Effects of opioid receptor and alpha2-adrenoceptor agonists on slow ventral root potentials and on capsaicin and formalin tests in neonatal rats

The inhibitory effects of morphine and alpha2-adrenoceptor agonists on slow ventral root potentials (slow VRP) following ipsilateral dorsal root stimulation in neonatal rat spinal cord were compared with the analgesic effects of these drugs on formalin and capsaicin tests in neonatal rats. Morphine, (D-Phe2, D-Pen5)-enkephalin (DPDPE), dexmedetomidine, clonidine and xylazine showed concentration-related inhibition of slow VRP. The order of potency was dexmedetomidine>morphine=DPDPE>clonidine>xylazine. The inhibitory effects of opioid agonists and alpha2-adrenoceptor agonists were abolished by naloxone, an opioid antagonist, and atipamezole, an alpha2-adrenoceptor antagonist, respectively. There was no cross antagonism. Morphine, dexmedetomidine and xylazine dose-dependently inhibited body movement induced by formalin or capsaicin. The order of potency was dexmedetomidine>morphine>xylazine. Although morphine and dexmedetomidine inhibited formalin- and capsaicin-induced body movement in the same dose range, xylazine inhibited formalin-induced body movement at lower concentrations than capsaicin-induced one. The inhibitory potency for slow VRP by these drugs seems to be correlated with that for capsaicin-induced body movement but not that for formalin-induced one. Dexmedetomidine and morphine in combination inhibited slow VRP and body movement induced by capsaicin in an additive manner. It is suggested that the antinociceptive effects of dexmedetomidine and morphine but not xylazine on the capsaicin test are mainly due to spinal effects and that there is no synergistic interaction between dexmedetomidine and morphine in the neonatal rat.     

Phase I dose-escalating study of docetaxel in combination with 5-day continuous infusion of 5-fluorouracil in patients with advanced gastric cancer

Background  

Published data suggests that docetaxel combined with 5-fluorouracil (5-FU) may have synergistic activity in treating advanced gastric cancer. We performed a phase I study of docetaxel and 5-FU to determine the maximum tolerated dose (MTD), the recommended dose for phase II studies, and the safety of this combination.     

Suppression of postganglionic sympathetic discharges by pentobarbital in endotoxic cats

Pentobarbital (7–9 mg/kg) profoundly suppressed the sympathetic postganglionic cardiac and splenic discharges in endotoxic cats under chloralose anesthesia. Concurrently, the pre-existent tachycardia was replaced by bradycardia, and the blood pressure fell further. The findings are interpreted to imply a pentobarbital-induced syrnpatolysis.     

Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) in the duodenum: the first visceral case

An ulcerated tumour was removed by a Whipple's operation from the descending part of the duodenum of a 38-year-old male. The tumour cells were mainly spindle-shaped, arranged in nests and had very prominent nucleoli. A few cells contained melanin and melanosomes. Immunoreactivity for S-100 protein and focally for HMB-45 was observed. These features are diagnostic for clear cell sarcoma of tendons and aponeuroses. Because no other primary tumour could be found and the search for similar cases from the literature was unsuccessful, we believe that this tumour is the first reported clear cell sarcoma in a visceral location.     

EMG-activity and muscular performance of lower leg during stretch-shortening cycle after cooling

To test the effect of cooling on EMG-activity of muscles working as an agonist and antagonist in the lower leg, 12 men dressed in shorts and jogging shoes performed a drop-jump exercise after 60 min exposures to 27 °C and 10 °C. Cooling decreased mean skin temperature 5.6±0.4 °C (mean±SD, P<0.001), whereas rectal temperature was unaffected. The muscle temperature measured from m. gastrocnemius medialis decreased 4.1±0.3 °C (P<0.01) at the depth of 30 mm below skin surface. To find the optimal stretching velocity for potentiation of elastic energy, the drop-jump exercise was performed from six different bench heights (10, 20, 30, 40, 50 and 60 cm). The optimal velocity was not altered on account of cooling. In cooled subjects during the stretch phase of the drop jumps the EMG-activity of m. triceps surae complex (agonist) increased (P<0.05–0.001) while the activity of m. tibialis anterior (antagonist) remained unchanged. After cooling during the shortening phase of the jumps the EMG-activity of m. triceps surae complex decreased (P<0.05–0.001), whereas the activity of m. tibialis anterior increased (P<0.05–0.001). In addition, after cooling the peak EMG-activity appeared on the average 28 ms earlier, which shifted the peak activity from the shortening phase (at 27 °C) to the stretch phase (at 10 °C). Cooling increased the mean duration of stretch and shortening phases by 28±3 ms (P<0.001) and 23±2 ms (P<0.001), respectively. The average force production during the shortening phase was 26% less (P<0.05) after cooling, which resulted in a decreased rise of body centre of gravity (P<0.05–0.01). It is concluded that during a stretch-shortening cycle cooling alters the EMG-activity of agonist and antagonist muscles on a contradictory manner and results in an earlier peak EMG-activity. Therefore, alterations in motor unit recruitment could be responsible for the prolonged muscle contraction and decreased force production on account of cooling.     

