Chih-Peng Lin

SDF-1alpha up-regulates interleukin-6 through CXCR4, PI3K/Akt, ERK, and NF-kappaB-dependent pathway in microglia.

Stromal cell-derived factor-1 (SDF-1), also known as CXCL12, and its receptor CXC chemokine receptor 4 (CXCR4) express in various kinds of cells in central nervous system. The SDF-1/CXCR4 signaling pathway is regulated by diverse biological effects. SDF-1 is up-regulated in the ischemic penumbra following stroke and has been known to be associated with the homing of bone marrow cells to injury. However, the effect of SDF-1alpha/CXCR4 on cytokine production in microglia is mostly unknown. Here, we demonstrated that SDF-1alpha enhanced IL-6 production in both primary cultured microglia and BV-2 microglia. We further investigated the signaling pathway involved in IL-6 production stimulated by SDF-1alpha in microglia. SDF-1alpha increased IL-6 production in both protein and mRNA levels. These effects were attenuated by ERK, phosphatidylinositol 3-kinase (PI3K), NF-kappaB inhibitors, and IkappaB protease inhibitor. Stimulation of microglia with SDF-1alpha also increased Akt and ERK1/2 phosphorylation. In addition, SDF-1alpha treatment also increased IkappaB kinase alpha/beta (IKK alpha/beta) phosphorylation, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation at Ser(276), translocation of p65 and p50 from cytosol to nucleus and kappaB-luciferase activity. Moreover, SDF-1alpha-mediated increase of kappaB-luciferase activity was inhibited by pre-transfection of DN-p85, DN-Akt or DN-ERK2. Increase of IKK alpha/beta phosphorylation and binding of p65 and p50 to the NF-kappaB element were both antagonized by PI3K and ERK inhibitors. Our results demonstrate a mechanism linking SDF-1alpha and IL-6, and provide additional support for the notion that SDF-1alpha plays a regulatory role in microglia activation.

Mechanism of cellular uptake and impact of ferucarbotran on macrophage physiology.

Superparamagnetic iron oxide (SPIO) nanoparticles are contrast agents used for magnetic resonance imaging. Ferucarbotran is a clinically approved SPIO-coated carboxydextran with a diameter of about 45–60 nm. We investigated the mechanism of cellular uptake of Ferucarbotran with a cell model using the murine macrophage cell line Raw 264.7. We observed a dose-dependent uptake of these SPIO particles by spectrophotometer analysis and also a dose-dependent increase in the granularity of the macrophages as determined by flow cytometry. There was a linear correlation between the side scattering mean value and iron content (P<0.001, R2 = 0. 8048). For evaluation of the endocytotic pathway of these ingested SPIO particles, different inhibitors of the endocytotic pathways were employed. There was a significant decrease of side scattering counts in the cells and a less significant change in signal intensity based on magnetic resonance in the phenylarsine oxide-treated macrophages. After labeling with SPIO particles, the macrophages showed an increase in the production of reactive oxygen species at 2, 24, and 48 h; a decrease in mitochondrial membrane potential at 24 h; and an increase in cell proliferation at 24 h. We concluded that Ferucarbotran was internalized into macrophages via the clathrin-mediated pathway and can change the cellular behavior of these cells after labeling.

Factors determining post-colonoscopy abdominal pain: prospective study of screening colonoscopy in 1000 subjects.

Background:  Factors determining post‐colonoscopy abdominal pain remain poorly understood. Accordingly, a prospective study was conducted to reveal the key determinants.

Prolonged retraction on the normal common carotid artery induced lethal stroke after cervical spine surgery.

Study Design. Case report. Objective. To report a previously undescribed complication of prolonged retraction on the normal common carotid artery after anterior cervical spine surgery. Summary of Background Data. Previous study showed that prolonged retraction could decrease the blood flow of the common carotid artery during anterior cervical spine surgery. A case report revealed that prolonged retraction could induce the formation of thrombosis in the atherosclerotic common carotid artery. Methods. Notes review. Computed tomography of the brain was performed on the first and the fourth postoperative day. Carotid Doppler ultrasound and transcranial Doppler ultrasound were performed to evaluate the left common carotid artery and the left intracranial cerebral arteries. Results. After lengthy anterior cervical spinal surgery, the patient did not regain his consciousness during the stay in the postoperative care unit. Large infarction of left cerebral hemisphere was revealed by computed tomography. The patient died on the seventh postoperative day of perioperative lethal stroke. Conclusion. We suggest that prolonged retraction, even on the normal common carotid artery, could induce lethal stroke after anterior cervical spine surgery. We recommend that retractor should be placed carefully and cerebral perfusion should be maintained adequately.

