of the genes identified by the microarrays (expression QTL; eQTL). This approach identified an eQTL for Csnkle on Chromosome 15 (LOD = 3.8) that comapped with a bQTL for the MA stimulation phenotype (LOD = 4.5), suggesting that a single allele may cause both traits. The chromosomal region containing this QTL has previously been associated with sensitivity to the stimulant effects of cocaine. These results suggest that selection was associated with (and likely caused) altered gene expression that is partially attributable to different frequencies of gene expression polymorphisms. Combining classical genetics with analysis of whole-genome gene expression and bioinformatic resources provides a powerful method for provisionally identifying genes that influence complex traits. The identified genes provide excellent candidates for future hypothesis-driven studies, translational genetic studies, and pharmacological interventions.

Animals↗

PubMed2005

Direct energy delivery improves tissue perfusion after resuscitated shock.

BACKGROUND: Conventional resuscitation (CR) from hemorrhagic shock (HS) does not restore intestinal blood flow. Indicators of anaerobic metabolism suggest that cellular energy production also is compromised. We hypothesize that the direct intravenous delivery of lipid-encapsulated high-energy phosphates to cells improves intestinal perfusion during HS and resuscitation (RES). METHODS: MAP (MAP) was monitored in male rats (200 g), terminal ileum microvessel diameters were measured by in vivo videomicroscopy, and blood flow (Doppler velocimetry) was calculated. Cellular energy delivery was accomplished by intravenous infusion during RES of fusogenic unilamellar lipid vesicles that contain adenosine triphosphate (ATP; VitaSol). Our protocol was HS to 50% baseline MAP for 60 minutes, 30 minutes of RES, and continued microscopy observation for 120 minutes. Experimental groups (n=8 each) were HS+CR (group I); HS+CR+ VitaSol (group II); HS+CR+Vehicle, Vehicle is the phospholipid vesicles without magnesium ATP, (group III); HS+ VitaSol (group IV); sham-operated control+VitaSol (group V); and a time-matched sham-operated control (group VI). The survival outcome and total tissue water from wet weight/dry weight ratio as a function of adjunct VitaSol resuscitation were evaluated in separate intact animal experiments. RESULTS: HS caused a selective vasoconstriction of the intestinal inflow arterioles (100 microm), which was not seen in the smaller intestinal premucosal arterioles (7-15 microm). CR, which restored baseline hemodynamics, resulted in an initial restoration of intestinal microvascular diameters at all arteriolar levels. However, this was followed by a progressive vasoconstriction and hypoperfusion in premucosal vessels at 120 minutes after RES (-20.48% +/- 2.95% from baseline diameters). In contrast, VitaSol with CR caused enhanced premucosal dilation (+34.27% +/- 4.62%) and augmented flow (+20.50% +/- 10.70%) above prehemorrhage baseline. Vesicles alone had no effect, and VitaSol alone caused only a modest dilation. CR of moderate HS (40% of baseline MAP for 60 minutes, n=10) caused 20% mortality, whereas adjunct VitaSol resuscitation had a 100% survival and less tissue water content. CONCLUSIONS: Our data confirms that CR causes progressive intestinal hypoperfusion. Cellular resuscitation with direct intravenous energy delivery improves intestinal perfusion after CR and results in improved survival and less tissue edema.

Adenosine Triphosphate↗