IL-22 relieves sepsis-induced liver injury via activating JAK/STAT3 signaling pathway.

The purpose of this study was to investigate the influence of interleukin(IL)-22 on the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway and sepsis-induced liver injury in rats. A total of 48 Sprague-Dawley rats were randomly divided into sham-operated group (n=12), model group (n=12), low-dose group (n=12) and high-dose group (n=12). Next, rat models of sepsis-induced liver injury were established through cecal ligation and puncture (CLP). At 12 h after surgery, blood was collected by heart puncture to detect liver function of the rats. It was found that the activity of alanine aminotransferase (ALT) and aspartame aminotransferase (AST) and the content of total bilirubin were reduced in low-dose group and high-dose group. Hematoxylin-eosin (HE) staining results revealed that after treatment with IL-22, the liver injury was relieved compared with model group. Moreover, the results of TUNEL staining assay revealed that the apoptosis level of liver cells declined after treatment with IL-22. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the levels of IL-6 and TNF-α were reduced, while the level of IL-10 was increased after treatment with IL-22. Moreover, it was discovered that the SOD content was overtly elevated in low-dose and high-dose groups compared with that in the model group. Finally, using Western blotting, it was confirmed that in comparison with the model group, the levels of Bcl-2/Bax and JAK/STAT3 signaling pathway-related proteins were markedly raised, while the level of Caspase-3 was decreased in the low-dose and high-dose groups. In conclusion, IL-22 can improve liver function, reduce the apoptosis level of liver cells, the expression of apoptosis-related proteins and the release of inflammatory factors, and alleviate liver injury by activating the JAK/STAT3 signaling pathway.

Effects of ultrasonic processing on degradation of salvianolic acid B in aqueous solution.

To evaluate the stability of salvianolic acid B (Sal B) under ultrasound-assisted extraction in the pharmaceutical industry, degradation of Sal B under ultrasonic irradiation was investigated as the function of buffer concentration, pH, and temperature. With regard to Sal-B concentration, a first-order degradation process was determined, with 10% change in assay from its initial concentration as t90=4.81h, under maximum stability acidic conditions (pH 2.0) and at 25°C. The logkpH-pH profile described by specific acid-base catalysis and water molecules supported the experimental results. Liquid chromatography-mass spectrometry (LC-MS) analyses revealed 7 major degradation products whose structures were characterized by electrospray ionization/mass spectrometry. A primary degradation pathway involved cleavage of the ester bond and ring-opening of benzofuran in Sal B was proposed. The complete degradation pathway of Sal B was also proposed. Results showed that ultrasonic irradiation leads to degradation of Sal B in aqueous solution.

Potential rapid solutions to maintain ventilation in the event of anaesthesia machine failure with no access to the patient's airway.

Anaesthesia machine failure requires rapid solutions to maintain ventilation and anaesthesia. During procedures with poor access to the patient's airway, it may not be possible to use a self-inflating mechanical ventilation device (SIMVD) for emergency ventilation, and alternative solutions are needed. We evaluated five methods for rescue ventilation using a patient simulator. In Method 1, we used the inspiratory and expiratory tubes and the alternative common gas outlet (ACGO) on the anaesthesia machine to produce a Mapleson E system. In Method 2, we used the tubes, ACGO and an open-ended reservoir bag to produce a Mapleson F system, controlling the bag to achieve ventilation. In Method 3, we attached a SIMVD to the inspiratory tube, and controlled occlusion of the expiratory tube. In Method 4, we used the tubes and ACGO in a Mapleson F configuration, replacing the open-ended bag with a SIMVD to facilitate manual ventilation. In Method 5, we attached a SIMVD to the expiratory tube and left the inspiratory tube attached to its mounting. We were able to achieve ventilation, maintain inhalational anaesthesia, and prevent expired gas rebreathing in Methods 1 and 2. In Method 3 ventilation was achieved with minimal rebreathing of expiratory gas, but with no inhalational agent. Methods 4 and 5 led to rebreathing. Our findings indicate that Methods 1 or 2 are the preferred rapid solutions to maintain ventilation and inhalational anaesthesia in the event of anaesthesia machine failure where there is poor airway access.

Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury.

Nerve injuries cause pain, paralysis and numbness that can lead to major disability, and newborns often sustain nerve injuries during delivery that result in lifelong impairment. Without a pharmacologic agent to enhance functional recovery from these injuries, clinicians rely solely on surgery and rehabilitation to treat patients. Unfortunately, patient outcomes remain poor despite application of the most advanced microsurgical and rehabilitative techniques. We hypothesized that the detrimental effects of traumatic neonatal nerve injury could be mitigated with pharmacologic neuroprotection, and tested whether the novel neuroprotective agent P7C3 would block peripheral neuron cell death and enhance functional recovery in a rat neonatal nerve injury model. Administration of P7C3 after sciatic nerve crush injury doubled motor and sensory neuron survival, and also promoted axon regeneration in a dose-dependent manner. Treatment with P7C3 also enhanced behavioral and muscle functional recovery, and reversed pathological mobilization of spinal microglia after injury. Our findings suggest that the P7C3 family of neuroprotective compounds may provide a basis for the development of a new neuroprotective drug to enhance recovery following peripheral nerve injury.

Risk factors for liver abscess formation in patients with blunt hepatic injury after non-operative management.

PURPOSE: To identify risk factors for liver abscess formation in patients with blunt hepatic injury who underwent non-operative management (NOM). METHODS: From January 2004 to October 2008, retrospective data were collected from a single level I trauma center. Clinical data, hospital course, and outcome were all extracted from patient medical records for further analysis. RESULTS: A total of 358 patients were enrolled for analysis. There were 13 patients with liver abscess after blunt hepatic injury. Patients with abscess had a significant increase in glutamic oxaloacetic transaminase (GOT, p = 0.006) and glutamic pyruvic transaminase (GPT, p < 0.0001), and a decrease in arterial blood pH (p = 0.023) compared to patients without abscess in the univariate analyses. In addition, high-grade hepatic injury and transarterial embolization (TAE, p < 0.001) were also risk factors for liver abscess formation. Five factors (GOT, GPT, pH level in the arterial blood sample, TAE, and high-grade hepatic injury) were included in the multivariate analysis. TAE, high-grade hepatic injury, and GPT level were statistically significant. The odds ratios of TAE and high-grade hepatic injury were 15.41 and 16.08, respectively. A receiver operating characteristic (ROC) analysis was used for GPT, and it suggested cutoff values of 372.5 U/L. A prediction model based on the ROC analysis had 100 % sensitivity and 86.7 % specificity to predict liver abscess formation in patients with two of the three independent risk factors. CONCLUSIONS: TAE, high-grade hepatic injury, and a high GPT level are independent risk factors for liver abscess formation.

UGT1A1 polymorphisms associated with risk of induced liver disorders by anti-tuberculosis medications.

First-line drug treatment for tuberculosis (TB) is frequently associated with liver toxicity. The goal of this study was to examine the association between UDP-glucuronosyl-transferase 1A1 (UGT1A1) genetic variations and anti-tuberculosis drug-induced hepatotoxicity (ATDH). A total of 98 patients, including 17 patients with ATDH, were enrolled; compound UGT1A1*27 and UGT1A1*28 were associated with an increased risk for developing ATDH after adjusting for age (OR 13.859; 95%CI 1.085-177.056). These findings require confirmation. However, screening for genetic variations prior to TB treatment may reduce the incidence of ATDH and improve treatment adherence.

Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathways.

