Xiumin Zhang

Acute stress reduces intraparenchymal lung natural killer cells via beta-adrenergic stimulation

There are lines of evidence that natural killer (NK) cells are sensitive to physical and psychological stress. Alterations in the immune system including NK cells are known to differ among tissues and organs. The effect of stress on the lung immune system, however, has not been well documented in spite of the fact that the lungs always confront viral or bacterial attacks as well as tumour cell metastasis. In this study, we intended to investigate the effect of restraint stress on lung lymphocytes including NK cells. C57BL/6 mice were exposed to 2 h restraint stress. The concentration of plasma epinephrine significantly rose immediately after the release from restraint as compared to home‐cage control mice. Flow cytometric analysis revealed that the numbers of most lymphocyte subsets including NK cells were decreased in the lungs and blood but not in the spleen, immediately after restraint stress. Immunohistochemical examination revealed that the number of NK cells was decreased in the intraparenchymal region of the lungs, while the number of alveolar macrophages did not change. The decrease in the number of NK cells in the lungs and blood was reversed by the administration of propranolol, a nonselective beta adrenergic antagonist. Taken together, our findings suggest that acute stress reduces the number of intraparenchymal lung NK cells via activation of beta adrenergic receptors.

Acute stress-induced colonic tissue HSP70 expression requires commensal bacterial components and intrinsic glucocorticoid

Induction of heat shock protein (HSPs) has a protective effect in cells under stress. Physical stressors, such as restraint, induce HSPs in colonic tissue in vivo, but the mechanism of HSP induction is not yet clear. Because commensal bacteria support basal expression of colon epithelial HSP70, we postulated that stress responses may enhance the interaction of commensal bacteria and the colonic tissue. Restraining C57BL/6 mice for 2h effectively induced HSP70 in colonic epithelia. Both blockade of stress-induced glucocorticoid by RU486 or elimination of commensal bacteria by antibiotics independently abrogated restraint-induced HSP70 augmentation. Oral administration of LPS to commensal-depleted mice restored restraint-induced HSP70 augmentation. Because TLR4 expression was absent from the epithelial surface, and was limited to lamina propria and muscularis externa, we examined how LPS reaches the lamina propria. Alexa-LPS administered in the colonic lumen was only detected in the lamina propria of the restrained mice. Expression of the tight junction component ZO-1 in the epithelia, which regulates the passage of luminal substances through the epithelia, was reduced after restraint, but reversed by RU486. In conclusion, HSP70 induction in colonic epithelial cells under restraint requires both stress-induced glucocorticoid and luminal commensal bacteria, and LPS plays a significant role. Glucocorticoid-dependent attenuation of epithelial tight junction integrity may facilitate the access of LPS into the lamina propria, where TLR4, known to be required for HSP70 induction, is abundantly expressed. Sophisticated regulation of colonic protection against stressors involving the general stress response and the luminal environment has been demonstrated.

Effects of Metabolic Syndrome on Cardio-Ankle Vascular Index in Middle-Aged and Elderly Chinese

Metabolic syndrome is characterized by multiple risk factors and is associated with increased risk of diabetes and cardiovascular disease. The rapid change in the lifestyle and food habits of Chinese people has resulted in metabolic syndrome becoming one of the most widespread health challenges in China. Recently, the cardio-ankle vascular index (CAVI) was developed as a new parameter reflecting arterial stiffness and providing an index of vascular status. The purpose of this study was to investigate the effect of metabolic syndrome on CAVI. A total of 222 Chinese subjects aged 50-92 years participated in this study. We measured CAVI and examined blood samples to define metabolic syndrome according to the International Diabetes Federation criteria. CAVI in the subjects with abnormal waist circumference was significantly higher than that obtained in the normal subjects (P < 0.01). In the abnormal high-density lipoprotein cholesterol (HDL-C) group, CAVI was significantly increased (P < 0.01) compared to the normal HDL-C group. CAVI showed a positive correlation with waist circumference and increased significantly with the number of metabolic syndrome components. In conclusion, subjects with metabolic syndrome have a high CAVI that indicated arterial stiffness and is closely associated with an increase in the number of metabolic syndrome risk factors. Elevated abdominal obesity and low HDL-C are the main players affecting arterial stiffness in the middle-aged and elderly Chinese. These findings suggest that interaction of the individual components of metabolic syndrome plays a role in the relationship between metabolic syndrome and arterial stiffness.

Biochemical evaluation of an artificial anal sphincter made from shape memory alloys

Severe anal incontinence is a socially incapacitating disorder and a major unresolved clinical problem that has a considerable negative impact on quality of life. In this study, we developed a new artificial anal sphincter using shape memory alloys (SMAs) in order to improve the quality of life of such patients and evaluated the influence of this sphincter on blood serum chemistry in animal experiments. The artificial anal sphincter was driven by two Ti-Ni SMA actuators sandwiching the intestine and was implanted in three female goats. Blood was collected from the jugular vein on days 1 and 4; at weeks 1 and 2; and at months 1, 2, and 3, postoperatively. Biochemical parameters including total protein, albumin, total bilirubin, aspartate amino-transferase, blood urea nitrogen, creatinine, and C-reactive protein were examined. The time courses of total bilirubin and aspartate amino transferase of the three goats were within the baseline levels after 1 week of implantation and remained normal, demonstrating no liver function complications. The blood urea nitrogen and creatinine levels remained within the normal range, indicating no renal function complications. The total protein and albumin fluctuated within the normal range throughout the duration of this study. In these goats, it was also found that the level of C-reactive protein did not increase and that there was no stricture of the intestine where the artificial sphincter was attached. Our findings indicate that the artificial sphincter SMA demonstrated no adverse influence on blood serum chemistry and exhibited an effective system performance.

