Ultrasound Sensing Using Packaged Microsphere Cavity in the Underwater Environment.

The technologies of ultrasound detection have a wide range of applications in marine science and industrial manufacturing. With the variation of the environment, the requirements of anti-interference, miniaturization, and ultra-sensitivity are put forward. Optical microcavities are often carefully designed for a variety of ultra-sensitive detections. Using the packaged microsphere cavity, we fabricated an ultrasound sensor that can work in an underwater environment. During practical detection, the optical resonance mode of the cavity can work with real-time response accordingly. The designed structure can work in various complex environments and has advantages in the fields of precision measurement and nano-particle detection.

Optimal photon-magnon mode matching in whispering-gallery mode cavities.

Optomagnonic structures are widely studied in the field of nanophotonics and quantum information science. They are the key platforms for the realization of magnon-mediated microwave to optical transducers in various applications of quantum computing. In order to enhance the coupling between light (photons) and spin waves (magnons), here in this work, we use the Lagrange multiplication method to find the optimum matching condition between the optical whispering-gallery mode and the magnon with Kittle and higher-order modes in microresonators. It is found that the magnon modes located near the edge of the resonator exhibits stronger coupling strength with the optical modes. Numerically, we find the coupling constant can approach 87.6×2π H z in Kittle mode, and 459×2π H z in high-order magnon mode for a yttrium iron garnet (YIG, Y3Fe5O12 ) microdisk cavity with a radius of 300 microns and a thickness of 10 microns. We believe these results may provide an efficient way for enhancing the magneto-optical interaction in the optical devices, which will facilitate the development of magneto-optical control, optical-microwave interaction, and optical nonlinearity.

The oncogenic role of MUC12 in RCC progression depends on c-Jun/TGF-ß signalling.

Renal cell carcinoma (RCC) is a common kidney cancer worldwide. Even though current treatments show promising therapeutic effectiveness, metastatic RCC still has limited therapeutic options so that novel treatments were urgently needed. Here, we identified that MUC12 was overexpressed in RCC patients and served as poor prognostic factor for RCC progression. Overexpression of MUC12 increased RCC cell growth and cell invasion while deficiency of MUC12 exerted opposite effects on RCC cells. Mechanistic dissection demonstrated that MUC12-mediated RCC cell growth and cell invasion were dependent of TGF-ß1 signalling because they could be blocked in the presence of TGF-ß1 inhibitor. Moreover, the regulation of TGF-ß1 by MUC12 relied on the transactivation of c-Jun. MUC12 promoted the recruitment of c-Jun on the promoter of TGF-ß1, leading to its transcription. Importantly, knockdown of c-Jun also attenuated MUC12-mediated TGF-ß1 induction and RCC cell invasion. In summary, our study defines the role of MUC12 in RCC progression and provides rational to develop novel targeted therapy to battle against RCC.

The association between three AXIN2 variants and cancer risk.

Plenty of epidemiological studies have assessed the effects of AXIN2 polymorphisms on the risk of developing cancer, but the available results were somewhat inconclusive. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the relationship between three AXIN2 variants (rs2240308 C/T, rs1133683 C/T, and rs4791171 A/G) and overall cancer susceptibility. In silico tools were undertaken to investigate the correlation of AXIN2 expression with cancer risk and survival time. Furthermore, we explored the serum expression of AXIN2 by enzyme-linked immunosorbent assay. A total of 4167 cancer patients and 3515 control subjects were evaluated. The overall results demonstrated that there was no major association of these polymorphisms on cancer risk. However, stratified analysis by cancer type showed evidence that rs2240308 C/T polymorphism had a lower risk in lung cancer (OR, 0.76; 95% CI, 0.63-0.92; Pheterogeneity = 0.865) and prostate cancer (OR, 0.54; 95% CI, 0.35-0.84; Pheterogeneity = 0.088) by heterozygote comparison. Similar results were indicated in Asian descendants and population-based studies. In silico analysis showed evidence that AXIN2 expressions in lung cancer and prostate cancer were lower than that in normal counterpart. High expression of AXIN2 may have longer overall survival time than low expression group for lung cancer participants. In addition, individuals who were CC/TC carriers had a higher serum expression level than TT carriers. In conclusion, this pooled analysis suggested that AXIN2 rs2240308 C/T variant may decrease both lung and prostate cancer susceptibility, particularly in Asian descendants and population-based studies. Future large scale and well-designed research are required to validate these effects in more detail.

