Nonsteroidal anti-inflammatory drugs increase expression of inducible COX-2 isoform of cyclooxygenase in spinal cord of rats with adjuvant induced inflammation.

Several lines of evidence have accumulated that release of excitatory amino acids, nitric oxide and prostaglandin E2 (PGE2) play a critical role in the development of peripheral tactile and thermal hypersensitivity in chronic inflammatory pain models. Synthesis of PGE2 is controlled by cyclooxygenase (COX), either the COX-1 or COX-2 isoform. COX-2 plays a central role in the inflammatory reactions. The relationship between central sensitization of a complete Freund's adjuvant (CFA) induced inflammation and expressions of COX-2 were assessed in a rat model of CFA injection induced inflammation. Moreover, the time course of analgesia and spinal COX-2 expression following intrathecal (IT) injection with a nonspecific COX inhibitor (ketorolac) and COX-2 inhibitor (celecoxib) were determined using Western blot and immunohistochemistry. COX-2 protein was slightly increased in the lumbosacral spinal cord at 24 h following subcutaneous injection of CFA in the plantar surface of the left hindpaw (p > 0.05). COX-1 was not detected in normal and CFA injection rats. Surprisingly, IT ketorolac or celecoxib significantly increased spinal COX-2 levels at 1 h post-IT injection (p < 0.05) both in inflamed and non-inflamed rats. Then, spinal COX-2 levels declined at 3 and 6 h post-IT injection. These results provide strong in vivo evidence that COX-2 activity but not level may play a central role in the Freund's adjuvant-induced inflammation. However, spinal COX-2 level was upregulated following IT ketorolac and celecoxib injection. These data implies that suppression of PGE2 activity may induce the expression of spinal COX-2 in Freund's adjuvant-induced pain model. Our study concludes that IT administration of COX-2 inhibitor or nonspecific COX inhibitor is associated with significant short-term increase in spinal COX-2 expression.

The effect of promethazine on postoperative pain: a comparison of preoperative, postoperative, and placebo administration in patients following total abdominal hysterectomy.

BACKGROUND: Histamine receptors are involved in the development of inflammatory pain and hyperalgesia, and the use of antihistamines is advocated as an alternative for pain therapy and treatment of postoperative nausea and vomiting. We investigated the influence of timing of promethazine administration on postoperative pain outcomes. METHODS: Ninety female patients undergoing total abdominal hysterectomy were randomly divided into three groups. All individuals received infusions of promethazine and normal saline before anaesthesia induction, and postoperatively the Pre group received promethazine 0.1 mg kg(-1) before anaesthesia and saline postoperatively, and the Post group received saline before anaesthesia and promethazine 0.1 mg kg(-1) postoperatively, while the Control group received two equivalent volumes of saline. Patients were treated using patient-controlled intravenous analgesia (PCA). The primary endpoint was pain intensity and morphine consumption. The secondary endpoint was postoperative nausea and vomiting. RESULTS: Postoperative morphine usage was significantly lower in the Pre group (24.1 +/- 3.9 mg) relative to the Post (30.0 +/- 4.6 mg) and Control groups (32.1 +/- 4.8 mg) during the first 24 h postoperatively (P<0.05). The number and incidence of patients suffering from postoperative nausea in the first 24 h was six (21%), seven (23%), and 15 (47%) in the Pre, Post, and Control groups, respectively (P<0.05). The number and incidence of patients vomiting in the first 24 h was three (10%), two (7%), and 10 (32%) in the Pre, Post, and Control groups, respectively (P<0.05). The number of patients asking for rescue antiemetic in the first 24 h was one (3%), two (7%), and seven (22%) in the Pre, Post, and Control groups, respectively (P<0.05). CONCLUSIONS: Our results suggest that preoperative administration of promethazine 0.1 mg kg(-1) reduces postoperative morphine consumption compared with postoperative and placebo administration, and that use of promethazine reduces PONV and the number of patients asking for rescue antiemetic in the first 24 h after surgery when compared with placebo.

High-molecular-mass alkaline phosphatase as a tumor marker for colorectal cancer: comparison of two test methods.

We measured high-molecular-mass alkaline phosphatase (HiMwALP) in serum samples from patients with colorectal cancer by polyacrylamide gel electrophoresis (PAGE) and by column chromatography on diethylaminoethyl (DEAE)-cellulose. Determination of carcinoembryonic antigen (CEA) by an enzyme immunoassay, a frequently used cancer assessment method, was used for comparison. We studied patients with primary colorectal cancer (n = 72), using others with hemorrhoids (n = 38) for a comparison group. HiMwALP activities twice those of pooled normal sera were adopted as cutoff values. The diagnostic sensitivity of the PAGE method for 72 colorectal cancer patients was 63% vs 36% for the DEAE method and 50% for the CEA method. The diagnostic specificities of the PAGE, DEAE, and CEA methods were 89%, 79%, and 95%, respectively. Using both HiMwALP (PAGE method) and CEA for the detection of primary colorectal cancer increased the sensitivity to 72% but decreased specificity to 87%.

Quantitative determination of high molecular weight alkaline phosphatase in patients with colorectal cancer by polyacrylamide gel electrophoresis.

We present a new method for the quantitative determination of high molecular weight alkaline phosphatase (ALP). This method consists of electrophoretic separation on polyacrylamide, incubation of the ALP isoenzymes with substrate, gel drying and quantitative evaluation by densitometric measurement. This method separates high molecular weight ALP from the other isoenzymes. Precision of the method is calculated by the coefficient of variation ranging from 1.2 to 9.5% for samples with different high molecular weight ALP values. The diagnostic sensitivity for detecting colorectal cancer is 60%.