Low-flow perfusion via the innominate artery during aortic arch operations provides only limited somatic circulatory support.

BACKGROUND: Aortic arch operations in pediatric patients using low-flow perfusion techniques have been standardized to a certain degree, but some of the often-stated beneficial effects have never been proven. Especially, the existence or efficacy of any subdiaphragmal perfusion still remains unclear. METHODS: Twenty-six newborn male piglets (10-15 kg) underwent aortic arch surgery under general anesthesia using either low-flow perfusion via the innominate artery (LF, 30 ml/(kg min), 25 degrees C, n=12) or conventional deep hypothermic circulatory arrest (DHCA, 20 degrees C, n=14). Cortical somatosensory-evoked potentials (SSEPs), carotid, and subdiaphragmal blood flows were measured. The animals of both groups have been randomized to either pH-stat or alpha-stat management on cardiopulmonary bypass (CPB). RESULTS: During low-flow perfusion via the innominate artery only negligible flows of maximum 1-3 ml/min in the femoral arteries were detected, whereas the right carotid artery flow doubled. During reperfusion, serum-lactate and aspartate amino-transferase (AST) levels were significantly higher compared to the circulatory arrest group, whereas alanine amino-transferase (ALT), gamma-glutamyl transpeptidase (gamma-GT), AP, and creatinine did not show any significant differences. Cortical SSEP returned to preoperative values in all but two low-flow animals. There was no return of SSEP in all piglets operated under deep hypothermic circulatory arrest (p<0.01). CONCLUSION: Compared to DHCA, low-flow perfusion via the innominate artery provides superior neuroprotection despite higher tissue temperatures. Although collateral blood flow via the subclavian artery and the circulus arteriosus willisii has often been presumed, only 'trickle-flow' with some protective potential was detectable in the femoral arteries during low-flow perfusion. Origin of elevated lactate and AST levels seems to be the lower limbs.     

The effect of season on the circulating concentrations of anterior pituitary, ovarian and adrenal cortex hormones and hormone binding proteins in the subarctic area; evidence of increased activity of the pituitary-ovarian axis in spring

To evaluate the effects of season on the function of the pituitary-ovarian axis and the adrenal cortex in a northern area with great seasonal variation in the length of daylight, 10 healthy women were investigated over 1 menstrual cycle in spring (May-June), autumn (August-September), early winter (November-December) and late winter (February-March). Serum concentrations of LH, FSH, prolactin, estradiol, progesterone, total and free testosterone, cortisol, sex hormone binding globulin (SHBG) and cortisol binding globulin (CBG) were measured, and the indices of free estradiol (FEI), free androgen (FAI) and free cortisol (FCI) were calculated on cycle days 3-4, 6-7, 10-11, on the presumed day of ovulation, and 6-7 and 9-10 days after the presumed ovulation. Spring was the season that most significantly differed from the other seasons. It was characterized by a significantly decreased concentration of SHBG and an increased FAI throughout the whole menstrual cycle, an increased FSH concentration during the follicular phase, significantly increased estradiol concentration and an increased FEI, and significantly decreased concentrations of FSH and LH during the luteal phase of the cycle. The concentration of cortisol and the FCI were significantly increased in the autumn compared with late winter, both seasons having similar day-length. The present data demonstrate that spring, with a long photoperiod, seems to be associated with increased pituitary-ovarian axis activity and androgenic activity, whereas adrenal cortex function did not show any association with day-length.     

The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis

The omptins are a family of enterobacterial surface proteases/adhesins that share high sequence identity and a conserved beta-barrel fold in the outer membrane. The omptins are multifunctional, and the individual omptins exhibit differing virulence-associated functions. The Pla plasminogen activator of Yersinia pestis contributes by several mechanisms to bacterial invasiveness and the systemic, uncontrolled proteolysis in plague. Pla proteolytically activates the human proenzyme plasminogen and inactivates the antiprotease alpha2-antiplasmin, and its binding to laminin localizes the uncontrolled plasmin activity onto basement membranes. These properties enhance bacterial migration through tissue barriers. Pla also degrades circulating complement proteins and functions in bacterial invasion into human epithelial cells. PgtE of Salmonella enterica and OmpT of Escherichia coli have been shown to degrade cationic antimicrobial peptides from epithelial cells or macrophages. PgtE and SopA of Shigella flexneri appear important in the intracellular phases of salmonellosis and shigellosis, whereas functions of OmpT have mainly been associated with protein degradation in E. coli cells. The differing virulence roles and functions have been attributed to minor sequence variations at the surface-exposed regions important for substrate recognition, to the dependence of omptin functions on lipopolysaccharide, and to the different regulation of omptin expression.     

