Ketamine,an N-methyl-D-aspartate receptor antagonist,inhibits the reflex responses to distension of the rat urinary bladder

BACKGROUND: Ketamine is analgesic in experimental and clinical studies of inflammatory, neuropathic, and postoperative pain. Its role in the treatment of visceral pain is less known. The authors investigated the effect and site of action of ketamine on reflex responses evoked by urinary bladder distension (UBD). The effects of other clinically available N-methyl-d-aspartate (NMDA) receptor antagonists on these responses were also studied. METHODS: The effect of intravenous ketamine (1, 3, and 10 mg/kg), dextromethorphan (5 mg/kg), and memantine (16 mg/kg) on mean arterial pressure changes (Delta MAP) and abdominal electromyographic activity (EMG) evoked by UBD was measured in anesthetized rats. Ketamine was also administered intravesically and intrathecally and its effect on Delta MAP and EMG responses to UBD recorded. The effect of pretreatment with intravenous ketamine on these responses was also assessed. RESULTS: The Delta MAP and EMG responses to UBD were reduced in a dose-dependent fashion by ketamine. Memantine and dextromethorphan also inhibited these responses. Ketamine administered intrathecally produced marked inhibition of Delta MAP and EMG responses to UBD. Pretreatment with ketamine only transiently reduced the vigor of responses to UBD. CONCLUSIONS: Ketamine inhibited, in a dose-dependent fashion, the Delta MAP and EMG responses to UBD, an effect likely caused by actions within the spinal cord. Similar inhibition observed with systemic dextromethorphan and memantine treatments suggests that the analgesic effect of ketamine is caused by antagonism of the NMDA receptor. Pretreatment with ketamine did not have a preventive effect in this model of bladder nociception.     

Insulin-like growth factor I,but not neurotrophin-3, sustains Akt activation and provides long-term protection of immature oligodendrocytes from glutamate-mediated apoptosis

Glutamate toxicity is a major contributor to death of oligodendroglia in diverse CNS disorders. The goal of these studies was to investigate the mechanisms of glutamate toxicity and trophic factor protection of the immature pro-oligodendroblast (pro-OL). Glutamate induced time- and dose-dependent DNA fragmentation and caspase-3 activation in pro-OLs. IGF-I or NT-3, but not CNTF, prevented apoptosis of pro-OLs by 24 h via a PI3-kinase-dependent pathway; however, only IGF-I protected pro-OLs from glutamate toxicity through 48 h. Long-term protection of pro-OLs by IGF-I was correlated with sustained activation of Akt while NT-3 activation of Akt was transient. The differential ability of IGF-I and NT-3 to maintain Akt activation was due to differences in receptor activation and stability. In the presence of NT-3, TrkC phosphorylation and protein expression decreased significantly while activation of the IGF-IR was maintained in the pro-OLs in the presence of IGF-I.     

Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an eastern cooperative oncology group study

Chromosome 13 abnormalities (Delta13) have been associated with an unfavorable prognosis in patients with multiple myeloma (MM). The significance of this has been unresolved because of diverse methods of detection and heterogeneous groups of patients. We conducted a study of Delta13 in patients entered into the Eastern Cooperative Oncology Group trial E9486/E9487. Patients with newly diagnosed MM (median follow-up of survivors >100 months) were studied for Delta13, using bone marrow samples obtained at study enrollment. We used interphase fluorescence in situ hybridization with the probes LSI13 (Rb)/D13S319 with simultaneous immunofluorescence detection of bone marrow plasma cells (PCs). We detected Delta13 in 176 of 325 (54%) evaluable patients. Patients with Delta13 were more likely to have a serum monoclonal protein at a concentration < or =1 g/dl (22 versus 13%; P = 0.04), light-chain-only MM (19.3 versus 10.8%; P = 0.04), gamma light chain (42 versus 28%; P = 0.027), stage III (56 versus 42%; P = 0.014), and be female (60 versus 50%; P = 0.087). The PC labeling index and Delta13 correlated (P = 0.03). Patients with Delta13 were less likely to respond to treatment (74 versus 63%; P = 0.041) and had a significantly shorter median overall survival (34.9 versus 51 months; P = 0.021). The association of Delta13 and survival remained an independent prognostic variable in a regression model. Among patients with Delta13, those receiving IFN had a worse overall survival that those not receiving the medication (P = 0.03). The presence of Delta13 is an important and independent adverse prognostic factor in newly diagnosed MM and is associated with specific biological features.     