New insights into the association between AXIN2 148 C/T, 1365 C/T, and rs4791171 A/G variants and cancer risk.

BACKGROUND: Many epidemiological studies have investigated association of AXIN2 variants on overall cancer risks; however, the available results remain inconsistent. METHODS: An updated analysis was conducted to ascertain a more accurate estimation of the correlation between AXIN2 148 C/T, 1365 C/T, and rs4791171 A/G polymorphisms and cancer risk. We also used in silico tools to assess the effect of AXIN2 expression on cancer susceptibility and overall survival time. RESULTS: A total of 4281 cases and 3955 control participants were studied. The overall results indicated that AXIN2 148 C/T variant was associated with cancer risk (allelic contrast: OR = 0.88, 95% CI 0.77-0.99, P heterogeneity = 0.004; dominant model: OR = 0.82, 95% CI 0.69-0.96, P heterogeneity = 0.022), especially for lung and prostate adenocarcinoma. Similar results were observed in 1365 C/T polymorphism (OR = 0.71, 95% CI 0.61-0.98, P heterogeneity = 0.873; dominant model: OR = 0.66, 95% CI 0.47-0.94, P heterogeneity = 0.775). Moreover, in subgroup analysis by ethnicity, similar findings were obtained for Asian and Caucasian populations. Results from in silico tools suggested that AXIN2 expressions in lung adenocarcinoma were lower than that in normal group. CONCLUSIONS: Our findings indicated that AXIN2 148 C/T and 1365 C/T variants may be associated with decreased cancer susceptibility.

Glissonian approach combined with major hepatic vein first for laparoscopic anatomic hepatectomy.

BACKGROUND: Laparoscopic anatomic hepatectomy remains challenging because of the complex interior structures of the liver. Our novel strategy includes the Glissonian approach and the major hepatic vein first, which serves to define the external and internal landmarks for laparoscopic anatomic hepatectomy. METHODS: Eleven cases underwent laparoscopic anatomic hepatectomy, including three right hepatectomies, three left hepatectomies, three right posterior hepatectomies, and two mesohepatectomies. The Glissonian approach was used to transect the hepatic pedicles as external demarcation. The major hepatic vein near the hepatic portal was exposed and served as the internal landmark for parenchymal transection. The liver parenchyma below and above the major hepatic vein was transected along the major hepatic vein. Fifty-nine subjects were used to compare the distance between the major hepatic vein and secondary Glisson pedicles among different liver diseases. RESULTS: The average operative time was 327 min with an estimated blood loss of 554.55 mL. Only two patients received three units of packed red blood cells. The others recovered normally and were discharged on postoperative day 7. The distance between right posterior Glissonian pedicle and right hepatic vein was shorter in the patients with cirrhosis than that without cirrhosis, and this distance was even shorter in patients with hepatocellular carcinoma. CONCLUSION: The Glissonian approach with the major hepatic vein first is easy and feasible for laparoscopic anatomic hepatectomy, especially in patients with hepatocellular carcinoma and cirrhosis.

Deregulated bile acids may drive hepatocellular carcinoma metastasis by inducing an immunosuppressive microenvironment.

