Effects of isometric exercise on blood cell adrenoceptors in essential hypertension

The effect of handgrip (HG) isometric exercise on plasma catecholamines, alpha 2-adrenoceptors on platelets and beta 2-adrenoceptors on lymphocytes was studied in normotensive subjects (NT) and essential hypertensive subjects (HT). Whereas systolic blood pressure (SBP) increases were similar in NT and HT subjects, diastolic blood pressure (DBP) and heart rate (HR) increased more in the former group. Baseline values and changes in plasma epinephrine (E) and norepinephrine (NE) did not differ between both groups. No differences were apparent in alpha 2-adrenoceptor density and affinity between NT and HT subjects before or after the test. HG isometric exercise induced a similar increase in beta 2-adrenoceptors on lymphocytes of 22 +/- 7 and 13 +/- 5% in NT and HT subjects, respectively. Affinity to the beta 2-adrenoceptors under baseline conditions was somewhat lower in HT (8.1 +/- 0.4 pM) than in NT subjects (6.5 +/- 0.5 pM), and this difference persisted during the test. Our results indicate that there are no differences in alpha 2- and beta 2-adrenoceptor densities either at baseline conditions or after HG isometric exercise between NT and HT subjects. Small differences noted in affinity to the beta 2-adrenoceptors require further investigation.     

Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes.

5-Amino-4-imidazolecarboxamide (AICA) riboside, the nucleoside corresponding to AICA ribotide (AICAR or ZMP), an intermediate of the de novo pathway of purine biosynthesis, was found to exert a dose-dependent inhibition on gluconeogenesis in isolated rat hepatocytes. Production of glucose from lactate-pyruvate mixtures was half-maximally inhibited by approximately 100 microM and completely suppressed by 500 microM AICA riboside. AICA riboside also inhibited the production of glucose from all other gluconeogenic precursors investigated, i.e., fructose, dihydroxyacetone, and L-proline. Measurements of intermediates of the glycolytic-gluconeogenic pathway showed that AICA riboside provoked elevations of triose phosphates and fructose-1,6-bisphosphate and decreases in fructose-6-phosphate and glucose-6-phosphate. The effects of AICA riboside persisted when the cells were washed 10 min after its addition but were suppressed by 5-iodotubercidin, an inhibitor of adenosine kinase. AICA riboside provoked a dose-dependent buildup of normally undetectable Z nucleotides. After 20 min of incubation with 500 microM AICA riboside, ZMP, ZTP, and ZDP reached 3, 0.3, and 0.1 mumol/g cells, respectively. Concentrations of ATP were not significantly modified by addition of up to 500 microM AICA riboside when the cells were incubated with lactate-pyruvate but decreased with fructose or dihydroxyacetone. The activity of rat liver fructose-1,6-bisphosphatase was inhibited by ZMP with an apparent Ki of 370 microM. It is concluded that AICA riboside exerts a suppressive effect on gluconeogenesis because it provokes an accumulation of ZMP, which inhibits fructose-1,6-bisphosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term Results of Primary Stent Placement to Treat Infrarenal Aortic Stenosis

OBJECTIVE: To determine the safety and the long-term results of primary stent placement for localized distal aortic occlusive disease. DESIGN: Retrospective observational study. PATIENTS AND METHODS: From July 1998 to July 2005 17 patients (14 female and 3 men, mean age 57 years (39-80)) were treated for intermittent claudication. Five of these patients underwent additional endovascular treatment of focal iliac lesions. RESULTS: Technical success defined as residual stenosis of less than 50% or a trans-stenotic systolic pressure gradient <10% was achieved in 14 of 17 (82%) patients. Major complications included dissection at the puncture site in one patient and thrombosis of additional iliac stents in another patient. Both of these complications were successfully treated. During a mean follow-up of 27 months (range 1-86), four patients had recurrence of symptoms due to in-stent restenoses (n=2), femoral (n=1) or iliac occlusion (n=1), respectively. By Kaplan-Meier analysis, primary aortic hemodynamic patency was 83% at 3 years. Secondary aortic hemodynamic patency was 100%. The primary clinical patency was 68% at 3 years. CONCLUSION: Primary stent placement for distal aortic stenoses is an alternative to surgical treatment because of its high patency and relatively low complication rates.     

