Unloading oxygen in a capillary vessel under a pathological condition

In this work, we study theoretically the unloading of oxygen from a hemoglobin molecule to the wall of a typical capillary vessel, considering that the hemoglobin under pathological conditions, obeys the rheological Maxwell model. Based on recent experimental evidences in hypertension, we consider that the red blood cells (RBCs) are composed by a single continuous medium in contrast with the classical particulate or discrete RBC models, which are only valid under normal physiological conditions. The analysis considers the hemodynamic interactions between the plasma and the hemoglobin, both circulating in a long horizontal capillary. We apply numerical and analytical methods to obtain the main fluid-dynamic characteristics for both fluids in the limit of low Reynolds and Womersley numbers. A diffusion boundary layer formulation for the oxygen transport in the combined plasma-hemoglobin core region is presented. The main aspects derived are the time and spatial evolution of the membrane. The hemoglobin and plasma velocities and the pressure distributions are shown. For the oxygen unloading the results are the oxy-hemoglobin saturation, the oxygen flux and the oxygen concentration in the cell-free plasma layer. The volume fraction of red blood cells and the Strouhal number have a great influence on the hemodynamic interactions.     

Hematological and plasma biochemical values for captive tufted capuchin monkeys (Cebus apella)

Hematological and blood biochemical parameters are of great importance in medical and veterinary practice. Unfortunately, normal reference range intervals for hematological and serum biochemical values in the tufted capuchin monkey (Cebus apella) have seldom been reported. The study reported here is based on data from blood samples collected from 44 monkeys over an 8-year period. Male and female data are displayed separately within two age categories: juveniles and adults, and effects for sex and age are examined. Significant differences between males and females are found for erythrocytes, hemoglobin, hematocrit, and α(1) globulin. Significant differences between juveniles and adults are found for neutrophils, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, inorganic phosphorus, glucose, total protein, serum iron, and some serum protein parameters and albumin/globulin ratio. These values are compared with values we previously reported, and their importance in care and well-being of captive tufted capuchin monkeys is discussed.     

人工感染羊嗜流产衣原体豚鼠流产模型的建立

目的通过人工感染怀孕豚鼠建立嗜流产衣原体发病模型,观察流产病理学变化的差异,确定豚鼠是否可以作为嗜流产衣原体的动物模型。方法35只清洁级怀孕40d的豚鼠随机分为7组,每组5只。将羊嗜流产衣原体分离株B10011、CG1株分别以三个剂量组（10^-1,10^-2,10^-3）腹腔攻毒1次,每只0．5mL,以灭菌生理盐水为阴性对照。攻毒后观察豚鼠的临床体征、流产和死亡数量。攻毒后20d安乐死处理剩余的大小豚鼠,无菌摘取组织,分成2份。一份-20℃冷冻保存,PCR检测病原在组织中的分布;另外一份固定于10％中性甲醛溶液,组织切片和免疫组化观察。结果（1）羊嗜流产衣原体分离株B10011和CG1均可造成怀孕豚鼠流产、产弱胎、畸形胎或死胎。2种分离株感染不同剂量造成豚鼠平均流产时间、流产数量、豚鼠死亡数量均有显著差异,且CG1株敏感性高于B10011株。（2）2个分离株均可造成肾脏、肝脏肿大,肺脏呈局灶性出血,卵巢出血坏死,胎盘子宫阜水肿;病理组织学显示肾小管上皮细胞变性、坏死,单核细胞大量增生;肝细胞颗粒样病变。脾髓质弥漫性出血,皮质区淋巴小结生发中心萎缩。（3）免疫组化结果显示衣原体包涵体主要分布于肾脏近曲小管、远曲小管,以及脾脏的髓质区。（4）PCR检测显示分离株感染后,肾脏、脾脏、肺脏、肝脏中均呈阳性。在卵巢组织中,高剂量组呈阳性。结论以B10011和CGl分离株人工感染怀孕豚鼠均可导致豚鼠出现流产,且CG1分离株敏感性较高,呈剂量一效应关系;感染豚鼠病理学变化与临床羊流产相似。因此,人工感染豚鼠流产模型可以用于反刍动物嗜流产衣原体病的研究。     

