Traditional Chinese medicine for acute mountain sickness prevention: A systematic review and meta-analysis of randomized controlled trials

Objective: To evaluate the efficacy of traditional Chinese medicine(TCM) for preventing acute mountain sickness(AMS).Methods: We included randomized controlled trials(RCTs) which evalueded the effect of TCM for preventing AMS, compared with a placebo, no treatment or acetazolamide. The literature was searched in 6major databases. RevMan 5.4 software was used for the meta-analysis. The relative risk for discrete variables and the mean difference for continuous variables with 95% confidence intervals(CIs) were applied to express the effect size. The risk of bias in the included studies was evaluated using the Cochrane risk assessment tool 2.0(RoB 2.0), and the evidence certainty was assessed using the Grading of Recommendations Assessment and the Development and Evaluation(GRADE) approach.Results: Twenty RCTs involving 3015 participants and 16 TCM patent drugs were included. The overall risk of bias in the majority of studies(15/20) was of some concerns. In terms of the AMS incidence,Rhodiola rosea(R. rosea, Hong Jing Tian) and Ginkgo biloba(G. biloba, Yin Xing Ye) were equivalent to the placebo/no treatment [RR(95% CI): 0.66(0.43-1.01), 0.82(0.63-1.06), respectively]. The AMS incidence in the G. biloba group was higher than that in the acetazolamide group [RR(95% CI): 2.92(1.69-5.06)]. In terms of improving the AMS symptom score on days 1 and 3 in the plateau, R. rosea and G. biloba were superior to the placebo or no treatment [MD(95% CI):-0.98(-1.71,-0.25),-2.05(-3.14,-0.95), respectively]. The other 14 Chinese patent medicines were evaluated in a single trial, and the majority of the results were negative. The subgroup analysis showed that the effect of R. rosea was related to the intervention time, way of ascending, and altitude.Conclusion: R. rosea and G. biloba were effective in improving AMS symptoms but had no effect in reducing the AMS incidence. There was insufficient evidence to support the use of other TCM patent drugs to prevent AMS. More randomized double-blind placebo-controlled trials are warranted to evaluate and screen effective Chinese patent medicines for AMS prevention.

Early Warning of Acute Altitude Sickness by Physiological Variables and Noninvasive Cardiovascular Indicators

Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude.Methods One hundred and six Han nationality male individuals were recruited to this research.Dynamic electrocardiogram,treadmill exercise test,echocardiography,routine blood examination and biochemical analysis were performed when subjects at sea level and entering the plateau respectively.Then multiple regression analysis was performed to construct a multiple linear regression equation using the Lake Louise Score as dependent variable to predict the risk factors at sea level related to acute mountain sickness(AMS).Results Approximately 49.05%of the individuals developed AMS.The tricuspid annular plane systolic excursion(22.0+2.66 vs.23.2+3.19 mm,t=l.998,P=0.048)was significantly lower in the AMS group at sea level,while count of eosinophil[(0.264+0.393)×109/L vs.(0.126+0.084)×109/L,t=-2.040,P—0.045],percentage of diflerences exceeding 50 ms between adjacent normal number of intervals(PNN50,9.66%±5.40%vs.6.98%±5.66%,t=-2.229,P=0.028)and heart rate variability triangle index(57.1+16.1 vs.50.6+12.7,t=-2.271,P=0.025)were significantly higher.After acute exposure to high altitude,C-reactive protein(0.098+0.103 vs.0.062+0.045 g/L,t=-2.132,P=0.037),aspartate aminotransferase(19.7+6.7275.17,3±3.95 U/L,t=-2.231,P=0.028)and creatinine(85.1±12.9 vs.77.7±11.2 mmol/L,t=3.162,P=0.002)were significantly higher in the AMS group,while alkaline phosphatase(71.7+18.2 vs.80.6+20.2 U/L,t=2.389,P=0.019),standard deviation of normal-to-normal RR intervals(126.5+35.9 vs.143.3+36.4 ms,t—2.320,P—0.022),ejection time(276.9+50.8 vs.313.8+48.9 ms,t—3.641,P—0.001)and heart rate variability triangle index(37.1+12.9 vs.41.9+11.1,t=2.O2O,P=0.047)were significantly lower.Using the Lake Louise Score as the dependent variable,prediction equation were established to estimate AMS:Lake Louise Score=3.783+0.281Xeosinophil-0.219Xalkaline phosphatase+O.O32XPNN50.Conclusions We elucidated the differences of pl^siological variables as well as noninvasive cardiovascular indicators for subjects after high altitude exposure compared with those at sea level.We also created an acute high altitude reaction early warning equation based on the physiological variables and noninvasive cardiovascular indicators at sea level.

