Daily variations in type II iodothyronine deiodinase activity in the rat brain as controlled by the biological clock

Type II deiodinase (D2) plays a key role in regulating thyroid hormone-dependent processes in, among others, the central nervous system (CNS) by accelerating the intracellular conversion of T4 into active T3. Just like the well-known daily rhythm of the hormones of the hypothalamo-pituitary-thyroid axis, D2 activity also appears to show daily variations. However, the mechanisms involved in generating these daily variations, especially in the CNS, are not known. Therefore, we decided to investigate the role the master biological clock, located in the hypothalamus, plays with respect to D2 activity in the rat CNS as well as the role of one of its main hormonal outputs, i.e. plasma corticosterone. D2 activity showed a significant daily rhythm in the pineal and pituitary gland as well as hypothalamic and cortical brain tissue, albeit with a different timing of its acrophase in the different tissues. Ablation of the biological clock abolished the daily variations of D2 activity in all four tissues studied. The main effect of the knockout of the suprachiasmatic nuclei (SCN) was a reduction of nocturnal peak levels in D2 activity. Moreover, contrary to previous observations in SCN-intact animals, in SCN-lesioned animals, the decreased levels of D2 activity are accompanied by decreased plasma levels of the thyroid hormones, suggesting that the SCN separately stimulates D2 activity as well as the hypothalamo-pituitary-thyroid axis.     

The use of autologous blood to improve exercise capacity after total hip arthroplasty: a preliminary report

BACKGROUND: Venesection of red blood cells in healthy well-trained subjects decreased the maximum oxygen uptake parallel with the reduction in hemoglobin (Hb) level. Based on the large Hb decrease that is seen after total joint surgery, one could expect a decrease in performance as well. The purpose of this study was to investigate whether autologous blood enhanced performance on a bicycle ergometer in patients after total hip arthroplasty. STUDY DESIGN AND METHODS: Nine patients scheduled for elective total hip arthroplasty in an accelerated stay program participated in a preoperative autologous blood donation (PABD) program. Weeks before the scheduled surgery, patients donated 4 units of blood and received standard erythropoietin treatment. Physical fitness was assessed during exercise test on a bicycle ergometer. Each patient was matched with three previously tested patients. RESULTS: Patients in both groups were 69.0 years old (range, 66-74 years vs. 61-77 years). None of the patients had relevant cardiovascular abnormalities. On average patients received 3.3 units of blood because 3 units were not transfused. The PABD group showed a Hb decrease of 0.5 g per dL (4%) on the fourth postoperative day versus 4.4 g per dL (31%) in the control group. The decline in power output on Day 4 was significantly less in the PABD group compared with the control group (t test, p = 0.026). CONCLUSION: From this pilot study it can be concluded that correction of the postoperative Hb decrease was associated with a lower decrease in maximum power output, compared to the control group. On Days 23 and 39, however, the difference in performance between the PABD group and control group had disappeared.     

Leukemic predisposition of pSca-1/Cb2 transgenic mice

OBJECTIVE: The gene encoding the peripheral cannabinoid receptor Cb2 is located in the common virus integration site Evi11 and is associated with hematopoietic malignancies in mice. To determine the effect of Cb2 overexpression on hematopoietic development in vivo, Cb2 transgenic mice were generated. MATERIALS AND METHODS: A Cb2 expression vector was constructed containing a Cb2 cDNA fragment cloned into the 14kb Sca-1 (Ly-6E.1) gene. Two transgenic lines in which Cb2 expression is controlled by the Sca-1 promoter were generated, and the effect on hematopoietic development was studied. Expression of Cb2 mRNA or protein was studied by RNase protection analysis and ligand binding assays, respectively. Leukemic predisposition was investigated by injecting newborn transgenic as well as control animals with Cas-Br-M murine leukemia virus (Cas-Br-M MuLV). RESULTS: Although increased expression of the Cb2 gene was observed in hematopoietic tissues, follow-up of more than 1 year did not reveal any hematologic defect. Interestingly, infection of newborn pSca-1/Cb2 transgenic mice with Cas-Br-M MuLV revealed that significantly more transgenic mice developed leukemia than virus-treated control littermates. Because these studies provide evidence for the cooperative potential of Cb2 in leukemia progression, we wished to identify genes that may collaborate with Cb2 in leukemic transformation. Our study suggests that Evi1, another common target for proviral integration in mouse leukemias, may be overexpressed in virus-induced leukemias in pSca-1/Cb2 transgenic mice. CONCLUSIONS: The data indicate that hematopoietic precursor cells that express high levels of Cb2 possess increased susceptibility for leukemia development and that Cb2 and Evi1 might collaborate in leukemogenesis.     

Transfusion-Induced Alloimmunization in Patients Awaiting Renal Allografts

Abstract. Lymphocytotoxic antibodies can be induced by the immunologic stimulus of pregnancy, blood transfusion, or tissue allograft. The presence of such antibodies can delay or prevent renal transplantation. However, a history of prior transfusion exposure has been strongly associated with excellent renal allograft survival. The problem of ensuring this 'transfusion effect' while minimizing the risk of alloimmunization is real for patients awaiting renal allografts. We examined the influence of pregnancy, allograft rejection, and transfusions on the levels of lymphocytotoxic antibodies in the sera of patients awaiting renal transplantation. The results indicate that transfusions alone have a minimal effect on alloimmunization in men and in nulliparous women. The influence of transfusions alone was seen with 77% of men and 86% of women showing less than 10% panel reactivity. Deliberate transfusion policies for patients awaiting renal allografts should be designed to minimize transfusion exposure to parous patients or those who have previously rejected a renal graft.     

