Jae Kwang Kim

Background In intra-articular fracture of distal radius, the intra-articular fragments can be divided into some specific fragments. In particular, the poor outcomes have been well documented for reduction loss of the volar lunate facet, but the effect of a displaced dorsal rim fracture has rarely been addressed. Materials and Methods The records of 26 patients with dorsal rim fragment displaced by more than 2 mm after volar locking plate (VLP) fixation for a dorsally displaced distal radius fracture (DRF) treated from March 2006 to March 2009 were retrospectively reviewed. Clinical assessments including grip strengths, wrist range of motions, and Disabilities of Arm, Shoulder, and Hand (DASH) scores were performed at 12 months postoperatively. Widths of the distal ends of dorsal rims were determined by preoperative computed tomography (CT). Dorsal rim fragment displacements were measured in immediate postoperative plain lateral radiographs. Radial inclination, volar tilt, and ulnar variance were measured on immediate postoperative wrist radiographs. Arthritic changes of radiocarpal joints were graded using radiographs obtained at 12 months postoperatively. Description of Technique DRFs were fixed using a VLP in the usual manner. Although DRF displacement was noticed after plate fixation, no further procedure was performed. The sizes of articular portions of dorsal rim fragments were measured arthroscopically in 5 of the 26 patients at the time of plate fixation. Results At 12 months postoperatively, mean grip strength, wrist flexion arc, and mean wrist extension arc were 86 ± 13, 87 ± 11, and 91 ± 10%, respectively, of contralateral sides. Mean forearm supination and pronation were 96 ± 8 and 99 ± 5%, respectively, of contralateral sides. Mean DASH score was 11 ± 10 points. Preoperatively, mean width of the distal end of dorsal rim fragments and mean displacements of dorsal rim fragments were 2.0 ± 0.6 and 3.0 ± 0.9 mm, respectively. Mean width of the articular portions of dorsal rim fragment by arthroscopic examination was 1.0 ± 0.4 mm. Mean radial inclination was 21 ± 4.8 degrees, mean volar angulation was 4.8 ± 3.9 degrees, and mean ulnar variance was 0.6 ± 1.8 mm at immediate postoperatively. Two patients showed grade I arthritic changes at 12 months postoperatively. Conclusions The articular portions of dorsal rim fragments measured arthroscopically were smaller than determined by CT. Furthermore, the study shows that displaced dorsal rim fragments in dorsally displaced DRFs treated by VLP do not adversely affect wrist clinical outcomes.

The β-lactam antibiotic ceftriaxone (CTX) reduces cocaine reinforcement and relapse in preclinical assays through a mechanism involving activation of glutamate transporter subtype 1 (GLT-1). However, its poor brain penetrability and intravenous administration route may limit its therapeutic utility for indications related to CNS diseases. An alternative is clavulanic acid (CA), a structural analog of CTX that retains the β-lactam core required for GLT-1 activity but displays enhanced brain penetrability and oral activity relative to CTX. Here, we tested the hypothesis that CA (1, 10 mg/kg ip) would enhance GLT-1 expression and decrease cocaine self-administration (SA) in mice, but at lower doses than CTX. Experiments revealed that GLT-1 transporter expression in the nucleus accumbens of mice treated with repeated CA (1, 10 mg/kg) was enhanced relative to saline-treated mice. Repeated CA treatment (1 mg/kg) reduced the reinforcing efficacy of cocaine (0.56 mg/kg/inf) in mice maintained on a progressive-ratio (PR) schedule of reinforcement but did not affect acquisition of cocaine SA under fixed-ratio responding or acquisition or retention of learning. These findings suggest that the β-lactamase inhibitor CA can activate the cellular glutamate reuptake system in the brain reward circuit and reduce cocaine’s reinforcing efficacy at 100-fold lower doses than CTX.

J. Neurochem. (2012) 121, 302–313. Mounting evidence suggests a potential link between cocaine abuse, disruptions in hypothalamic‐pituitary‐thyroid axis signaling, and neuroplasticity, but molecular mechanisms remain unknown. Neurogranin (Ng) is a gene containing a thyroid hormone‐responsive element within its first intron that is involved in synaptic plasticity. Transcriptional activation requires heterodimerization of thyroid hormone receptor (TR) and retinoid X receptor (RXR) bound by their respective ligands, tri‐iodothryonine and 9‐cis‐retinoic acid (9‐cis‐RA), and subsequent binding of this complex to the thyroid hormone‐responsive element of the Ng gene. In this study, the effects of chronic cocaine abuse on Ng expression in euthyroid and hypothyroid mice were assessed. In cocaine‐treated mice, decreased Ng expression was observed in the absence of changes in levels of thyroid hormones or other hypothalamic‐pituitary‐thyroid signaling factors. Therefore, we hypothesized that cocaine decreases Ng expression via alterations in 9‐cis‐RA availability and TR/RXR signaling. In support of this hypothesis, RXR‐γ was significantly decreased in brains of cocaine‐treated mice while CYP26A1, the main enzyme responsible for neuronal RA degradation, was significantly increased. Results from this study provide the first evidence for a direct effect of cocaine abuse on TR/RXR signaling, RA metabolism, and transcriptional regulation of Ng, a gene essential for adult neuroplasticity.

No medication is approved to treat cocaine addiction, but mounting evidence suggests that glutamate-directed approaches may reduce cocaine dependence and relapse. We tested the hypotheses that the glutamate transporter subtype 1 activator, ceftriaxone, disrupts acquisition of cocaine self-administration, motivation to self-administer cocaine, and conditioned place preference in mice. Repeated ceftriaxone (200 mg/kg) reduced the ability of mice to acquire cocaine and the motivation to self-administer cocaine after successful acquisition without affecting acquisition of or motivation for sweet food. Repeated ceftriaxone had no effect on cocaine-conditioned place preference. These results suggest that a β-lactam antibiotic reduces the direct reinforcing strength of cocaine without producing nonspecific deficits in conditioned learning processes.

We investigated the short- and long-term effects of ceftriaxone on glutamate transporter subtype 1 (GLT-1) transporter activity and extracellular glutamate in the rat nucleus accumbens. Repeated ceftriaxone administration (50, 100 or 200 mg/kg, i.p.) produced a dose-dependent reduction in glutamate levels that persisted for 20 days following discontinuation of drug exposure. The ceftriaxone effect was prevented by the GLT-1 transporter inhibitor dihydrokainate (1 μM, intra-accumbal). These results suggest that β-lactam antibiotics produce an enduring reduction in glutamatergic transmission in the brain reward center.

β-Lactam antibiotics enhance cellular glutamate uptake. As increased glutamatergic transmission is a primary mediator of opiate dependence, we tested the hypothesis that a β-lactam antibiotic (ceftriaxone) prevents development of morphine physical dependence in rats. Morphine (20 mg/kg) was injected twice daily for 10 days to induce physical dependence. Naloxone (10 mg/kg) administration 1, 48, and 96 h after the last morphine injection induced a withdrawal syndrome characterized by the appearance of wet-dog shakes, teeth chattering, eye blinking, jumping, and paw tremor. Ceftriaxone (150, 200 mg/kg) injected once daily during chronic morphine exposure inhibited each naloxone-precipitated withdrawal sign. Ceftriaxone efficacy persisted even after the 96 h-naloxone (10 mg/kg) injection. These results suggest that β-lactam antibiotics inhibit processes leading to development of morphine physical dependence.