Alpha 2-adrenergic receptors regulate generation of cyclic AMP in the pineal gland, but not in cerebral cortex of chick

A beta-adrenoceptor agonist isoprenaline potently stimulated cyclic AMP formation in chick cerebral cortical slices. L-Noradrenaline (10-1000 microM) also increased cortical nucleotide synthesis, the effect being antagonized by beta-adrenoceptor blocker propranolol, and not affected by alpha 1- and alpha 2-adrenoceptor blockers, prazosin and yohimbine, respectively. Clonidine, a selective alpha 2-agonist, had no effect on cerebral cyclic AMP production stimulated by both isoprenaline and forskolin. However, clonidine (0.001-10 microM) concentration-dependently suppressed forskolin-driven cyclic AMP synthesis in intact chick pineal glands. In living chicks clonidine suppressed the nocturnal activity of cyclic AMP-dependent serotonin N-acetyltransferase, a rate-limiting enzyme in melatonin biosynthesis, the effect being prevented by yohimbine. The data suggest that the cyclic AMP generating system of the pineal gland, but not that of cerebral cortex in chick, is negatively regulated by alpha 2-adrenergic receptor-mediated signal.     

Evaluation of Dielectric Properties of CCTO-BT/Epoxy Composites for Electronic Applications

In the current study, the calcium copper titanate (CCTO)/epoxy, barium titanate (BT)/epoxy and CCTO-BT/epoxy composite samples with variable volume fractions of CCTO and BT are fabricated using hand lay-up and compression moulding process. The composite samples are characterized for the frequency dependence on dielectric properties, conductivity, impedance spectroscopy and electrical modulus. X-ray diffraction (XRD) representation of CCTO-BT/epoxy composite samples confirmed the presence of both CCTO and BT ceramic samples separately. The dielectric characteristics of hybrid CCTO-BT/epoxy composite samples with CCTO∶BT ratio of 40∶60, 60∶40, and 50∶50 was found relatively better than those of single ceramic filler reinforced epoxy composites. AC conductivity analysis shows improvement in the results of hybrid filler-filled CCTO-BT/epoxy composites in comparison with single filler-filled epoxy composite. 50∶50 CCTO-BT/epoxy composite shows the best AC conductivity value of ~2.2×10^-5 ohm^-1·m-1 at a higher frequency of 1 MHz. The impedance analysis confirms the higher insulating properties for hybrid 40∶60 and 60∶40 CCTO-BT/epoxy composites with respect to the single and other hybrid ceramic epoxy composites. The analysis suggests the hybrid CCTO-BT/epoxy composites to be adopted as a potential dielectric material for energy storage devices and other electronic applications.     

Effects of chronic U50,488H treatment on binding and mechanical responses of the rat hearts

The effects of chronic injection of U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamidel++ +), a selective kappa opioid agonist, on the properties of the binding sites of tritiated U69593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro (4,5)dec-8-yl)benzeneacetamide], another selective kappa opioid agonist, and mechanical responses to U50,488H of the heart were studied. Rats received injection twice a day with U50,488H for 4 days. Binding studies on the crude membrane homogenates revealed that there was no change in maximum binding, but a significant increase in Kd after the treatment, indicating that the number of kappa binding sites remained unchanged whereas the affinity of the binding sites to kappa-agonist decreased. The study on the mechanical responses to U50,488H in the isolated perfused heart preparation showed that although the agonist at 10(-6) M caused MR2266 reversible reductions in heart rate and force of contraction as well as ventricular ectopic beat in the heart of rats in the control group, its effects were absent in the U50,488H-treated group, indicating the development of tolerance to the mechanical effects of U50,488H on the heart. The results indicate that the development of tolerance to the mechanical effects of a kappa-agonist after chronic treatment with the agonist was not accompanied by down-regulation, but only a slight and significant reduction in affinity of kappa binding sites in the rat heart.     