A specific objective supplemental factor in evaluating acute mountain sickness: ΔHR in combination with SaO_2

Background: So far, there have been no measurements confirmed useful in diagnosing acute mountain sickness(AMS). The aim of this study was to determine the role of heart rate(HR) difference(ΔHR) and oxygen saturation(Sa O2) as objective risk factors in aiding the diagnosis of AMS.Methods: A total of 1,019 participants were assigned to either the acute exposure group(AEG): from 500 m to 3,700 m by flight within 2.5 hours(n=752); or the pre-acclimatization group(PAG): ascended to 4,400 m from 3,650 m within three hours by car after adapting 33 days at 3,650m(n=267). The questionnaires or measurements of resting Sa O2 and HR were completed between 18 and 24 hours before departure and after arrival.Results: Incidence of AMS was 61.3%(461) in AEG, with 46.1%(347) mild cases and 15.2%(114) severe cases. In PAG, the incidence was 38.9%(104), with 30.7%(82) mild cases and 8.2%(22) severe cases. The AMS subjects showed a significant increase in HR and a decrease in Sa O2 levels compared with the non-AMS subjects in both groups. ΔHR and post-exposure Sa O2 were significantly correlated with the Lake Louise Score(LLS) in both groups. Stepwise logistic regression analysis revealed the ΔHR >25 and Sa O2 <88% in AEG as well as ΔHR >15 and Sa O2 <86% in PAG to be independent risk factors of AMS. Combining these two measurements could specifically indicate participants with AMS, which showed a positive predictive value of 89% and specificity of 97% in AEG as well as 85% and 98% in PAG.Conclusion:ΔHR or Sa O2, as objective measurements, correlate with AMS. Combination of these two measurements may be useful as an additional specific and objective factor to further confirm the diagnosis of AMS.

Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent

Background:Acute mountain sickness(AMS)is the mildest form of acute altitude illnesses,and consists of nonspecific symptoms when unacclimatized persons ascend to elevation of≥2500 m.Risk factors of AMS include:the altitude,individual susceptibility,ascending rate and degree of pre-acclimatization.In the current study,we examined whether physiological response at low altitude could predict the development of AMS.Methods:A total of 111 healthy adult healthy volunteers participated in this trial;and 99(67 men and 32 women)completed the entire study protocol.Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude(500 m).Heart rate,blood pressure(BP)and pulse oxygen saturation(SpO2)were recorded prior to and during the last minute of exercise.The ascent from 500 m to 4100 m was completed in 2 days.AMS was defined as≥3 points in a 4-item Lake Louise Score,with at least one point from headache wat 6–8 h after the ascent.Results:Among the 99 assessable subjects,47(23 men and 24 women)developed AMS at 4100 m.In comparison to the subjects without AMS,those who developed AMS had lower proportion of men(48.9%vs.84.6%,P<0.001),height(168.4±5.9 cm vs.171.3±6.1 cm,P=0.019),weight(62.0±10.0 kg vs.66.7±8.6 kg,P=0.014)and proportion of smokers(23.4%vs.51.9%,P=0.004).Multivariate regression analysis revealed the following independent risks for AMS:female sex(odds ratio(OR)=6.32,P<0.001),SpO2 change upon exercise at low altitude(OR=0.63,P=0.002)and systolic BP change after the ascent(OR=0.96,P=0.029).Women had larger reduction in SpO2 after the ascent,higher AMS percentage and absolute AMS score.Larger reduction of SpO2 after exercise was associated with both AMS incidence(P=0.001)and AMS score(P<0.001)in men but not in women.Conclusions:Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent.Such an association was more robust in men than in women.Trial registration:Chinese Clinical Trial Registration,ChiCTR1900025728.Registered 6 September 2019.

