Early imaging in heart failure: Exploring novel molecular targets

Conclusions  Noninvasive imaging of neurohumoral upregulation in remodeled myocardium suggests that an imaging strategy can be developed for predicting the rate of remodeling and likelihood of HF development. This should allow a more judicious use of neurohumoral antagonists especially in subjects who do not have manifest HF.⁷⁴ In others specific targeted imaging may allow timely selection of individualized treatment strategies and ensure optimization of therapeutic intervention. Similar to ACE and AII receptors, multiple other targets in the hormonal cascades can identify the likelihood of adverse and favorable remodeling.⁷⁴     

Chronic opioid treatment of neuroblastoma X dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents

Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via G_s regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K⁺ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the G_s/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc.     

Cannabinoid receptor down-regulation without alteration of the inhibitory effect of CP 55,940 on adenylyl cyclase in the cerebellum of CP 55,940-tolerant mice

The objective of this study was to determine whether the development of tolerance to CP 55,940, a potent cannabinoid agonist, was due to changes in the receptor or second messenger system. ICR mice treated with CP 55,940 (2 mg/kg) twice a day for 6 and one-half days developed a high degree of tolerance to the pharmacological effects of CP 55,940. The ability of CP 55,940 to produce motor hypoactivity, hypothermia and immobility was reduced 163-, 97- and 19-fold, respectively. Evaluation of 3H-CP 55,940 binding to rat brain membranes indicated no difference in receptor affinity between the vehicle- and CP 55,940-treated animals. However, these binding studies revealed a 50% decrease in receptor number in the cerebellum of the CP 55,940-tolerant mice. Although cAMP is generally considered to be the second messenger for cannabinoid receptors, little difference was observed in the inhibitory effects of CP 55,940 on adenylyl cyclase activity in cerebellum between vehicle and drug-treated mice. However, there was an increase in receptor mRNA which suggests a compensation for receptor loss. There are several possible explanations for these results. There may be sufficient spare receptors such that CP 55,940-tolerant mice are capable of producing a maximal effect on the second messenger system. On the other hand, one could conclude that cannabinoid receptor down-regulation does not account for the development of tolerance to all of the effects of CP 55,940 in mice.     

胎盘组织液氨基酸的含量测定及层析鉴别

本文采用层析法进行鉴定,用氨基酸分析仪测氨基酸的含量,为胎盘组织液的质量标准提供可靠依据。本法准确率为99%。     

Definition of An Optimal First-line Chemotherapy in Metastatic Breast Cancer

Single-agent chemotherapy of metastatic breast cancer is the treatment of choice in patients with slow tumor progression and asymptomatic disease. In this patient group, the choice of drugs is based more on good tolerability than on efficacy. By contrast, symptomatic or rapidly progressing disease requires the use of highly active regimens where more weight is put on reliable antitumor activity. While anthraycline-based combination regimens have set the standard of effective treatment, the addition of docetaxel (and to a lesser extent paclitaxel) has improved tumor response, but failed to induce a consistent prolongation of survival. Based on retrospective analyses, it is hypothesised that the combined use of anthracyclines and taxanes in first-line therapy may be most beneficial in defined subgroups: after adjuvant chemotherapy, in patients with HER-2 gene amplification, possibly also in patients with rapidly progressing visceral disease.     

Antegrade interlocking nailing of humeral shaft fractures

The results of 39 humeral shaft fractures (37 patients) treated with antegrade locked nailing using a Russell–Taylor nail were reviewed. There were 30 acute fractures, 6 fractures malaligned in a hanging cast or brace, and 3 pathological fractures. Patient age ranged from 26 to 80 years (average, 59.7 years) and average follow-up was 25.7 months (range, 6–48 months). Fracture union was achieved in 92.3% of our cases, while shoulder function was excellent or good in 87.2% of cases. Antegrade locked nailing offers a dependable solution for the treatment of humeral shaft fractures, especially in polytrauma patients and cases of segmental or pathological fractures. Far less satisfactory results were obtained in comminuted fractures of the proximal third in the humerus, especially in osteoporotic patients, and we therefore advocate caution with the use of intramedullary nailing in this type of fracture. Certain technical aspects such as avoiding nailing the fracture in distraction, properly countersinking the tip of the nail, and achieving adequate fixation stability have been found to be of paramount importance to reduce the incidence of delayed union/non-union rate and to obtain better functional results from the shoulder joint.