Health risk assessment of heavy metals and disinfection by-products in drinking water in megacities in China: A study based on age groups and Monte Carlo simulations.

Heavy metal(loid)s (HMs) and disinfection by-products (DBPs) in drinking water pose risks to human health and jeopardize drinking water. Water-related behaviors vary significantly among different age groups and regions. In this study, the carcinogenic and non-carcinogenic risks of HMs (As, Cd, Cr6+, Cu, Pb, and Zn) and DBPs (bromodichloromethane (BDCM), bromoform, chloroform, dibromochloromethane (DBCM), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA)) in drinking water in two Chinese megacities (Beijing in North China and Guangzhou in South China) via multiple exposure pathways were assessed. The results showed that children aged 9 months to 2 years had a total carcinogenic risk (TCR) and hazard index (HI) above acceptable levels, indicating that despite the drinking water quality in the selected megacities meeting the current Chinese national standards (GB 5749-2022), the health risks of exposure to HMs and DBPs in drinking water for local young children should not be neglected. Specifically, the carcinogenic risk (CR) of exposure to As in drinking water for children < 18-years-old, who were divided into different age groups, was 1.5-2.0- and 4.5-5.9-times higher than the TCR of exposure to DBPs in Beijing and Guangzhou, respectively. Regarding children aged 9 months to 2 years, the exposure to TCAA accounted for the largest proportion (35.6 %) of the TCR of exposure to DBPs in Beijing drinking water, 5.4-times higher than that in Guangzhou; whereas, the TCR of exposure to DBPs in Guangzhou drinking water was predominantly caused by exposure to chloroform, accounting for 40.6 % of the TCR and 1.5-times higher than that in Beijing. In addition, the CR of exposure to DCAA in drinking water in both megacities accounted for a large proportion of the TCR for children aged 9 months to 2 years. Monte Carlo simulations showed that 62.2 % and 42.6 % of the TCR of simultaneous exposure to As and DBPs in drinking water exceeded the acceptable level for sensitive populations, that is, children aged 1-2 years in Beijing (95th percentile = 4.2 × 10-4) and children aged 9-12 months in Guangzhou (95th percentile = 5.2 × 10-4), respectively. This elaborate health risk assessment sheds light on improving the water quality indices to guarantee drinking water safety in China.

Antifungal activity of thymol and carvacrol against postharvest pathogens Botrytis cinerea.

Botrytis cinerea is a primary pathogen causing stem and fruit rot during pre- and post-harvest. In the present study, the main purpose was to inquire into the antifungal activity and potential mechanisms of thymol and carvacrol against B. cinerea. During the experiment, the effects of thymol and carvacrol on physical and biochemical parameters of B. cinerea were evaluated. Results indicated that thymol and carvacrol exhibited strong antifungal activity against the targeted pathogen, with minimum inhibitory concentration and minimum fungicidal concentration of 65 mg/L and 100 mg/L for thymol, and 120 µL/L and 140 µL/L for carvacrol. Thymol and carvacrol changed obviously the morphology of B. cinerea hyphae by disrupting and distorting the mycelia through scanning electron microscopy. The membrane permeability of B. cinerea hyphae was prompted with the increment of two chemical agents' concentration, as evidenced by extracellular conductivity increase, the release of cell constituent, and the decrease of extracellular pH. Furthermore, a marked decline in total lipid content of B. cinerea cells was induced by the two chemical agents, suggesting that the cell membrane structures were destructed. Therefore, present results indicated that thymol and carvacrol may be used as a good alternative to conventional fungicides against B. cinerea in controlling grey molds in horticultural products.

Soil microbial responses to simultaneous contamination of antimony and arsenic in the surrounding area of an abandoned antimony smelter in Southwest China.

