Chondroitin/dermatan sulphate promotes the survival of neurons from rat embryonic neocortex

Recently we have shown that biglycan, a small chondroitin sulphate proteoglycan of the extracellular matrix, supports the survival of cultured neurons from the developing neocortex of embryonic day 15 rats. Here we investigate the structure-function relationship of this neurotrophic proteoglycan and show that chondroitin/dermatan sulphate chains are the active moieties supporting survival. Heparin, a highly sulphated glucosaminoglycan, is less active than the galactosaminoglycans (chondroitin-4-sulphate, chondroitin-6-sulphate and dermatan sulphate), whereas hyaluronic acid, an unsulphated glucosaminoglycan, does not support neuron survival. Galactosaminoglycans must be in direct contact with neurons to cause survival. Experiments with elevated potassium concentrations and antagonists of voltage-gated calcium channels exclude the involvement of membrane depolarization. However, genistein and an erbstatin analogue, which are inhibitors of tyrosine kinases with low specificity, abolished neuron survival in the presence of chondroitin/dermatan sulphate, whereas a selective inhibitor of neurotrophin receptor kinases (K252a) had no suppressive effect. Thus, yet unidentified tyrosine kinases are involved in the chondroitin/dermatan sulphate-dependent survival of neocortical neurons. In the embryonic stages of rat neocortical development chondroitin sulphate is mainly located in layers I, V and VI and the subplate. Chondroitin sulphate expression is maintained after birth, extends up to cortical layer IV on postnatal day 7, and is down-regulated until postnatal day 21 concomitant with the period of naturally occurring cell death. The latter observation is consistent with a putative role of chondroitin sulphate in the control of neuron survival during cortical histogenesis.     

Cerebral blood flow in hypertensive patients: an initial report of reduced and compensatory blood flow responses during performance of two cognitive tasks

We asked whether the altered cerebral vasculature associated with essential hypertension might dampen or redirect the regional cerebral blood flow (rCBF) response to cognitive work. Relative rCBF was assessed with [(15)O]water positron emission tomography during a working memory task, a memory span task, and two perceptual control tasks. Unmedicated hypertensive patients and control subjects differed in rCBF response during both memory tasks. Hypertensives showed relatively diminished rCBF responses in right hemisphere areas combined with compensatory activation of homologous areas in the left cerebral cortex. Essential hypertension appears to selectively influence the circulatory reserve of portions of cerebral cortex and secondarily induce recruitment of other cortical areas to process certain tasks.     

Definitive surgical treatment for cholelithiasis in selected patients with liver cirrhosis

Attitudes of 40 interns towards rational drug use (RDU) were assessed, using a standardized Likert type scale. The assessment was repeated after 4 months to evaluate the effect of usual working conditions of the hospital. After this period, the attitudes had slided towards negative side (p < 0.01). At this point, an intervention in the form of a workshop was provided for half the group while other half served as control. A repeat assessment after another period of 4 months revealed that the attitudes of test group returned towards positive side (p < 0.01) while control group maintained its negative attitudes.     

Transrectal and transurethral hyperthermia versus sham treatment in benign prostatic hyperplasia: a double-blind randomized multicentre clinical trial. The French BPH Hyperthermia

OBJECTIVE: To compare the safety and efficacy of hyperthermia for the treatment of benign prostatic hyperplasia (BPH), by either the transrectal or transurethral approach, relative to sham treatment. PATIENTS AND METHODS: Two hundred patients from seven urological departments were randomized and treated in a single centre. Principal inclusion criteria were a peak flow rate (PFR) < 15 mL/s and residual urine < 300 mL/s. Comparisons were made between transurethral hyperthermia (TUH) and transurethral sham (TUS) and between transrectal hyperthermia (TRH) and transrectal sham (TRS) 12 months after treatment. Outcome was assessed by improvements in the Madsen score and PFR, and the incidence of side-effects. RESULTS: After 12 months, 145 patients were evaluated; 12 patients withdrew during treatment, 43 withdrew during follow-up and two were lost to follow-up. Withdrawals were mainly due to side-effects during treatment (17% in the TRH and 1.5% in the TUH group) and to a lack of improvement during follow-up (14% in the TUH group, 19% in the TUS, 15% in the TRH and 10.5% in the TRS group received other treatments for BPH). Complications during treatment consisted mainly of local pain, urethral bleeding, urethral pain and acute retention, and were five times more frequent in the TRH than the TUH group (34% versus 6%). There was no improvement in PFR after TUH and TRH (response < 20%). Only TUH improved the Madsen score (TUH, +50% and TUS, +17%). CONCLUSION: Hyperthermia was not an effective treatment for BPH.     

Arachidonic acid stimulates the intrinsic activity of ubiquitous glucose transporter (GLUT1) in 3T3-L1 adipocytes by a protein kinase C-independent mechanism

Exposure of adipocytes to arachidonic acid rapidly enhanced basal 2-deoxyglucose uptake, reaching maximal effect at approximately 8 hr. Insulin-stimulated 2-deoxyglucose uptake was not altered over the experimental period. While the short-term (2-h exposure) effect of arachidonic acid was negligibly influenced by cycloheximide, the enhancement of glucose transport by long-term (8-h) exposure to arachidonic acid was markedly decreased by the simultaneous presence of protein-synthesis inhibitors, implying that the short-term and long-term effects of arachidonic acid may involve distinct mechanisms. Immunoblot analysis revealed that 8-h but not 2-h exposure to arachidonic acid increased the content of the ubiquitous glucose transporter (GLUT1) in both total cellular and plasma membranes. The insulin-responsive glucose transporter (GLUT4), on the other hand, was not affected. Following 2-h exposure to arachidonic acid, kinetic studies indicated that the apparent Vmax of basal 2-deoxyglucose uptake was more than doubled, while the apparent Km for 2-deoxyglucose remained unchanged. Protein kinase C (PKC) depletion by pretreating cells with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) for 24 h had little influence on the subsequent enhancing effect of arachidonic acid on 2-deoxyglucose uptake. In addition, PMA was able to stimulate 2-deoxyglucose uptake in arachidonic-acid-pretreated cells with similar increments as in non-treated cells. Thus, our data seem to suggest that arachidonic acid may enhance the intrinsic activity of GLUT1 by a PKC-independent mechanism.     

What''s so funny? A comparison of students who are deaf or hard of hearing and hearing students'' appreciation of cartoons

The aim of this study was to explore the association between stressful life events (SLE) and the development of panic disorder (PD) in an Israeli sample. A total of 44 PD patients and a matched control group were studied with regard to SLE over the life cycle (in childhood, adolescence, adulthood and the year preceding the outbreak of the disorder). The major findings were as follows. (i) With regard to the total number of life events experienced in childhood and adolescence, the PD group had experienced significantly more life events than the control group. (ii) No differences were detected in the total amount of SLE between the PD group and the control group with regard to adulthood and the year preceding the outbreak of the disorder, although the PD group had more life events relating to loss in adulthood, whereas in the year before the outbreak of PD life events relating to 'love and family', negative and loss events were more prevalent. These results expand previous findings by demonstrating that SLE in childhood and adolescence may contribute to the development of PD in adulthood.