Association between smoking and the risk of acute mountain sickness： a meta-analysis of observational studies

Background: People rapidly ascending to high altitudes(>2500m) may suffer from acute mountain sickness(AMS). The association between smoking and AMS risk remains unclear. Therefore, we performed a meta-analysis to evaluate the association between smoking and AMS risk.Methods: The association between smoking and AMS risk was determined according to predefined criteria established by our team. Meta-analysis was conducted according to the PRISMA guidelines. We included all relevant studies listed in the Pub Med and Embase databases as of September 2015 in this meta-analysis and performed systemic searches using the terms "smoking", "acute mountain sickness" and "risk factor". The included studies were required to provide clear explanations regarding their definitions of smoking, the final altitudes reached by their participants and the diagnostic criteria used to diagnose AMS. Odds ratios(ORs) were used to evaluate the association between smoking and AMS risk across the studies, and the Q statistic was used to test OR heterogeneity, which was considered significant when P<0.05. We also computed 95% confidence intervals(CIs). Data extracted from the articles were analyzed with Review Manager 5.3(Cochrane Collaboration, Oxford, UK).Results: We used seven case-control studies including 694 smoking patients and 1986 non-smoking controls to analyze the association between smoking and AMS risk. We observed a significant association between AMS and smoking(OR=0.71, 95% CI 0.52–0.96, P=0.03).Conclusion: We determined that smoking may protect against AMS development. However, we do not advise smoking to prevent AMS. More studies are necessary to confirm the role of smoking in AMS risk.

Sex-based differences in the prevalence of acute mountain sickness: a meta-analysis

Background:When lowlanders rapidly ascend to altitudes>2500 m,they may develop acute mountain sickness(AMS).The individual susceptibility,ascending velocity,time spent at altitude,activity levels and altitude reached are considered risk factors for AMS.However,it is not clear whether sex is a risk factor.The results have been inconclusive.We conducted a meta-analysis to test whether there were sex-based differences in the prevalence of AMS using Lake Louise Scoring System.Methods:Systematic searches were performed in August 2019 in EMBASE,PubMed,and Web of Science for prospective studies with AMS data for men and women.The titles and abstracts were independently checked in the primary screening step,and the selected full-text articles were independently assessed in the secondary screening step by the two authors(YPH and JLW)based on pre-defined inclusion criteria.The meta-analysis was performed using by the STATA 14.1 software program.A random-effects model was employed.Results:Eighteen eligible prospective studies were included.A total of 7669 participants(2639[34.4%]women)were tested.The results showed that there was a statistically significant higher prevalence rate of AMS in women than in men(RR=1.24,95%CI 1.09–1.41),regardless of age or race.However,the heterogeneity was significant in the analysis(Tau2=0.0403,Chi2=50.15,df=17;I2=66.1%,P=0.000),it was main caused by different numbers of subjects among the studies(coefficient=–2.17,P=0.049).Besides,the results showed that there was no evidence of significant publication bias in the combined studies on the basis of Egger’s test(bias coefficient=1.48,P=0.052)and Begg’s test(P=0.130).Conclusions:According to this study,the statistically significant finding emerging from this study was that women have a higher prevalence of AMS.However,the authors could not exclude studies where patients were on acetazolamide.Our analysis provided a direction for future studies of the relationship of sex and the risk of AMS,such as the pathological mechanism and prevention research.

