Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease:A systematic review

BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease(IBD)patients,complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.METHODS We searched PubMed/MEDLINE,Embase,and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included.The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6μg/mL in IBD.Blood concentration of infliximab reaching 5.0-12.7μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease.Blood concentration of adalimumab reaching 7.2-16.2μg/mL or more could predict mucosal healing in IBD.The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8μg/mL in perianal fistulizing Crohn's disease.Blood concentration of vedolizumab surpassing 25.0μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9μg/mL.CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies,whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.

Changes in blood alcohol concentration and driving ability after alcohol intake

Objective: To study the relationship between the amount of consumed alcohol, blood alcohol concentration (BAC), and driving ability among a part of the population in Southwest China and to provide reference for the formulation of the legal limits for safe driving. Methods: Seventy-six randomly selected volunteer drivers each had three times of alcohol intake (100 ml each time). After each drank, BAC was measured with gas chromatograph and driving ability was evaluated. The drivers were grouped according to age, weight, alcohol tolerance and driving experience respectively and changes in BAC and driving ability were analyzed. Results: Average BAC and the percentage of drivers showing impaired driving ability in the groups increased after each intake of 100 ml alcohol. BAC in Group≤60 kg was more susceptible to alcohol than that in Group>60 kg. When each drank, alcohol had greater influence on drivers who had comparatively shorter driving experience. Conclusion: Volume of consumed alcohol, BAC and driving ability have direct associations among one another and are all under the influence of various factors including individual conditions. To set an appropriate legal BAC limit for safe driving should take an overall consideration of all factors.

Natural Compound Formula RM88 Significantly Reduces Blood Alcohol Concentration in Humans

There is extensive worldwide use for the social consumption of alcohol. Abuse of alcohol causes substantial personal, psychological and medical health issues. In addition, there are significant national economic costs from lost productivity. However, there are limited pharmaceutical drugs for the treatment of alcohol overuse. Historically, many cultures have used herbs and other natural compounds to reduce problematic alcohol induced behaviour but the evidence is anecdotal. This study investigated if a natural compound formula (RM88) that was developed could reduce blood alcohol concentration (BAC) in a controlled case series. Thirteen subjects (5 males, 8 females, age range 18 to 85 years) completed 16 paired sessions of alcohol only versus RM88 with alcohol. Subjects consumed one to three standard drinks of beer, wine or spirits (14.7 to 29.4 gm alcohol). Measurements were made by a fuel cell breathalyzer for a period of 90 minutes. Summated BAC showed a reduction in 94% (15/16) of paired test sessions (BAC reduction range 23% - 79%, mean 50.9% ± 16.5%, p = 0.0005). Data normalized to 20 gm alcohol (two standard drinks) showed a significance of p = 0.00026. One subject on prednisone and hydroxychloroquine drugs had increased BAC from RM88. The average reductions of BAC for the beverages were spirits 34% (n = 3), beer 36% (n = 3), and wine 52% (n = 10). RM88 showed that this combination of natural compounds was very effective in reducing maximal peak concentrations of alcohol.

Study of blood sugar concentration based on serum UV absorption spectra＊

UV absorption spectrum and neural network theory was used for the analysis of blood sugar concentration. Experimental investigation shows that absorption spectrum has the following characteristics in the wave band of 200-300 nm： （1） The absorption spectrum is of complex shape, there is more absorption peak in UV-band, it shows that there is a complex absorption phenomenon in blood group macromolecules; （2） The curve shapes of absorption spectra are similar to different samples ,the reason is that the spectrum is synthesis of some group macromolecules absorption spectrum; （3） There is a degree of displacement of absorption peak to different samples; （4） There is no significant correlation between absorbance and blood sugar concentration at 278 nm, but random. Based on the wave band of 280 nm to 300 nm, a neural network model was built to determine the blood sugar concentration.

The clinical value of enzyme-multiplied immunoassay technique monitoring the plasma concentrations of cyclosporine A after renal transplantation

The feasibility and the clinical value of the enzyme-multiplied immunoassay technique （EMIT） monitoring of blood concentrations of cyclosporine A （CsA） in patients treated with CsA were investigated after kidney transplantation. The validation method was performed to the EMIT determination of CsA blood concentration, the CsA whole blood trough concentrations （Co） of patients in different time periods after renal transplantation were monitored, and combined with the clinical complications, the statistical results were analyzed and compared. EMIT was precise, accurate and stable, also with a high quality control. The mean postoperative blood concentration of CsA was as follows： 〈1 month, （281.4± 57.9）ng/mL; 2 - 3 months, （264.5 ± 41.2） ng/mL; 4 - 5 months, （236.4 ± 38.9） ng/mL; 6 - 12 months, （206.5± 32.6）ng/mL; 〉12 months, （185.6± 28.1）ng/mL. The toxic reaction rate of CsA blood concentration within the recommended therapeutic concentration was 14.1%, significantly lower than that of the none-recommended dose group （37.2%） （P〈0.05）; the transplantation rejection rate was 4.4%, significantly lower than that of the none- recommended dose group （22.5%） （P〈0.05）. Using EMIT to monitor the blood concentration of CsA as the routine laboratory method is feasible, and is able to reduce the CsA toxicity and rejection significantly, leading to achieving the desired therapeutic effect.