Role of spinal CXCL1 (GROα) in opioid tolerance: a human-to-rodent translational study.

Background:The pivotal role of glial activation and up-regulated inflammatory mediators in the opioid tolerance has been confirmed in rodents but not yet in humans. Here, the authors investigated the intraspinal cytokine and chemokine profiles of opioid-tolerant cancer patients; and to determine if up-regulated chemokines could modify opioid tolerance in rats. Methods:Cerebrospinal fluid samples from opioid-tolerant cancer patients and opioid-naive subjects were compared. The cerebrospinal fluid levels of tumor necrosis factor-alpha, CXCL1, CXCL10, CCL2, and CX3CL1 were assayed. The rat tail flick test was utilized to assess the effects of intrathecal CXCL1 on morphine-induced acute antinociception and analgesic tolerance. Results:CXCL1 level in cerebrospinal fluid was significantly up-regulated in the opioid-tolerant group (n = 30, 18.8 pg/ml vs. 13.2 pg/ml, P = 0.02) and was positively correlated (r2 = 0.49, P < 0.01) with opioid dosage. In rat experiment, after induction of tolerance by morphine infusion, the spinal cord CXCL1 messenger RNA was up-regulated to 32.5 ± 11.9-fold. Although CXCL1 infusion alone did not affect baseline tail-flick latency, the analgesic efficacy of a single intraperitoneal injection of morphine dropped significantly on day 1 to day 3 after intrathecal infusion of CXCL1. After establishing tolerance by intrathecal continuous infusion of morphine, its development was accelerated by coadministration of CXCL1 and attenuated by coadministration of CXCL1-neutralizing antibody or CXCR2 antagonist. Conclusions:CXCL1 is up-regulated in both opioid-tolerant patients and rodents. The onset and extent of opioid tolerance was affected by antagonizing intrathecal CXCL1/CXCR2 signaling. Therefore, the CXCL1/CXCR2 signal pathway may be a novel target for the treatment of opioid tolerance.

Compatibility and stability of binary mixtures of ketorolac tromethamine and tramadol hydrochloride injection concentrate and diluted infusion solution.

OBJECTIVE Ketorolac added to tramadol as an injection mixture convenient for clinical use has been shown to be an effective balanced analgesic regimen in alleviating moderate-to-severe pain. However, analytical confirmation of the compatibility and stability of this combination is not available. This study examined the compatibility and stability of this combination. METHODS Two different mixtures containing ketorolac tromethamine and tramadol hydrochloride were examined: ketorolac (10 mg/mL) and tramadol (33.3 mg/mL) prepared as injection concentrate in ampoule mingled together in the ratio of one ampoule to one ampoule; diluted ketorolac (2 mg/mL) and tramadol (20 mg/mL) prepared in saline infusion solution, with or without pH adjustment. The mixtures were visually inspected for precipitation and color change. Quantitative chemical analysis was performed on days 0, 1, 3 and 7 by high-performance liquid chromatography. RESULTS When stored at room temperature under ambient light, the ketorolac (10 mg/mL)-tramadol (33.3 mg/mL) injection concentrate and ketorolac (2 mg/mL)-tramadol (20 mg/mL) solution, without pH adjustment and adjusted to pH 5-8, were physico-chemically stable, and neither visible precipitation nor loss of concentration was found. With the ketorolac (2 mg/mL)-tramadol (20 mg/mL) solution adjusted to pH 9, however, precipitation occurred immediately, resulting in a significant loss of tramadol. CONCLUSION This study suggests that a ready-to-use ketorolac-tramadol mixture, either undiluted or diluted in physiological saline solution, can be prepared, with a shelf life of at least 7 days when stored at room temperature under ambient light.