Prior transfusion of umbilical cord mesenchymal stem cells can effectively alleviate symptoms of motion sickness in mice through interleukin 10 secretion

BACKGROUND Motion sickness(MS)is a disease that occurs during unbalanced movement,characterized by gastrointestinal symptoms and autonomic nervous system activation.Current clinical treatments for MS are limited.Recent evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune imbalance.In the present study,mesenchymal stem cells(MSCs)have been shown to exert strong immunosuppressive effects.AIM To explore whether umbilical cord-derived mesenchymal stem cells(UC-MSCs)can prevent the occurrence of MS,and the underlying mechanism regulated by MSCs in a mouse model of MS.METHODS A total of 144(equal numbers of males and females)5wkold BALB/c mice were randomly divided into five groups:Normal group(n=16),MS group(n=32),MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32).The MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32)were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs(1×106 cells/mouse).Mice in the MS(n=32),MS+MSCs,and MS+AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8×g/min for MS model establishment on days 3,5,8,and 10 after UC-MSCs injection.The Morris water maze(MWM)test was used to observe the symptom of dizziness.Enzyme-linked immunosorbent assay(ELISA)and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone samples.Western blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear tissues.Histological examination was performed by hematoxylin and eosin(HE)staining for conventional morphological evaluation in the petrous part of temporal bone samples.RESULTS The MWM test demonstrated that UC-MSCs improved the symptoms of MS.The MS+MSCs group was faster than the MS group on days 3 and 5(P=0.036 and P=0.002,respectively).ELISA and RT-qPCR showed that the serum and mRNA levels of interleukin-10(IL-10)in the cochlear tissues were increased after transplantation with UC-MSCs(MS+MSCs group vs MS group at 3 and 5 d,P=0.002 and cP<0.001,respectively).RT-qPCR results confirmed a significant increase in IL-10 levels at four time points(MS+MSCs group vs MS group,P=0.009,P=0.009,P=0.048,and P=0.049,respectively).This suggested that UCMSCs reduced the sensitivity of the vestibular microenvironment by secreting IL-10.Moreover,Western blot analysis showed that the MSCs activated the JAK2/STAT3 signaling pathway in the cochlear tissues.The levels of IL-10,IL-10RA,JAK2,STAT3,and phosphorylated JAK2 and STAT3 in the MS+MSCs group were increased compared to those of the MS group(P<0.05).The morphological changes in the four groups showed no significant differences.The role of IL-10 secretion on the ability of UC-MSCs to successfully improve the symptoms of MS was confirmed by the diminished therapeutic effects associated with treatment with the IL-10 inhibitor ammonium trichloro(dioxoethylene-o,o′)tellurate(AS101).CONCLUSION Prophylactic transplantation of UC-MSCs can alleviate the clinical symptoms of MS in mice,particularly at 3-5 d after preventive transplantation.The mechanism for UC-MSCs to reduce the sensitivity of vestibular cortex imbalance may be the secretion of IL-10.The next step is to demonstrate the possibility of curing MS in the vestibular environment by intermittent transplantation of MSCs.Above all,MSCs are expected to become a new method for the clinical prevention and treatment of MS.

