Subarachnoid blood infusion versus raised intracranial pressure: Effects on the amino acid pattern in the extracellular fluid of the rabbit hippocampus

Abstract

In order to evaluate the role of a hemorrhage versus that of a transient increase in intracranial pressure in subarachnoid hemorrhage, the two components were induced separately in rabbits. Extracellular glutamate, sampled from the hippocampus with microdialysis, was used to evaluate the degree of CNS tissue damage. In four rabbits, autologous arterial blood was infused in the cisterna magna in a volume that would not affect the intracranial pressure. The other group of animals was infused with saline to elevate the intracranial pressure from 10 to > 100 mmHg. The increase of intracranial pressure per se did not induce significant changes in extracellular glutamate. However, 20-60 min after infusion of blood, a significant glutamate increase was recorded. Furthermore, aspartate, alanine, glycine and serine were also raised. The results indicate that blood in the subarachnoid space damages the brain primarily by inducing ischemia. Furthermore, the parameters employed gave no indication that an increase in intracranial pressure had a deleterious effect on CNS tissue. [Neurol Res 1999; 21: 404-408]     

Relationship between the flow pattern and vasomotor reactivity in the ophthalmic artery,siphon and vessels within the circle of Willis in the unilateral internal carotid artery occlusion

Abstract

The aim was to study a relationship between the flow pattern in the ophthalmic artery (OA), the siphon and vessels within the circle of Willis. 27 patients, 22 males and 5 females; mean age 63 ± 15 years (SD) with unilateral occlusion of the internal carotid artery (ICA) were examined by 3-dimensional Transcranial Doppler scanner Flow signals from the OA, the siphon and intracranial vessels were registered before and after i.v. injection of 1 g acetazolamide. Pathological flow pattern was found in 18 patients in the OA on the occluded side consisting of 12 retrograde and 6 isoelectric flow directions. After acetazolamide injection retrograde systolic velocities (SV) increased significantly (p < 0.01), but anterograde velocities remained unchanged as did 3 isoelectric flow patterns, 2 turned to retrograde and one to anterograde flow direction. In the siphon lower resting anterograde mean velocities (MV) were found on both sides (p < 0.05) compared to normal subjects. Six patients had the same retrograde flow as in the OA. After acetazolamide MV in the siphon increased (p <0.01) only on the nonoccluded side. Baseline retrograde ophthalmic SVand MV in the siphon correlated (p < 0.01 and p < 0.05 respectively) with MV in the middle cerebral artery (MCA) according to linear regression analysis (x - 0.78 and 0.59 respectively). All patients, having impaired vasomotor reactivity (VMR) <11% in the anterior cerebral artery (ACA) on the occluded side, had pathological flow pattern in the OA. Patients with greatest difference (A) between MV in the ACA on the nonoccluded and occluded side had a tendency to anterograde flow (r = 0.56, p < 0.05). Pulsative index (PI) in the ACA on the occluded side was lowest in the category with retrograde flow in the OA (0.67± 0.14) and differed (p < 0.05) from normals and from the category with isoelectric and anterograde flow. Correlation of retrograde flow direction in the OA and baseline MV in the MCA and low PI in the ACA on the occluded side indicates a supplying ophthalmic collateral to the anterior brain circulation. Impaired VMR in the ACA on the occluded side in connection with pathological flow pattern in the OA may reflect an exhaustion of the ACA as a supplying vessel. [Neurol Res 1996; 18: 521-527]     

Practical aspects of differential ventilation with selective peep in acute respiratory failure

Hypoxaemia in association with acute respiratory failure continues to be a severe problem in some intensive care patients. Among strategies proposed, we want to focus attention on differential ventilation with selective PEEP, administered in the lateral position. This ventilation technique has proved successful in the treatment of refractory hypoxaemia due to severe bilateral lung disease.The rationale of this concept is briefly presented in this paper, where the main emphasis is laid on the practical aspects of its clinical application. Two case reports are included as examples of our experiences.     