失血性休克大鼠模型的改进及胃黏膜血流量的测定

目的探讨失血性休克大鼠模型的建立及胃黏膜血流量的测定。方法16只健康雄性SD大鼠随机分为两组：对照组（n=8）、失血性休克组（n=8）。失血性休克组使用颈动脉失血-颈静脉失血回输的方式制备失血性休克大鼠模型。维持平均动脉压40mmHg 1h后复苏,复苏后2h动物模型制作成功。使用激光多普勒血流仪测定大鼠胃黏膜血流量;采用光镜及透射电镜观察胃黏膜损伤情况。结果失血性休克组胃黏膜血流量较对照组明显降低,差异非常显著（P〈0．01）,胃黏膜细胞坏死、脱落、溶解,局部溃疡形成。结论失血性休克大鼠胃黏膜血流量明显降低,存在广泛的胃黏膜损伤。     

BimEL-dependent apoptosis induced in peripheral blood lymphocytes with n-butyric acid is moderated by variation in expression of c-myc and p21(WAF1)

We have examined the effect of sodium butyrate (SB) on the viability of normal peripheral blood lymphocytes (PBLs) in vitro and the effect of this agent on the expression of 20 apoptosis-related genes. Data suggest that PBL treated with 2 mmol L(-1) SB resisted for at least 8 h the destructive activity of the agent, but eventually 30% of cells died within 72 h. As documented by flow cytometry and cytochrome c release study, cells underwent mitochondrial-derived apoptosis. While the expression of the majority of genes examined by RT-PCR and Western blots remained indifferent to 2 mmol L(-1) SB, the cellular levels of BimEL, c-myc, p53, and p21(WAF1) varied profoundly with the time of SB treatment. The Bax activator BimEL increased rapidly, driving cells toward apoptosis likely controlled by c-myc and p21(WAF1) activities. The c-myc, exercising the role of mediator of the function of BimEL and inhibitor of p21(WAF1) expression, decreased significantly for several hours after adding SB but within 48 h it returned to close to its original value. An apoptosis inhibitor and executive caspase substrate p21(WAF1) increased early at the beginning of treatment but subsequently, within a time frame of 72 h, profoundly dropped in terms of both a caspase-dependent and caspase-independent way. We suggest that variations in c-myc and p21(WAF1) expression delay apoptosis making PBL resistant to SB for several hours, and together with fast catabolism of SB in vivo protect PBL against the destructive activity of this anti-cancerous metabolite of colonic bacteria.     

Expression of the vascular endothelial growth factor-receptor system in the porcine endometrium throughout the estrous cycle and early pregnancy

The objective of this study was to investigate the protein and mRNA expression of vascular endothelial growth factor (VEGF), VEGFR-1 (fms-like tyrosine kinase, Flt-1) and VEGFR-2 (fetal liver kinase-1/kinase insert domain-containing receptor, Flk-1/KDR) in the endometrium during the estrous cycle and early pregnancy in pigs. The VEGF-receptor system was localized in epithelial and stromal cells, blood vessels, and myometrium. Western blot analysis showed higher levels of VEGF protein during the periovulatory and periimplantation periods (P < 0.001, and P < 0.05, respectively). Constant expression of VEGF mRNA during the cycle and significant upregulation on Days 22-25 of gestation (vs. Days 9-17; P < 0.001) was observed. Stable levels of VEGFR-1 mRNA and protein were detected in the endometrium of cyclic animals. However, higher VEGFR-1 protein expression was found on Days 16-17 of the estrous cycle (P < 0.01) and Days 13-15 of gestation (P < 0.05). Protein expression of VEGFR-2 was elevated on Days 2-4 of the estrous cycle (P < 0.001), but mRNA levels were constant during the cycle. In pregnancy, VEGFR-2 protein expression started to increase after Day 15 (vs. Days 9-12; P < 0.05), but induction of VEGFR-2 mRNA expression occurred earlier on Days 13-15. It appears from the present study that the VEGF-receptor system is regulated in a temporal and spatial manner during the estrous cycle and early pregnancy in pigs. The results suggest that VEGF-A family members are probably involved in appropriate preparation of endometrium for implantation and in vascular events during implantation in pigs.     

