Soji Maruo

Modulation of P2X receptors via adrenergic pathways in rat dorsal root ganglion neurons after sciatic nerve injury

Abstract The present study examined noradrenaline‐induced modulation of ATP‐evoked currents in dorsal root ganglion (DRG) neurons after sciatic nerve injury (transection). ATP (10 μM) generated fast/mixed type of whole‐cell membrane currents, possibly as mediated via P2X3/P2X3‐like receptors, and slow type of the currents, possibly as mediated via P2X2/3 receptors, in acutely dissociated L4/5 DRG neurons, without significant difference between sham and injury group. For sham group, noradrenaline (10 μM) enhanced fast/mixed type of ATP‐evoked currents in ipsilateral DRG neurons, that is not inhibited by H‐7, a broad inhibitor of protein kinases, but otherwise it had no effect on slow type of the currents. For injury group, noradrenaline (10 μM) significantly potentiated slow type of ATP‐evoked currents in ipsilateral DRG neurons, that is abolished by H‐7 or GF109203X, a selective inhibitor of protein kinase C (PKC), while it depressed fast/mixed type of the currents. In the analysis of real‐time reverse transcription‐polymerase chain reaction, an increase in the mRNAs for α1b, α2a, α2d, and β2 adrenergic receptors was found with the ipsilateral DRGs after sciatic nerve injury. Collectively, the results of the present study suggest that noradrenaline potentiates P2X2/3 receptor currents by activating PKC via α1 adrenergic receptors linked to Gq protein, perhaps dominantly α1b adrenergic receptors, in DRG neurons after sciatic nerve injury. This may account for a nociceptive pathway in response to noradrenergic sprouting after peripheral nerve injury.

Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a potential therapeutic target of cartilage degradation.

Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic joint changes. Interleukin (IL)-18 is a potent inducer of prostaglandin (PG) E2 in vitro. We determined the relation between IL-18 and PGE2 in synovial fluid (SF) of human OA, and discussed the role of IL-18 in the pathogenesis of OA and also its therapeutic consequences. SF was collected from 30 patients with knee OA. The concentrations of IL-18 and other cytokines including IL-1&bgr;, tumor necrosis factor (TNF)-&agr;, IL-6, and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of PGE2 was also assessed by inhibitory ELISA. The average value of IL-18 was 248 ± 310 pg/mL. The average value of PGE2 was 93 ± 103 pg/mL. There was a relatively strong correlation between IL-18 and PGE2 (r = 0.78, p = 0.0001). In contrast, IL-1&bgr; was undetectable (cutoff point of 20 pg/mL), except for one case. TNF-&agr; was also undetectable (cutoff point of 20 pg/mL), except for two cases. The average value of IL-6 was 1,310 ± 2,623 pg/mL (n = 17), whereas IL-8 was 5,208 ± 6,031 pg/mL (n = 5). Furthermore, IL-6 and IL-8 correlated with IL-18 (r = 0.69, p = 0.0024 and r = 0.87, p = 0.0527, respectively). Our results suggest that IL-18 could play a major role in vivo in inducing the production of PGE2, which in turn can cause cartilage degradation in OA pathogenesis. Thus, targeting this cytokine appears to be an important therapeutic approach in OA.

Osteosarcoma of the Thoracolumbar Spine: Total en Bloc Spondylectomy. A Case Report*

Primary osteosarcoma of the spine is rare. The reported prevalence of osteosarcoma of spinal origin is less than 3 per cent of all osteosarcomas1,2,7; Shives et al., for example, reported such a lesion in only twenty-seven of 1122 patients who had a primary osteosarcoma. We believe that en bloc resection with a wide margin is the ideal treatment for any osteosarcoma; however, this procedure is very difficult to perform for an osteosarcoma of the spine because of the proximity of the spinal cord and the major vessels. Because it is difficult to excise the spinal tumor completely7,9, the prognosis after treatment of an osteosarcoma of the spine continues to be poor compared with that after treatment of an osteosarcoma in an extremity. We report the case of a patient who was managed successfully with total en bloc spondylectomy10,11 for a primary osteosarcoma of the spine involving the eleventh thoracic through second lumbar vertebral levels. A sixteen-year-old boy was seen because of a four-month history of stiffness and severe pain in the thoracolumbar region of the back. Physical examination demonstrated tenderness in the area of the posterior elements of the eleventh and twelfth thoracic and first lumbar vertebrae, without neurological deficit. Plain radiographs showed increased bone density at the level of the twelfth thoracic vertebra and diffuse sclerotic changes in the paravertebral soft tissues at the levels of the eleventh thoracic through second lumbar vertebrae (Figs. 1-A and 1-B). The computerized tomography scan demonstrated that the tumor included the entire twelfth thoracic vertebra as well as segments of the eleventh thoracic vertebra. There was extensive paravertebral and epidural involvement in the region of the eleventh thoracic through first lumbar vertebrae as well as bilateral invasion of the paraspinous …

Tunicamycin inhibits NMDA and AMPA receptor responses independently of N-glycosylation

In a whole-cell patch-clamp configuration, currents through N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels were monitored in cultured rat hippocampal neurons, and those currents were depressed to 25 and 28% of basal levels, respectively, by 3-min treatment with tunicamycin (10 microM), an inhibitor of protein N-glycosylation. Tunicamycin (10 microM) reduced amplitude of population spikes elicited in the dentate gyrus of rat hippocampal slices, reaching 78% of basal levels 60 min after the beginning of treatment, and long-term potentiation (LTP) of the perforant path was never induced in the presence of tunicamycin. Tunicamycin, thus, appears to serve as a modulator for NMDA and AMPA receptors, regardless of N-glycosylation, thereby inhibiting neurotransmission and LTP in the dentate gyrus.