Sex-related hormonal influences on pain and analgesic responses

Considerable evidence indicates sex-related differences in pain responses and in the effectiveness of various analgesic agents. Specifically, females are at greater risk for experiencing many forms of clinical pain and are more sensitive to experimentally induced pain relative to males. Regarding analgesic responses, nonhuman animal studies indicate greater opioid analgesia for males, while a limited human literature suggests the opposite. Though the mechanisms underlying these effects remain unclear, the influence of gonadal hormones on nociceptive processing represents one plausible pathway whereby such sex differences could emerge. The present article reviews the complex literature concerning sex steroid effects on pain responses and analgesia. First, nonhuman animal research related to hormonal effects on nociceptive sensitivity and analgesic responses is presented. Next, human studies regarding gonadal hormonal influences on experimental pain responses are reviewed. Several potential mechanisms underlying hormonal effects on nociceptive processing are discussed, including hormonal effects to both peripheral and central nervous system pathways involved in pain transmission. Finally, based on these findings we draw several conclusions and make specific recommendations that will guide future research as it attempts to elucidate the magnitude and importance of sex-related hormonal effects on the experience of pain.     

Increased level of polymerase Ⅲ transcribed Alu RNA in hepatocellular carcinoma tissue

There have been extensive observations that RNA containing repetitive elements accumulates in transformed cells and tumor tissues. In the present study, we first obtained result consistent with previous observations by in situ hybridization.     

Immunohistochemical expressions of Ki-67, cyclin D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor in human colorectal adenoma: a validation study of tissue microarrays.

BACKGROUND: Tissue microarray (TMA) holds promise as a high-throughput method for the analysis of biomarkers in tissue specimens. The validity and reliability of this method, however, may vary for different biomarkers in different tissue specimens. OBJECTIVES: In this study, we evaluated the validity and reliability of using TMA to assess biomarkers in colorectal adenomas. METHODS: Sixty-three consecutive patients with colorectal adenomas were recruited in this study. Two TMA blocks were constructed using four punches from each adenoma (one periphery, one deep, and two middle zones). The immunostaining of five markers (Ki-67, cyclin D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor) was analyzed, and the concordance between data obtained from TMAs and standard whole-tissue sections was evaluated by Spearman's correlation and kappa analysis. RESULTS: Colorectal adenoma exhibited zonal, heterogeneous expression patterns for all five markers. The concordance rates for the semiquantitative evaluation of markers between data from TMAs and whole sections ranged from 87% to 93% with corresponding kappa statistics of 77% to 90%. In addition, both quantitative and semiquantitative methods were used to score TMA sections, and good correlations between these two methods were shown for all five markers with intraclass correlation coefficients ranging from 0.5 to 0.8. CONCLUSION: Our study indicates that TMA can be used to reliably assess the expression levels of Ki-67, cyclin D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor in colorectal adenoma tissues.     

Seizures in children with low-grade tumors： outcome after tumor resection and risk factors for uncontrolled seizures

OBJECT： The goals of this study were to define the incidence of seizures in children with low-grade tumors, study seizure outcome after lesionectomy in these children, and identify risk factors for poor seizure outcome, METHODS： The authors performed a retrospective chart review of children who harbored low-grade brain tumors, experienced seizures, and were treated in a single institution, Statistical analyses included step-wise as well as single-variable binary logistic regression analyses.