Exercise training enhances in vivo tuberculosis purified protein derivative response in the elderly

We investigated the effect of 25 wk of exercise training on in vivo immune measures that depend on T helper 1 (Th1) and T helper 2 (Th2) immune responses in the elderly as a substudy of a randomized controlled trial to investigate health benefits of regular exercise training for the elderly. Sixty-five healthy elderly volunteers were randomly assigned to either an exercise training group (n = 32) or a sedentary control group (n = 33). The area of skin reaction to purified protein derivative (PPD) of tuberculin that depends on Th1 activation and the concentrations of serum IgG subclasses and IgE were evaluated before and after 25-wk intervention. All participants completed 25 wk of training. Thirty-one participants of the exercise group and all control group underwent immunological analyses, but only 30 from the exercise group and 21 from the control group had the PPD skin reaction assessment. Repeated-measures ANOVA revealed a significant interaction between time and exercise intervention, which appeared as an enhanced skin reaction to tuberculin PPD (P < 0.05) and a reduced serum IgG4 concentration, the production of which depends on Th2-dependent class switching (P < 0.05), in the exercise group after 25 wk. No immune variables changed in the control group. These result supports the hypothesis that exercise training favors in vivo Th1 immune response in elderly persons.

Female scent mobilizes leukocytes to airways in BALB/c male mice.

The scent of receptive females as a signal to reproduction stimulates male mice to olfactory search of a potential breeding partner. This searching behavior is coupled with infection risk due to bacterial contamination of the fecal and urine scent marks. We hypothesized that sniffing of female soiled bedding induced the migration of immuno-competent cells into airways as a possible adaptation to breeding-related infection. Using bronchoalveolar lavage in a study on mice, we found the number of leukocytes to be significantly higher in male mice that were provided new portions of soiled bedding daily from female cages, in comparison with male mice that were kept in isolation from female scent. The number of leukocytes in blood was equal in both groups. However, monocytes were fewer in number in male mice exposed to female scent than in male mice isolated from female mice. Scent-induced migration of leukocytes was accompanied by typical behavioral (increased sniffing activity and aggressiveness) and morphological (increase preputial glands and seminal vesicles) responses to olfactory sexual stimulus.

Analysis of Baroreflex Sensitivity During Undulation Pump Ventricular Assist Device Support

The aim of this study was to examine the baroreflex sensitivity (BRS), which involves the autonomic nervous system, in a goat with a chronically implanted undulation pump ventricular assist device (UPVAD). The UPVAD involved transforming the rotation of a brushless DC motor into an undulating motion by a disc attached via a special linking mechanism, and a jellyfish valve in the outflow cannula to prevent diastolic backflow. The pump was implanted into the thoracic cavity of a goat by a left thoracotomy, and the inflow and outflow cannulae were sutured to the apex of the left ventricle and to the descending aorta, respectively. The driving cable was wired percutaneously to an external controller. Electrocardiogram and hemodynamic waveforms were recorded at a sampling frequency of 1 kHz. BRS was determined when awake by the slope of the linear regression of R-R interval against mean arterial pressure changes, which were induced by the administration of methoxamine hydrochloride, both with continuous driving of the UPVAD as well as without assistance. BRS values during the UPVAD support and without assistance were 1.60 +/- 0.30 msec/mm Hg and 0.98 +/- 0.22 msec/mm Hg (n = 5, P < 0.05), respectively. BRS was significantly improved during left ventricular assistance. Therefore, UPVAD support might decrease sympathetic nerve activity and increase parasympathetic nerve activity to improve both microcirculation and organ function.

BIOLOGICAL EFFECTS OF THE ARTIFICIAL ANAL SPHINCTER IN THE GOAT MODEL

Artificial anal sphincters could provide an alternative solution for severe anal incontinence when conventional surgical methods are not possible. We have created an artificial anal sphincter using a shape memory alloy (SMA) and evaluated its validity. The aim of this study was to determine the biological effects and safety after implantation of the SMA artificial anal sphincter in an animal model. The artificial anal sphincter consists of two all-round SMA plates as the main functional parts which perform two basic functions: occlusion at normal body temperature and release upon heating. The SMA artificial anal sphincter was implanted into three female goats under anesthesia. Blood was collected postoperatively from the jugular vein on days 1 and 4, at week 1, and months 1, 2, and 3, and biochemical parameters were examined. Biochemical test results were within normal limits during the 3-month study period. All biochemical measurements of organ function remained within normal range. The results demonstrated that the SMA artificial anal sphincter caused no significant failure of liver, renal, autonomic or digestive functions or damage to smooth muscle. This long-term animal experiment supported the concept and design of implantation with an SMA artificial anal sphincter, and the results demonstrate very good biocompatibility and effective system performance.