Preoperative carbohydrate load to reduce perioperative glycemic variability and improve surgical outcomes:A scoping review

The detrimental effects of both diabetes mellitus(DM)and hyperglycemia in the perioperative period are well established and have driven extensive efforts to control blood glucose concentration(BGC)in a variety of clinical settings.It is now appreciated that acute BGC spikes,hypoglycemia,and high glycemic variability(GV)lead to more endothelial dysfunction and oxidative stress than uncomplicated,chronically elevated BGC.In the perioperative setting,fasting is the primary approach to reducing the risk for pulmonary aspiration;however,prolonged fasting drives the body into a catabolic state and therefore may increase GV.Elevated GV in the perioperative period is associated with an increased risk for postoperative complications,including morbidity and mortality.These challenges pose a conundrum for the management of patients typically instructed to fast for at least 8 h before surgery.Preliminary evidence suggests that the administration of an oral preoperative carbohydrate load(PCL)to stimulate endogenous insulin production and reduce GV in the perioperative period may attenuate BGC spikes and ultimately decrease postoperative morbidity,without significantly increasing the risk of pulmonary aspiration.The aim of this scoping review is to summarize the available evidence on the impact of PCL on perioperative GV and surgical outcomes,with an emphasis on evidence pertaining to patients with DM.The clinical relevance of GV will be summarized,the relationship between GV and postoperative course will be explored,and the impact of PCL on GV and surgical outcomes will be presented.A total of 13 articles,presented in three sections,were chosen for inclusion.This scoping review concludes that the benefits of a PCL outweigh the risks in most patients,even in those with well controlled type 2 DM.The administration of a PCL might effectively minimize metabolic derangements such as GV and ultimately result in reduced postoperative morbidity and mortality,but this remains to be proven.Future efforts to standardize the content and timing of a PCL are needed.Ultimately,a rigorous data-driven consensus opinion regarding PCL administration that identifies optimal carbohydrate content,volume,and timing of ingestion should be established.

Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

AIM： To investigate the tacrolimus dosage requirements and blood concentrations in adult-to-adult right lobe living donor liver transplantation （AALDLT） recipients with small-for-size （SFS） grafts. METHODS： During January 2007 and October 2008, a total of 54 cases of AALDLT with an observation period of 6 mo were enrolled in this study. The 54 patients were divided into two groups according to graftrecipient body weight ratio （GRBW）： SFS grafts group （Group S, GRBW 〈 0.8%, n = 8） and non-SFS grafts group （Group N, GRBW ≥ 0.8%, n = 46）. Tacrolimus 12-hour blood levels and doses were recorded during weeks 1, 2, 3 and 4 and months 2, 3, 4, 5 and 6 in group S and group N. Meanwhile, acute rejection rates, liver and renal function test results, and the number of potentially interacting medications were determined at each interval in the two groups. A comparison of tacrolimus dosage requirements and blood levels were made weekly in the first month post-surgery, and monthly from months 2 to 6. RESULTS： There were no differences in the demo-graphic characteristics, acute rejection rates, liver and renal function test results, or the number of potentially interacting medications administered between the two groups. The tacrolimus dosage requirements in group S were significantly lower than group N at 2 wk （2.8 ± 0.4 mg/d vs 3.6 ± 0.7 mg/d, P = 0.006）, 3 wk （2.9± 0.7 mg/d vs 3.9±0.8 rag/d, P = 0.008）, 4 wk （2.9 ± 0.8 mg/d vs 3.9 ± 1.0 mg/d, P = 0.023） and 2 mo （2.8 ±0.7 mg/d vs 3.8±1.1 mg/d, P = 0.033）. Tacrolimus 12-h trough concentrations were similar between the two groups at all times except for 2 wk post-transplantation, when the concentrations were significantly greater in group S recipients than in group N recipients （11.3 ± 4.8 ng/mL vs 7.0 ± 3.8 ng/mL, P = 0.026）. CONCLUSION： SFS grafts recipients have significantly decreased tacrolimus dosage requirements compared with non-SFS grafts recipients in AALDLT during the first 2 mo post-surgery.

