Diagnostic potential of urinary monocyte chemoattractant protein-1 for Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. METHODS: A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. RESULTS: In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. CONCLUSIONS: Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.

VOC exposures in California early childhood education environments.

Little information exists about exposures to volatile organic compounds (VOCs) in early childhood education (ECE) environments. We measured 38 VOCs in single-day air samples collected in 2010-2011 from 34 ECE facilities serving California children and evaluated potential health risks. We also examined unknown peaks in the GC/MS chromatographs for indoor samples and identified 119 of these compounds using mass spectral libraries. VOCs found in cleaning and personal care products had the highest indoor concentrations (d-limonene and decamethylcyclopentasiloxane [D5] medians: 33.1 and 51.4 µg/m³, respectively). If reflective of long-term averages, child exposures to benzene, chloroform, ethylbenzene, and naphthalene exceeded age-adjusted "safe harbor levels" based on California's Proposition 65 guidelines (10-5 lifetime cancer risk) in 71%, 38%, 56%, and 97% of facilities, respectively. For VOCs without health benchmarks, we used information from toxicological databases and quantitative structure-activity relationship models to assess potential health concerns and identified 12 VOCs that warrant additional evaluation, including a number of terpenes and fragrance compounds. While VOC levels in ECE facilities resemble those in school and home environments, mitigation strategies are warranted to reduce exposures. More research is needed to identify sources and health risks of many VOCs and to support outreach to improve air quality in ECE facilities.

Experimental studies of laser myocardial revascularization in rats.

Myocardial revascularization by Nd: YAG laser used in rats with myocardial infarction was studied. The left coronary artery was ligated and the laser channels with a diameter of 300 microns were made immediately by 2.5-4.2 W lasersonics YAG unit. After 24 hours, the rats were killed. Evaluation included hemodynamics, lactate dehydrogenase of myocardium and myocardial infarct size. The results showed that laser myocardial revascularization reduced myocardial infarct size and enzyme leakage, and improved left ventricular function. The study may provide theoretical basis for the clinical applications of this new technique in the treatment of ischemic heart disease.

[The relationship between Na overload and Na/H exchange--a study in the isolated isovolumic rat hearts].

Thirty min after stabilization perfusion with oxygenated buffer, hearts were divided in four groups: (1) CONTROL GROUP: 75 min. of aerobic perfusion; (2) Low flow anoxia group: 45 min. of low flow anoxic perfusion (95% N2:5%CO2, 0.15 ml/min.) followed by 30 min. of aerobic perfusion; (3) Ouabain group: protocol same as (2), except that ouabain (200 mumol/L) was added to anoxic perfusate during low flow anoxia; (4) Ouabain+Amiloride group: protocol same as (3) except that amiloride (0.5 mmol/I) was added to perfusate during low flow anoxia. Compared with the low flow anoxia group, ouabain resulted in an additional increase in Na during reperfusion accompanied with a depressed ventricular function. The deleterious effects of ouabain could be significantly combatted by amiloride. It is concluded that a decrease in Na/K ATPase activity may contribute to Na gain in reperfused myocardium, the mechanism of which might result from stimulation of Na/H exchange.

[Protection of superoxide dismutase on hypoxia-reoxygenation injury to endothelial cell].

Short term hypoxia induced endothelial cells (ECs) injury, as manifested in increasing lactate dehydrogenase (LDH) release and malondialdehyde (MDA) content, decreasing nitric oxide (NO) production and antioxidant enzyme glutathione peroxidase (GSH-Px) activity and increased intracellular calcium concentration, which were further exaggerated by reoxygenation. Administration of 200 U/ml superoxide dismutase (SOD) before hypoxia could partially prevent EC from such injuries, suggesting that the presence of oxygen free radicals may be one of the main factors involved in hypoxia-reoxygenation injury. The ameliorative effect of SOD in case is obviously due to elimination of oxygen free radicals.

[Effect of magnesium on postischemic reperfused myocardial mitochondria].

Isovolumic rat heart preparations were exposed to low flow ischemia (0.2 ml/min) for 60 min, followed by 30 min of reperfusion. The concentration of Mg2+ was maintained 1.2 mmol/L throughout the study in group 2, while increased to 15 mmol/L or depleted to zero during ischemia only in group 3 and group 1 respectively. High concentration Mg2+ showed a significantly protective effect on Ca-ATPase activity and synthesis ability of ATP in myocardial mitochondria, and decreased its calcium overload. Thus it appears that high concentration Mg2+ infusion may partially reverse postischemic reperfusion injury to heart.

[Effects of amiloride and glycogen depletion on post-ischemic reperfusion injury of isovolumic perfused rat hearts].

The effects of amiloride (0.5 nmol/L) and glycogen depletion were studied to find out the possible roles of Na(+)-H+ exchange of ischemia reperfusion injury in the isovolumic perfused isolated rat hearts. The data indicated that, compared to control group, both amiloride and glycogen depletion accelerated recovery of hemodynamics and reduced leakage of LDH and the formation of myocardial MDA which was accompared by a higher activity of mitochondrial GSH-Px and lesser accumulation of intracellular Na+, Ca2+. That Na(+)-H+ and Na(+)-Ca2+ exchanges might play a critical role in post-ischemic reperfusion injury is discussed.

