Effectiveness of subarachnoid drug infusion for pediatric tumor‐related pain

Although the effectiveness of subarachnoid continuous drug infusion has been established in cancer pain management, its clinical use in children is rare. A 14‐year‐old girl with neurofibromatosis type I complained of right leg pain stemming from a growing tumor on her right buttock. Continuous and breakthrough right leg pain were unbearable, even at high doses of systemic opioids that caused severe constipation and deep sedation. Subsequent continuous infusion of bupivacaine and morphine through a subarachnoid catheter effectively relieved the girl's pain. The corresponding decrease in systemic opioid also improved her activities of daily living. The patient eventually died of cachexia due to the rapidly growing buttock lesion that was pathologically confirmed post‐mortem as a malignant peripheral nerve sheath tumor. Subarachnoid continuous drug infusion may be very useful in controlling severe pain with few side‐effects, even in the field of pediatric palliative care.     

Predisposing factors for surgical site infection of spinal instrumentation surgery for diabetes patients

Purpose

Diabetes mellitus (DM) is known as an important risk factor for surgical site infection (SSI) in spine surgery. It is still unclear however which DM-related parameters have stronger influence on SSI. The purpose of this study is to determine predisposing factors for SSI following spinal instrumentation surgery for patients with DM.

Methods

110 DM patients (66 males and 44 females) who underwent spinal instrumentation surgery in one institute were enrolled in this study. For each patient, various preoperative or intraoperative parameters were reviewed from medical records. Patients were divided into two groups (SSI or non-SSI) based on the postoperative course. Each parameter between these two groups was compared. Univariate and multivariate analyses were performed to determine predisposing factor for SSI.

Results

The SSI group consisted of 11 patients (10 %), and the non-SSI group of 99 patients (90 %). Univariate analysis revealed that preoperative proteinuria (p = 0.01), operation time (p = 0.04) and estimated blood loss (p = 0.02) were significantly higher in the SSI group compared to the non-SSI group. Multivariate logistic regression identified preoperative proteinuria as a statistically significant predictor of SSI (OR 6.28, 95 % CI 1.58–25.0, p = 0.009).

Conclusions

Proteinuria is a significant predisposing factor for SSI in spinal instrumentation surgery for DM patients. DM patients with proteinuria who are likely to suffer latent nephropathy have a potential risk for SSI. For them less invasive surgery is recommended for spinal instrumentation. In this retrospective study, there was no significant difference of preoperative condition in glycemic control between the two groups.     

Complex formations involving both SP-1 and SP-3 at the transcriptional regulatory sequence correlate with the activation of the Keratin 14 gene in human oral squamous cell carcinoma cells

We have previously reported that significantly higher levels of Keratin 14 (Ker-14) was observed in oral squamous cell carcinoma (OSCC) and severely dysplastic tissues, whereas this expression was reversed in hyperplasia and in mild to moderate dysplasia. In this study, the mechanism of Keratin 14 activation in oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3 and Ca9-22) was investigated. Reporter analysis demonstrated that an upstream region (-1759/-1629) accounted for efficient promoter activity. Furthermore, electromobility sift and supershift assay demonstrated that interactions of the SP-1/SP-3 complex at the elements resided in -1737/-1702 and -1680/-1652 and may be essential for this activation in OSCC cells.     

G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration

In the early development of the central nervous system, neural progenitor cells divide in an asymmetric manner and migrate along the radial glia cells. The radial migration is an important process for the proper lamination of the cerebral cortex. Recently, a new mode of the radial migration was found at the intermediate zone where the neural progenitor cells become multipolar and reduce the migration rate. However, the regulatory signals for the radial migration are unknown. Using the migration assay in vitro, we examined how neural progenitor cell migration is regulated. Neural progenitor cells derived from embryonic mouse telencephalon migrated on laminin-coated dishes. Endothelin (ET)-1 inhibited the neural progenitor cell migration. This ET-1 effect was blocked by BQ788, a specific inhibitor of the ETB receptor, and by the expression of a carboxyl-terminal peptide of Galpha q but not Galpha i. The expression of constitutively active mutant of Galpha q, Galpha qR183C, inhibited the migration of neural progenitor cells. Moreover, the inhibitory effect of ET-1 was suppressed by the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the expression of the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of the JNK pathway. Using the slice culture system of embryonic brain, we demonstrated that ET-1 and the constitutively active mutant of Galpha q caused the retention of the neural progenitor cells in the intermediate zone and JNK-binding domain of JNK-interacting protein-1 abrogated the effect of ET-1. These results indicated that G protein-coupled receptor signaling negatively regulates neural progenitor cell migration through Gq and JNK.     

Oxidative stress-induced apoptosis is associated with alterations in mitochondrial caspase activity and Bcl-2-dependent alterations in mitochondrial pH (pHm)

Oxidative stress, the result of cellular production of reactive oxygen species (ROS), has been implicated in a number of diseases of the eye. Exposure of eye tissues (e.g. the cornea and retina) to oxidative stress over time has been hypothesized to underlie the development of age-related macular degeneration (AMD) and maturity onset cataract formation. Light-induced free radicals can damage the eye, and alterations in the antioxidant defenses of the eye have been suggested to play a role in the etiology of glaucoma. Mitochondria are both a major endogenous source and target of ROS, and oxidative stress has been shown to induce apoptotic cell death by targeting the mitochondria directly. Mitochondrial-dependent apoptosis has been shown to require release of cytochrome c from mitochondria and subsequent activation of a specific class of cytoplasmic proteases known as caspases. Bcl-2, an anti-apoptotic protein localized to mitochondria, has been shown to inhibit cytochrome c release and protect against oxidative stress-induced apoptosis. Here we demonstrate that oxidative stress causes activation of mitochondrial matrix caspase-2 and -9 activity that is associated with Bcl-2-inhibitable acidification of mitochondrial pH (pH(m)). In conjunction with recent reports that caspase activation is maximal at acidic pH, these findings have led us to hypothesize that Bcl-2 may modulate cytochrome c release following oxidative stress by modifying the pH-dependent activation of mitochondrial caspase activity. These studies provide an increased understanding of the mechanism(s) by which oxidative stress damages tissues, and may have important therapeutic implications for treatment of opthamological diseases.     