Application of transcutaneous diffuse reflectance spectroscopy in the measurement of blood glucose concentration

In this paper, the propagation characteristics of near-infrared (NIR) light in the palm tissue are analyzed, and the principle and feasibility of using transcutaneous diffuse reflectance spectroscopy for non-invasive blood glucose detection are presented. An optical probe suitable for measuring the diffuse reflectance spectrum of human palm and a non-invasive blood glucose detection system using NIR spectroscopy are designed. Based on this system, oral glucose tolerance tests are performed to measure the blood glucose concentrations of two young healthy volunteers. The partial least square calibration model is then constructed by all individual experimental data. The final result shows that correlation coefficients of the two experiments between the predicted blood glucose concentrations and the reference blood glucose concentrations are 0.9870 and 0.9854, respectively. The root mean square errors of prediction of full cross validation are 0.54 and 0.52 mmol/1, respectively.

Environmental mercury exposure, semen quality and reproductive hormones in Greenlandic Inuit and European men： a cross-sectional study

Several animal studies indicate that mercury is a male reproductive toxicant, but human studies are few and contradictory. We examined semen characteristics and serum levels of reproductive hormones in relation to environmental exposure to mercury. Blood and semen samples were collected from 529 male partners of pregnant women living in Greenland, Poland and Ukraine between May 2002 and February 2004. The median concentration of the total content of mercury in whole blood was 9.2 ng ml-1 in Greenland （0.2- 385.8 ng ml-1）, 1.0 ng m1-1 in Poland （0.2-6.4 ng ml-z） and 1.0 ng ml-I in Ukraine （0.2-4.9 ng ml-1）. We found a significantly positive association between the blood levels of mercury and serum concentration of inhibin B in men from Greenland （p=0.074, 95% confidence interval （CI）=0.021 to 0.126） and in an analysis including men from all three regions （p=0.067, 95% C1=0.024 to O. 110）. The association may be due to beneficial effects of polyunsaturated fatty acids （PUFAs）, which are contained in seafood and fish. No significant association （P〉O.05） was found between blood concentrations of mercury and any of the other measured semen characteristics （semen volume, total sperm count, sperm concentration, morphology and motility） and reproductive hormones （free androgen index {FAI）, follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone and LH xtestosterone） in any region. In conclusion, the findings do not provide evidence that environmental mercury exposure in Greenlandic and European men with median whole blood concentration up to 10 ng m1^-1 has adverse effects on biomarkers of male reproductive health.

Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers

AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was perform- ed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg.

Spectrophotometric Assay for the Quantification of Plasma Ethanol Levels in Mice through Chromium-Ethanol Oxidation-Reduction Reaction

The quantification of blood/plasma ethanol concentration (BEC/PEC) is of great importance in experiments involving basic research, clinical studies, and bioethanol production. Traditional methods commonly used to measure BEC can be expensive and require high-cost equipment and qualified labor. The aim of this study was to develop a low-cost method that can be performed with simple infrastructure commonly available in research laboratories. For this, we developed a protocol to quantify PEC in mice, using the method of reduction of potassium dichromate by ethanol. However, this oxidation-reduction (redox) reaction is not specific to ethanol. Thus, the PEC was measured following a sequence of chemical reactions to eliminate the reductive interfering substances presented in the samples. Firstly, we evaluated the sensitivity of the dichromate reactive to ethanol and to different reducing substances found in the plasma, in order to determine which the main interfering substances are. Next, once the main interfering substances were determined in the dichromate reduction, plasma was assayed for PEC. First, mice received intraperitoneally (i.p.) saline (basal reading, 0% ethanol) or ethanol injections (0.5, 1, 2, 3, and 4 g/kg) and had their plasma collected. After plasma deproteinization and plasma glucose oxidation, it was mixed with the dichromate/acetic acid reactive, and then the products of the redox reaction were determined by the spectrophotometric method. Then, we determined the PEC with the same plasma samples using a commercial ethanol assay kit as a positive control. We found an excellent correlation between the administered ethanol doses and PECs in both the methods analyzed. The values of PEC found in the dichromate reaction method were similar to those obtained in the literature with the same ethanol doses, and to the commercial enzyme activity assay. Therefore, despite the need for a background reading, this method can be successfully applied to determine PEC using low-cost chemical reagents.