Association between acute mountain sickness(AMS) and age: a meta-analysis

Background: Acute mountain sickness(AMS) is a potentially lethal condition caused by acute hypoxia after ascending to altitudes higher than 2500 m in a short time. The main symptom of AMS is headache. Numerous risk factors of AMS have been examined, including gender, obesity, ascent rate, age and individual susceptibility. In previous studies, age was considered a predisposing factor for AMS. However, different opinions have been raised in recent years. To clarify the association between AMS and age, we conducted this meta-analysis.Methods: We obtained observational studies that explored risk factors for AMS by searching PubMed, Embase, China National Knowledge Internet(CNKI), the Wanfang database and CQVIP for articles published before March 2017.The studies included were required to provide the mean age and its standard deviation for subjects with and without AMS, the maximum altitude attained and the mode of ascent. The Lake Louse Score(LLS) or the Chinese AMS score(CAS) was used to judge the severity of AMS symptoms and incidence. Studies were pooled for the analysis by using a random effects model in RevMan 5.0. Meta-regression and subgroup analyses were conducted to identify sources of heterogeneity using Stata 14.2 and RevMan 5.0.Results: In total, 17 studies were included, and the overall number of subjects with and without AMS was 1810 and3014, respectively. The age ranged from 10 to 76 years. Analysis of the 17 included studies showed that age was not associated with AMS(mean difference(MD)=0.10; 95%CI: —0.38-0.58; P=0.69).Conclusions: This meta-analysis suggests that there is no association between age and the risk of AMS. Race, age,and ascent mode are common sources of heterogeneity, which may provide an analytical orientation for future heterogeneity analyses.

Identifying changes in punitive transcriptional factor binding sites from regulatory single nucleotide polymorphisms that are significantly associated with disease or sickness

AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.

Establishment of an animal model of acute mountain sickness

Aim To simulate the condition when people travel to the plateau. To make a primary investigation about the mice models, which are respectively provoked by exhaustive exercise, cold and fatigue, and epinephrine. Methods Divide the Kunming mice into 8 groups in random, with 10 in a single group, control group in plain; exhaustive exercise group in plain; fatigue ＆ cold group in plain; epinephrine stimulating group in plain; control group in plateau; exhaustive exercise group in plateau; fatigue ＆ cold group in plateau; epinephrine stimulating group in plateau. To simulate the condition when people travel to Lhasa whose altitude reaches 3700m, those mice were carried there during a five-day period. Day 1： Weight the mice after fasting for 12hrs, then treated different with corresponding methods. Day 2： Collect the data of mortality in each group and sacrifice the alive. Weight the cardiac, pulmonary and cerebral tissues and calculate for the Viscera Index. Results After the journey to the plat- eau, the weight of mice decreases significantly, in exhaustive exercise group and fatigue ＆ cold group also with the increase of pulmonary and cerebral index and decrease of cardiac index compared with groups in plain. As for those who are stimulated with epinephrine, the ones in plateau suffer more from pneumonedema but have a longer life span. The sensitivity to epinephrine can decrease in female mice in plateau, which can be reversed in plain. Con- clusions After the journey to plateau, acute plateau pneumonedema and cerebral edema can be provoked by ex- haustive exercise, fatigue and cold, and starvation; The severity of pneumonedema caused by epinephrine are relat- ed to the environment, strength and gender.

Oxidative stress is not involved in motion sickness of mice

Aim Some indirect evidences indicate a possible correlation between oxidative stress and motion sick- ness. The aim of this research was to investigate whether oxidative stress contributing to motion sickness in mice or not. Methods We examined the mRNA levels of peroxiredoxin 6 （PRDX6） , catalase and enzyme superoxide dis- mutase 1 （SOD1）; reactive oxygen species （ROS）; total antioxidant capacity and SOD activity in different brain regions after rotary stimulation. Mice motion sickness index was recorded after rotation when pretreated with pa- raquat, vitamin C or vitamin E. Results The R0S level and antioxidant capacity were both increased in cerebel- lum plus brainstem （CB） after rotation, a critical region determines motion sickness. However, manipulation of ox- idants or antioxidants using pharmacological method in vivo had no influence on motion sickness index in mice. Conclusion Oxidative stress is not involved in the development of motion sickness in mice.

EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population: a cross-sectional study

Background: More people ascend to high altitude(HA) for various activities, and some individuals are susceptible to HA illness after rapidly ascending from plains. Acute mountain sickness(AMS) is a general complaint that affects activities of daily living at HA. Although genomic association analyses suggest that single nucleotide polymorphisms(SNPs) are involved in the genesis of AMS, no major gene variants associated with AMS-related symptoms have been identified.Methods: In this cross-sectional study, 604 young, healthy Chinese Han men were recruited in June and July of 2012 in Chengdu, and rapidly taken to above 3700 m by plane. Basic demographic parameters were collected at sea level, and heart rate, pulse oxygen saturation(Sp O2), systolic and diastolic blood pressure and AMS-related symptoms were determined within 18–24 h after arriving in Lhasa. AMS patients were identified according to the latest Lake Louise scoring system(LLSS). Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders(age, body mass index and smoking status).Results: In total, 320 subjects(53.0%) were diagnosed with AMS, with no cases of high-altitude pulmonary edema or high-altitude cerebral edema. Sp O2 was significantly lower in the AMS group than that in the non-AMS group(P=0.003). Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction. The rs6756667(EPAS1) was associated with mild gastrointestinal symptoms(P=0.013), while rs3025039(VEGFA) was related to mild headache(P=0.0007). The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS(OR=2.70, P<0.001).Conclusions: Under the latest LLSS, we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population;this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA.Trial registration: Chinese Clinical Trial Registration, Chi CTR-RCS-12002232. Registered 31 May 2012.

Role of Histamine H1 Receptors in Vestibular Nucleus in Motion Sickness

Objectives To investigate the expression of histamine H1 receptors （H1R） in the vestibular nucleus of brainstem in rats and the role of H1R in motion sickness （MS）. Methods A total of 24 healthy Sprague-Dawley rats were divided randomly into four groups （n=6 each） which determined if the animals would receive induction of MS or drug （promethazine） treatment： MS （ - ）/Drug （ - ）; MS（＋）/Drug （ - ）; MS （ - ）/Drug （ ＋ at 0.25 mg）; and MS （ ＋ ）/ Drug（＋）. MS was induced by complex motion stimulation and the conditioned taste aversion was used as a behavioral indicator of MS. The volume of 0.15% sodium saccharin solution （SS） intake within 45 minutes after motion stimulation was measured. H1R in the vestibular nucleus was examined by immunofluorescence staining. The expression of H 1R protein in brainstem tissue at vestibular nucleus level was detected by western blot. Results The mean SS intake volume in the MS （ ＋ ）/Drug （ - ） group （8.8 ml） was significantly less than that of the MS （ - ）/Drug （ - ） group （15.1 ml） （P 〈 0.01）. The mean SS intake volume of the MS （-）/Drug （＋） group （14.8 ml） was similar to that of the MS（-）/Drug（-） group. The mean SS intake volume （9.6 ml） of the MS（＋）/Drug（＋） group was more than that of the MS（＋）/Drug（-）group （P〈0.01）, but less than that of the MS（-）/Drug（-） group or MS（-）/Drug（＋） group （P 〈 0.01）. Immunofluorescence staining showed positive expression of H1R in the vestibular nucleus of brainstem and the expression was enhanced by motion stimulation. Western blot analysis showed that H1R protein expressed in the brainstem tissue at vestibular nucleus level and the expression also increased significantly after motion stimulation. The MS-induced increase of H1R was not affected significantly by promethazine. Conclusions H1Rs exist in the vestibular nucleus in rats and H 1R expression is up-regulated by motion stimulation, but not affected by promethazine. The findings indicate that the histaminergic system is involved in MS. Promethazine, as an H1R blocker, may play its anti-MS role by competing the binding site on H1Rs with histamine rather than inhibiting H1R expression.