Bile acids (BAs) are physiological detergents that can not only promote the digestion and absorption of lipids, but also may be a potential carcinogen. The accumulation of BAs in the body can lead to cholestatic liver cirrhosis and even liver cancer. Recently, studies demonstrated that BAs are highly accumulated in metastatic lymph nodes, but not in normal healthy lymph nodes or primary tumors. Lymph node metastasis is second only to hematogenous metastasis in liver cancer metastasis, and the survival and prognosis of hepatocellular carcinoma (HCC) patients with lymph node metastasis are significantly worse than those without lymph node metastasis. Meanwhile, component of BAs was found to significantly enhance the invasive potential of HCC cells. However, it is still poorly understood how deregulated BAs fuel the metastasis process of liver cancer. The tumor microenvironment is a complex cellular ecosystem that evolves with and supports tumor cells during their malignant transformation and metastasis progression. Aberrant BAs metabolism were found to modulate tumor immune microenvironment by preventing natural killer T (NKT) cells recruitment and increasing M2-like tumor-associated macrophages (TAMs) polarization, thus facilitate tumor immune escape and HCC development. Based on these available evidence, we hypothesize that a combination of genetic and epigenetic factors in cancerous liver tissue inhibits the uptake and stimulates the synthesis of BAs by the liver, and excess BAs further promote liver carcinogenesis and HCC metastasis by inducing immunosuppressive microenvironment.

Genome-wide methylation profiling of early colorectal cancer using an Illumina Infinium Methylation EPIC BeadChip.

BACKGROUND: DNA methylation is a part of epigenetic modification, that is closely related to the growth and development of colorectal cancer (CRC). Specific methylated genes and methylated diagnostic models of tumors have become current research focuses. The methylation status of circulating DNA in plasma might serve as a potential biomarker for CRC. AIM: To investigate genome-wide methylation pattern in early CRC using the Illumina Infinium Human Methylation 850K BeadChip. METHODS: The 850K Methylation BeadChip was used to analyze the genome-wide methylation status of early CRC patients (n = 5) and colorectal adenoma patients (n = 5). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were performed on the selected differentially methylated sites to further discover candidate methylation biomarkers in plasma. RESULTS: A total of 1865 methylated CpG sites with significant differences were detected, including 676 hypermethylated sites and 1189 hypomethylated sites. The distribution of these sites covered from the 1st to 22nd chromosomes and are mainly distributed on the gene body and gene promoter region. GO and KEGG enrichment analysis showed that the functions of these genes were related to biological regulation, molecular binding, transcription factor activity and signal transduction pathway. CONCLUSION: The study demonstrated that the Illumina Infinium Human Methylation 850K BeadChip can be used to investigate genome-wide methylation status of plasma DNA in early CRC and colorectal adenoma patients.

Rat colitis induced by intrathecal injection of substance P.

The aim of this study was to, from the point of neurogenic inflammation, explore the pathogenesis of colitis and to provide direct evidence for the neurogenic colitis hypothesis. Male Sprague-Dawley rats (180-220 g) anesthetized with chloral hydrate were intrathecally (ith) implanted with polyethylene-10 (PE-10) catheter to reach the spinal cord T12-L5 level. Substance P (SP) was ith injected once a day for 14 d. The disease active index (DAI) score was calculated by rat body weight and stool. The macroscopic and HE staining-microscopic pathologies of colon/spinal tissue were evaluated. By immunofluorescence staining, the protein expression of a pro-inflammatory cytokine, migration inhibitory factor (MIF), in colon tissue was detected and was semi-quantitatively analyzed. The results showed that in the colon tissue, inflammation was dose-dependently aggravated by ith SP 10 µ and 20 µ, whereas in the spinal tissue, only slight edema and congestion were seen in SP 20 µ group. The MIF protein of colon tissue was increased in ith SP 10 µ and 20 µ groups (P<0.05, P<0.01 as compared to normal saline group respectively), but in the spinal tissue, there was no obvious MIF protein expression either in SP groups or in normal saline group. Pretreatment with neurokinin-1 (NK1) receptor antagonist ([D-Pro2, D-Trp7, 9] -SP, 22.4 µ, ith, 10 min before ith SP) prolonged the latency of DAI rising and reduced the DAI amplitude, as well as prevented the high MIF expression induced by ith SP. These results suggest that rat colitis can be induced by direct SP stimulation in lumbar spine via activating central NK1 receptor; and that colonic MIF is possibly one of the inflammatory factors involved in this pathogenesis. These data provide a reasonable support to the hypothesis of colitis being a neurogenic inflammation. In addition, a potential clinical significance for the finding that higher concentration of spinal SP can induce colitis via NK1 receptor is discussed.