Soil contamination with heavy metal(loid)s may influence microbial activities in the soil, and consequently jeopardize soil health. Microbial responses to soil contamination play an important role in ecological risk assessment. This study investigated the effect of heavy metal(loid)s contamination on microbial community structure and abundance in the surrounding soil of an abandoned antimony (Sb) smelter in Qinglong county, Guizhou province, Southwest China. A total of 46 soil samples were collected from ten sampling sites (labelled as A-I, and CK) across the study area at depths of 0-2, 2-10, 10-20, 20-30, 30-40, and 40-50 cm. The soil samples were analyzed for total and bioavailable heavy metal(loid) concentrations, bacterial, fungal, and archaeal community structures, diversities, and functions, together with soil basic physicochemical properties. Much greater ecological risk of Sb and arsenic (As) was present in the surface soil (0-2 cm) compared to that in the subsoils. The activities of dominant microorganisms tended to be associated with soil pH and heavy metal(loid)s (i.e., Sb, As, lead (Pb), cadmium (Cd), and chromium (Cr)). Bacteria associated with IMCC26256, Rhizobiales, Burkholderiales, and Gaiellales, and archaea associated with Methanocellales were estimated to be tolerant to high concentrations of Sb and As in the soil. In addition, the magnitude of soil microbial responses to Sb and As contamination was in the order of archaea > bacteria > fungi. In contrast to the negligible response of fungi and negative response of bacteria to Sb and As contamination, there was a strongly positive correlation between archaeal activity and total Sb and As concentrations in the soil. Our findings provide a theoretical basis for the remediation of Sb smelter-affected soil.

Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats.

BACKGROUND: We have previously reported that electroacupuncture (EA) pretreatment induced tolerance against cerebral ischemic injury, but the mechanisms underlying this effect of EA are unknown. In this study, we assessed the effect of EA pretreatment on the expression of α7 nicotinic acetylcholine receptors (α7nAChR), using the ischemia-reperfusion model of focal cerebral ischemia in rats. Further, we investigated the role of high mobility group box 1 (HMGB1) in neuroprotection mediated by the α7nAChR and EA. METHODS: Rats were treated with EA at the acupoint "Baihui (GV 20)" 24 h before focal cerebral ischemia which was induced for 120 min by middle cerebral artery occlusion. Neurobehavioral scores, infarction volumes, neuronal apoptosis, and HMGB1 levels were evaluated after reperfusion. The α7nAChR agonist PHA-543613 and the antagonist α-bungarotoxin (α-BGT) were used to investigate the role of the α7nAChR in mediating neuroprotective effects. The roles of the α7nAChR and HMGB1 release in neuroprotection were further tested in neuronal cultures exposed to oxygen and glucose deprivation (OGD). RESULTS: Our results showed that the expression of α7nAChR was significantly decreased after reperfusion. EA pretreatment prevented the reduction in neuronal expression of α7nAChR after reperfusion in the ischemic penumbra. Pretreatment with PHA-543613 afforded neuroprotective effects against ischemic damage. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and HMGB1 release following reperfusion, and the beneficial effects were attenuated by α-BGT. The HMGB1 levels in plasma and the penumbral brain tissue were correlated with the number of apoptotic neurons in the ischemic penumbra. Furthermore, OGD in cultured neurons triggered HMGB1 release into the culture medium, and this effect was efficiently suppressed by PHA-543,613. Pretreatment with α-BGT reversed the inhibitory effect of PHA-543,613 on HMGB1 release. CONCLUSION: These data demonstrate that EA pretreatment strongly protects the brain against transient cerebral ischemic injury, and inhibits HMGB1 release through α7nAChR activation in rats. These findings suggest the novel potential for stroke interventions harnessing the anti-inflammatory effects of α7nAChR activation, through acupuncture or pharmacological strategies.

Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

BACKGROUND: Electroacupuncture (EA) pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. RESULTS: EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. CONCLUSIONS: EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

Anesthesia with sevoflurane and remifentanil under spontaneous respiration assisted with high-frequency jet ventilation for tracheobronchial foreign body removal in 586 children.

