Efficacy of scrambler therapy in patients with painful diabetic peripheral neuropathy: A single-arm, prospective, pilot study.

BACKGROUND: A variety of medications are available to manage painful diabetic peripheral neuropathy (DPN), but the proper treatment remains challenging. Accordingly, various neuromodulation modalities have been used. However, no prospective clinical trials have evaluated the use of scrambler therapy (ST) in painful DPN. This study aimed to explore the long-term effects of ST in managing painful DPN. METHODS: The patients received 10 consecutive STs of 45 minutes every 1 to 2 days. The primary outcome was pain score. We measured the visual analog scale (VAS) pain scores at baseline, during ST, immediately after ST, and at 1, 2, 3, and 6 months after ST. The secondary outcomes were Michigan Neuropathy Screening Instrument (MNSI), Semmes-Weinstein monofilament test, and Leeds Assessment of Neuropathic Symptoms and Signs pain scores, which were measured at baseline, immediately after ST, and at 1, 2, 3, and 6 months after ST. RESULTS: VAS scores showed significant improvement at the 8th, 9th, and 10th sessions during ST and 1 month after ST. The MNSI self-report component score was decreased 1 month after the ST. However, all other outcomes did not show significant differences compared to the baseline. CONCLUSION: ST may have short-term effects and limited long-term effects on painful DPN.

Assessment of Perioperative Atelectasis Using Lung Ultrasonography in Patients Undergoing Pneumoperitoneum Surgery in the Trendelenburg Position: Aspects of Differences according to Ventilatory Mode.

BACKGROUND: During robotic gynecologic pneumoperitoneum surgery in the Trendelenburg position, aeration loss leads to perioperative atelectasis. Recently developed ventilator mode pressure-controlled ventilation volume-guaranteed (PCV-VG) mode could provide adequate ventilation with lower inspiratory pressure compared to volume-controlled ventilation (VCV); we hypothesized that PCV-VG mode may be beneficial in reducing perioperative atelectasis via low tidal volume (VT) of 6 mL/kg ventilation during robotic gynecologic pneumoperitoneum surgery in the Trendelenburg position. We applied lung ultrasound score (LUS) for detecting perioperative atelectasis. We aimed to compare perioperative atelectasis between VCV and PCV-VG with a low VT of 6 mL/kg during pneumoperitoneum surgery in the Trendelenburg position using LUS. METHODS: Patients scheduled for robotic gynecologic surgery were randomly allocated to the VCV (n = 41) or PCV-VG group (n = 41). LUS, ventilatory, and hemodynamic parameters were evaluated at T1 (before induction), T2 (10 minutes after induction in the supine position), T3 (10 minutes after desufflation of CO2 in the supine position), and T4 (30 minutes after emergence from anesthesia in the recovery room). RESULTS: Eighty patients (40 with PCV-VG and 40 with VCV) were included. Demographic data showed no significant differences between the groups. The total LUS has changed from baseline to T4, 0.63 (95% confidence interval [CI], 0.32, 0.94) to 1.77 (95% CI, 1.42, 2.21) in the VCV group and 0.86 (95% CI, 0.56, 1.16) to 1.43 (95% CI, 1.08, 1.78) in the PCV-VG group (P = 0.170). In both groups, total LUS increased significantly compared to the baseline values. CONCLUSION: Using a low VT of 6 mL/kg during pneumoperitoneum surgery in the Trendelenburg position, our study showed no evidence that PCV-VG ventilation was superior to VCV in terms of perioperative atelectasis. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0006404.

Development of a simple and sensitive HPLC-MS/MS method for determination of diazepam in human plasma and its application to a bioequivalence study.

We developed a simple, sensitive, and effective ultra-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method with an electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) and positive ion modes to determine diazepam concentrations in human plasma using voriconazole as an internal standard (IS). Diazepam and IS were detected at transition 285.2→193.1 and 350.2→127.1, respectively. After liquid-liquid extraction (LLE) using 1.2 ml of ethyl acetate:n-hexane (80:20, v/v), diazepam and IS were eluted on a Phenomenex Cadenza CD-C18 column (150 × 3.0 mm, 3 µm) with an isocratic mobile phase (10 mM ammonium acetate in water:methanol [5:95, v/v]) at a flow rate of 0.4 mL/min. The peak retention time was 2.32 min for diazepam and 2.01 min for IS, respectively. The lower limit of quantitation (LLOQ) was 0.5 ng/mL (S/N > 10) using 50 µL of plasma, and no interferences were observed in chromatograms. Our analytical method was fully validated and successfully applied to a bioequivalence study of two formulations of diazepam in healthy Korean volunteers.

Anti-Neuroinflammatory Effects of Uncaria sinensis in LPS-Stimulated BV2 Microglia Cells and Focal Cerebral Ischemic Mice.

Uncaria sinensis (US) has long been used as a traditional Korean medicine to treat cardiovascular and central nervous system diseases, including hypertension and cerebral ischemia. Several recent studies have indicated that US has neuroprotective and cerebrovascular protective effects in ischemic brain injury; however, little is known about the anti-inflammatory effects of US. Therefore, the present study was designed to validate the anti-inflammatory effects of US. The anti-neuroinflammatory properties of US on pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated murine BV2 microglia and injured brains induced by photothrombotic cortical ischemia. Hexane extracts of US (HEUS) significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia and inhibited LPS-induced expression of iNOS and COX-2 in a dose-dependent manner without causing cytotoxicity in BV2 cells. In addition, HEUS significantly reduced the generation of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6. Moreover, HEUS treatment inhibited the transcriptional activity and nuclear translocation of NF-κB in LPS-stimulated BV2 cells. In an in vivo study, treatment of HEUS resulted in significantly reduced infarct volume and improved neurological function 48 h after ischemic brain injury, possibly through the inhibition of the production of pro-inflammatory cytokines. HEUS inhibits LPS-stimulated production of pro-inflammatory mediators and prevents cerebral ischemic damage, suggesting that US may have therapeutic potential for the prevention and treatment of ischemic stroke accompanied by microglia activation.

Partially purified components of Uncaria sinensis attenuate blood brain barrier disruption after ischemic brain injury in mice.

BACKGROUND: Uncaria sinensis (US) has long been used in traditional Korean medicine to relieve various nervous-related symptoms and cardiovascular disease. We recently showed the neuroprotective and cerebrovascular protective effects of US on cerebral ischemia; however, its effects on the blood-brain barrier (BBB) are poorly understood. In this study, the effects of partially purified components of US (PPUS) on BBB disruption were investigated in mice subjected to ischemic brain injury. METHODS: Focal cerebral ischemia was induced in C57BL/6J mice by photothrombotic cortical ischemia. PPUS was injected intraperitoneally 30 min before ischemic insults. Infarct volume, neurological score, wire-grip test, Evans blue leakage and brain water content were then examined 24 h after ischemic brain injury. RESULTS: Infarct volume was significantly reduced and neurological deficit and motor deficit were greatly improved in PPUS-pretreated mice relative to those treated with vehicle following photothrombotic cortical ischemia. Brain edema-induced change of Evans blue extravasation and water content in the ipsilateral hemisphere were alleviated by treatment with PPUS. In addition, PPUS significantly reduced ischemic brain injury-induced degradation of tight junction proteins and elevation of matrix metalloproteinase-9 (MMP-9). CONCLUSIONS: PPUS prevents cerebral ischemic damage by BBB protection, and these effects were associated with inhibition of tight junction degradation and MMP-9 induction.