Preparation of biointeractive glycoprotein-conjugated hydrogels through metabolic oligosacchalide engineering.

In the current study, synthetic hydrogels containing metabolically engineered glycoproteins of mammalian cells were prepared for the first time and selectin-mediated cell adhesion on the hydrogel was demonstrated. A culture of HL-60 cells was supplemented with an appropriate volume of aqueous solution of N-methacryloyl mannosamine (ManMA) to give a final concentration of 5 mM. The cells were then incubated for 3 days to deliver methacryloyl groups to the glycoproteins of the cells. A transparent hydrogel was formed via redox radical polymerization of methacryloyl functionalized glycoproteins with 2-methacryloyloxyethyl phosphorylcholine and a cross-linker. Conjugation of the glycoproteins into the hydrogel was determined using Coomassie brilliant blue (CBB) and periodic acid-Schiff (PAS) staining. The surface density of P-selectin glycoprotein ligand-1 (PSGL-1) on the hydrogels was also detected using gold-colloid-labeled immunoassay. Finally, selectin-mediated cell adhesion on hydrogels containing glycoproteins was demonstrated. Selectin-mediated cell adhesion is considered an essential step in the progression of various diseases; therefore, hydrogels having glycoproteins could be useful in therapeutic and diagnostic applications.

[Antiemetic-induced extrapyramidal symptoms seen by our palliative care team].

BACKGROUND: Antiemetic drugs, which are usually prescribed with opioids, occasionally induce extrapyramidal symptoms(EPS). METHODS: In 109 patients treated with our palliative care team, we retrospectively investigated the appearance of antiemetic-induced EPS; its incidence, latent period, onset age, symptoms, causing agents and clinical outcomes. RESULTS: EPS were observed in 6 of 109 patients. Six EPS patients, 2 men and 4 women, were between the age of 53 and 66 years. Prochlorperazine was used in all EPS patients. Two EPS were induced with unnecessary antiemetic drugs. Onset of EPS was from 11 to 162 days after beginning of antiemetic drugs. There were 5 patients with slow movement or speech, 3 patients with expressionless face, 2 patients with akathisia, and one patient with dysphagia. Five EPS patients were improved by using biperiden and one patient was by changing prochlorperazine to perospirone. CONCLUSIONS: EPS were found in 6 of 109 patients during palliative care. We concluded that it was important not to forget the appearance of antiemetic-induced EPS when prescribing antiemetic drugs in palliative

Clinically relevant concentrations of olprinone reverse attenuating effect of propofol on isoproterenol-induced cyclic adenosine monophosphate accumulation in cardiomyocytes.

Propofol has been shown to attenuate beta-adrenoreceptor-mediated signal transduction in cardiomyocytes. Cyclic adenosine monophosphate (cAMP) is an essential second messenger of beta-signal transduction, while olprinone, a phosphodiesterase-III inhibitor, improves poor cardiac performance by increasing cAMP levels. In the present study, we investigated the effects of olprinone toward the reducing effect of propofol on beta-adrenoreceptor-mediated increases in cAMP production. First, suspensions of rat ventricular myocytes were incubated with isoproterenol or olprinone and the effects on cAMP concentrations were assessed. Next, propofol was added prior to the addition of isoproterenol or olprinone. Finally, following preincubation with propofol, isoproterenol with or without olprinone was added. Both isoproterenol and olprinone increased cAMP production in a dose-dependent manner. However, clinically relevant concentrations of olprinone (up to 10(-7) M) did not cause a significant increase. Propofol (10(-7)-10(-4) M) attenuated isoproterenol-stimulated increases in cAMP production (decrease of 2 +/- 4% approximately 43 +/- 1%, as compared to the isoproterenol-stimulated state). However, the agent did not alter olprinone (10(-7) M)-stimulated cAMP production. Olprinone (10(-8)-10(-6) M) reversed the attenuating effect of propofol (10(-5) M) toward isoproterenol (10(-7) M)-stimulated cAMP production dose-dependently (increase of 10 +/- 5% approximately 79 +/- 4% as compared to the propofol-attenuated state). Our results suggest that an improvement in cardiac function is provided by olprinone when the beta-adrenoreceptor-mediated signaling pathway is inhibited by propofol.

Intrathecally administered COX-2 but not COX-1 or COX-3 inhibitors attenuate streptozotocin-induced mechanical hyperalgesia in rats.