The human brain processes visual changes that are not cued by attended auditory stimulation

Event-related potentials (ERPs) to visual stimuli were recorded from the scalp of eight adult humans performing a task in which they counted vowels from a heard story. In the oddball condition, a repeated (standard) light bar of 50 ms in duration was rarely (P = 0.1) replaced by a (deviant) one differing in orientation from the standard. In the control condition, standards were simply omitted from the series and only (alone-) deviants retained. In both conditions, visual stimuli were asynchronous with auditory-task-relevant stimuli. ERPs to deviants significantly differed in amplitude from those to standards in the midline electrodes centrally, parietally and occipitally at 160-200 ms from stimulus onset. Occipitally, such a difference was absent between ERPs to alone-deviants and those to standards. The occipital differential ERPs to deviants, which thus could be found only when standards were present in the series, are discussed in the context of the mismatch negativity (MMN).     

Tumor necrosis factor-mediated interactions between inflammatory response and tumor vascular bed

Summary: Solid tumor therapy with chemotherapeutics greatly depends on the efficiency with which drugs are delivered to tumor cells. The typical characteristics of the tumor physiology promote but also appose accumulation of blood-borne agents. The leaky tumor vasculature allows easy passage of drugs. However, the disorganized vasculature causes heterogeneous blood flow, and together with the often-elevated interstitial fluid pressure, this state results in poor intratumoral drug levels and failure of treatment. Manipulation of the tumor vasculature could overcome these barriers and promote drug delivery. Targeting the vasculature has several advantages. The endothelial lining is readily accessible and the first to be encountered after systemic injection. Second, endothelial cells tend to be more stable than tumor cells and thus less likely to develop resistance to therapy. Third, targeting the tumor vasculature can have dual effects: (i) manipulation of the vasculature can enhance concomitant chemotherapy, and (ii) subsequent destruction of the vasculature can help to kill the tumor. In particular, tumor necrosis factor α is studied. Its action on solid tumors, both directly through tumor cell killing and destruction of the tumor vasculature and indirectly through manipulation of the tumor physiology, is complex. Understanding the mechanism of TNF and agents with comparable action on solid tumors is an important focus to further develop combination immunotherapy strategies.     

cDNA arrays: gene expression profiles of Hodgkin's disease and anaplastic large cell lymphoma cell lines

cDNA arrays are a powerful tool for the identification of differentially expressed genes in malignant tumors. We used this technique to study the gene expression profiles of anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). Gene expression of 11 lymphoma cell lines was analyzed covering 1176 cDNA sequences. Comparing these data to the expression profiles of B- and T-lymphocytes, we identified 27 genes that were deregulated in all cell lines or in a particular entity. For the establishment of gene expression profiles the 27 genes were assigned to four groups composed of genes deregulated in (i) all lymphoma cell lines, (ii) ALCL and HD, (iii) only HD, and (iv) ALCL exclusively. Our results indicate that ALCL and HD share the differential expression of at least five genes. In addition, both entities are characterized by the differentially deregulated expression of four genes in HD and seven genes in ALCL. Because the expression profiling was performed on cell lines, further studies are needed to clarify the biological significance of the differentially expressed genes.     

Self-reinforced polylactide/polyglycolide 80/20 screws take more than 1(1/2) years to resorb in rabbit cranial bone

The aim of this study was to assess tissue reactions to bioabsorbable self-reinforced polylactide/polyglycolide (SR-PLGA) 80/20 miniscrews in rabbit cranial bone. One PLGA screw was implanted on one side and one titanium screw on the other side of the sagittal suture (n = 21). Three animals were sacrificed after 2, 4, 8, 16, 24, 54, and 72 weeks. In histological examination the numbers of macrophages, giant cells, active osteoblasts, and fibrous tissue layers were assessed and degradation of the bioabsorbable screws was evaluated. After 2 weeks, macrophages were seen near the heads of both screws. After 4 and 8 weeks, the bioabsorbable screws were surrounded by fibrous tissue. Osteoblastic activity and groups of several giant cells were seen. After 24 weeks, a significant change in the morphology of the PLGA screws had occurred. Osteoblastic activity and the amount of giant cells had decreased. After 1 year, some PLGA biomaterial was still present. PLGA screws had been replaced by adipose tissue, fibrous tissue, and "foamy macrophages" that had PLGA particles inside them. After 1(1/2) years, the amount of biomaterial remaining had decreased remarkably. The particles of biomaterial were inside foamy macrophages. SR-PLGA 80/20 screws are biocompatible and have no clinically manifested complications when used in the cranial bone of rabbits. No contraindications as regards their clinical use in craniofacial surgery was found when these screws were studied in the cranial bones of rabbits.     

'Fat mass and obesity associated' gene (<Emphasis Type="Italic">FTO</Emphasis>): No significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents

Background  

We have previously identified strong association of six single nucleotide polymorphisms (SNPs) in FTO (fat mass and obesity associated gene) to early onset extreme obesity within the first genome wide association study (GWA) for this phenotype. The aim of this study was to investigate whether the obesity risk allele of one of these SNPs (rs9939609) is associated with weight loss in a lifestyle intervention program. Additionally, we tested for association of rs9939609 alleles with fasting blood parameters indicative of glucose and lipid metabolism.