Leukocyte-endothelium interaction during the early stages of hypercholesterolemia in the rabbit: role of P-selectin, ICAM-1, and VCAM-1

The early effects of hypercholesterolemia on leukocyte-endothelium interaction were studied in vivo in the rabbit mesenteric microcirculation. Rabbits fed a 0.5% high-cholesterol (HC) diet showed elevated plasma cholesterol levels during the 1 to 2 weeks of HC feeding (P<0.001 versus control diet-fed rabbits). Intravital microscopy of mesenteric venules revealed that leukocyte rolling had increased 10-fold (P<0.001 versus control-fed group) at the end of the first week of the HC diet, which was sustained after 2 weeks of HC feeding (P<0.001 versus control-fed rabbits). Firm adherence of leukocytes to the endothelium was moderately increased after a 1-week period of hypercholesterolemia (P<0.05) but increased by 12-fold at 2 weeks (P<0.001 versus control diet-fed and P<0.01 versus 1-week HC-fed rabbits). Upregulation of the endothelial cell adhesion molecules P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was observed immunohistochemically on the intestinal microvascular endothelium of HC-fed rabbits. P-selectin was maximally expressed within the first week of the HC diet and remained elevated during the second week of cholesterol feeding (P<0.01 versus control). In contrast, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were moderately upregulated at 1 week but were highly expressed after 2 weeks of the HC diet (P<0.05 and P<0.001 versus control, respectively). Basal release of NO from both mesenteric microvascular and aortic endothelium in cholesterol-fed rabbits was progressively reduced after 1 (P<0.05) and 2 (P<0.01) weeks. Our data suggest that enhanced leukocyte-endothelium interaction occurs in vivo in the rabbit microcirculation during the first 2 weeks of hypercholesterolemia. This phenomenon is associated with impaired basal NO release and progressive endothelial surface expression of endothelial cell adhesion molecules (ie, P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1) in the microvasculature.     

Cyclin synthesis controls the progression of meiotic maturation in mouse oocytes

To study the mechanisms involved in the progression of meiotic maturation in the mouse, we used oocytes from two strains of mice, CBA/Kw and KE, which differ greatly in the rate at which they undergo meiotic maturation. CBA/Kw oocytes extrude the first polar body about 7 hours after breakdown of the germinal vesicle (GVBD), whilst the oocytes from KE mice take approximately 3-4 hours longer. In both strains, the kinetics of spindle formation are comparable. While the kinetics of MAP kinase activity are very similar in both strains (although slightly faster in CBA/Kw), the rise of cdc2 kinase activity is very rapid in CBA/Kw oocytes and slow and diphasic in KE oocytes. When protein synthesis is inhibited, the activity of the cdc2 kinase starts to rise but arrests shortly after GVBD with a slightly higher level in CBA/Kw oocytes, which may correspond to the presence of a larger pool of cyclin B1 in prophase CBA/Kw oocytes. After GVBD, the rate of cyclin B1 synthesis is higher in CBA/Kw than in KE oocytes, whilst the overall level of protein synthesis and the amount of messenger RNA coding for cyclin B1 are identical in oocytes from both strains. The injection of cyclin B1 messenger RNA in KE oocytes increased the H1 kinase activity and sped up first polar body extrusion. Finally, analysis of the rate of maturation in hybrids obtained after fusion of nuclear and cytoplasmic fragments of oocytes from both strains suggests that both the germinal vesicle and the cytoplasm contain factor(s) influencing the length of the first meiotic M phase. These results demonstrate that the rate of cyclin B1 synthesis controls the length of the first meiotic M phase and that a nuclear factor able to speed up cyclin B synthesis is present in CBA/Kw oocytes.     

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.     

The role of endoscopic third ventriculostomy in the management of shunt malfunction

OBJECTIVE: To evaluate the effectiveness of third ventriculostomy as an alternative to shunt revision in the management of shunt malfunction and infection in obstructive hydrocephalus. METHODS: All of the clinical notes of 30 patients treated with third ventriculostomy for malfunctioning or infected shunts between January 1, 1974, and December 31, 1996, were retrospectively reviewed. Third ventriculostomy was performed under fluoroscopic control in the first seven patients and endoscopically in the remainder. A successful outcome was achieved if further shunt revision surgery was avoided. The median follow-up duration was 8.7 years RESULTS: Twenty-three patients (76.7%) experienced successful outcomes, resulting in shunt independence. Of the seven failures, three were technical failures at the time of surgery and the remaining four were manifest within a median of 10 days, resulting in shunt revision. There have been no delayed failures. CONCLUSION: Third ventriculostomy is a valuable alternative to shunt revision in patients affected by obstructive hydrocephalus presenting with shunt malfunction or infection. It should be considered in all suitable cases as the first-line treatment for obstructive hydrocephalus of all causes. Because all failures were manifest within a short time, it is likely that these successes will be durable.