[Migration inhibitory factor is involved in experimental colitis induced by intrathecal injection of haptten to rat].

In recent years, there has emerged academic tendency towards the neurogenic mechanism of ulcerative colitis (UC). As one of the supports to the hypothesis of UC being a neurogenic inflammation, we have built a colitis model by intrathecal (ith) injection of a haptten 2,4-dinitrochlorobenzene (DNCB) to DNCB-sensitized rats. In order to explore further the neuroimmunal mechanism of this colitis model, we here focused on a pro-inflammatory cytokine, migration inhibitory factor (MIF), to observe its expression in rat colon nervous tissue and spinal cord in the colitis induced by ith injection of DNCB. At the same time we also observed the effect of MIF antibody pretreatment on the disease active index (DAI) score and the colon pathology by HE staining in the colitis rats. The results obtained showed that the immunofluorescence intensity of double staining of MIF protein in colon nervous tissue and spinal cord was increased in 0.8% and 1.6% DNCB-induced colitis groups than that in the control (60% ethanol) group. Both the colon pathology and the DAI score were significantly reduced by MIF antibody ith pretreatment. Ith injection of 0.8% DNCB after MIF antibody (1:10, 1:5) pretreatment could only induce lower DAI score (P<0.01 as compared, respectively, to the IgG pretreatment group). The colon pathological changes in ith 0.8% DNCB rats were mild, even little after MIF antibody (1:10, 1:5) pretreatment. These results suggest that MIF in spinal cord and enteric nervous system is possibly involved in the rat colitis induced by ith injection of DNCB, which reflects a neuroimmunal mechanism underlying this kind of colitis. MIF is possibly one of the important neurochemical factors in this experimental colitis, even in the UC.

Acceleration after-effects on learning and memory in rats: +10 Gz or +6 Gz for 3 min.

High sustained positive Gz (+Gz) exposures have been shown to have a pathophysiological impact on the brain in rats. However, the consequence for brain function such as learning and memory remains elusive. In the present study, we investigated locomotor activity, learning ability and memory in rats over 6 days (d) following +6 Gz/3 min and +10 Gz/3 min exposures. In an open field test, rats treated with +10 Gz showed a significant increase in the time spent in the center square immediately and 2d after exposure compared with control rats. In contrast, the number of grid crosses and number of rears of rats decreased significantly immediately after +6 Gz and +10 Gz exposures. In addition, a Y-maze test revealed that +Gz exposures reduced the number of correct responses and increased total reaction time in rats, and the number of correct responses was negatively correlated with the total reaction time in all groups throughout the period of study. Moreover, the passive avoidance test exhibited that the latency increased significantly on 0 d and decreased significantly on 6 d after +Gz exposures compared with control. Thus, +6 Gz/3 min and +10 Gz/3 min exposures may transiently decrease locomotor activity, impair learning, and induce a deficit in memory retention in rats.

Urea-containing peptide boronic acids as potent proteasome inhibitors.

A novel class of urea-containing peptide boronic acids as proteasome inhibitors was designed by introducing a urea scaffold to replace an amido bond. Compounds were synthesized and their antitumor activities were evaluated. After two rounds of optimizations, the compound I-14 was found to be a potent proteasome inhibitor. Compared with Bortezomib, I-14 showed higher potency against the chymotrypsin-like activity of human 20S proteasome (IC50 < 1 pM), similar potency against four different cancer cell lines (IC50 < 10 nM), and better pharmacokinetic profile. Furthermore, I-14 significantly inhibited tumor growth in Bel7404 mouse xenograft model. The excellent proteasome inhibition by I-14 was rationalized through docking and molecular dynamics studies.

