Aversive responses of captive sandbar sharks Carcharhinus plumbeus to strong magnetic fields.

This experimental study focused on the possible deterrent effect of permanent magnets on adult sandbar sharks Carcharhinus plumbeus. Results showed that the presence of a magnetic field significantly reduced the number of approaches of conditioned C. plumbeus towards a target indicating that adult C. plumbeus can be deterred by strong magnetic fields. These data, therefore, confirm that the use of magnetic devices to reduce shark by-catch is a promising avenue.

The location of paravertebral catheters placed using the landmark technique.

The aim of this prospective clinical study was to evaluate the location of paravertebral catheters that were placed using the classical landmark puncture technique and to correlate the distribution of contrast dye injected through the catheters with the extent of somatic block. Paravertebral catheter placement was attempted in 31 patients after video-assisted thoracic surgery. In one patient, an ultrasound-guided approach was chosen after failed catheter placement using the landmark method. A fluoroscopic examination in two planes using contrast dye was followed by injection of local anaesthetic and subsequent clinical testing of the extent of the anaesthetised area. In nine patients (29%), spread of contrast dye was not seen within the paravertebral space as intended. Misplaced catheters were in the epidural space (three patients), in the erector spinae musculature (five patients), and in the pleural space (one patient). There was also a discrepancy between the radiological findings and the observed distribution of loss of sensation. We have demonstrated an unacceptably high misplacement rate of paravertebral catheters using the landmark method. Additional research is required to compare the efficacy and safety of continuous paravertebral block using ultrasound-guided techniques or surgical inserted catheters.

Predicting drug efficacy in chronic low back pain by quantitative sensory tests.

BACKGROUND: Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain. METHODS: Oxycodone 15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were compared to active placebo tolterodine 1 mg in a randomized, double-blinded, crossover fashion. Electrical, pressure and thermal QST were performed at baseline and after 1 and 2 h. Pain intensity was assessed on a 0-10 numeric rating scale every 30 min for up to 2 h. The ability of baseline QST to predict pain reduction after 2 h was analysed using linear mixed models. Genetic variants of drug-metabolizing enzymes and genes affecting pain sensitivity were examined as covariables. RESULTS: No predictor of analgesic effect was found for oxycodone and clobazam. Thermal QST was associated with analgesic effect of imipramine: patients more sensitive to heat or cold were more likely to experience an effect of imipramine. Pharmacogenetic variants and pain-related candidate genes were not associated with drug efficacy. CONCLUSIONS: Thermal QST have the potential to predict imipramine effect in chronic low back pain. Oxycodone and clobazam effects could not be predicted by any of the selected QST or genetic variants. SIGNIFICANCE: Predicting drug efficacy in chronic low back pain remains difficult. There is some evidence that patients more sensitive to heat and cold pain respond better to imipramine.

Analgesic effect of clobazam in chronic low-back pain but not in experimentally induced pain.

BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests. METHODS: In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake. RESULTS: Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed. CONCLUSIONS: This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds. SIGNIFICANCE: Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target.

Role of DDC-4/sFRP-4, a secreted frizzled-related protein, at the onset of apoptosis in mammary involution.

Using differential display, we isolated DDC-4, a secreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the DDC-4/sFRP-4 cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3beta (GSK-3beta), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.

Field observations of time-place behaviour in scavenging birds.

Encoding the spatial location and the time at which significant biological events occur is thought to be a fundamental way in which one form of memory is organized in animals (Gallistel, 1990, The Organization of Learning. MIT Press, Cambridge, MA). If this is true, one would expect to find evidence of this process in a wide variety of animals and in a wide number of situations. We report field observations of scavenging birds at two outdoor locations at which people tend to congregate and eat food, primarily around midday. Scavenging birds appeared to anticipate this peak in food availability and arrived at these locations before the number of people was at a maximum; time of day, not the absolute number of people, was the best predictor of the number of birds at both sites. At a third location where food is not consumed this relationship was not observed. Taken together these observations support the notion that animals represent the spatial and temporal characteristics of biologically important events and use this knowledge to forage efficiently.

The value of children to lesbian and non-lesbian mothers.

This study compares the responses of a sample of lesbian and non-lesbian mothers to items on the Value of Children (VOC) Scale. This instrument measures the reasons that may explain why adults become parents and the values and functions for children in the lives of adults. Results indicate that there are more similarities than differences between lesbian and non-lesbian mothers in responses on the VOC Scale. Only one subscale that measures goals and incentives for assuming parenthood and having children differentiated between the groups. The lack of differences in response patterns on the VOC scale between lesbian and non-lesbian mothers may be attributed to the similar socialization experiences of women in our society regarding parenthood and the expectations of individuals upon assuming this role in adulthood. The significant differences in responses on the one subscale may be attributed to differences in world-views of lesbian and non-lesbian mothers.

The prevalence of widespread central hypersensitivity in chronic pain patients.

BACKGROUND: Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. METHODS: We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. RESULTS: Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. CONCLUSIONS: Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment.

Perioperative nerve blockade: clues from the bench.

Peripheral and neuraxial nerve blockades are widely used in the perioperative period. Their values to diminish acute postoperative pain are established but other important outcomes such as chronic postoperative pain, or newly, cancer recurrence, or infections could also be influenced. The long-term effects of perioperative nerve blockade are still controversial. We will review current knowledge of the effects of blocking peripheral electrical activity in different animal models of pain. We will first go over the mechanisms of pain development and evaluate which types of fibers are activated after an injury. In the light of experimental results, we will propose some hypotheses explaining the mitigated results obtained in clinical studies on chronic postoperative pain. Finally, we will discuss three major disadvantages of the current blockade: the absence of blockade of myelinated fibers, the inappropriate duration of blockade, and the existence of activity-independent mechanisms.