Coeruleotrigeminal suppression of nociceptive sensorimotor function during inflammation in the craniofacial region of the rat

Descending action from the locus coeruleus (LC) on the trigeminal sensorimotor function was evaluated in a rat model of oral-facial inflammation. For the induction of oral-facial inflammation, mustard oil (20% solution in 20microl mineral oil) was injected into the region of the temporomandibular joint (TMJ). One week before testing, rats received bilateral lesions of the LC using a cathodal current. The electromyogram (EMG) threshold, which is the threshold intensity for the onset of EMG activity of the masseter muscle evoked by pressure on the TMJ region, was used in the present study as an indicator of the trigeminal sensorimotor function. Following mustard oil injection, in the LC-lesioned rats, EMG thresholds significantly decreased at 30min, which lasted up to 240min. In contrast, EMG thresholds in the LC-intact rats returned to the level before injection after 180min. Systemic naloxone (1.3mg/kg, i.v.) produced a further decrease of EMG thresholds in both the LC-intact and LC-lesioned rats. Under the existence of naloxone, EMG thresholds in the LC-lesioned rats were significantly lower than those of the LC-intact rats. These results suggest that oral-facial inflammation activates the coeruleotrigeminal modulating system and that an action of this system is independent of the opioid depressive mechanism.     

Synergistic Effects of Highly Unsaturated Fatty Acid-containing Phosphatidyl-ethanolamine on Differentiation of Human Leukemia HL-60 Cells by Dibutyryl Cyclic Adenosine Monophosphate

Highly unsaturated fatty acid-containing phospholipid (HUFA-PL) has many nutritional and medical applications. We investigated the effect of HUFA-PL on differentiation of human leukemia HL-60 cells induced by dibutyryl cyclic adenosine monophosphate (dbcAMP). HUFA-containing phosphatidylethanolamine (HUFA-PE), such as salmon testis PE, significantly enhanced dbcAMP -induced cell differentiation. A combined treatment of 200 μM dbcAMP with 50 μ M HUFA-PE increased the nitroblue tetrazolium (NBT)-reducing activity, which is an indicator of differentiation, to a level comparable to that in the case of 500 μ M dbcAMP treatment. In contrast, HUFA-lyso PE (a monoacyl form) did not exert an enhancing effect on dbcAMP-induced differentiation. The enhancing effect of HUFA-PE was suppressed by a protein kinase C inhibitor, staurosporine, while a protein kinase A inhibitor, H-8, did not suppress the enhancing effect. These findings suggest that HUFA-PE might enhance dbcAMP-induced differentiation through modulation of the protein kinase C signaling pathway in HL-60 cells.     

Changes in left ventricular preload and contractility following severe burns in the dog

Summary To examine the effects of severe burns on preload and left ventricular (LV) contractility, we continuously measured LV pressures and dimensions in severely burned dogs throughout the early part of the postburn period. Hemodynamic parameters, including cardiac output (CO), mean aortic pressure (MAP), heart rate (HR), LV pressures and their first derivatives (dP/dt), and the LV regional dimension, were measured and compared before and every 30 min after burns were produced (up to 360 min) in four groups: group A (n=7), dogs with sham burns; group B (n=5), dogs with nonresuscitated full-thickness burns involving 50% of the total body surface area; group C (n=6), dogs with burns resuscitated with lactated Ringer's solution at 4 ml × kg × % burn/24 h; and group D (n=6), dogs with burns resuscitated with 1.5% dextran in lactated Ringer's solution at 2 ml × kg × % burn/24 h. From these measurements, we obtained the LV end-diastolic segment length (EDL) as an index of preload and three indices of cardiac contractility, i.e., peak dP/dt, the percentage of shortening (%L), and mean V_cf. Our results showed that CO, MAP, and preload (i.e., EDL) decreased significantly more in the three burn groups (groups B, C, and D) than in the sham burn group, but that there were no significant differences in CO, MAP, and EDL among the three burn groups. The three indices of contractility also decreased significantly more in the three burn groups than in the sham burn group. When changes in LV end-diastolic pressure (LVEDP) and EDL during the experiment were examined, apparent discrepancies were found in the changes between LVEDP and EDL in the burn-resuscitated groups (C and D); the postburn decreases in LVEDP in the burn-resuscitated groups were significantly smaller than those in the burn-nonresuscitated group, but there were no significant differences in the postburn decreases in EDL among the three burn groups. These findings indicate that: (1) the fall in cardiac output following severe burns was due to both the decreased preload and decreased LV contractility; (2) the decreased preload and LV contractility could not be restored to preburn levels by conventional fluid therapy during the 6-h experimental period; and (3) the possible decrease in LV compliance was more prominent in the burn-resuscitated groups.