[The effect of lycium barbarum polysaccharide on vascular tension in two-kidney, one clip model of hypertension].

In the present study, the effects of lycium barbarum polysaccharide (LBP) on endothelial function in the two-kidney, one clip model of hypertension were observed. The results showed that the increase of blood pressure in hypertension rats (HR) could be prevented significantly by treatment with 10% LBP. In isolated aortic rings of LBP-treated rats, the contraction of phenylephrine (PE) was reduced as compared with HR rats. Removal of the endothelium abolished the difference of PE-induced vasoconstriction among groups. In vitro incubation of aortic rings from LBP-treated rats with methyl blue (MB) or N-nitro-L-arginine methyl ester (L-NAME) increased the magnitude of PE-induced contraction. Meanwhile the response to acetylcholine (ACh) was significantly increased in LBP-treated rats, but the response to nitroprusside had no significant difference among groups. Pretreatment with L-arginine partially restored ACh-induced relaxation in RH rats, but no effect in LBP-treated rats. These results suggested that the role of LBP in decreasing vasoconstriction to PE may be mediated by increase of the effects or/and production of endothelium-derived relaxation factor (EDRF). LBP increased formation of EDRF may be related to increase the substrate of EDRF.

[Expression of heme oxygenase-1 in neonatal rat cardiocytes induced by lipopolysaccharide].

To study the alterations of heme oxygenase-1 mRNA in neonatal rat cardiomyocytes (NRCMs) induced by lipopolysaccharide (LPS) and the role of heme oxygenase-1 (HO-1) in the LPS induced disorders of myocardium function, 10 (L, 6 h), 30 (M, 6 h), 50 micrograms/ml (H, 6 h) LPS and 10 micrograms/ml LPS + 10 mumol/ml Zn-protoporphyrin-IX (ZnPPIX; L + I, 6 h) and 10 mumol/ml ZnPPIX alone (I, 6 h) were added to the medium for a 6-hour culture of NRCMs, and 10 micrograms/ml LPS for 9 h (L, 9 h) and 18 h (L, 18 h) cultures. LDH release and MDA contents of the cells were measured. When NRCMs were collected, Trypan blue stain method was used to examine the mortality (the rate of Trypan blue uptake) of NRCMs. HO-1 mRNA expression was examined by Northern blot. The results showed that HO-1 mRNA expression of NRCMs increased gradually along with the increase of LPS concentration below the level of 30 micrograms/ml. When the final concentrations of LPS were 10 and 30 micrograms/ml, the HO-1 mRNA expression of NRCMs increased by 81.2% and 126.3% respectively compared with control. When the final concentration of LPS was 50 micrograms/ml, the HO-1 mRNA expression decreased to the level of 10 micrograms/ml group. When the final concentration was 10 micrograms/ml, the HO-1 mRNA expression increased gradually along with the culture time. After a 9- or 18-hour culture, the HO-1 mRNA expression of NRCMs increased by 93.6% and 105.8% respectively compared with control. Only when NRCMs had been cultured with 30, 50 micrograms/ml LPS and 10 micrograms/ml LPS + 10 mumol/ml ZnPPIX for 6 h and 10 micrograms/ml LPS for 18 h, the rate of Trypan blue stain uptake, MDA contents and LDH release significantly increased. With 10 micrograms/ml LPS alone and 10 mumol/ml ZnPPIX alone for 6 h, the above parameters were not significantly increased (P > 0.05). The results demonstrate that LPS induces HO-1 mRNA expression of NRCMs dose- and time-dependently to some extent. The inducible HO can protect NRCMs from injury and thus play an important role in pathogenesis of myocardium under LPS.

Na+/H+ exchange is not operative under low-flow ischemic conditions.

Using 31P-NMR the existence of Na+/H+ exchange system and its contribution to intracellular pH (pHi) regulation were examined in the isolated isovolumic rat heart under physiological and pathophysiological conditions. Ethylisopropylamiloride (EIPA) was used as a tool to search into the role of Na+/H+ exchange system. In the normal well-oxygenated heart dose-dependent negative chronotropic effects were observed with 10(-6) to 10(-5) M EIPA. After 10(-4) M the heart ceased to beat and a progressive fall of high energy phosphates compounds occurred. However, contrary to expectation pHi did not fall but rose after EIPA. In NH4Cl-loaded hearts removal of NH4Cl resulted in a fall of the pHi followed by a rapid recovery to the normal pHi. After 10(-5) M EIPA the fall of pHi became greater and there was no recovery within 35 min of observation period. This dose of EIPA, however, did not affect the time course of changes in the pHi during 60 min of low-flow ischemia (0.2 ml/min). It is concluded that pHi regulation following an acute acid loading is dependent on amiloride-sensitive Na+/H+ exchange. However, Na+/H+ exchange system does not play an important role in maintenance of the pHi under normoxic or ischemic condition. In the normoxic heart EIPA produced a decrease in heart rate without producing any change either in myocardial energy metabolism or in pHi. Thus, the compound could be categorized as a bradycardic agent.

