HN Group Research Articles

Predictors and Prognostic Impact of Nutritional Changes After Transcatheter Aortic Valve Replacement

BackgroundLittle is known about changes in nutritional status as an index of frailty on clinical outcomes after transcatheter aortic valve replacement (TAVR). This study aimed to assess the clinical impact of serum albumin changes after TAVR. MethodsChanges in serum albumin levels from baseline to 1 year after TAVR were evaluated in 1524 patients who were classified as having hypoalbuminemia (<3.5 g/dl) and normoalbuminemia (≥3.5 g/dl) at each timepoint. The patients were categorized into 4 groups: NN (baseline normoalbuminemia, 1-year normoalbuminemia: n = 1119), HN (baseline hypoalbuminemia, 1-year normoalbuminemia: n = 202), NH (baseline normoalbuminemia, 1-year hypoalbuminemia: n = 121), and HH (baseline hypoalbuminemia, 1-year hypoalbuminemia: n = 82). We also defined late hypoalbuminemia as hypoalbuminemia identified at the 1-year assessment. Clinical outcomes were compared among 4 groups. Multivariable analysis was driven to assess the variables associated with late hypoalbuminemia and long-term mortality. ResultsThe cumulative 3-year mortality was significantly different among the 4 groups (NN: 11.4%, HN: 10.7%, NH: 25.4%, HH: 44.4%, p < 0.001). Multivariable Cox regression analysis revealed that the NH group had a higher mortality risk (hazard ratio [HR]; 2.80 and 3.53, 95% confidence interval [CI]; 1.71–4.57 and 2.06–6.06, p < 0.001 and p < 0.001, respectively), whereas the HN group had a similar risk (HR; 1.16, 95% CI; 0.66–2.06, p = 0.61) compared with the NN group. Baseline hypoalbuminemia, low body mass index, liver disease, peripheral artery disease, and hospital readmission within 1 year were predictors of late hypoalbuminemia (all p < 0.05). ConclusionSerial albumin assessment may identify poor prognostic subsets in patients with persistent and late acquired malnutrition after TAVR.

Restoring Blood Pressure in Hypertensive Mice Fails to Fully Reverse Vascular Stiffness.

BackgroundHypertension is a well-established driver of vascular remodeling and stiffening. The goal of this study was to evaluate whether restoring normal blood pressure (BP) fully restores vascular stiffness toward that of normotensive controls.MethodsC57Bl6/J male mice received angiotensin II (angII; 1 μg/kg/min) via infusion pump for 8 weeks (hypertension group: HH), angII for 4 weeks (hypertension group: H4), angII for 4 weeks followed by 4 weeks of recovery (reversal group: HN), or sham treatment (normotensive group: NN). BP, heart rate, and pulse wave velocity (PWV) were measured longitudinally. At the end of the study period, aortas were harvested for testing of vasoreactivity, passive mechanical properties, and vessel structure.ResultsThe HH group exhibited a sustained increase in BP and PWV over the 8-week period (p < 0.01). In the HN group, BP and PWV increased during the 4-week angII infusion, and, though BP was restored during the 4-week recovery, PWV exhibited only partial restoration (p < 0.05). Heart rate was similar in all cohorts. Compared to NN controls, both HH and HN groups had significantly increased wall thickness (p < 0.05 HH vs. NN, p < 0.01 HN vs. NN), mucosal extracellular matrix accumulation (p < 0.0001 HH vs. NN, p < 0.05 HN vs. NN), and intralamellar distance (p < 0.001 HH vs. NN, p < 0.01 HN vs. NN). Both intact and decellularized vessels were noted to have significantly higher passive stiffness in the HH and H4 cohorts than in NN controls (p < 0.0001). However, in the HN cohort, intact vessels were only modestly stiffer than those of NN controls, and decellularized HN vessels were identical to those from the NN controls. Compared to NN controls, the HH and HN cohorts exhibited significantly diminished phenylephrine-induced contraction (p < 0.0001) and endothelium-dependent vasodilation (p < 0.05).ConclusionHypertension causes a significant increase in in vivo aortic stiffness that is only partially reversible after BP normalization. Although hypertension does lead to matrix stiffening, restoration of BP restores matrix mechanics to levels similar to those of normotensive controls. Nevertheless, endothelial and vascular smooth muscle cell dysfunction persist after restoration of normotension. This dysfunction is, in part, responsible for augmented PWV after restoration of BP.

The impact of the duration of HAART on cytokine profiles in pregnancy.

To determine the cytokine profile of HIV infected women treated with highly active anti-retroviral therapy (HAART) of variable duration in pregnancy. HIV infected women were enrolled at a large tertiary hospital in Durban, South Africa in their antenatal period and stratified into those that initiated HAART before pregnancy (pre-pregnancy HAART or PPH group) and those who initiated HAART during pregnancy (in-pregnancy HAART or IPH group). These were compared with HIV negative women (HN group), matched for gestational age at the time of enrolment. Serum was obtained and Th1 and Th2 cytokines expression determined using the Bio-Plex Pro™ Human Cytokine Treg Panels. The overall cytokine profile of the cohort was pro-inflammatory as a result of significant IL-6 and TNF alpha expression. The anti-inflammatory markers (i.e. Th2 cytokines, namely IL4 and IL10) were poorly expressed by the whole cohort, with IL 4 seen almost exclusively in the IPH group, thus counter-balancing the predominantly pro-inflammatory milieu only in this group. PPH group had a pro-inflammatory milieu comparable to the HN control. IL 6 was the predominant cytokine in all groups, and as expected, it increased with advancing gestation in all the groups. This highly pro-inflammatory milieu was unexpected and needs further review CONCLUSION: Long use of HAART suppresses the anti-inflammatory markers previously reported to be conducive for the wellbeing of pregnancy. This effect needs further review as it was similarly observed in our HIV uninfected controls.