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively active Akt construct markedly abrogated PEITC-mediated JNK activation, Mcl-1 downregulation, caspase activation, and apoptosis, and also interruption of the JNK pathway by pharmacological or genetically (e.g., siRNA) attenuated PEITC-induced apoptosis. Finally, administration of PEITC markedly inhibited tumor growth and induced apoptosis in U937 xenograft model in association with inactivation of Akt, activation of JNK, as well as downregulation of Mcl-1. Taken together, these findings represent a novel mechanism by which agents targeting Akt/JNK/Mcl-1 pathway potentiate PEITC lethality in transformed and primary human leukemia cells and inhibitory activity of tumor growth of U937 xenograft model.

Significant human beta-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating.

AIMS: Diabetes mellitus results from an absolute or relative deficiency of insulin-producing pancreatic ß-cells. The turnover rate of adult human ß-cells remains unknown. We employed two techniques to examine adult human islet ß-cell turnover and longevity in vivo. METHODS: Subjects enrolled in National Institutes of Health clinical trials received thymidine analogs [iododeoxyuridine (IdU) or bromodeoxyuridine (BrdU)] 8 d to 4 yr prior to death. Archival autopsy samples from 10 patients (aged 17-74 yr) were employed to assess ß-cell turnover by scoring nuclear analog labeling within insulin-staining cells. Human adult ß-cell longevity was determined by estimating the cells' genomic DNA integration of atmospheric (14)C. DNA was purified from pancreatic islets isolated from cadaveric donors; whole islet prep DNA was obtained from a 15-yr-old donor, and purified ß-cell DNA was obtained from two donors (ages 48 and 80 yr). (14)C levels were then determined using accelerator mass spectrometry. Cellular "birth date" was determined by comparing the subject's DNA (14)C content relative to a well-established (14)C atmospheric prevalence curve. RESULTS: In the two subjects less than 20 yr of age, 1-2% of the ß-cell nuclei costained for BrdU/IdU. No ß-cell nuclei costained in the eight patients more than 30 yr old. Consistent with the BrdU/IdU turnover data, ß-cell DNA (14)C content indicated that the "birth date" of cells occurred within the subject's first 30 yr of life. CONCLUSIONS: Under typical circumstances, human ß-cells and their cellular precursors are established by young adulthood.

An evaluation of the laryngeal mask airway supreme' in 100 patients.

The Laryngeal Mask Airway (LMA) Supreme is a new supraglottic airway incorporating features of the LMA Proseal, LMA Fastrach and LMA Unique. We evaluated the LMA Supreme in 100 patients with normal airways having elective surgery. Our success rates of insertion and ventilation were 96% at the first attempt and 100% after two attempts. The median time to successful placement was 15 seconds (interquartile range 12 to 18 seconds). Forty-five patients breathed spontaneously and 55 patients had controlled ventilation. The incidence of blood staining on removal was 7% and 7% of patients had mild sore throat one hour postoperatively. One patient who had been placed in the left lateral position during surgery had left lingual nerve palsy postoperatively, which recovered completely after one month. Our findings suggest that in patients with normal airways, the LMA Supreme is easy to insert and provides a satisfactory airway with adequate seal pressures for ventilation.

The impact of manual in-line stabilisation on ventilation and visualisation of the glottis with the LMA CTrach: a randomised crossover trial.

The LMA CTrach (CTrach) enables ventilation, glottis visualisation and tracheal intubation via a laryngeal mask conduit. The CTrach has been successfully used in patients with cervical spine pathology, but it is unclear if cervical spine immobilisation affects its ease of use. In this randomised crossover trial, the CTrach was used once with and once without manual in-line stabilisation of the cervical spine in every patient. With manual in-line stabilisation, the median [IQR] time to achieve ventilation was 22 [16-32] s, compared with 19 [13-30] s without stabilisation (p = 0.065). With manual in-line stabilisation, the time to achieving a glottic views was 42 [30-63] s compared with 39 [25-53] s without stabilisation (p = 0.019). There was no difference in the success rates of achieving ventilation and glottic views. These results suggest that manual in-line stabilisation does not affect use of the CTrach.

Tracheal intubation with videolaryngoscopes in patients with cervical spine immobilization: a randomized trial of the Airway Scope and the GlideScope.

