Protein kinase C regulates ionic conductance in hippocampal pyramidal neurons: electrophysiological effects of phorbol esters.

The vertebrate central nervous system contains very high concentrations of protein kinase C, a calcium- and phospholipid-stimulated phosphorylating enzyme. Phorbol esters, compounds with inflammatory and tumor-promoting properties, bind to and activate this enzyme. To clarify the role of protein kinase C in neuronal function, we have localized phorbol ester receptors in the rat hippocampus by autoradiography and examined the electrophysiological effects of phorbol esters on hippocampal pyramidal neurons in vitro. Phorbol esters blocked a calcium-dependent potassium conductance. In addition, phorbol esters blocked the late hyperpolarization elicited by synaptic stimulation even though other synaptic potentials were not affected. The potencies of several phorbol esters in exerting these actions paralleled their affinities for protein kinase C, suggesting that protein kinase C regulates membrane ionic conductance.     

Pilot study of a novel pain management strategy: evaluating the impact on patient outcomes

Background

Our objective was to evaluate the impact of a novel multimodal pain management strategy on intraoperative opioid requirements, postoperative pain, narcotic use, and length of stay.

Methods

Consecutive patients undergoing elective laparoscopic colorectal resection were managed with an experimental protocol. The protocol uses a post-induction, pre-incision bilateral TAP block and local peritoneal infiltration at port sites with long-acting liposomal bupivacaine (20 mL long-acting liposomal bupivacaine, 30 mL 0.25 % bupivacaine, 30 mL saline). Experimental patients were matched on age, body mass index, gender, comorbidity, diagnosis, and procedure to a control group that received no block or local wound infiltration. Both groups followed a standardized enhanced recovery pathway. Demographics, perioperative, and postoperative outcomes were evaluated. The main outcome measures were intraoperative opioids, postoperative pain, opioid use, and length of stay.

Results

Fifty patients were analyzed—25 experimental and 25 controls. Patients were well matched on all demographics. In both cohorts, the main diagnosis was colorectal cancer and primary procedure performed a segmental resection. Operative times were similar (p = 0.41). Experimental patients received significantly less intraoperative fentanyl (mean 158 mcg experimental vs. 299 mcg control; p < 0.01). The experimental group had significantly lower initial (p < 0.01) and final PACU pain scores (p = 0.04) and shorter LOS (3.0 vs. 4.1 days, p = 0.04) compared to controls. Experimental patients trended toward shorter PACU times and lower opioid use and daily pain scores throughout the hospital stay. Postoperative complication and readmission rates were similar across groups. There were no reoperations or mortality.

Conclusions

Our multimodal pain management strategy reduced intraoperative opioid administration. Postoperatively, improvements in PACU time, postoperative pain and narcotic use, and lengths of stay were seen in the experimental cohort. With the favorable finding from the pilot study, further investigation is warranted to fully evaluate the impact of this pain management protocol on patient satisfaction, clinical and financial outcomes.

     

单核细胞向巨噬细胞分化过程中CD44mRNA表达和黏附功能的变化

目的探讨单核细胞向巨噬细胞分化过程中CD44 mRNA表达和黏附功能的变化。方法应用豆蔻佛波醇乙酯(PMA)诱导单核细胞系U937向巨噬细胞分化;应用RT-PCR分析U937细胞CD44 mRNA表达变化,并以β-actin作为内参进行半定量评价,并对主要条带进行测序;应用荧光染料BCECF/AM作为探针,测定黏附于激活的内皮细胞上的U937细胞数目。结果与对照组比较,PMA诱导的U937细胞CD44 mRNA总体表达显著增加(P=0.01037),异构体/标准CD44比例显著上升(P=0.0005551),测序结果显示PMA刺激后显著增加的是947 bp(V8 V9 V10)和1208 bp(V7 V8 V9 V10)CD44异构体。同时,PMA刺激后U937细胞黏附功能显著增加(P=0.0029)。结论单核细胞向巨噬细胞分化过程中CD44 mRNA,特别是947bp(V8 V9 V10)和1208 bp(V7 V8 V9 V10)CD44异构体的表达显著增加,可能与细胞黏附功能的增强相关。     

RNA Synthesis in Cultures of Normal Human Peripheral Blood

RNA and DNA synthesis were measured in cultures of normal human peripheral blood using tritiated cytidine and thymidine and autoradiographictechnics. RNA synthesis preceded DNA synthesis by 24 hours. RNA synthesisoccurred predominantly in the large and medium-sized "blast-like" cells, butdid occur, to a lesser extent, in the small lymphocytes. RNA synthesis did notoccur in the absence of phytohemagglutinin, nor did DNA synthesis. Mechanisms of action of phytohemagglutinin are discussed with particular referenceto its possible antigenic nature.