BACKGROUND: Foreign body aspiration is a common life-threatening event in young children. Tracheobronchial foreign body removal is usually performed by rigid tracheobronchoscopy under general anesthesia. Anesthetic and ventilation techniques vary greatly among anesthesiologists and institutions. In the present retrospective study, we report our anesthetic experience over 5 years. We describe complications and outcomes and analyze the clinical characteristics of anesthesia and ventilation. METHODS: We retrospectively reviewed relevant clinical findings of 586 pediatric patients treated with rigid tracheobronchoscopy under general anesthesia. All procedures were performed under inhaled sevoflurane anesthesia combined with remifentanil infusion, with spontaneous respiration assisted by high-frequency jet ventilation (HFJV) and topical airway anesthesia. RESULTS: Among 586 patients, the foreign body was successfully removed by rigid tracheobronchoscopy in 558 patients, and no foreign body was found in 28 patients. Laryngospasm was observed during the procedure in five patients. Hypoxemia was observed in 15 patients (2.6%). No severe complications or deaths occurred. The mean operation time was 22 min and the average hospital stay was 2 days. CONCLUSION: Inhaled sevoflurane anesthesia combined with remifentanil infusion, with spontaneous respiration assisted by HFJV and topical airway anesthesia, is safe and effective for tracheobronchial foreign body removal.

Comprehensive evaluation of environmental dimension reduction of multi-type islands: a sustainable development perspective.

In recent years, the sustainable development of islands has attracted increasing attention from countries all over the world. An important prerequisite for promoting sustainable development is to understand the foundation and sustainable development potential of islands. Constructing index systems and models is an important means of evaluating the sustainability of islands. This study used factor analysis (FA) to construct an indicator system and set weights. Thirty-eight indicators were set from both natural and social directions to evaluate the sustainable development of seven typical islands in China. The FA removed the 10 indicators that were too relevant, and the 28 effective indicators were reduced into 9 main factors for evaluation. The results showed that the evaluation results are in line with the actual development of the island, which verifies the applicability of the model to different types of islands. The study also found that the changing trends of island social sustainability, tourism sustainability, ecological sustainability, resource sustainability, and economic sustainability are consistent. The value of fully balanced islands is higher than that of unbalanced or undeveloped islands. Among the seven islands, social islands have the highest total value, and ecological islands have the lowest total value.

Sensitization of Non-Small Cell Lung Cancer Cells to Gefitinib and Reversal of Epithelial-Mesenchymal Transition by Aloe-Emodin Via PI3K/Akt/TWIS1 Signal Blockage.

Objective: To explore the impacts of AE (aloe-emodin) in gefitinib-resistant NSCLC (non-small cell lung cancer) cells and the corresponding mechanism. Methods: PC9 and PC9-GR cells were cultured and treated by gefitinib, AE, or the combination of the two drugs. Then, viability, apoptosis, migration and invasion of cells were investigated using CCK-8, TUNEL, wound healing assay, and transwell assay, respectively. Female BALB/c nude mice were employed for the establishment of xenograft tumor models to examine the role of AE in tumor growth. Results: PC9-GR cells showed reduced apoptosis and enhanced cell viability, migration and invasion upon treatment by gefitinib, compared with PC9 cells. E-cahherin in PC9-GR cells was down-regulated, while Vimentin, Snail2 (or Slug) and Twist1 in PC9-GR cells were up-regulated, compared with PC9 cells. Meanwhile, treatment by a combination of gefitinib and AE significantly strengthened apoptosis of PC9-GR cells, while attenuated their migration and invasion, compared with the control group or treatment by gefitinib or AE alone. WB results showed that AE could reverse EMT and activation of PI3K/AKT signalling pathway in PC9-GR cells. In vivo experiments showed that tumor growth and EMT of PC9-GR cells were dramatically repressed after treatment by a combination of AE and gefitinib. Additionally, the use of SC97 (a PI3K/Akt pathway activator) could counteract the effects of AE in gefitinib-resistant PC9 cells. Conclusions: AE could enhance the gefitinib sensitivity of PC9-GR cells and reverse EMT by blocking PI3K/Akt/TWIS1 signal pathway.