Time- and concentration-dependent activation of TRPA1 by hydrogen sulfide in rat DRG neurons

Hydrogen sulfide (H(2)S) is considered as a gasotransmitter. Although several reports have shown that H(2)S stimulates sensory neurons, the primary targets of H(2)S remain controversial. We investigated the effects of H(2)S on cultured sensory neurons isolated from rat dorsal root ganglion (DRG) using Ca(2+) imaging and whole-cell voltage-clamp techniques. Brief (2 min) application of NaHS (1mM), a donor of H(2)S, evoked marked increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) in a subset of DRG neurons. These neurons also responded to both capsaicin and mustard oil (MO), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) agonists, respectively. The NaHS-evoked [Ca(2+)](i) increases were inhibited by a removal of external Ca(2+) and antagonists for TRPA1, but not for TRPV1 or voltage-dependent Ca(2+) channels. At -80 mV, NaHS evoked inward currents in MO-sensitive neurons, which were also inhibited by a TRPA1 antagonist. Even at lower concentration (≤1 μM), the 10-min application of NaHS increased [Ca(2+)](i) in a time- and concentration-dependent manner. These results suggest that H(2)S stimulates sensory neurons via activation of TRPA1. Endogenous H(2)S may be involved in physiological processes through TRPA1.     

HAART and the liver: friend or foe?

The overall effect of HAART on the liver is the result of the balance between hepatotoxicity and the consequences of immunoreconstitution on the evolution of HIV-associated liver diseases, particularly viral hepatitis. HAART may lead to the emergence of acute toxic hepatitis, steatosis, steatohepatitis, liver fibrosis, and noncirrhotic portal hypertension. On the other hand, HAART use has been associated with slower fibrosis progression in HIV/HCV-coinfected patients in most studies dealing with this issue. As well, an improvement of the clinical outcome of liver disease has been reported in patients taking HAART. For these reasons, the short- and mid-term effects of HAART on the liver are mostly beneficial.     

Unilateral spinal anaesthesia for outpatient surgery: a comparison between hyperbaric bupivacaine and bupivacaine–clonidine combination

Backround: Low-dose hyperbaric bupivacaine has been used to produce unilateral spinal anaesthesia for outpatient surgery. Unilateral spinal anaesthesia is associated with reduction of hypotension, faster recovery and increased patient satisfaction. Small doses of clonidine have shown effectiveness in intensifying spinal anaesthesia. We investigated the effect of adding 15 μg of clonidine to 5 mg hyperbaric bupivacaine on unilaterality.
Methods: Sixty patients undergoing outpatient knee arthroscopy were randomly allocated to receive either 1.2 ml (6 mg) of hyperbaric bupivacaine or a 1.2 ml solution containing 1.0 ml (5 mg) hyperbaric bupivacaine, 0.1 ml (75 μg) clonidine and 0.1 ml sterile water. The motor block was assessed by a modified Bromage scale and the sensory block by a pinprick.
Results: There was a significant difference in the spread of anaesthesia between the operated and contralateral sides in both groups. Seventy-seven per cent of the blocks were unilateral in group B and 73% in group B-C. There was no significant difference between the groups, in unilaterality. The motor block was prolonged in group B-C but it did not affect home-readiness. Patients receiving clonidine needed more vasopressors. There was a significant difference in blood pressures between the groups, being lower in group B-C after 1 h 45 min.
Conclusion: Using 5 mg hyperbaric bupivacaine with 15 μg of clonidine, the unilaterality can be achieved and spinal anaesthesia intensified without affecting home-readiness. More vasopressors are needed in the beginning, but after the surgery patients experienced less pain.