Submitted on August 12, 1963 Accepted on January 6, 1964     

PRETREATMENT WITH PARACETAMOL INHIBITS METABOLISM OF ENFLURANE IN RATS

We studied the interaction between paracetamol (acetaminophenU.S.P.) and enflurane. Sixteen rats were assigned to four groups(n=4) to receive: paracetamol 7.5 mg/100 g body weight; paracetamolplus 1% enflurane; 1% enflurane alone, or no treatment (controls).Animals were killed 6 h later. A second series of 16 were treatedidentically, but were killed after 24 h. Measurements were madeof fluoride concentrations in serum, liver and urine (indicatorsof biotransformation of enflurane), paracetamol concentrationsin urine, pathological changes in liver samples, and concentrationsof the enzymes aspartate aminotransferase (AST) and alanineaminotransferase (ALT) in serum. Pretreatment with paracetamolsignificantly decreased urinary fluoride at 6 and 24 h afterexposure to enflurane, but decreased fluoride concentrationsin serum and liver only at 6 h after exposure to enflurane.Paracetamol concentrations in urine did not change after exposureto enflurane. Exposure to paracetamol alone increased AST andALT. At 24 h after exposure to enflurane, serum concentrationsof enzymes in rats pretreated with paracetamol were similarto those of control rats. Pretreatment with paracetamol maytherefore inhibit metabolism of enflurane. Although no hepaticdamage was observed, the increased in AST and AL T suggestedsubclinical liver damage in rats given only paracetamol.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

ALFENTANIL PLASMA CONCENTRATION v. EFFECT RELATIONSHIPS IN CARDIAC SURGICAL PATIENTS

Effects of alfentanil, preceded by lorazepam, on suppressionof haemodynamic and somatic responses to noxious stimuli wasstudied in patients undergoing CABG. Plasma concentration ofalfentanil, somatic and haemodynamic responses were measuredat loss of consciousness, tracheal intubation, sternotomy andduring multiple applications of electrocoagulation. Additionalalfentanil was administered i.v. to control unwanted responses.Study 1 (six patients): lorazepam 0.08 mg kg^–1 by mouth1–2 h before operation, alfentanil priming infusion (60µg kg^–1 min^–1 for 10 min) followed by maintenanceinfusion (4.5 µg kg^–1 min^–1). With mean plasmaalfentanil 1178 (SEM 54) ng ml^–1, two patients requiredsupplementary alfentanil to suppress somatic motor responses;one patient required nitroglycerin to control an increase inarterial pressure which was unresponsive to additional alfentanilfollowing sternotomy. Study 2 (13 patients): lorazepam 0.04mg kg^–1 by mouth as premedication; one of three maintenanceinfusion rates of alfentanil: 5.4 (n=4), 6.6 (n=5), or 7.8 (n=4)µg kg^–1 min^–1, each preceded by a proportionalpriming infusion. With plasma alfentanil 2181 (62)ng ml^–1,somatic motor responses requiring additional alfentanil occurredin nine patients; haemodynamic responses in four of seven patientstested could not be controlled by alfentanil. The highest plasmaconcentration of alfentanil to prevent response to a stimulusother than tracheal intubation was different between the twostudies (P<0.05). We conclude that alfentanil alone is insufficientto suppress haemodynamic and somatic motor responses to noxiousstimulation during CABG and that the role of premedication issignificant. *Department of Anesthesia, Bowman-Gray School of Medicine Winston-Salem,NC 27103, U.S.A. 2114 de Mayo Road, Del Mar, Ca. 92014, U.S.A.