The dynamic distribution of nitric oxide synthase in the small intestine of mice with intestinal radiation sickness

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Effects of endothelial nitric oxide synthase uncoupling on pulmonary endothelial dysfunction in rats with decompression sickness

Background: To investigate the effects of unsafe decompression on rat pulmonary endothelial function and its relevant mechanisms.Methods: Sixty male Sprague-Dawley(SD) rats were randomly divided into a control group(n=30) and a decompression sickness(DCS) group(n=30). The DCS model was established by placing the rats in the DCS group in a pressurized cabin where they were exposed to a 600 k Pa compressed air environment for 60 min, and the pressure was then reduced by 100 k Pa/min until it reached atmospheric pressure. After the surviving rats in the DCS group and the rats in the control group were anesthetized, their pulmonary arteries were stripped to test the in vitro pulmonary artery endothelium-dependent vasodilation capacity. Western blotting was used to measure the expression and dissociation of endothelial nitric oxide synthase(e NOS) in pulmonary artery tissues and all protein nitration levels in pulmonary artery tissues; reactive oxygen species(ROS) formation was measured via in vitro pulmonary artery superoxide anion probe dihydroethidium(DHE) staining.Results: After experiencing unsafe decompression, 10 of the 30 rats in the DCS group died. The pulmonary artery endothelium-dependent vasodilation capacity in the surviving rats decreased significantly(P<0.05). The difference in e NOS expression between the DCS group and the control group was statistically insignificant(P>0.05), but the ratio of e NOS monomer/dimer in the DCS group was significantly higher than that in the control group(P<0.05). All protein tyrosine nitration levels in the pulmonary artery tissues of the DCS group were significantly higher than those of the control group(P<0.05). The results of DHE staining showed that the amount of ROS formation in the pulmonary arteries of the DCS group was significantly higher than that of the control group(P<0.05).Conclusion: Unsafe decompression during a simulated submarine escape process can lead to e NOS dimer uncoupling in the pulmonary artery endothelium. The dissociated e NOS monomer cannot synthesize nitric oxide(NO) and thus affect the endothelium-dependent vasodilation capacity. The e NOS monomer can promote peroxynitrite(ONOO–) synthesis, leading to an increase in protein tyrosine nitration levels in pulmonary artery tissues and causing disorder in cell cycle regulation. The e NOS monomer can also cause an increase in the formation of ROS and thus mediate peroxidation damage.

Clinical report of seven cases of bone marrow form of acute radiation sickness

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Restraint Induces Sickness Responses Independent of Injection with Epstein-Barr Virus (EBV)-Encoded dUTPase

Most adult humans have been infected by Epstein-Barr virus (EBV), a putative cause of chronic fatigue syndrome, and carry latent EBV. The EBV-encoded dUTPase can induce sickness responses in mice and chronic stress exacerbates this response. Because individuals often adapt to chronic stress, we tested the hypothesis that acute restraint stress would potentiate these sickness responses elicited by EBV-encoded dUTPase. Male CD-1 mice were injected daily for one or three days with either saline or EBV-encoded dUTPase. Additionally, mice from each condition were either restrained for three hours daily or left undisturbed during the light phase when mice are inactive. Restraint decreased weight gain during the one- and three-day experiments. Restraint in saline injected mice increased anxiety-like behavior in the open field during the three-day experiment. There were no behavioral differences during the one-day experiment. Restraint stress had no effect when experienced acutely on one day, but did produce a sickness response after three days of exposure regardless of saline or dUTPase injection. In contrast to the effects of chronic stress and EBV-encoded dUTPase on the sickness response, acute stress did not affect sickness responses in association with EBV-encoded dUTPase. Thus, dUTPase does not appear to provoke the same sickness responses after acute stress as compared to chronic stress.