Ultrasound-assisted percutaneous catheterization of the axillary vein for totally implantable venous access device

BACKGROUND Placing a totally implantable venous access device (TIVAD) using the classical subclavian vein puncture method carries the risk of certain complications including hemothorax, pneumothorax and pinch-off syndrome. We set out to determine whether percutaneous axillary vein catheterization can decrease the incidence of these complications. METHOD This is a prospective, observational, uni-institutional study. We analyzed the outcome of 113 TIVADs performed by ultrasound-assisted percutaneous axillary vein catheterization from Jun. 2008 to Dec. 2008. Junior residents novice to subclavian and axillary vein catheterization performed the procedures. Insertion and indwelling catheter complications were recorded. RESULT In our study population, 100% of TIVAD placements were successful. 27 patients (23.9%) required 3 or more repeated punctures; only one patient (0.9%) had clinically insignificant pneumothorax. Neither arterial puncture nor brachial plexus injury was recorded in our study. CONCLUSION Ultrasound-assisted percutaneous axillary vein catheterization for TIVAD is a safe and relatively simple method for inexperienced operators.

Does Different Time Interval Between Staggered Bilateral Total Knee Arthroplasty Affect Perioperative Outcome? A Retrospective Study

Staggered bilateral total knee arthroplasty (BTKA) performed 4 to 7 days apart has been shown to have fewer postoperative complications than sequential or staged BTKA. However, there has been no comparison of staggered BTKA with different intervals. A retrospective study involving 79 patients who underwent BTKA from 2002 to 2004 was performed to determine whether the interval between each TKA influenced the clinical outcome. Staggered operations performed 2 days (n = 46) or 7 days (n = 33) apart had similar incidence of major (acute myocardial infarction, pulmonary embolism, etc) and minor complications (transient hypotension or low Sp(o)(2)) throughout hospitalization. Perioperative complications in the first and second TKAs were similar when TKAs were performed with a 2- or a 7-day interval.

Analgesic efficacy of tramadol/acetaminophen and propoxyphene/acetaminophen for relief of postoperative wound pain

BACKGROUND/PURPOSE Weak opioid combined with acetaminophen (APAP) has been proven to provide better analgesic efficacy and cause fewer complications than either drug alone. However, there are questions about whether different opioids, tramadol and propoxyphene, provide similar efficacy or safety. Thus, we investigated Ultracet (37.5 mg tramadol/325 mg APAP) and Depain-X (65 mg propoxyphene/650 mg APAP). The primary aims of this study were to compare the analgesic efficacy and adverse effects of single-dose oral Ultracet versus Depain-X in acute postoperative pain. MATERIALS AND METHODS This was a randomized, open-label, active-controlled parallel study on patients with postsurgical pain. Sixty patients who sustained moderate postsurgical pain (visual analog scale(3)3 cm) after undergoing implantation of venous access were randomized to two groups to receive either Ultracetor Depain-X for postoperative analgesia. Assessment items included pain intensity and pain relief ratings at the first 4 hours, and adverse events. RESULTS There were initially 107 patients who were enrolled in this trial, but up to 45 (42.1%) of them were withdrawn during the study. In these 62 patients who complied with treatment (Ultracet: Depain-X = 29: 33), pain relief scale indicated that Ultracet could provide a better analgesic effect than Depain-X provided at 1 hour (p < 0.05). At 4 hours, the pain score in the Ultracet group was significantly lower than that in the Depain-X group (p < 0.05). Adverse events, such as drowsiness, dizziness, and skin itching did not differ in both groups. CONCLUSION Among patients with mild to moderate postoperative wound pain, single-dose Ultracet can provide slightly better analgesic efficacy than Depain-X in terms of onset and duration. Depain-X is no longer marketed in Europe, America, Taiwan and other countries, therefore, Ultracet can serve as a good substitute for treating postoperative pain.

Sonographic Nerve Tracking in the Cervical Region: A Pictorial Essay and Video Demonstration.

ABSTRACTImaging of the nerves in the cervical region is more complicated than those of the extremities. Although high-resolution ultrasound enables the depiction of peripheral nerves’ morphology and their associations with the adjacent soft tissues, precise identification of the nerves in the neck is still challenging. Familiarization with the cervical nerve tracking techniques can help interventional physiatrists explore/treat relevant entrapment syndromes, so does guiding proper electrode placement during nerve conduction studies. The present article integrates serial ultrasound images and videos to demonstrate how to scan brachial plexus, superficial cervical plexus, cranial nerves in the neck region, and certain branches of the major cervical nerves.