Adamgammadex in patients to reverse a moderate rocuronium-induced neuromuscular block.

AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.

[Panax notoginseng: a review on chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology in recent five years].

As a famous and precious Chinese medicinal material, Panax notoginseng(PN) has been commonly used for a long history in China. As reported, PN exhibits significant pharmacological actions in protecting cardiocerebral vascular system and nervous system and suppressing tumors. In recent years, with the innovation in ideas, as well as the development of methods and equipment, PN has been extensively investigated, and notable progress has been made. This paper reviewed the advancements of PN in recent five years from chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology, in which the application of PN extracts in quality control was first summarized. The present study aims to provide a theoretical basis for quality control, product development, and rational medication of PN.

Microscopic treatment of benign eyelid margin lesions with ultrapulse carbon dioxide (CO2) laser.

Surgical treatment of eyelid margin lesions is challenging, and few studies focused on laser therapy of such type of lesions. To evaluate the safety and effectiveness of ultrapulse CO2 laser treatment under a microscope for benign eyelid margin lesions, we performed microscopic ultrapulse CO2 laser treatment win 132 patients with benign eyelid margin lesions for cosmetic reasons. Measurements included cosmetic results, complications and patients' satisfaction. Eighty lesions involved the gray line and 24 lesions were in the lacrimal region. All patients achieved satisfactory cosmetic and therapeutic outcomes. Eyelid contour recovered well with no scar and no malposition. No secondary epiphora was noted after the lesions adjacent to the lacrimal punctum were removed. At the end of follow-up, only 2 patients had mild hypopigmentation and only 1 patient required repeat laser therapy for recurrence. It turned out that ultrapulse CO2 laser treatment under a microscope is a dependable, safe, and effective method for the treatment of benign eyelid margin lesions. It is an excellent alternative to traditional surgery, especially for lesions involving the gray line or positioned in proximity to the lacrimal punctum. It is beneficial for simplifying the treatment, improving the cosmetic result, and maintaining eyelid function.

Effect modification by aging on the associations of nicotine exposure with cognitive impairment among Chinese elderly.

Active and passive exposure to tobacco smoke may increase risk of cognitive decline. However, effects of enhanced the aging process on the association of urinary nicotine metabolites with cognitive impairment remain unclear. In this study, 6657 Chinese older adults completed the physical examinations and cognitive tests. We measured urinary nicotine metabolite levels, mitochondrial DNA copy number (mtDNA-CN), and relative telomere length (RTL) and analyzed effects of urinary nicotine metabolites and their interaction with mtDNA-CN or RTL on cognitive impairment by generalized linear models and qg-computation, respectively. Each 1-unit increase in urinary 3-OHCot, 3-OHCotGluc, CotGluc, or NicGluc levels corresponded to a 1.05-, 1.09-, 1.04-, and 0.90-fold increased risk of cognitive impairment. Each 1-quantile increment in the mixture level of 8 nicotine metabolites corresponded to an increment of 1.40- and 1.34-fold risk of cognitive impairment in individuals with longer RTL or low mtDNA-CN. Urinary 3-OHCotGluc and RTL or mtDNA-CN exhibited an additive effect on cognitive impairment in addition to the mixture of 8 nicotine metabolites and mtDNA-CN. The findings suggested that aging process may increase the risk of tobacco-related cognitive impairment.

Kindlin-2 Mediates Lipopolysaccharide-Induced Acute Lung Injury Partially via Pyroptosis in Mice.

