Effects of goal-directed fluid therapy with different lactated Ringer's: hydroxyethyl starch ratios in hemorrhagic shock dogs.

The effects of goal-directed fluid therapy, with lactated Ringer's (LR) and 6% hydroxyethyl starch (HES) solution, on hemorrhagic shock dogs are unknown. We aimed to determine the optimal LR: HES ratio for the resuscitation of hemorrhagic shock dogs. Hemorrhagic shock was induced in 40 ventilated dogs by drawing an estimated 60% blood volume. The animals were randomly divided into five groups (N = 8) according to the LR: HES ratio of the resuscitation fluid (3:1, 2:1, 1:1, 1:2, and 1:3), and were then resuscitated for 24 h to reach the stroke volume variation (SVV) and hemoglobin (Hb) goals by fluid infusion and autologous blood perfusion. The extravascular lung water index (EVLWI), pH, partial pressure of oxygen (PaO2), base excess (BE), sodium, chloride, Hb and creatinine clearance (Clearcrea) were checked after 24 h (R24). The EVLWI of the 3:1 group at R24 were higher than that of the 1:3 group and the baseline value (P < 0.05), whereas the PaO2 was lower (P < 0.05). In contrast to the 3:1 group at R24 and baseline, plasma chloride and sodium in the 1:3 and 1:2 groups increased; however, pH, BE, and Clearcrea decreased (P < 0.05). No significant differences were found in the 1:1 and 2:1 groups at R24 compared with baseline (P > 0.05). Resuscitation with LR and HES at 2:1 and 1:1 ratios are superior in maintaining the acid-base, electrolyte, and lung water balances as well as renal function in hemorrhagic shock dogs than at ratios of 3:l, 1:2, and1:3.

Mechanism of ALDH2 improves the neuronal damage caused by hypoxia/reoxygenation.

OBJECTIVE: To investigate the protective effect and mechanism of ALDH2 on PC12 cells and brain nerve tissue injury under hypoxia. MATERIALS AND METHODS: The hypoxia model of PC12 cells with low ALDH2 expression was established and screened. The eukaryotic expression vector of wild type pEGFP-N1-ALDH2 and blank plasmid pEGFP-N1 were constructed and transfected into PC12 hypoxia cells respectively. After reoxygenation culture, the morphology, quantity, ALDH2 expression level and apoptosis rate of the two groups were observed, and the role of ALDH2 in cell hypoxia injury was analyzed. Eighty SD rats were randomly divided into model group (ischemia-reperfusion injury group), Alda-1 group (intraperitoneal injection of alda-1 12 hours before and after modeling), DMSO group (intraperitoneal injection of dimethyl sulfoxide) and sham operation group, with 20 rats in each group. The neurobehavioral score, apoptosis rate of nerve cells, the content and activity of ALDH2 in active cerebral cortex and hippocampal CA1 area were compared. RESULTS: The number of PC12 cells in hypoxia group was lower than that in control group. The expression level of ALDH2 protein in PC12 cells after 4 hours of hypoxia was lower than that in normal culture group. The number of PC12 cells transfected with wild-type recombinant plasmid was significantly more than that of blank plasmid group. Compared with the hypoxia group, the pre apoptotic and post apoptotic cells in wild type transfection group decreased after hypoxia treatment. Compared with sham operation group, nerve injury and apoptosis were increased in group M and DMSO, while ALDH2 activity and expression did not change significantly. Compared with M group and DMSO group, the nerve injury and apoptosis in Alda-1 group were improved, ALDH2 activity was increased, and ALDH2 expression was not significantly changed in Alda-1 group. CONCLUSIONS: Increasing the expression of ALDH2 or enhancing the activity of ALDH2 can improve the injury of neurons induced by hypoxia/reoxygenation.

The effects of nitric oxide donors on the sporulation of Eimeria tenella oocysts.

Nitric oxide (NO) is involved in many physiological processes including regulation of blood pressure, immune response, and neural communication. The effects of NO donors on the sporogony of Eimeria tenella oocysts and the blocking effects of NO scavenger, hemoglobin (Hb), against NO donors were investigated in this study. The results showed that the sporulation of oocysts could be completely inhibited by acidic sodium nitrite (NaNO2), S-nitroso-glutathione (GSNO) or S-nitroso-N-acetyl-dl-penicillamine (SNAP) in profound dose-dependent and time-dependent manners, and the inhibiting process was irreversible and not affected by feces of chickens. However, not all NO donors in this study, such as sodium nitroprusside (SNP), demonstrated above-mentioned effect. The NO scavenger Hb could significantly prevent the detrimental effects of NO donors on the sporogony of oocysts in a dose-dependent manner. At present, the inhibiting mechanism of NO donors on the sporulation of oocysts was still unclear.

Pathogenic effects of the coccidium Eimeria ninakohlyakimovae in goats.