Temporal delimitation of the healing phases via monitoring of fracture callus stiffness in rats

The healing process consists of at least three phases: inflammatory, repair, and remodeling phase. Because callus stiffness correlates with the healing phases, it is suitable for evaluating the fracture healing process. Our aim was to develop a method which allows determination of callus stiffness in vivo, the healing time and the duration of the repair phase. The right femurs of 16 Wistar rats were osteotomized and stabilized with either more rigid or more flexible external fixation. Fixator deformation was measured using strain gauges during gait analysis. The strains were recalculated as the callus stiffness over the time course of healing, and the healing phases were identified based on stiffness thresholds. Our hypothesis was that stabilization with more flexible external fixation prolongs the repair phase, therefore resulting in an extended healing time. Confirming our hypothesis, the duration of the repair phase (rigid: approximately 15 days, flexible: approximately 41 days) and the healing time (rigid: approximately 27 days, flexible: approximately 62 days) were significantly longer for more flexible external fixation. Our method allows the quantitative detection of differences in the healing time and duration of the repair phase without multiple time‐point sacrifices, which reduces the number of animals in experimental studies. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1589–1595, 2014.     

Liver-derived insulin-like growth factor-I is involved in the regulation of blood pressure in mice

IGF-I has been suggested to be of importance for cardiovascular structure and function, but the relative role of locally produced and liver-derived endocrine IGF-I remains unclear. Using the Cre-LoxP recombination system, we have previously created transgenic mice with a liver-specific, inducible IGF-I knockout (LI-IGF-I-/-). To examine the role of liver-derived IGF-I in cardiovascular physiology, liver-derived IGF-I was inactivated at 4 wk of age, resulting in a 79% reduction of serum IGF-I levels. At 4 months of age, systolic blood pressure (BP) was increased in LI-IGF-I-/- mice. Echocardiography showed increased posterior wall thickness in combination with decreased stroke volume and cardiac output, whereas other systolic variables were unchanged, suggesting that these cardiac effects were secondary to increased peripheral resistance. Acute nitric oxide-synthase inhibition increased systolic BP more in LI-IGF-I-/- mice than in control mice. LI-IGF-I-/- mice showed impaired acetylcholine-induced vasorelaxation in mesenteric resistance vessels and increased levels of endothelin-1 mRNA in aorta. Thus, the increased peripheral resistance in LI-IGF-I-/- mice might be attributable to endothelial dysfunction associated with increased expression of endothelin-1 and impaired vasorelaxation of resistance vessels. In conclusion, our findings suggest that liver-derived IGF-I is involved in the regulation of BP in mice.     

Expression of Phosphofructokinase in Skeletal Muscle Is Influenced by Genetic Variation and Associated With Insulin Sensitivity

Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression quantitative trait loci [eQTLs]) as well as expression associated with measures of insulin sensitivity. We investigated associations of 3,799,401 genetic variants in expression of >7,000 genes from three cohorts (n = 104). We identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P < 1.96 × 10⁻⁵) and 49 expression–insulin sensitivity phenotype associations (i.e., fasting insulin, homeostasis model assessment–insulin resistance, and BMI) (FDR <5%; P = 1.34 × 10⁻⁴). One of these associations, fasting insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL (rs4547172; P = 7.69 × 10⁻⁶) was nominally associated with glucose uptake, glucose oxidation rate, intramuscular triglyceride content, and metabolic flexibility (P = 0.016–0.048; n = 178). We explored eQTL results using published data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for the PFKM eQTL (rs11168327; r² = 0.75) was nominally associated with T2D (DIAGRAM P = 2.7 × 10⁻³). Taken together, our analysis highlights PFKM as a potential regulator of skeletal muscle insulin sensitivity.     

Genome-wide association studies on serum sex steroid levels

Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown. With the advent of genome-wide association studies (GWAS), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroepiandrosterone sulfate, testosterone and sex hormone-binding globulin. The variants identified so far only explain a small amount of the overall heritability, but may help to elucidate the role of sex steroid hormones in common disorders such as hypogonadism, type 2 diabetes and hormone-sensitive cancers. This review provides an overview of the current state of knowledge of the genetic determinants of sex steroid hormones, with a focus on recent GWAS and brief directions for elucidating the remaining heritability.