Security risk assessment and visualization study of key nodes of sea lanes: case studies on the Tsugaru Strait and the Makassar Strait.

Key nodes of sea lanes are important hubs for global trade and cargo transportation and play important roles in ensuring the safety of maritime transportation and maintaining the stability of the global supply chain. The safety guarantee of key nodes of sea lanes is facing more risks and higher requirements currently because the global shipping industry is gradually recovering. This paper focuses on key nodes of sea lanes, conducting regional security risk assessment and risk spatial scale visualization. A set of security risk assessment and visualization study methods for key nodes of sea lanes is constructed, which includes constructing a security risk assessment index system of key nodes of sea lanes with 25 indicators selected from three risk categories (hazard, vulnerability and exposure, and mitigation capacity) and using geospatial analysis to form the multi-criteria spatial mapping layers and then creating comprehensive risk layers to realize the risk visualization in the strait area by weighted overlaying based on the combined weights calculated by Analytic Hierarchy Process and Grey Relational Analysis. After taking the Tsugaru Strait and Makassar Strait as case studies, the results show that the comprehensive risk layers can effectively present the spatial distribution of security risks of key nodes of sea lanes, reflecting the spatial changes of risk levels (i.e., very low, low, medium, high and very high) and the methods can precisely identify and analyze crucial factors affecting the security risk of key nodes. These findings may strengthen the risk prevention and improve the safety of the navigation environment in the strait to ensure the safety and stability of maritime trade.

Activation of epsilon protein kinase C-mediated anti-apoptosis is involved in rapid tolerance induced by electroacupuncture pretreatment through cannabinoid receptor type 1.

BACKGROUND AND PURPOSE: Our previous study has demonstrated that the rapid tolerance to cerebral ischemia by electroacupuncture (EA) pretreatment was possibly mediated through an endocannabinoid system-related mechanism. The purpose of this study was to investigate whether activation of epsilon protein kinase C (εPKC) was involved in EA pretreatment-induced neuroprotection via cannabinoid receptor type 1 in a rat model of transient focal cerebral ischemia. METHODS: The activation of εPKC in the ipsilateral brain tissues after EA pretreatment was investigated in the presence or absence of cannabinoid receptor antagonists. At 2 hours after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 minutes in rats. The neurobehavioral scores, infarction volumes, neuronal apoptosis, and the expression of Bcl-2 and Bax were evaluated after reperfusion in the presence or absence of εPKC-selective peptide inhibitor (TAT-εV1-2) or activator (TAT-ψεRACK). RESULTS: EA pretreatment enhanced εPKC activation. Systemic delivery of TAT-ψεRACK conferred neuroprotection against a subsequent cerebral ischemic event when delivered 2 hours before ischemia. Pretreatment with EA reduced infarct volumes, improved neurological outcome, inhibited neuronal apoptosis, and increased the Bcl-2-to-Bax ratio after reperfusion, and the beneficial effects were attenuated by TAT-εV1-2. In addition, the blockade of cannabinoid receptor type 1, but not cannabinoid receptor type 2 receptor, reversed the increase in εPKC activation and neuroprotection induced by EA pretreatment. CONCLUSIONS: EA pretreatment may activate endogenous εPKC-mediated anti-apoptosis to protect against ischemic damage after focal cerebral ischemia via cannabinoid receptor type 1, which represents a new mechanism of EA pretreatment-induced rapid tolerance to focal cerebral ischemia in rats.

Preconditioning with repeated hyperbaric oxygen induces myocardial and cerebral protection in patients undergoing coronary artery bypass graft surgery: a prospective, randomized, controlled clinical trial.