Physiological and perceptual responses to sprint interval exercise using arm versus leg cycling ergometry

Increases in power output and maximal oxygen consumption(V_O2max)occur in response to sprint interval exercise(SIE),but common use of“all-out”intensities presents a barrier for many adults.Furthermore,lower-body SIE is not feasible for all adults.We compared physiological and perceptual responses to supramaximal,but“nonall-out”SIE between leg and arm cycling exercise.Twenty-four active adults(mean±SD age:[25±7]y;cycling VO_(2)max:[39±7]mL·kg^(-1)·min^(-1))performed incremental exercise using leg(LCE)and arm cycle ergometry(ACE)to determine VO_(2)max and maximal work capacity(Wmax).Subsequently,they performed four 20 s bouts of SIE at 130% Wmax on the LCE or ACE at cadence=120-130 rev/min,with 2 min recovery between intervals.Gas exchange data,heart rate(HR),blood lactate concentration(BLa),rating of perceived exertion(RPE),and affective valence were acquired.Data showed significantly lower(p<0.001)absolute mean([1.24±0.31]L·min^(-1) vs.[1.59±0.34]L·min^(-1);d=1.08)and peak VO_(2)([1.79±0.48]L·min^(-1) vs.[2.10±0.44]L·min^(-1);d=0.70)with ACE versus LCE.However,ACE elicited significantly higher(p<0.001)relative mean([62%±9%]VO_(2)max vs.[57%±7%]VO_(2)max,d=0.63)and peak VO_(2)([88%±10%]VO_(2)max vs.[75%±10%]VO_(2)max,d?1.33).Post-exercise BLa was significantly higher([7.0±1.7]mM vs.[5.7±1.5]mM,p=0.024,d?0.83)for LCE versus ACE.There was no significant effect of modality on RPE or affective valence(p>0.42),and lowest affective valence recorded(2.0±1.8)was considered“good to fairly good”.Data show that non“all-out”ACE elicits lower absolute but higher relative HR and VO_(2) compared to LCE.Less aversive perceptual responses could make this non-all-out modality feasible for inactive adults.

Cavitation erosion in bloods

The cavitation in a mechanical heart valve（MHV） is a serious concern. In most of the investigations of the MHV cavitation in vitro, the tap water, the distilled water, or the glycerin are used as the test liquids, instead of the real blood. Therefore, the effects of the liquid properties on the cavitation can not be well revealed. In this paper, the cavitation erosion in the porcine bloods is experimentally investigated as well as in the tap water and the distilled water by means of a vibratory apparatus. The results show that the blood produces a weaker intensity of the cavitation erosion than the tap water or the distilled water. The cavitation erosion decreases with the decrease of the liquid temperature or with the increase of the concentration of the blood, especially with the increase of the liquid viscosity. It is the viscosity that could be a major dominant factor affecting this erosion. The temperature or the concentration of the blood changes the viscosity, and in turns changes the intensity of the cavitation erosion.

Determination of 8,2′-diprenylquercetin 3-methyl ether in plasma by UPLC-MS-MS and its pharmacokinetic application in rats

8,2＇-Diprenylquercetin 3-methyl ether with significant anti-breast cancer activity is the main constituent of Tibetan medicine Sinopodophylli Fructus. In the present study, we developed and validated a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the determination of 8,2＇-diprenylquercetin 3-methyl ether in rat plasma. 8-Prenylkaempferol was used as the internal standard. The separation was carried out using Waters ACQUITY UPLC BEH C18 column （2.1 mm×100 ram, 1.7 μm） with a mobile phase consisting of acetonitrile and 0.1% formic acid in water on a gradient program at a flow rate of 0.4 mL＇min-1 and temperature of 30 ℃. Triple quadrupole mass spectrometric detection in negative ion mode was used for multiple-reaction monitoring of the transitions at m/z 451.30→177.25 and m/z 353.25→298.15 for 8,2＇-diprenylquercetin 3-methyl ether and 8-prenylkaempferol, respectively. The calibration curves were linear within the concentration range 0.1-2000 ng/mL （r = 0.9954）. The recoveries were 103%-115%, and the results were consistent across low, middle and high concentration levels. The intra- and inter-day precisions were within 15%, and the bias was between --6%-15%. This method was simple, rapid and sensitive, which could be applied to the determination of 8,2＇-diprenylquercetin 3-methyl ether in plasma and pharmacokinetic study in rats. Pharmacokinetic test indicated that the peak plasma concentration occurred in 2 h after the female rats were intragastrically administered with 8,2＇-diprenylquercetin 3-methyl ether at the dose of 100 mg/kg, and the biological half-life was 6.79 h. The blood drug concentration maintained equal amount for 20 h, which was conducive to the in vivo effects of drugs.

Forensic appraisal of death due to acute alcohol poisoning:three case reports and a literature review

Death due to acute alcohol poisoning lacks specific anatomical characteristics,compared with other deaths due to drug poisoning.We report three forensic cases of death from acute alcohol poisoning due to inhibition of the respiratory centre and eventual asphyxia.Blood alcohol concentrations in the three fatalities were 5.28,3.33 and 3.78mg/mL,respec-tively.Lethal doses and blood alcohol concentrations showed differences between individu-als.Detailed auxiliary tests besides autopsy were undertaken.These cases show that forensic scientists should exclude other causes of death,combine the autopsy with auxiliary tests,and then make an appraisal.