Transmission of intrathoracic pressure to the intracranial space during cardiopulmonary resuscitation in dogs.

Elevation of intrathoracic pressure during cardiopulmonary resuscitation generates carotid pressure and flow, but also increases intracranial pressure. This increase in intracranial pressure may limit cerebral blood flow. Therefore, we performed studies designed to quantify the extent of this transmission and to identify the mechanism of transmission of intrathoracic pressure to the intracranial space during cardiopulmonary resuscitation in dogs. Intracranial pressure increased during the chest compression phase of all modes of cardiopulmonary resuscitation tested. During simultaneous compression-ventilation cardiopulmonary resuscitation, change in intracranial pressure (mm Hg) = 0.33 change in intrathoracic pressure (mm Hg) + 2.02 (r = 0.86) and was not significantly different from the relationship observed during conventional cardiopulmonary resuscitation. The magnitude of transmission of intrathoracic pressure to the intracranial space was increased by binding the abdomen and by raising the baseline intracranial pressure. No single route accounted for transmission of intrathoracic pressure to the intracranial space during cardiopulmonary resuscitation. Intracranial pressure fluctuations were unrelated to either carotid arterial or jugular venous pressure, and were found instead to be the result of pressure transmission by blood in non-valved veins and by cerebrospinal fluid. This was determined by three maneuvers. First, obstruction of cerebrospinal fluid flow by ligation of the cervical spinal cord reduced intracranial pressure (P less than 0.001) and made the change in intracranial pressure equivalent to pressure changes at the confluence of the intracranial venous sinuses, without affecting pressure changes at the confluence of the intracranial venous sinuses. Second, ligation of the cervical spinal cord and one of the two longitudinal vertebral veins adjacent to the cervical cord reduced the pressure changes in the intracranial space and at the confluence of the intracranial venous sinuses to about 60% of the levels observed when the cervical cord alone was ligated. Thus, the non-valved longitudinal vertebral veins appear to be the vascular channels of critical importance to pressure transmission. Finally, pressure changes in the thoracic cerebrospinal fluid were increased (P less than 0.05) by cord ligation, even after exsanguination minimized pressure transmission via blood-filled channels, indicating direct transmission of intrathoracic pressure through intervertebral foramina to the cerebrospinal fluid.(ABSTRACT TRUNCATED AT 400 WORDS)

Determinants of blood flow to vital organs during cardiopulmonary resuscitation in dogs.

Whether blood flow during cardiopulmonary resuscitation (CPR) results from intrathoracic pressure fluctuations or direct cardiac compression remains controversial. From modeling considerations, blood flow due to intrathoracic pressure fluctuations should be insensitive to compression rate over a wide range, but dependent on the applied force and compression duration. If direct compression of the heart plays a major role, however, flow should be dependent on compression rate and force, but above a threshold, insensitive to compression duration. These differences in hemodynamics produced by changes in rate and duration form a basis for determining whether blood flow during CPR results from intrathoracic pressure fluctuations or from direct cardiac compression. Manual CPR was studied in eight anesthetized, 21 to 32 kg dogs after induction of ventricular fibrillation. There was no surgical manipulation of the chest. Myocardial and cerebral blood flows were determined with radioactive microspheres. At nearly constant peak sternal force (378 to 426 newtons), flow was significantly increased when the duration of compression was increased from 14 +/- 1% to 46 +/- 3% of the cycle at a rate of 60/min. Flow was unchanged, however, after an increase in rate from 60 to 150/min at constant compression duration. The hemodynamics of manual CPR were next compared with those produced by vest inflation with simultaneous ventilation (vest CPR) in eight other dogs. Vest CPR changed intrathoracic pressure without direct cardiac compression, since sternal displacement was less than 0.8 cm. At a rate of 150/min, with similar duration and right atrial peak pressure, manual and vest CPR produced similar flow and perfusion pressures. Finally, the hemodynamics of manual CPR were compared with the hemodynamics of direct cardiac compression after thoracotomy. Cardiac deformation was measured and held nearly constant during changes in rate and duration. As opposed to changes accompanying manual CPR, there was no change in perfusion pressures when duration was increased from 15% to 45% of the cycle at a constant rate of 60/min. There was, however, a significant increase in perfusion pressures when rate was increased from 60 to 150/min at a constant duration of 45%. Thus, vital organ perfusion pressures and flow during manual external chest compression are dependent on the duration of compression, but not on rates of 60 or 150/min. These data are similar to those observed for vest CPR, where intrathoracic pressure is manipulated without sternal displacement, but opposite of those observed for direct cardiac compression.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs.

The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min . 100 g (41 +/- 15% of control) and an average myocardial blood flow of 18 ml/min . 100 g (15 +/- 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 +/- 1% of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 +/- 2 ml/min . 100 g (73 +/- 25% control) and left ventricular blood flow at 38 +/- 9 ml/min . 100 g (28 +/- 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation.(ABSTRACT TRUNCATED AT 400 WORDS)