Compliance changes in femoral veins of rabbits after 21 days of simulated weightlessness.

Increased venous compliance in lower limbs may be contributed to postflight orthostatic intolerance; however, direct animal studies to address the changes of venous compliance to microgravity have been rare. The purpose of this study was to determine compliance changes in femoral veins of rabbits after 21 days of head-down rest. Head-down rest -20 dgrees rabbit model was used to simulate weightlessness. 24 healthy male New Zealand Rabbits were randomly divided into 21 days of head-down rest group (HDR), horizontal immobilization group (HIG) and Ctrl group (Ctrl), with 8 in each. We constructed pressure-volume relationships from femoral veins in vivo for all groups after simulation by changing the venous internal volume and measuring the corresponding pressure. Microstructure of femoral vein wall in 3 groups was observed. Compared among the groups, the corresponding intravenous pressure of Ctrl was the highest when intravenous volume was expanded and HDR was the lowest. The parameter 3 , and P 2 in quadratic equations of femoral venous P-V relationship of HDR group were significantly higher than these values of HIG group and Ctrl group. The structure of femoral vein wall of HDR rabbits changed significantly, outlines of some endothelium cells (EC) became short and columnar or cubic, some of EC fell off and smooth muscle layer became thinner. These results indicate that, the femoral venous compliance increased after weightlessness simulation. This may partially underlie the mechanism of orthostatic hypotension seen in astronauts during an orthostatic stress after exposure to microgravity.

[Effects of low gravity preconditioning on rat learning and memory impairment induced by high gravity exposure].

OBJECTIVE: To study the protective effects of low gravity preconditioning against learning and memory function impairment induced by high gravity exposure in rats. METHOD: Twenty-four male SD rats were randomized equally into control group, high gravity exposure group (+10 Gz/3 min) and low gravity preconditioning group (LGP group, preconditioned by a daily exposure to +4 Gz/3 min for 3 days before +10 Gz/3 min exposure). Both the learning and memory abilities of the rats in the 3 groups were examined after +10 Gz/3 min exposure. RESULTS: In open field test, the rats exposed to +10 Gz/3 min, in comparison with the control rats, exhibited significantly declined total square-crossing and rearing (SCR) on days 0 and 2 (P<0.05), with also significantly prolonged stay in the central square at 0 d(P<0.01). In the low gravity preconditioned rats, SCR declined and length of stay in the central square increased significantly on day 0 (P<0.01). Compared with the rats in +10 Gz/3 min group, the rats in the LGP group showed decreased length of stay in the central square on day 2, and such changes was statistically significant on day 6 (P<0.05), but there was no difference in SCR at all time points. In Y-maze test, the number of times of right reaction (RR) decreased and the reaction time (RT) increased significantly in +10 Gz/3min group compared with those of the control group (P<0.01), whereas no significant differences were found between the control group and LGP group. Compared with +10 Gz/3 min group, the RR was increased (P<0.01) and RT shortened significantly (P<0.01) in LGP group. In the step-through test, the latent time (LT) increased (P<0.05) on day 0 but was then shortened significantly on day 6 in + 10 Gz/3min group (P<0.01), and no difference was found between LGP group and the control group. LT on day 6 increased significantly (P<0.01) in LGP group as compared with the +10 Gz/3 min group. CONCLUSION: High gravity exposure-induced rat learning and memory impairment can be markedly improved by lower gravity preconditioning.

[Effects of simulated weightlessness on ALP, ACP, collagen I, and biomechanics of hind-limb bones in rats].