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is overexpressed in endothelial cells of different human tumors. Expression knockdown in cultured endothelial cells inhibits cell proliferation and migration. The importance of gal-1 in angiogenesis is illustrated in the zebrafish model, where expression knockdown results in impaired vascular guidance and growth of dysfunctional vessels. The role of gal-1 in tumor angiogenesis is demonstrated in gal-1-null mice, in which tumor growth is markedly impaired because of insufficient tumor angiogenesis. Furthermore, tumor growth in gal-1-null mice no longer responds to antiangiogenesis treatment by anginex. Thus, gal-1 regulates tumor angiogenesis and is a target for angiostatic cancer therapy.     

Feedback-controlled and programmed stretching of the ankle plantarflexors and dorsiflexors in stroke: effects of a 4-week intervention program

OBJECTIVE: To investigate the effect of repeated feedback-controlled and programmed "intelligent" stretching of the ankle plantar- and dorsiflexors to treat subjects with ankle spasticity and/or contracture in stroke. DESIGN: Noncontrolled trial. SETTING: Institutional research center. PARTICIPANTS: Subjects with spasticity and/or contracture after stroke. INTERVENTIONS: Stretching of the plantar- and dorsiflexors of the ankle 3 times a week for 45 minutes during a 4-week period by using a feedback-controlled and programmed stretching device. MAIN OUTCOME MEASURES: Passive and active range of motion (ROM), muscle strength, joint stiffness, joint viscous damping, reflex excitability, comfortable walking speed, and subjective experiences of the subjects. RESULTS: Significant improvements were found in the passive ROM, maximum voluntary contraction, ankle stiffness, and comfortable walking speed. The visual analog scales indicated very positive subjective evaluation in terms of the comfort of stretching and the effect on their involved ankle. CONCLUSIONS: Repeated feedback-controlled or intelligent stretching had a positive influence on the joint properties of the ankle with spasticity and/or contracture after stroke. The stretching device may be an effective and safe alternative to manual passive motion treatment by a therapist and has potential to be used to repeatedly and regularly stretch the ankle of subjects with spasticity and/or contracture without daily involvement of clinicians or physical therapists.     

Effects of slouching and muscle contraction on the strain of the iliolumbar ligament

The study consisted of biomechanical modelling and in vitro experiments. The objective of the study was to find a mechanical cause of acute low back pain (LBP) in everyday situations. The precise mechanism producing LBP is still under discussion. Most biomechanical studies link the concepts of stooped postures and buckling instability of the spine under high compressive load. No biomechanical model addresses situations with small or neglectable compressive spinal load. The proposed conceptual model describes strain on the iliolumbar ligaments (ILs) when slouching from standing upright. Delayed or absent recruitment of back muscles that protect against hyperkyphosis of the lumbar spine is a conditional factor. Erector spinae and multifidus muscle forces are included, representing a bifurcation in back muscle force: one part acting on the iliac bones and one part acting on the sacrum. The multifidus muscle action on the sacrum may produce nutation which can be counteracted by pelvic floor muscles, which would link back problems and pelvic floor problems. The effect of simulated muscle tension on the ILs and the L5-S1 intervertebral disc angle was measured using embalmed specimens. Forces were applied to simulate erector spinae and sacral part of multifidus tension, bilateral up to 100 N each. Strain gauge sensors registered elongation of the ILs. Explorative biomechanical model calculations show that dynamic slouching, driven by upper body weight and (as an example) rectus abdominis muscle force may produce failure load of the spinal column and the ILs. The quasi-static test on embalmed specimens showed a significant increase of IL elongation with simulated rectus abdominis muscle force. Adding erector spinae or multifidus muscle tension eased the ILs. Sudden slouching of the upright trunk may create failure risk for the spine and ILs. This loading mode may be prevented by controlling loss of lumbar lordosis with erector spinae and multifidus muscle force.     

Knowledge of pressure ulcer prevention: a cross-sectional and comparative study among nurses

Background  

Pressure ulcers are a common, painful and costly condition. Results of a 1991 study into the knowledge among Dutch hospital nurses on the usefulness of measures to prevent pressure ulcers showed moderate knowledge. Results were confirmed by subsequent studies. In recent years, Dutch guidelines have been updated and the attention given to pressure ulcer care has been increased. This was expected to improve pressure ulcer care and to increase nurses' knowledge. The aims of the current study were to investigate (1) how much nurses employed in Dutch hospitals know about the usefulness of 28 preventive measures considered in the most recent national pressure ulcer guideline; (2) whether differences in knowledge exist between nurses working in hospitals that audit pressure ulcers and those employed in hospitals that do not; and (3) to study whether knowledge among Dutch hospital nurses regarding the usefulness of preventive measures had changed between 1991 and 2003.