Twenty-four coccidia-free goats were reared artificially in indoor cages and allocated to 6 groups of 4 animals each. At 20 days of age, goats in groups 1-3 received 10(4),10(5) and 10(6) sporulated oocysts of Eimeria ninakohlyakimovae per goat, respectively, each as a single dose. Goats in group 4 received daily doses increasing over a 3-week period, starting with 100/day for the first week, followed by 1000, and 10,000/day in weeks 2, 3, respectively. Goats in group 5 received 10(4) oocysts following a challenge dose of 10(6) oocysts on day 32. Goats in group 6 were kept as uninoculated controls. Infected animals showed diarrhoea and weight loss. Goats in group 4 showed longer periods of diarrhoea and patency than other infected goats. Goats in group 5 showed the same severe clinical signs as those in group 3 but produced very low oocyst output after a challenge dose. The diarrhoea was associated with a reduction in alkaline phosphatase activity and increases in packed cell volume and haemoglobin. No significant differences were found in serum aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, Na+, K+,Cl- between groups during 48 days after inoculation. There were no serum enzyme indications of damage to the liver. Histological examination performed 100 days after inoculation revealed that inoculated goats had mild subacute to chronic proliferative enteritis in the lower small intestine and the large intestine, and the mesenteric lymph nodes, gallbladders and livers also showed slight histological lesions. The results showed that E. ninakohlyakimovae was highly pathogenic.

Stimulated mast cells promote maturation of myocardial microvascular endothelial cell neovessels by modulating the angiopoietin-Tie-2 signaling pathway.

Angiopoietin (Ang)-1 and Ang-2 interact in angiogenesis to activate the Tie-2 receptor, which may be involved in new vessel maturation and regression. Mast cells (MCs) are also involved in formation of new blood vessels and angiogenesis. The present study was designed to test whether MCs can mediate angiogenesis in myocardial microvascular endothelial cells (MMVECs). Using a rat MMVEC and MC co-culture system, we observed that Ang-1 protein levels were very low even though its mRNA levels were increased by MCs. Interestingly, MCs were able to enhance migration, proliferation, and capillary-like tube formation, which were associated with suppressed Ang-2 protein expression, but not Tie-2 expression levels. These MCs induced effects that could be reversed by either tryptase inhibitor [N-tosyl-L-lysine chloromethyl ketone (TLCK)] or chymase inhibitor (N-tosyl-L-phenylalanyl chloromethyl ketone), with TLCK showing greater effects. In conclusion, our data indicated that MCs can interrupt neovessel maturation via suppression of the Ang-2/Tie-2 signaling pathway.

Stimulated mast cells promote maturation of myocardial microvascular endothelial cell neovessels by modulating the angiopoietin-Tie-2 signaling pathway

Angiopoietin (Ang)-1 and Ang-2 interact in angiogenesis to activate the Tie-2 receptor, which may be involved in new vessel maturation and regression. Mast cells (MCs) are also involved in formation of new blood vessels and angiogenesis. The present study was designed to test whether MCs can mediate angiogenesis in myocardial microvascular endothelial cells (MMVECs). Using a rat MMVEC and MC co-culture system, we observed that Ang-1 protein levels were very low even though its mRNA levels were increased by MCs. Interestingly, MCs were able to enhance migration, proliferation, and capillary-like tube formation, which were associated with suppressed Ang-2 protein expression, but not Tie-2 expression levels. These MCs induced effects that could be reversed by either tryptase inhibitor [N-tosyl-L-lysine chloromethyl ketone (TLCK)] or chymase inhibitor (N-tosyl-L-phenylalanyl chloromethyl ketone), with TLCK showing greater effects. In conclusion, our data indicated that MCs can interrupt neovessel maturation via suppression of the Ang-2/Tie-2 signaling pathway.

Molecular characterization of the surface glycoprotein genes of an H5N1 influenza virus isolated from a human in Guangdong, China.

In March 2006, a human H5N1-infected case was found in Guangdong province, China. Here, we molecularly characterized the hemagglutinin (HA) and neuraminidase (NA) genes of the A/China/GD01/06 (GD01) strain causing the infection. The phylogenetic analyses suggested that the HA and NA genes of GD01 and recent human H5N1 viruses from different provinces of China were probably derived from a common ancestor and the H5N1 human infection was acquired directly from affected poultry. At the cleavage site of HA, GD01 contained multiple basic amino acids, a feature characteristic of highly pathogenic avian influenza A viruses. The virus possessed Gln222, Gly224, Ser223, Asn182, Gln192 residues adjacent to the receptor-binding site, preferential for recognizing SAalpha2, 3Gal. In addition, the GD01 NA amino acid sequence possessed Asn344 and Phe466, which might be related to the low-pH stability of the sialidase activity and gastrointestinal symptoms of the patient.