BACKGROUND: The GlideScope (Verathon Inc., Bothell, WA, USA) and Airway Scope (Hoya Corp., Tokyo, Japan) have both been used for difficult airway management, including in patients with cervical spine pathology. The Airway Scope's disposable blade has a tube channel to guide tracheal tube insertion through the glottis. Our hypothesis is that this tube guidance system improves the ease of tracheal intubation compared with the GlideScope, which does not have a tube guiding system. We tested this hypothesis in a randomized comparison of the two videolaryngoscopes in patients whose cervical spines were immobilized. METHODS: Seventy consenting patients were randomized to have tracheal intubation with the GlideScope (n=35) or the Airway Scope (n=35). In all patients, we applied manual in-line stabilization of the cervical spine throughout airway management. All the airway procedures were carried out by two anaesthetists experienced in the use of both videolaryngoscopes. RESULTS: The tracheal intubation time was 34.2 (sd 25.1) s with the Airway Scope compared with 71.9 (47.9) s with the GlideScope (P<0.001). Tracheal intubation was successful with the Airway Scope in 35 (100%) patients compared with 31 (88.6%) patients with the GlideScope (P=0.114). Tracheal intubation was successful within 60 s in 33 (94.3%) patients with the Airway Scope and 22 (62.9%) patients with the GlideScope (P=0.003). CONCLUSIONS: These results suggest that the Airway Scope's tube guide system enables more rapid tracheal intubation compared with the GlideScope in patients with cervical spine immobilization.

Pancreatic beta cell function persists in many patients with chronic type 1 diabetes, but is not dramatically improved by prolonged immunosuppression and euglycaemia from a beta cell allograft.

AIMS/HYPOTHESIS: We measured serum C-peptide (at least 0.167 nmol/l) in 54 of 141 (38%) patients with chronic type 1 diabetes and sought factors that might differentiate those with detectable C-peptide from those without it. Finding no differences, and in view of the persistent anti-beta cell autoimmunity in such patients, we speculated that the immunosuppression (to weaken autoimmune attack) and euglycaemia accompanying transplant-based treatments of type 1 diabetes might promote recovery of native pancreatic beta cell function. METHODS: We performed arginine stimulation tests in three islet transplant and four whole-pancreas transplant recipients, and measured stimulated C-peptide in select venous sampling sites. On the basis of each sampling site's C-peptide concentration and kinetics, we differentiated insulin secreted from the individual's native pancreatic beta cells and that secreted from allografted beta cells. RESULTS: Selective venous sampling demonstrated that despite long-standing type 1 diabetes, all seven beta cell allograft recipients displayed evidence that their native pancreas secreted C-peptide. Yet even if chronic immunosuppression coupled with near normal glycaemia did improve native pancreatic C-peptide production, the magnitude of the effect was quite small. CONCLUSIONS/INTERPRETATION: Some native pancreatic beta cell function persists even years after disease onset in most type 1 diabetic patients. However, if prolonged euglycaemia plus anti-rejection immunosuppressive therapy improves native pancreatic insulin production, the effect in our participants was small. We may have underestimated pancreatic regenerative capacity by studying only a limited number of participants or by creating conditions (e.g. high circulating insulin concentrations or immunosuppressive agents toxic to beta cells) that impair beta cell function.

Ease of intubation with the GlideScope or Airway Scope by novice operators in simulated easy and difficult airways--a manikin study.

The GlideScope and Airway Scope are video laryngoscopes that have been found to be useful in difficult airway situations. With the GlideScope, there are frequently problems associated with insertion of the tracheal tube despite the ability to view the glottis. The Airway Scope's imaging system and disposable PBlade aid alignment of the PBlade with the glottis and guide insertion of the tracheal tube. We performed a randomised crossover study of 20 medical students using both videolaryngoscopes in a manikin, with simulated normal and difficult airway scenarios. We found that the students required less time for tracheal intubation with the Airway Scope and reported greater ease of intubation with the Airway Scope in both scenarios. A greater number of students chose the Airway Scope as their device of choice. Our results suggest that the Airway Scope's features may improve the ease of tracheal intubation compared with the GlideScope.