OBJECTIVES: To evaluate the cerebral and myocardial protective effects of hyperbaric oxygen preconditioning in both on-pump and off-pump coronary artery bypass graft surgery. DESIGN: A prospective, randomized, single-blinded study including patients scheduled for elective on-pump or off-pump surgery between December 2007 and February 2009. SETTING: A tertiary care university teaching hospital. PARTICIPANTS: Forty-nine elective on-pump or off-pump coronary artery bypass graft surgery patients. INTERVENTIONS: Patients were randomized to either the control (15 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) or hyperbaric oxygen (HBO; 14 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) groups. Patients in the HBO groups underwent preconditioning for 5 days before surgery. MEASUREMENTS AND MAIN RESULTS: On-pump coronary artery bypass graft surgery patients preconditioned with HBO had significant decreases in S100B protein, neuron-specific enolase, and troponin I perioperative serum levels compared with the on-pump control group. Postsurgically, patients in the on-pump HBO group had a reduced length of stay in the intensive care unit and a decreased use of inotropic drugs. Serum catalase activity 24 hours postoperatively was significantly increased compared with the on-pump control group. In the off-pump groups, there was no difference in any of the same parameters. CONCLUSIONS: Preconditioning with HBO resulted in both cerebral and cardiac protective effects as determined by biochemical markers of neuronal and myocardial injury and clinical outcomes in patients undergoing on-pump coronary artery bypass graft surgery. No protective effects were noted in off-pump coronary artery bypass graft surgery.

Liver transplantation in a patient with pulmonary hypertension at high altitude.

Chronic hypoxia at high altitude stresses many of the body's homeostatic mechanisms. As a consequence, the body develops alveolar hypoxia, hypoxemia, and polycythemia, which in turn causes vasoconstriction, pulmonary hypertension, and an increased risk of atherothrombotic complications. We report a successful liver transplantation in a patient with pulmonary hypertension who lives 4500 m above sea level. Pulmonary hypertension and hypercoagulable state induced by chronic hypoxia at high altitude may increase the risk of cardiopulmonary complication and perioperative mortality. The patient was discharged in good condition with normal liver function at the 34th postoperative day. After 41 months of follow-up, the patient is alive and well with a continued normalization of hepatic function and is continuing to live at 4500 m above sea level.

Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system.

BACKGROUND AND PURPOSE: Our previous study demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. The present study was aimed to investigate the involvement of the endocannabinoid system in the early neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia. METHODS: Two hours after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 minutes in male Sprague-Dawley rats or male C57BL/6 mice. The neurobehavioral scores, infarction volumes, and neuronal apoptosis were evaluated at 24 hours or 7 days after reperfusion in the presence or absence of AM251 (a selective cannabinoid receptor type 1 [CB1] receptor antagonist) or CB1 short interfering RNA. The expression of CB1 receptor and the content of endocannabinoids in the brains were also investigated. RESULTS: EA pretreatment reduced infarct size, improved neurological outcome, and inhibited neuronal apoptosis at 24 hours or 7 days after reperfusion. The beneficial effects were abolished by AM251. CB1 knockdown by CB1 short interfering RNA attenuated EA pretreatment-induced neuroprotection. EA pretreatment upregulated the neuronal expression of CB1 receptor in the rat brains and elevated the brain tissue content of the endocannabinoid 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide. Pretreatment with 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide also reduced infarct size and improved neurological outcome. CONCLUSIONS: We conclude that pretreatment with EA increases the production of endocannabinoid 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide, which elicits protective effects against transient cerebral ischemia through CB1 receptors. These results suggest a novel mechanism of EA pretreatment-induced rapid tolerance to focal cerebral ischemia.

TAT-mediated protein transduction of Nogo extracellular peptide 1-40 and its biological activity.