The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres.

Encapsulation of proteins in poly(lactide-co-glycolide) microspheres via emulsion is known to cause insoluble protein aggregates. Following protein emulsification and encapsulation in PLGA microspheres, we used circular dichroism to show that the recoverable soluble protein fraction also suffers subtle conformational changes. For a panel of proteins selected on the basis of molecular size and structural class, conformational stability measured by chemical denaturation was not indicative of stability during emulsion-encapsulation. Partial loss of structure was observed for alpha-helical proteins released from freeze-dried microspheres in aqueous buffer, with dramatic loss of structure for a beta-sandwich protein. The addition of sucrose (a lyoprotectant) did not prevent the loss of protein conformation upon encapsulation. Therefore, the conformational changes seen for the released soluble protein fraction originates during emulsification rather than microsphere freeze-drying. Analysis of the burst release for all proteins in buffer containing denaturant or surfactant showed that the degree of protein solubilisation was the dominant factor in determining the initial rate and extent of release. Our data for protein release into increasing concentrations of denaturing buffer suggest that the emulsion-denatured protein fraction remains insoluble; this fraction may represent the protein loss encountered upon comparison of protein encapsulated versus protein released.     

On verification of hyperthermia treatment planning for cervical carcinoma patients.

PURPOSE: The aim of this study was to verify hyperthermia treatment planning calculations by means of measurements performed during hyperthermia treatments. The calculated specific absorption rate (SAR(calc)) was compared with clinically measured SAR values, during 11 treatments in seven cervical carcinoma patients. METHODS: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide system. Temperatures were measured using multisensor thermocouple probes. One invasive thermometry catheter in the cervical tumour and two non-invasive catheters in the vagina were used. For optimal tissue contact and fixation of the catheters, a gynaecological tampon was inserted, moisturized with distilled water (4 treatments), or saline (6 treatments) for better thermal contact. During one treatment no tampon was used. At the start of treatment the temperature rise (DeltaT(meas)) after a short power pulse was measured, which is proportional to SAR(meas). The SAR(calc) along the catheter tracks was extracted from the calculated SAR distribution and compared with the DeltaT(meas)-profiles. RESULTS: The correlation between DeltaT(meas) and SAR(calc) was on average R = 0.56 +/- 0.28, but appeared highly dependent on the wetness of the tampon (preferably with saline) and the tissue contact of the catheters. Correlations were strong (R approximately 0.85-0.93) when thermal contact was good, but much weaker (R approximately 0.14-0.48) for cases with poor thermal contact. CONCLUSION: Good correlations between measurements and calculations were found when tissue contact of the catheters was good. The main difficulties for accurate verification were of clinical nature, arising from improper use of the gynaecological tampon. Poor thermal contact between thermocouples and tissue caused measurement artefacts that were difficult to correlate with calculations.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

Table 1     

Importance of speech production for phonological awareness and word decoding: The case of children with cerebral palsy

The goal of this longitudinal study was to investigate the precursors of early reading development in 52 children with cerebral palsy at kindergarten level in comparison to 65 children without disabilities. Word Decoding was measured to investigate early reading skills, while Phonological Awareness, Phonological Short-term Memory (STM), Speech Perception, Speech Production and Nonverbal Reasoning were considered reading precursors. Children with cerebral palsy lag behind on all reading precursors at the beginning of the second year of kindergarten. For the children without disabilities, early reading skills in Grade 1 were best predicted by Phonological Awareness and Phonological STM while Speech Production was the most important predictor of early reading success for the children with cerebral palsy, followed by Phonological Awareness and Speech Perception. Furthermore, for children with cerebral palsy, Speech Production appears to dominate reading development, as Speech Production measured at the beginning of the second year of kindergarten was strongly predictive of all other reading precursors measured at the end of the second year of kindergarten. The results of this study reveal that children with cerebral palsy with additional speech impairments are at risk for limited literacy development. Clinical implications are discussed.