OBJECTIVE: To investigate effects of 3 weeks simulated weightlessness on biomechanical parameters, alkaline phosphatase (ALP), acid phosphatase (ACP) and collagen I of hind-limb bones in tail-suspended rats. METHOD: Fourteen male SD rats were divided equally into control group (CON) and experimental group; tail-suspended (TS) was used to simulate weightlessness. After 3 weeks tail-suspension, biomechanical parameters of femur were measured; ALP, ACP and collagen I of tibia were observed. RESULT: Elastic load, maximum load, and bending rigidity coefficient decreased significantly (P<0.01), while the maximum deformation and bending toughness coefficient increased markedly (P<0.01 or P<0.05). Morphological results showed that ALP declines significantly in TS group, ACP and type I collagen increased significantly in TS group. CONCLUSION: After tail-suspension for 3 weeks, growth of rat's weight bearing bones are suppressed, biomechanical capability declines, and collagen I metabolism becomes disordered.

Changes of hippocampus somatostatin and learning ability in rats after +Gz exposure.

OBJECTIVE: To investigate changes of learning ability and somatostatin (SS) changes after positive acceleration (+Gz) exposures. METHOD: Eighty male SD rats were randomly divided into 3 groups: control group (Con), +6 Gz/3 min group (+6 Gz), and +10 Gz/3 min group (+10 Gz), 8 rats in each group. Changes of learning ability in rats were observed at 0 d, 2 d, 4 d and 6 d after +Gz exposure. SS in hippocampus was measured by RIA at 0 d, 2 d and 4 d after +Gz exposures (there were 8 rats every time, in each group). RESULT: In Y-maze test, number of correct response decreased significantly (P<0.01), and total reaction time increased significantly (P<0.01) in +6 Gz and +10 Gz groups as compared with control group; number of correct response and total reaction time in +10 Gz group changed significantly at 0 d (P<0.01 or P<0.05) as compared with +6 Gz group. RIA showed that, content of SS in hippocampus declined at 0 d and 2 d (P<0.05 or P<0.01) in +6 Gz and +10 Gz groups as compared with control group. CONCLUSION: +Gz exposure could impair learning ability of rats, and inhibit expression of SS in hippocampus.

Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity.

This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.

Model of depressed myocardium shows orthostatic intolerance with or without reduced blood volume.

INTRODUCTION: The development of orthostatic hypotension (OH) is complex and multi-factorial. Previous simulation work indicates that myocardial contractility depression (MCD) may increase OH when there is a total blood volume decrease. This paper hypothesized that MCD increased OH in both humans with and without decrease in blood volume. METHODS: A model, which was previously used to reproduce cardiovascular response to lower body negative pressure (LBNP), hypovolemia, and MCD, was modified by incorporating the physiologic mechanism of plasma filtration into the interstitium during LBNP. The model was evaluated by human experimental results. Using the model, HR and BP response to LBNP were simulated at conditions of 10%, 20%, and 30% MCD. Additionally, HR and BP response to LBNP were simulated at conditions of 10% and 20% MCD with a 12% decrease in blood volume. RESULTS: Simulation results indicate that the increments of HR and decrements of systolic BP (SBP) and mean arterial pressure (MAP) rise with the increases of MCD. Specifically, simulation results indicate that about 30% MCD would cause OH (HR: 117 bpm; SBP: 92 mmHg; MAP: 78 mmHg). It also indicates that about 20% MCD would cause OH (HR: 134 bpm, SBP: 84 mmHg, MAP: 73 mmHg) with a 12% decrease in total blood volume. CONCLUSION: It is suggested that MCD increases OH whether or not there is a total blood decrease, and further suggested that MCD induced by both spaceflight and heart disease may increase OH.

Effects of repeated brain ischemia induced by rapid lower body negative pressure on brain water and Na+,K+-ATPase activity in rats.