Acute lung injury (ALI) is characteristic of the wholesale destruction of the lung endothelial barrier, which results in protein-rich lung edema, influx of pro-inflammatory leukocytes, and intractable hypoxemia, contributing to high mortality. Kindlin-2 is involved in the process of tumor- and wound healing-associated inflammation. However, the effects of kindlin-2 on lipopolysaccharide (LPS)-induced ALI and its mechanisms remain unknown. In this study, we found that the concentration of kindlin-2 was elevated in the lungs of ALI mice. The specific deletion of kindlin-2 by kindlin-2 siRNA attenuated the severity of lung injury, which was demonstrated by the reduced number of pro-inflammatory cells in bronchoalveolar lavage fluid and lung wet/dry weight ratio, and ameliorated pathologic changes in the lungs of ALI mice. Furthermore, kindlin-2 siRNA decreased the mRNA levels of pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) and the protein levels of pyroptosis-related proteins. In vitro studies confirmed that LPS + ATP promoted the expressions of pro-inflammatory factors and pyroptosis-related proteins, which was prevented by kindlin-2 siRNA pretreatment in endothelial cells (ECs). In conclusion, inhibition of kindlin-2 developes protective effects against LPS-induced ALI and the cytotoxicity of ECs, which may depend on blocking pyroptosis.

Non-linear relationships between seasonal exposure to polycyclic aromatic hydrocarbons and urinary 8-hydroxy-2'-deoxyguanosine levels among Chinese young students.

Limited data are available on seasonal associations of polycyclic aromatic hydrocarbons (PAHs) exposure with oxidative DNA damage. We conducted a pilot study with 20 postgraduates, and measured urinary levels of mono-hydroxyl PAHs (OH-PAHs) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for 7 consecutive days in the four seasons. We assessed the relationships of urinary OH-PAHs with urinary 8-OHdG in the whole year as well as cold- and warm-seasons. Summed OH-PAHs (∑OH-PAHs) were higher in cold season than in warm season. Each ln-unit (ln-transformed unit) increase in ∑OH-PAHs in the whole year corresponded to a 34%, 16% or 23% increase in urinary 8-OHdG levels at lag0, lag1 or lag2 day as well as a 26% increase in urinary 8-OHdG levels at lag0-2 days (cumulative effects). Each ln-unit increase in ∑OH-PAHs corresponded to a 36%, 26% or 46% increase in urinary 8-OHdG levels in cold season at lag0 day, lag1 day or lag2 day as well as a 36% increase in urinary 8-OHdG in warm season at lag0 day. Distributed non-linear cumulative lag models (DLNMs) indicated that each ln-unit increase in ∑OH-PAHs within the range of 5.7-8.1 nmol/mmol Cr had a stronger effect (coefficient ß: 1.11-2.97 nmol/mmol Cr) on urinary 8-OHdG rather than non-cumulative DLNMs (coefficient ß: 1.08-1.43 nmol/mmol Cr) as well as the non-linear dose-response relationships of ∑OH-PAHs with urinary 8-OHdG. PAHs exposure exhibited the lagged and cumulative effects on urinary 8-OHdG levels.

[Influence of obesity on pharmacokinetics and pharmacodynamics of isoflurane].

OBJECTIVE: To observe the effect of obesity on pharmacokinetics and pharmacodynamics of isoflurane. METHODS: Twenty-six patients undergoing cholecystectomy were divided into obese group (Group A, BMI > or = 27, n = 13) and normal body weight group (Group N, BMI < or = 24, n = 13) according to body mass index (BMI). All patients were given to the same isoflurane anesthesia. Inspired and end-expired concentrations of isoflurane were monitored and uptake fraction of isoflurane were calculated. RESULTS: Isoflurane concentrations of vaporizer in Group A [(1.8 +/- 0.3)%] were evidently higher than those in Group N [(1.5 +/- 0.1)%] at all observed points (P < 0.05 or P < 0.01). Uptake fraction of isoflurane in Group A were higher than those in Group N at observed points (P < 0.05, P < 0.01 or P < 0.001), but there were no differences in the time when isoflurane concentration was lowered to 50% and awake time between the two groups after discontinuing inhaling isoflurane. CONCLUSIONS: Obese patients demand higher inspired concentration and uptake of isoflurane than those in normal weight patients but discharge of isoflurane was influenced by obesity within the observed period of (66 +/- 33) min.