Effect of pulsed radiofrequency for postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most intractable pain disorders, particularly among elderly patients. Lesioning of dorsal root ganglion (DRG) using pulsed radiofrequency (PRF) has shown pain reduction for PHN. We assessed the efficacy of PRF lesioning of DRG for PHN via an open, nonrandomized study. METHODS: Forty-nine patients with PHN refractory to conservative therapy were involved. After impedance and sensory electrical nerve stimulation thresholds were assessed, PRF was performed three times adjacent to the DRG of corresponding levels at 42 degrees C for 120 s under the fluoroscopic guidance. Pain ratings were conducted on a visual analogue scale at 4-, 8- and 12-week follow-up. The data were analyzed using the one-way ANOVA test. P<0.05 was considered to be statistically significant. RESULTS: There was excellent pain relief (about 55%) at 4 weeks after PRF lesioning adjacent to the DRG and the effectiveness was maintained at the subsequent 12-week follow-up. The pain duration, age and stimulation level did not influence the outcome. There were no procedure-related complications. CONCLUSIONS: PRF lesioning of DRG showed significant pain relief compared with the conventional treatments in patients with intractable PHN. In order to elucidate the mode of action of PRF, further research is needed and the optimal electrical parameters of PRF have to be determined.

Human papillomavirus type 16 E6 protein interacts with cystic fibrosis transmembrane regulator-associated ligand and promotes E6-associated protein-mediated ubiquitination and proteasomal degradation.

The PDZ proteins such as hDLG, hScrib and MAGIs function as the membrane-associated protein scaffolds and have been shown to interact with the high-risk human papillomavirus (HPV) E6s. In this report, we identify a Golgi-associated PDZ protein, cystic fibrosis transmembrane regulator-associated ligand (CAL) as a cellular target of HPV16 E6 by the proteomic approach. The carboxy-terminal PDZ-binding motif of HPV16 E6 specifically interacts with the PDZ domain of CAL, and the interaction enhances proteasome-mediated degradation of CAL. HPV16 E6 interacts with CAL more strongly and degrades it better than HPV18 E6 owing to the more compatible PDZ-binding motif. CAL is ubiquitinated by the E6/E6-associated protein (E6AP) complex or by E6AP alone, albeit less efficiently, which indicates that it could be a normal target of E6AP. Although it downregulates CAL at the transcript level, small interfering RNA-induced depletion of HPV16 E6 in Caski cells stabilizes CAL at the protein level, suggesting that HPV16 E6 mediates the proteasomal degradation of CAL in HPV-positive cervical cancer cells. HPV16 E6 may tightly regulate the vesicular trafficking processes by interacting with CAL, and such a modification can contribute to the development of cervical cancer.

Amiodarone offsets the cardioprotective effects of ischaemic preconditioning against ischaemia/reperfusion injury.

Both ischaemic preconditioning (IPC) and amiodarone protect against myocardial ischaemia. We examined whether a combination of IPC and amiodarone demonstrated an additive protective effect in isolated rat hearts (n = 40). The controls (group I) were subjected to ischaemia/ reperfusion injury; group II was subjected to cycles of IPC prior to ischaemia/ reperfusion injury; group III was subjected to ischaemia in the presence of amiodarone (10(-10) mol/1); and group IV was subjected to IPC followed by ischaemia in the presence of amiodarone (10(-10) mol/l). Amiodarone produced the best preserved left ventricular end-systolic pressure and dP/dtmax, less developed ventricular stiffness, the shortest arrhythmia duration, and the smallest infarct size among the groups. All of the myocardial protective effects against ischaemia/reperfusion injury were diminished or abolished when IPC and amiodarone were applied sequentially.