BACKGROUND: It has been demonstrated that during +Gz exposure cerebral blood flow is significantly reduced resulting in brain ischemia. Animal centrifuge models are commonly used to investigate the mechanisms of +Gz-induced loss of consciousness (G-LOC) and their pathophysiological effects on the brain. These dynamic models are limited because we currently are unable to obtain accurate measures of membrane ion flux or single cell electrophysiological responses from animals under centrifugation. HYPOTHESIS: The aim of the present study was to develop a non-centrifuge animal model of short-term, repeatable and complete brain ischemia using a rodent lower body negative pressure (LBNP), and to investigate the effects of repeated complete brain ischemia induced by LBNP on brain Na+,K+-ATPase activity, Na+, K+ and water contents in rats. METHODS: Eight anesthetized rats were exposed randomly to LBNP of -2.67 kPa, -4.00 kPa, and -5.33 kPa, respectively, at the rate of -0.67 kPa x s(-1). The pressure rapidly returned to control level when EEG became isoelectric (flat). The mean arterial BP (MAP), EEG and ECG were recorded. Twenty-one rats were divided randomly into control, single LBNP exposure, and three LBNP exposures groups (n = 7 in each group). Brain samples were analyzed for Na+,K+-ATPase activity, Na+, K+ and water contents 1 h after single and three 2-min LBNP exposures (-4.00 kPa at a rate of 0.67 kPa x s(-1)), respectively. RESULTS: MAP decreased rapidly during LBNP exposure. The mean time to isoelectric EEG was 41.33 +/- 11.48, 30.67 +/- 3.88 and 25.67 +/- 3.45 s during -2.67, -4.00 and -5.33 kPa LBNP, respectively. Heart rate (HR) significantly decreased when EEG became isoelectric. MAP, HR and EEG rapidly returned after releasing LBNP. The brain Na+,K-ATPase activity decreased significantly after single LBNP exposure and decreased further after three LBNP exposures. The brain K+, Na+ and water contents increased significantly after three LBNP exposures. CONCLUSIONS: A rat model of short-term, repeatable brain ischemia was developed using rapid LBNP. Three -4.00 kPa LBNP exposures (2 min each) cause a significant reduction in brain Na+,K+-ATPase activity and brain edema in rats.

Effect of lower body negative pressure against orthostatic intolerance induced by 21 days head-down tilt bed rest.

BACKGROUND: Exposure to actual or simulated weightlessness is known to induce orthostatic intolerance in humans. Many different methods have been suggested to counteract orthostatic hypotension. The repetitive or prolonged application of lower body negative pressure (LBNP) has shown beneficial effects to counter orthostatic intolerance, but devoting so much time to countermeasures is not compatible with space mission objectives or costs. The purpose of the present study was to assess the effects of brief LBNP sessions against orthostatic intolerance during a 21-d head-down tilt (HDT) bed rest. METHODS: There were 12 healthy male volunteers who were exposed to -6 degrees HDT bed rest for 21 d. Six subjects received -30 mm Hg LBNP sessions for 1 h x d(-1) from day 15 to day 21 of the HDT, and six others served as control. Orthostatic tolerance was assessed by means of standard tilt test. RESULTS: Before HDT, all the subjects in the two groups completed the tilt tests. After 21 d of HDT, five subjects of the control group and one subject of the LBNP group could not complete the tilt test due to presyncopal or syncopal symptoms. The mean upright time in the control group 13.0 +/- 4.0 min) was significantly shorter (p < 0.05) than that in the LBNP group (19.0 +/- 2.2 min). Body weight decreased significantly in the control group during HDT, while increasing significantly on day 21 of HDT in the LBNP group. Urine volume increased on days 15-21 of HDT in the control group, but remained unchanged throughout HDT in the LBNP group. A significant decrease in cardiac output and cardiac index, and a significant increase in total peripheral resistance, pre-ejection period, plasma renin activity, aldosterone, and prostaglandin 12 were observed during HDT in both groups. There were no significant differences in these parameters between the two groups. CONCLUSIONS: Brief daily LBNP sessions were effective in preventing orthostatic intolerance induced by 21 d HDT bed rest. However, it did not improve cardiac pump and systolic functions and did not preserve volume regulating hormones.