AIM: Nogo extracellular peptide 1-40 (NEP1-40), a Nogo-66 antagonistic peptide, is one of the potential candidates for therapeutic intervention after central nervous system injury. This study is focused on the generation of TAT-NEP1-40 fusion protein and its transducible effects and biological activity. METHODS: TAT-NEP1-40 fusion protein was expressed in vitro. Transducible effects of TAT-NEP1-40 were analyzed by using immunofluorescence staining or Western blot in vitro and in vivo. The biological activity of TAT-NEP1-40 was assessed by its effects against oxygen and glucose deprivation (OGD)-induced PC12 cell damages. RESULTS: Our results showed that the TAT-NEP1-40 fusion protein was successfully expressed, purified, and refolded. Western blot analysis and immunofluorescence staining confirmed the delivery of TAT-NEP1-40 protein into PC12 cells and rat brains. OGD caused cell apoptosis or death, decreased cell viability, increased lactate dehydrogenase release in medium and the Bax/Bcl-2 ratio, all of which were prevented by the TAT-NEP1-40 fusion proteins when added exogenously to culture medium. In addition, TAT-NEP1-40 promoted neurite outgrowth of PC12 cells exposed to OGD. CONCLUSION: These results demonstrate that the TAT-NEP1-40 can be successfully generated and efficiently transduced into PC12 cells and rat brains. The TAT-NEP1-40 can protect PC12 cells against OGD and promote neurite outgrowth. This finding suggests that the transducible TAT-NEP1-40 fusion protein offers a possibility of the development of novel therapy for cerebral injuries via delivery of the biologically active TAT-NEP1-40 fusion protein into injured sites.

Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits.

BACKGROUND: Ethyl pyruvate (EP) has been reported to offer a protective effect against ischemic injury through its antiinflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. This study was designed to investigate the neuroprotective effect of EP against spinal cord ischemic injury and the potential role of HMGB1 in this process. METHODS: EP was administered at various time points before or after 20 min of spinal cord ischemia in male New Zealand rabbits. All animals were sacrificed at 72 h after reperfusion with modified Tarlov criteria, and the spinal cord segment (L4) was harvested for histopathological examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. The HMGB1 levels in serum and spinal cord tissue were analyzed by enzyme-linked immunosorbent assay. RESULTS: The treatment of EP at 30 min before ischemia or at 6 h after reperfusion significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons, which was accompanied with reduction of the number of apoptotic neurons and levels of HMGB1 in serum and spinal cord tissue. The HMGB1 contents of spinal cord tissue correlated well with the numbers of apoptotic motor neurons in the anterior spinal cord at 72 h after reperfusion. CONCLUSION: These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release.

Therapeutic time window and mechanism of tetramethylpyrazine on transient focal cerebral ischemia/reperfusion injury in rats.

The purpose of this study was to explore the therapeutic time window and mechanism of tetramethylpyrazine on transient focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20mg/kg tetramethylpyrazine was injected intraperitoneally at different time points. Neurological deficit scores and brain infarction volumes were measured 72 h after reperfusion started. The expression of thioredoxin and thioredoxin reductase were examined at 6h and at 24h after reperfusion. Our results included the findings of a significant reduction in neurological deficit scores and infarction volume in the treatment group as compared to the control group. Ischemia/reperfusion injury resulted in a decrease in the expression of thioredoxin, while tetramethylpyrazine administration greatly elevated the expression of thioredoxin-1/thioredoxin-2 mRNA and thioredoxin reductase-1/thioredoxin reductase-2 mRNA. These findings suggest that administration of tetramethylpyrazine, within a 4h time period post-transient focal stroke, may reduce cerebral ischemic reperfusion damage. Moreover, the neuroprotective effect of tetramethylpyrazine may be mediated, in part, by an increase in genetic transcription of thioredoxin.

The early effect of Voluven, a novel hydroxyethyl starch (130/0.4), on cerebral oxygen supply and consumption in resuscitation of rabbit with acute hemorrhagic shock.

