Effects of intrathecal sufentanil on plasma oxytocin and cortisol concentrations in women during the first stage of labor

BACKGROUND AND OBJECTIVES: Intrathecal sufentanil provides analgesia comparable to epidural bupivacaine for the first stage of labor. Both epidural local anesthetics and intrathecal opioid reduce some parameters of the neuroendocrine response to labor pain and the reflex release of oxytocin in animals. In humans, epidural local anesthetics only reduce the spurt release of oxytocin. This study compared the effect of intrathecal sufentanil and epidural bupivacaine administration on the plasma concentration of oxytocin and cortisol in women with labor pain during the first stage of labor. METHODS: Thirty healthy parturients requesting analgesia were enrolled in this randomized and open-label study. Each patient was in spontaneous labor at greater than 5 cm cervical dilatation. Using a combined spinal and epidural technique, patients received either intrathecal sufentanil 10 microg (SUF = intrathecal sufentanil group) or epidural plain bupivacaine 0.25%, 12 mL (BUPIV = epidural bupivacaine group). Analgesia was assessed using a visual analog scale, and blood samples for oxytocin and cortisol plasma concentration measurements were collected immediately before analgesia and 15, 30, 60, and 90 minutes after induction of the analgesia. Plasma cortisol and oxytocin concentrations were determined by specific radioimmunoassay. The values were expressed as mean +/- SEM. RESULTS: Intrathecal sufentanil provided faster and more complete analgesia within 15 and 30 minutes of its administration, compared with epidural bupivacaine. Plasma oxytocin concentrations were similar in the 2 groups before analgesia (7.24 +/- 2.1 and 6.6 +/- 3.1 pg/mL SUF and BUPIV, respectively). It decreased significantly in the SUF and increased in the BUPIV after analgesic administration. Cortisol concentrations were elevated in both groups before analgesia (51.6 +/- 5.3 and 54.2 +/- 4.8 microg/dL SUF and BUPIV, respectively). Both analgesic treatments significantly decreased the plasma cortisol levels. CONCLUSIONS: Intrathecal sufentanil analgesia decreases plasma concentrations of oxytocin and cortisol in women with labor pain during the first stage of labor, but epidural bupivacaine only reduced the cortisol concentration.     

The potential role of extracellular regulatory kinase in the survival of patients with early stage adenocarcinoma

Background

Lung cancer is among the most common types of neoplasias, and adenocarcinoma is the most frequent histological type. There is currently an extensive search for prognostic biomarkers of nonsmall cell lung cancer (NSCLC).

Methods

We analyzed the correlation of clinical data and patient survival with the levels of activated extracellular regulatory kinase (ERK) in histological samples of surgically resected early stage lung adenocarcinoma. We randomly selected 36 patients with stage I or II lung adenocarcinoma who underwent pulmonary lobectomy between 1998 and 2004. Patients were divided into the following two groups according to immunohistochemical profile: a group with <15% ERK-positive tumor cells and a group with ≥15% ERK-positive tumor cells. For data comparison, an enrichment analysis of a microarray database was performed ({"type":"entrez-geo","attrs":{"text":"GSE29016","term_id":"29016"}}GSE29016, n=72).

Results

Activated ERK levels were ≥15% and <15% in 21 (58%) and 15 (42%) patients, respectively. There were no statistically significant differences in age, sex, smoking history, and body mass index (BMI) among the groups stratified by ERK levels. The survival rate was lower in the ERK ≥15% group than in the ERK <15% group (P=0.045). Enrichment analyses showed no correlation between variations in gene expression of ERK in patients with adenocarcinoma and survival rates in patients with stage I and combined stage II + III disease.

Conclusions

Our findings suggest that high ERK positivity in cells from biological samples of lung adenocarcinoma is related with tumor aggressiveness and a poorer prognosis.     

Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms

The Wilms' tumor gene WT1 plays a key role in genitourinary development and subsequent normal function. Homozygous mutations of WT1 can be found in approximately 15% of Wilms' tumors. Furthermore, somatic heterozygous loss of WT1 is known to lead to cryptorchidism and hypospadias in males. A much more severe phenotype is seen in patients with Denys-Drash syndrome which results from heterozygous dominant- negative mutations of the gene. Characteristic features are mesangial sclerosis with early kidney failure, varying degrees of gonadal dysgenesis and high risk of Wilms' tumors. Here we show that a related disease, Frasier syndrome, characterized by focal glomerular sclerosis, delayed kidney failure and complete gonadal dysgenesis, is probably caused by specific intronic point mutations of WT1 that preferentially affect a CpG dinucleotide. Disruption of alternative splicing at the exon 9 splice donor site prevents synthesis of the usually more abundant WT1 +KTS isoform from the mutant allele. In contrast to Denys- Drash syndrome, no mutant protein is produced. The splice mutation leads to an imbalance of WT1 isoforms in vivo , as detected by RT-PCR on streak gonadal tissue. Thus, WT1 isoforms must have quite different functions, and the pathology of Frasier syndrome suggests that especially gonadal development may be particularly sensitive to imbalance or relative underrepresentation of the WT1 +KTS isoform.      

Effect of radiotherapy on the eruption rate and morphology of the odontogenic region of rat incisors

Objective

The goal in this study was to evaluate the results of doses of 5 and 15 Gy of radiation in odontogenic region of the rats inferior mandibular-incisors by a histological analysis and the rate of eruptions.

Design

Animals were divided into three groups: control, radiotherapy 5 Gy and radiotherapy 15 Gy. In which tooth-eruption-rate was measured every two days.

Results

Animals in Group 5 Gy presented values similar to those of the control group. Animals in Group 15 Gy presented reduction in tooth-eruption-rate as of the sixth day of the experiment, vast disorganization of odontoblasts and ameloblasts, apparent reduction in cell population in the follicle region and alterations in cervical loop formation of the dental organ.

Conclusions

It was concluded that there was a difference between the researched doses, and histological alteration at 15 Gy lead to statistical reduction in tooth-eruption-rate.     

Effects of lamotrigine on pain-induced chemo-somatosensory evoked potentials

Lamotrigine, a sodium channel blocker that selectively inhibits the neuronal release of glutamate, has been shown to produce analgesia in acute and chronic pain models in rats without causing noticeable sedation. After oral administration it also reduces pain scores, as assessed by the cold pain test, in volunteers. The purpose of this study was to determine the analgesic effect of lamotrigine given by mouth to healthy volunteers as evidenced by alterations in chemo-somatosensory evoked potentials. The following factors were measured: latency to N1 and P100 peak (ms); amplitude between the N1 and P100 peak (microV); visual analogue pain intensity scores. A double-blind, randomised and crossover design was used in which 12 volunteers received either placebo or lamotrigine 300 mg on separate occasions as determined by the randomisation schedule. Volunteers were tested before and 2 h after the treatment. The plasma lamotrigine concentration was measured immediately after the end of the experimental sessions. Lamotrigine produced a significantly higher latency to P100 values at 2 h postdrug than placebo (p < 0.05) but had no significant effects on the other factors. Although plasma concentrations were similar to those observed in the cold pain test, we conclude that lamotrigine 300 mg by mouth had no analgesic effect in this acute pain model.     

Epidural infusion of clonidine or clonidine plus ropivacaine for postoperative analgesia in children undergoing major abdominal surgery

STUDY OBJECTIVE: To investigate the analgesic efficacy and safety of epidural infusion of clonidine in children undergoing major abdominal surgery. DESIGN: Randomized open-label study. SETTING: Postoperative anesthetic unit and pediatric ward of a metropolitan hospital. PATIENTS: Forty children aged 0 to 3 years undergoing major abdominal surgery. INTERVENTIONS: Children were randomly allocated to receive a 24-hour epidural infusion of clonidine 1 microg.mL(-1) at rate of 0.2 mL.kg -1.h -1 preceded by a bolus of 2 microg.kg -1 (CLON group) or a mixture of clonidine 1 microg.mL -1 and ropivacaine 0.1% at rate of 0.2 mL.kg -1.h -1. Both groups received intravenous (IV) ketoprofen 2 mg.kg -1 every 8 hours. Breakthrough pain was treated with IV tramadol 1 mg.kg(-1). MEASUREMENTS: Tramadol requirement, sedation and respiratory and hemodynamic changes were measured. MAIN RESULTS: Approximately 77% and 59.3% of the CLON and CLON+ROPIV groups, respectively, required no tramadol or only one dose over a 24-hour period. Except for those patients who exhibited frequent coughing during the night (4 and 5 patients in the CLON and CLON+ROPIV groups, respectively), no study patients required an analgesic and all had good sleep quality during the first night. Sedation and decreased systolic blood pressure were observed after the clonidine bolus was given. CONCLUSION: For children undergoing major abdominal surgery, the addition of epidural infusion of clonidine or clonidine plus ropivacaine to IV ketoprofen provided good analgesia quality for postoperative rest pain.     