The Contribution of Tanzanian National Parks in Controlling the Vectors of Sleeping Sickness

This paper summarises efforts to control Sleeping sickness [Human African Trypanosomiasis (HAT)] by Tsetse flies and Trypanosomiaisis (T & T) control for the 7 consecutive years although started a decade ago in Tanzania National Parks (TANAPA). These efforts are critical for curbing HAT incidences and HAT epidemics. HAT cases have had profound negative impacts on human health, affecting local residents and international travel as well as tourism industry resulting into human and animal health burden and reduction in tourism income. Understanding the current efforts is essential in the proper planning and decision making on developing effective control strategy against T & T control. In this paper, we summarize the recent efforts in the control of T & T in National Parks and discuss the constraints faced. The information will enable TANAPA and other concerned authorities to make informed decision on optimal ways of controlling HAT in National Parks. The results show that much control efforts have so far concentrated in Serengeti, Ruaha, Tarangire and Katavi National Parks where tsetse fly challenges are high. A total 21,143 (average 3020) Insecticide Treated Targets (ITT) were deployed in different areas in the parks and 82,899 (average 20,725) cars entering these parks were sprayed from 2007/2008 to 2014/2015 and 2007/2008 to 2010/2011 respectively. Deployed ITTs lead to a drastic reduction of FTDs of the two dominant tsetse species to 1.3 and 1.4 of G. swynnertoni and G. pallidipes respectively, and the decline was significant at P = 0.011. The major challenges faced include tsetse re-invasion in controlled areas;resurgence of HAT cases when control efforts are relaxed, ITT maintenance and inadequate health education programs. The control strategy should be continuous and scaled up as failure to implement an effective and sustainable system for HAT control will increase the risk of new epidemic that would impede tourism development.

Chronic Physical Stress Does Not Interact with Epstein-Barr Virus (EBV)-Encoded Dutpase to Alter the Sickness Response

Most adult humans have been infected with Epstein-Barr virus (EBV), which is thought to contribute to the development of chronic fatigue syndrome. Stress is known to influence the immune system and can exacerbate the sickness response. Although a role for psychological stress in the sickness response, particularly in combination with EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) has been established, and the role of physical stressors in these interactions remains unspecified. In this study, we seek to determine the interaction of chronic physical (swim) stress and EBV-encoded dUTPase injection. We hypothesize that a chronic physical stressor will exacerbate the sickness response following EBV-encoded dUTPase injection. To test this hypothesis mice receive daily injections of EBV-encoded dUTPase or vehicle and are subjected to 15 min of swim stress each day for 14 days or left unmanipulated. On the final evening of injections mice undergo behavioral testing. EBV-encoded dUTPase injection alone produces some sickness behaviors. The physical swimming stress does not alter the sickness response.

Alteration of Human Chorionic Gonadotropin Levels among Pregnant Women with Morning Sickness Attending Antenatal Care Services at Ishaka Adventist Hospital, Uganda

Globally, 50% - 90% of pregnant women are affected by morning sickness of pregnancy, especially during the first trimester. Therefore this study was carried out to establish if there is association between urinary hCG levels and severity of nausea, retching and vomiting among pregnant women attending antenatal care (ANC) services at Ishaka Adventist Hospital (IAH). It was a quantitative cross-sectional study in which a pre-tested and standardized questionnaire with a mixture of both open and closed ended questions was used to collect data from respondents to determine the clinical history, socio-demographic characteristics, and clinical features of morning sickness and/or hyperemesis gravidarum. Urine samples were also collected from each participant and analyzed using the Beckman Coulter Access 2 immunoassay system and Access Total hCG reagent pack at Mbarara University of Science and Technology. The findings showed that 63% of the respondents experienced morning sickness with the majority having a mild form. There was also no significant relationship between hCG levels and severity of morning sickness and no correlation between physiological characteristics (gravidity, age and weight) (correlation coefficient -0.05186, -0.0469 and 0.157 respectively). In addition, there was no correlation between cravings, aversions and morning sickness (correlation coefficient -0.0262 and 0.227 respectively). In conclusion, the study revealed that there was a high prevalence of morning sickness of pregnancy although, it was mild;no association between severity of morning sickness and levels of hCG as well as correlation between cravings and aversions with hCG levels in the study population. Considering the limitations of this study, it is recommended that studies should be undertaken for the quantitative determination of total hCG levels in urine for all pregnant women with morning sickness to be able to draw a definitive conclusion.