BACKGROUND: Voluven (hydroxyethyl starch [HES] 130/0.4), a new generation of HES product with low molecular weight, has been widely used for the treatment of traumatic and hemorrhagic shock in clinics. However, no data are available whether it affects the balance of cerebral oxygen supply and consumption when applied to resuscitate hemorrhagic shock. The purpose of this study was to address this question in rabbits subjected to a severe hemorrhagic shock. METHODS: In New Zealand rabbits, an acute hemorrhagic shock was induced by withdrawing 45% to 50% of total blood volume from the femoral vein in 10 minutes when the mean arterial pressure was reduced to 60% of the baseline level. Thirty minutes after the hemorrhage, animals were infused with either an equal amount of Voluven (group V) or a tripled amount of lactated Ringer's solution (group R). The saturation of oxygen was obtained in arterial (Sao2) and venous (SjvO2) blood samples from the femoral artery and jugular bulb, respectively. Arterial oxygen content (Cao2), jugular oxygen content (CjvO2), arteriovenous oxygen difference (AVDO2), and cerebral oxygen extraction rate (CERO2) were calculated accordingly to evaluate the oxygenation state in the brain. RESULTS: Levels of SjvO2 and CjvO2 were decreased after hemorrhagic shock, and there were increases in AVDO2 and CERO2 values. After resuscitation, the SjvO2, AVDO2, and CERO2 levels in group V were quickly recovered to the basal levels, whereas the values in group R remained in the abnormal levels (p < 0.05). There were significant differences between the groups in their SjvO2 and CERO2 levels at 30 minutes after resuscitation. In addition, the mean arterial pressure was restored to the basal levels in group V but not in group R after resuscitation (p < 0.05). CONCLUSION: We conclude that early infusion of Voluven is beneficial for maintenance of the hemodynamic stability and for the balance of cerebral oxygen supply and consumption during the resuscitation of acute hemorrhagic shock.

Trans-activator of transcription-mediated delivery of NEP1-40 protein into brain has a neuroprotective effect against focal cerebral ischemic injury via inhibition of neuronal apoptosis.

BACKGROUND: The Nogo-66 antagonistic peptide (NEP1-40) is a potential candidate for therapeutic intervention of neuronal injury. However, delivery of the proteins across the blood-brain barrier is severely limited by its size and biochemical properties. The current study was designed to evaluate the transducible effects of the trans-activator of transcription (TAT) transduction system for NEP1-40 to cross the blood-brain barrier and to clarify whether intraperitoneal administration of TAT-NEP1-40 could protect cerebral neurons from ischemic injury. METHODS: Adult male Sprague-Dawley rats were submitted to a 120-min focal ischemia and received an intraperitoneal injection of No-TAT-NEP1-40, TAT-NEP1-40, TAT-beta-galactosidase, or vehicle. The existence of the proteins in the brain was analyzed with immunofluorescence and Western blot techniques at 6 h after injection. Brain ischemic injury was evaluated by neurologic deficit scores, infarction volumes, terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling staining, and assay of caspase-3 activity. RESULTS: Western blot analysis and immunofluorescence staining confirmed the presence of TAT-NEP1-40 protein in the brains 6 h after injection. Intraperitoneal injection of TAT-NEP1-40 could attenuate the numbers of terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling-positive cells and activated caspase-3 positive cells, and increase the viability of the cells in the ischemic bounder zone, compared with that treated with No-TAT-NEP1-40, TAT-beta-Gal, or vehicle. Furthermore, treatment with TAT-NEP1-40 significantly improved the neurologic outcomes and reduced the size of the infarction in rats. CONCLUSIONS: The results demonstrate that the TAT-NEP1-40 could be efficiently delivered into the rat brains and improve ischemia-induced neurologic outcomes through attenuating cell apoptosis in ischemic brains.