Members of the cyclooxygenase (COX) family are known to catalyze the rate-limiting steps of prostaglandins synthesis and reported to be involved in neuropathic pain. Diabetic neuropathy is a type of neuropathic pain, though it is not clear if COX is relevant to the condition. Recently, spinal COX-2 protein was found to be increasing in streptozotocin-induced rats as compared to the constitutive expression. We attempted to determine which cyclooxygenase isoforms are involved in streptozotocin-induced mechanical hyperalgesia, which was induced by a single intraperitoneal injection of 75 mg/kg of streptozotocin. Intrathecal administrations of the COX-2 inhibitors SC-58125 (7-100 microg) and NS-398 (7-60 microg), as well as a high dose (100 microg) of the COX-1 inhibitor SC-560 attenuated hyperalgesia, whereas intrathecal administrations of a low dose (10 microg) of SC-560 and the COX-3 inhibitor acetaminophen (1-7 mg) did not. Further, intrathecal administration of SC-58125 (100 microg) did not produce an analgesic effect in normal rats. These results indicate that intrathecal administration of COX-2 inhibitors has an anti-hyperalgesic effect on streptozotocin-induced mechanical hyperalgesia and we concluded that spinal COX-2 is pivotal in streptozotocin-induced hyperalgesia.

Spinal orexin-1 receptors mediate anti-hyperalgesic effects of intrathecally-administered orexins in diabetic neuropathic pain model rats.

Orexin-A and orexin-B are endogenous ligands of orexin receptors that contain orexin-1 and orexin-2. Activation of the orexinergic system can produce antinociceptive effects in acute inflammatory, mono-neuropathic, and postoperative pain animal models, though the effects of orexins on diabetic neuropathic pain have not been previously investigated. In this study, we studied the anti-hyperalgesic effects of intrathecally administered orexins in a streptozotocin-induced diabetic rat. First, dose-dependent effects were investigated by measuring hind paw withdrawal thresholds in response to noxious-heat and punctate stimuli, after which orexin levels in the cerebrospinal fluid of diabetic rats were measured and compared with those of normal rats using a radioimmunoassay method. The functional role of spinal orexin-1 receptors with the anti-hyperalgesic effects of orexins was also investigated using intrathecal pretreatment with SB-334867, a selective orexin-1 receptor antagonist. Intrathecally administered orexins produced an antinociceptive effect in diabetic rats, however, not in normal rats, though the orexin levels in the cerebrospinal fluid of diabetic rats were similar to those in normal rats. In addition, the anti-hyperalgesic effects of orexins were significantly inhibited by pretreatment with SB-334867. These findings demonstrate that the anti-hyperalgesic effects of orexins in diabetic rats are unlikely due to any direct effect by the supplement on decreased endogenous orexins in the cerebrospinal fluid and that orexin-1 receptors in the spinal cord may be involved in the modulation of nociceptive transmission in diabetic neuropathy. We conclude that the spinal orexinergic system may be a possible target for elucidating the mechanisms of diabetes-induced hyperalgesia.

[Study of nausea and vomiting accompanying intravenous patient-controlled analgesia with fentanyl after cervical spine surgery].

BACKGROUND: Serious side effects of postoperative analgesia with opioid drugs include nausea and vomiting. METHODS: We investigated the effects of various factors (patient background, anesthesia duration, and intraoperative drug use) on the frequency and degree of postoperative nausea and vomiting (PONV) during the first 24 hours of intravenous patient-controlled analgesia (PCA) with fentanyl. RESULTS: PONV occurred in 34% of the male patients and 68% of the female, and in 31% and 58% of smokers and non-smokers, respectively. CONCLUSIONS: Consideration should be given to gender and smoking status prior to starting preventive antiemetic therapy using PCA with fentanyl following cervical spine surgery.

[Optimal application time of lidocaine adhesive tape examined using current perception threshold measurement].

BACKGROUND: We often use lidocaine adhesive tape (Penles, Wyeth Lederle Japan, Ltd., Tokyo, Japan) as a topical anesthetic prior to puncturing a vein with a needle. Since the tape is usually in place for a long time, we often experience problems with creasing and flaring when inserting the needle. We attempted to determine the optimal time for application of the tape as well as for vein puncture after its removal by measuring pain sensation in human subjects. METHODS: Lidocaine tape was applied to the dorsum of volunteer hands for 2, 4, 6, and 12 hours, and we evaluated changes after removal by determining current perception threshold (CPT), pain score, touch sensation score, diameter of the vein, pruritus, and flare. RESULTS: CPT levels were found to increase within 1 hour after removal of the lidocaine tape with all 3 electrical stimulus rates used (2000 Hz, 250 Hz, 5 Hz). Further, pain and touch sensation scores were low within 2 hours of removal regardless of application time. Notably, with 4 and 6 hours of application, scores were stable 4 and 6 hours after removal. However, vein diameter and pruritus results did not change regardless of application time, while crease and flare were only observed within 30 minutes after removal. CONCLUSIONS: We concluded that lidocaine tape provided maximum pain relief when applied 4 to 6 hours prior to vein puncture and up to 1 hour after removal.