Cricoid pressure prevents placement of the laryngeal tube and laryngeal tube-suction II.

BACKGROUND: The laryngeal tube has a potential role in patients with a difficult airway, but cricoid pressure is required if the patient is at risk of aspiration. The effect of cricoid pressure on insertion of these devices is unknown. METHODS: In a randomized cross-over study, the laryngeal tube (25 patients) or the laryngeal tube-suction II (15 patients) was inserted with cricoid pressure applied on one occasion and with sham pressure on the other occasion. Adequacy of ventilation, time to achieve adequate ventilation, and the leak pressure were assessed. RESULTS: Ventilation was adequate in all patients when sham pressure was applied. Cricoid pressure significantly reduced the rate of adequate ventilation to 6 of 25 patients for the laryngeal tube [P < 0.001; 95% confidence interval (CI) for difference: 59-93%] and to 5 of 15 patients for the laryngeal tube-suction II (P < 0.05; 95% CI for difference: 43-91%). The median time taken to achieve adequate ventilation for the laryngeal tube was 10 s [inter-quartile range (IQR): 8-15] (range 5-26) for sham pressure and 25 s (15-32) (15-33) for cricoid pressure; the median leak pressure was 30 (IQR: 30-30) (range 20-30) cm H2O for sham pressure and 15.5 (14.3-20.5) (12-22) cm H2O for cricoid pressure. CONCLUSIONS: Continuous cricoid pressure prevents correct placement of the laryngeal tube and the laryngeal tube-suction II such that placement and ventilation via these devices are ineffective. The effect of cricoid pressure on ventilation via these devices, after correct placement, remains unknown.

Nocistatin attenuated the nociceptin induced c-Fos expression in the mouse hippocampus.

Nocistatin and nociceptin/orphaninFQ (N/OFQ) are the two new peptides which may have roles in nociception, memory, anxiety, and other biological functions. Nocistatin acts as a functional antagonist to N/OFQ in several functions, but their neuro-anatomical sites of interaction are unknown. We investigated the effect of combined intracerebroventricular (i.c.v.) injection of nocistatin with N/OFQ, on N/OFQ induced c-Fos expression in the mouse hippocampus, using c-Fos immunohistochemistry. We found that co-injection of nocistatin with N/OFQ significantly attenuated N/OFQ induced c-Fos expression in the hippocampus.

The accuracy of surrogate decisions in intensive care scenarios.

Critically ill patients are often unable to make decisions about life-sustaining treatments and surrogate decision-makers are relied upon. However, it is unclear how accurately the surrogates' decisions reflect patients' intentions and expectations. We interviewed 36 pairs of patients and their appointed surrogate decision-makers about their decisions regarding nine treatments in each of three scenarios. The scenarios were persistent vegetative state, coma with likely neurological damage and chronic disease with dementia. The patients were interviewed 24 hours after they had undergone elective surgery under general anaesthesia. The surrogates were interviewed separately by the same interviewer. There was poor agreement between decisions made by the patients and their surrogates. The patients' and surrogates' summary scores (median (interquartile range) [range]) for treatments were 0 (0-4) [0-9] vs 8 (0-9) [0-9] for the vegetative state scenario, 3 (0-9) [0-9] vs 9 (0-9) [0-9] for the coma scenario and 3 (0-9) [0-9] vs 9 (4-9) [0-9] for the chronic disease scenario. The significantly higher surrogate scores suggest that the surrogates' decisions would have resulted in the patients having far more treatment than the patients would have wanted. In our participants, there was poor agreement between the decisions made by surrogates and patients. Further study is needed on measures such as facilitated discussions, advance directives and the difficulties that surrogates face, in order to improve the accuracy of surrogates' decisions and respect of patients' autonomy.