Antinociception and behavioral changes induced by carbachol microinjected into identified sites of the rat brain

The sites of the rat brain in which intracerebral administration of carbachol (0.4 microgram/0.5 microliter) elevates the nociceptive threshold to thermic (tail-flick test) and mechanical (calibrated-pinch test) noxious stimuli were examined. An extensive mapping (510 sites) ranging from AP + 10.5 to AP-0.1 mm revealed that antinociception was obtained from 119 sites (23%) widely scattered in the brain, and reached structures distant from, or within the immediate vicinity of the ventricular system. The effects from most placement were demonstrated using the tail-flick test, whereas a smaller proportion (approximately 13%) of sites was effective in reducing the response to mechanical stimuli only. Structures containing sensitive sites include the dorsal raphe nucleus, lateral border of the superior cerebellar peduncle, caudal portion of the superior colliculus, medial geniculate body, habenular complex, amygdala, temporal pole of the ventral hippocampus, rostral aspect of the dorsal hippocampus, lateral septal area, and triangular nucleus of the septum. Analysis of the distribution of responsive sites indicated that they are poorly superposed to the known distribution of opiate-sensitive areas. Most of the structures found to be responsive to carbachol are also known to possess cholinergic receptors and to evoke antinociception following focal electrical stimulation. In various placements, particularly in limbic structures, microinjection of carbachol evoked jumping to mechanical noxious stimulation, hyperexcitability to non-noxious stimuli, convulsive reactions, and other less frequent reactions. On few occasions, however, these changes were accompanied by antinociception.     

Neonatal iron exposure induces oxidative stress in adult Wistar rat

Oxidative stress and excess of iron in the brain has been implicated in a variety of acute and chronic neurological conditions. The neonatal period is critical for the establishment of normal iron content in the adult brain. In the present study, the long-term oxidative effects of iron exposure during this period were assessed by treating Wistar rats orally with 0, 7.5 or 15 mg Fe(+2)/kg of body weight on postnatal days 10-12. Thiobarbituric acid reactive species, protein carbonyl, superoxide dismutase activity were measured at the age of 3 months. It was found that there was an increase in thiobarbituric acid reactive species and protein carbonyl in the substantia nigra of iron treated rats. In contrast, oxidative stress in the striatum was decreased. Superoxide dismutase activity was decreased in the substantia nigra iron treated rats. There were no differences in cerebellum measures among the groups. Our results demonstrated that iron supplementation in a critical neonatal period induced oxidative stress and modulated SOD activity in the adult life in selective brain regions.     

Analgesic and adverse effects of a low dose of intrathecally administered hyperbaric neostigmine alone or combined with morphine in patients submitted to spinal anaesthesia: pilot studies

We report the analgesic and adverse effects of intrathecally administered hyperbaric neostigmine, alone or combined with morphine, in two patients suffering from severe lower limb ischaemic pain (group 1), five patients undergoing Caesarean section (group 2) and 19 patients scheduled for orthopaedic surgery (group 3) under spinal anaesthesia. These patients were enrolled in three pilot studies undertaken before the initiation of the planned controlled studies. Hyperbaric neostigmine (50 micrograms in glucose 8%) produced analgesia lasting more than 6 h in patients of group 1, but the effect was accompanied by episodes of vomiting. A lower dose of hyperbaric neostigmine (25 micrograms), alone (two patients) or combined with morphine (50 micrograms) (one patient) produced no discernible analgesic effect but was followed by severe nausea and vomiting within 15 min of intrathecal injection in patients of group 2. Two patients who received hyperbaric morphine (100 micrograms) had analgesia for more than 24 h and exhibited mild pruritus. In patients of group 3, hyperbaric neostigmine alone (25 micrograms) produced analgesia of shorter duration than neostigmine (25 micrograms) plus morphine (50 micrograms) or morphine (100 micrograms). Neostigmine alone or combined with morphine was associated with adverse events, mainly nausea and vomiting that lasted up to 9-12 in some patients. Other adverse events observed included anxiety, somnolence and involuntary defaecation. Most patients who received the combination of neostigmine and morphine exhibited more severe nausea, vomiting and somnolence. The low clinical efficacy of intrathecally administered neostigmine alone or in combination with morphine impairs the design of a double-blind protocol and might restrict the clinical usefulness of the drug combination.