Changes in expression of 11beta-hydroxysteroid dehydrogenase type-1, type-2 and glucocorticoid receptor mRNAs in porcine corpus luteum during the estrous cycle

The objective of the present study was to determine whether glucocorticoid (GC) and its receptor (GC-R) are expressed in the porcine corpus luteum (CL), and whether GC influences porcine luteal hormone production. The gene expressions of 11beta-hydroxysteroid dehydrogenase type 1 (11-HSD1), type 2 (11-HSD2), GC-R, and the concentrations of GC were determined in the CL of Chinese Meishan pigs during the estrous cycle. Moreover, the effects of GC on progesterone (P(4)), estradiol-17beta (E(2)), and prostaglandin (PG) F2alpha secretion by cultured luteal cells were investigated. Messenger RNAs of the 11-HSD1, 11-HSD2, and GC-R were clearly expressed in the CL throughout the estrous cycle. The 11-HSD1 mRNA level in the CL was higher at the regressed stage than at the other stages (P < 0.05), whereas 11-HSD2 mRNA was lower at the regressed stage than at the other stages (P < 0.05). GC-R mRNA level was higher at the regressed stages than at the other stages (P < 0.01). Concentrations of GC were lower in the regressed CL than in the other stages (P < 0.01). When the cultured luteal cells obtained from mid-stage CL (Days 8-11) were exposed to GC (50-5,000 ng/ml), P(4) and PGF2alpha secretion by the cells were reduced (P < 0.05), whereas GC had no effect on E(2) secretion by the cells. The overall results suggest that GC is regulated locally by 11-HSD1 and 11-HSD2 in the porcine CL. GC inhibits P(4) and PGF2alpha production from luteal cells via their specific receptors, implying GC plays some roles in regulating porcine CL function throughout the estrous cycle.     

The influence of embryo presence on prostaglandins synthesis and prostaglandin E2 and F2alpha content in corpora lutea during periimplantation period in the pig

We determined the expression of PGE2 synthase (mPGES-1), PGF synthase (PGFS), carbonyl reductase/prostaglandin 9-ketoreductase (CBR1) genes and the content of PGE2, PGF2alpha in porcine corpora lutea on Days 12-14 of pregnancy and Days 12-14 of the estrous cycle. For this study we used a surgically-generated model in which one of the uterine horns was cut transversely and a part of this horn was detached from the uterine corpus. The expression of mPGES-1, PGFS, and CBR1 genes and mPGES-1/PGFS ratio were significantly higher in corpora lutea of the pregnant gilts compared to the corpora lutea from the parallel ovaries of the cyclic gilts. There was no difference in mPGES-1, PGFS, CBR1 genes expression and mPGES-1/PGFS ratio between corpora lutea ipsi-(CL1) and contralateral (CL2) to the uterine horn with the developing embryos. The highest content of PGE2 was found in CL1 of the pregnant gilts. The PGE2/PGF2alpha ratio was significantly higher in CL1 of the pregnant gilts compared to corpora lutea from parallel ovary of the cyclic gilts. We suggest that the activity of the investigated genes is induced by compounds of embryonic origin which are not distributed only to the ipsilateral ovary but are transported within the mesometrium to both ovaries in a more systemic manner.     

Aberrant DNA methylation in porcine in vitro-, parthenogenetic-, and somatic cell nuclear transfer-produced blastocysts

Early embryonic development in the pig requires DNA methylation remodeling of the maternal and paternal genomes. Aberrant remodeling, which can be exasperated by in vitro technologies, is detrimental to development and can result in physiological and anatomic abnormalities in the developing fetus and offspring. Here, we developed and validated a microarray based approach to characterize on a global scale the CpG methylation profiles of porcine gametes and blastocyst stage embryos. The relative methylation in the gamete and blastocyst samples showed that 18.5% (921/4,992) of the DNA clones were found to be significantly different (P < 0.01) in at least one of the samples. Furthermore, for the different blastocyst groups, the methylation profile of the in vitro-produced blastocysts was less similar to the in vivo-produced blastocysts as compared to the parthenogenetic- and somatic cell nuclear transfer (SCNT)-produced blastocysts. The microarray results were validated by using bisulfite sequencing for 12 of the genomic regions in liver, sperm, and in vivo-produced blastocysts. These results suggest that a generalized change in global methylation is not responsible for the low developmental potential of blastocysts produced by using in vitro techniques. Instead, the appropriate methylation of a relatively small number of genomic regions in the early embryo may enable early development to occur.