Antidepressant Effect of Enzymatic Porcine Placenta Hydrolysate in Repeated Immobilization Stress-Induced Ovariectomized Female Mice.

When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1ß) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic the symptoms of women with menopause-related depression, a stressed ovariectomized (OVX) female mouse model was used to evaluate the antidepressant effects of EPPH. The female mice were randomly divided into five groups: (1) the sham-operated (Sham) group, (2) the OVX + repeated stress + saline-treated (OVX + ST) group, (3) the OVX + repeated stress + estradiol (0.2 mg/kg)-treated (positive control) group, (4) the OVX + repeated stress + EPPH (300 mg/kg)-treated (300) group, and (5) the OVX + repeated stress + EPPH (1500 mg/kg)-treated (1500) group. Female mice were OVX and repeatedly immobilization-stressed for 2 weeks (2 h/day). A tail suspension test was conducted on the 13th day, followed by the forced swimming test on the 14th day to assess the antidepressant effects of EPPH. After the behavioral tests, the levels of CORT, PGE2, and IL-1ß were evaluated. In addition, c-Fos expression in the paraventricular nucleus (PVN) was evaluated using immunohistochemistry. The concentrations of NO, PGE2, and IL-1ß stimulated by LPS were significantly reduced via the addition of EPPH to RAW 264.7 cells. EPPH significantly promoted neurite outgrowth in PC12 cells compared to that of the controls. In the tail suspension test, the duration of immobility was reduced in mice treated with EPPH 1500 compared to the OVX + ST group. The EPPH 1500 group had significantly decreased levels of c-Fos-positive neurons in the PVN and reduced levels of CORT and IL-1ß in the serum of the Sham group. These results suggested that the high dose of EPPH administration induced the antidepressant-like effect in the ovariectomized mice with repeated stress via downregulating the levels of CORT, IL-1ß, and PGE2 in the serum through reducing the expression of c-Fos in the PVN regions.

A Dose-finding Study of Sugammadex for Reversal of Rocuronium in Cardiac Surgery Patients and Postoperative Monitoring for Recurrent Paralysis.

BACKGROUND: The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less than 2 but there is a posttetanic count of at least 1. The purpose of this dose-finding study was to titrate sugammadex to produce a train-of-four ratio 0.9 or greater at the conclusion of cardiac surgery, and to continue monitoring neuromuscular blockade in the intensive care unit to identify recurrent paralysis. The hypothesis was that many patients would require less than the recommended dose of sugammadex, but that some would require more, and that recurrent paralysis would not occur. METHODS: Neuromuscular blockade was monitored using electromyography during cardiac surgery. Administration of rocuronium was at the discretion of the anesthesia care team. During sternal closure, sugammadex was titrated in 50-mg increments every 5 min until a train-of-four ratio 0.9 or greater was obtained. Neuromuscular blockade was monitored with electromyography in the intensive care unit until sedation was discontinued before extubation or for a maximum of 7 h. RESULTS: Ninety-seven patients were evaluated. The dose of sugammadex required to achieve a train-of-four ratio of 0.9 or greater varied from 0.43 to 5.6 mg/kg. There was a statistically significant relationship between the depth of neuromuscular blockade and the sugammadex dose required for reversal, but there was a large variation in dose required at any depth of neuromuscular blockade. Eighty-four of 97 patients (87%) required less than the recommended dose, and 13 (13%) required more. Two patients required additional sugammadex administration for recurrent paralysis. CONCLUSIONS: When sugammadex was titrated to effect, the dose was usually less than the recommended dose, but it was more in some patients. Therefore, quantitative twitch monitoring is essential for ascertaining that adequate reversal has taken place after sugammadex administration. Recurrent paralysis was observed in two patients.

Comparison of a Modern Digital Mechanomyograph to a Mechanomyograph Utilizing an Archival Grass Force Transducer.

BACKGROUND: Mechanomyography is the traditional gold standard research technique for quantitative assessment of neuromuscular blockade. Mechanomyography directly measures the isometric force generated by the thumb in response to ulnar nerve stimulation. Researchers must construct their own mechanomyographs since commercial instruments are no longer available. A mechanomyograph was constructed, and its performance was compared against an archival mechanomyography system from the 1970s that utilized an FT-10 Grass force transducer, hypothesizing that train-of-four ratios recorded on each device would be equivalent. METHODS: A mechanomyograph was constructed using 3D-printed components and modern electronics. An archival mechanomyography system was assembled from original components, including an FT-10 Grass force transducer. Signal digitization for computerized data collection was utilized instead of the original paper strip chart recorder. Both devices were calibrated with standard weights to demonstrate linear voltage response curves. The mechanomyographs were affixed to opposite arms of patients undergoing surgery, and the train-of-four ratio was measured during the onset and recovery from rocuronium neuromuscular blockade. RESULTS: Calibration measurements exhibited a positive linear association between voltage output and calibration weights with a linear correlation coefficient of 1.00 for both mechanomyography devices. The new mechanomyograph had better precision and measurement sensitivity than the archival system: 5.3 mV versus 15.5 mV and 1.6 mV versus 5.7 mV, respectively (P < 0.001 for both). A total of 767 pairs of train-of-four ratio measurements obtained from eight patients had positive linear association (R 2 = 0.94; P < 0.001). Bland-Altman analysis resulted in bias of 3.8% and limits of agreement of -13% and 21%. CONCLUSIONS: The new mechanomyograph resulted in similar train-of-four ratio measurements compared to an archival mechanomyography system utilizing an FT-10 Grass force transducer. These results demonstrated continuity of gold standard measurement of neuromuscular blockade spanning nearly 50 yr, despite significant changes in the instrumentation technology.