Effects of oxygen concentration on differentiation of human IPS cells into cartilage tissue

Purpose: Cartilage is a type of tissue characterized by poor self-repair capacity due to the absence of blood vessels and nerve tissue. As such, cartilaginous tissue does not self-repair after sustaining extensive damage. Treatments to address cartilaginous tissue damage include bone perforation, osteochondral column transplantation, and autologous cultured cartilage transplantation. Each of these treatment methods has achieved a degree of success, but problems related to the number of procedures required and the quality of regenerated tissue remain to be overcome. In recent years, regenerative medical techniques have come to be regarded as promising new therapy options. Among these, induced pluripotent stem cells (iPSCs) have attracted attention as a potential new source of cells for therapeutic uses. iPSCs exhibit high self-renewal capacity and have excellent potential as a cell source owing to their maintenance of the ability to undergo cell division while remaining undifferentiated. Although the formation of cartilage tissues from iPSCs has been established, regenerative medicines utilizing iPSCs also face obstacles, such as long culture periods, the risk of oncogenesis, and compromised tissue purity. We hypothesized that if cartilaginous tissues could be prepared from iPSCs in a hypoxic environment, it would be possible to produce tissues more quickly than under a stable oxygen environment. In this study, the effects of oxygen concentration on the differentiation of human iPSC cells (hiPSCs) into cartilage were studied. Methods: The established hiPSC line Toe was maintained in feeder-free medium in 6-well dishes coated with laminin. The hiPSCs formed high-density cell colonies consisting of 1-2 × 105 cells at 10 days after the start of maintenance. Subsequently, chondrogenic differentiation of the iPSCs was induced. The hiPSCs were initially differentiated into mesendodermal cells in mesendodermal medium for 3 days (M-phase). On day 3, the medium was changed to chondrogenic medium, hiPSCs were cultured in chondrogenic medium for 10 days (C-phase) to induce differentiation into chondrocytes. Then, four groups were formed based on oxygen concentration in the M-phase and C-phase: NN (21%, 21%), HN (5%, 21%), NH (21%, 5%), and HH (5%, 5%). On day 14, total RNA was extracted from differentiated cells. The expression of sox9, aggrecan, and col2a1, which are cartilage differentiation markers, and of T and FOXF1, which are undifferentiated mesoderm markers, was assessed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Moreover, cells were detached and digested to form a single-cell suspension using trypsin for flowcytometry, and the sox9-positive cell rate was measured. Results: In qRT-PCR analysis, sox9 expression was higher in NH than in NN and HN groups. col2a1 expression was higher in NH than in the other groups. Aggrecan expression was higher in NH group compared with HN group. T and FOXF1 expression was higher in HN group than NH group, and the groups cultured in hypoxic condition on C-phase (NH and HH groups) were lower than the groups cultured in normoxic condition on C-phase (NN and HN groups). In flowcytometry analysis, sox9-positive cell rate was higher in the NH and HH groups (5% C-phase oxygen concentration) than in the NN and HN groups (21% C-phase oxygen concentration). Conclusions: Chondrocyte differentiation was promoted by culture under hypoxic conditions during the production of cartilaginous tissues from human embryonic stem (ES) cells. Thus, it is possible that a hypoxic environment may also promote differentiation of cartilaginous tissue from iPSCs. In this study, a period of culturing in a hypoxic environment was provided during differentiation from hiPSCs into cartilage tissue. C-phase culturing with the oxygen concentration of 5% raised cartilage differentiation markers and lowered undifferentiated mesoderm markers. An oxygen concentration of 5% promotes differentiation from hiPSCs into cartilage tissue and raises purity levels. Therefore, adjusting the culture period or oxygen concentration (hypoxic environment) may allow engineering of high-purity cartilage tissues in a short time.

Anatomical study of the ventral neurovascular structures and hypoglossal canal for the surgery of the upper cervical spine

The aim of this study is to evaluate the anatomical relationship between the bony structures and ventral neurovascular structures around craniovertebral junction (CVJ).Eleven fresh-frozen cadaveric specimens were dissected around CVJ. The anatomical relationships were evaluated between C1 bony structures (midline, lateral margin of the C1 lateral mass (LM) and C1 transverse process (TP)) and ventral neurovascular structure such as ICA and HN. Morphometric evaluation of occipital condyle was also performed.The diameter of the HN and the ICA was 2.4 ± 0.5 mm and 5.1 ± 0.2 mm. The ICA was located lateral to the C1 LM in 44.4% (ICA Group 1) and in front of lateral half of the C1 LM in 55.6% (ICA Group 2). The HN was located lateral to the C1 LM in 85% (HN Group 1) and in front of lateral half of the C1 LM in 15% (HN Group 2). HN Group 2 was significantly more common in ICA Group 2 (p < 0.05, OR = 2.00, 95% CI: 1.07–3.71). There was significant correlation between ICA and HN in terms of the distance from the midline, C1 LM and TP (r = 0.67, 0.87 and 0.76 respectively, P < 0.01).In conclusion, the HN location is related with ICA location and the medially located ICA is a risk factor of the HN located ventral to the C1 LM. These results demonstrate the vulnerability of the neurovascular structures during CVJ surgery and suggest that preoperative 3D-CTA or enhanced CT scan can be useful in guiding surgical technique.

Prognostic value of baseline carcinoembryonic antigen and cytokeratin 19 fragment levels in advanced non-small cell lung cancer

Serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) levels are prognostic predictors in non-small cell lung cancer (NSCLC). However, even in patients with the same stage of cancer, the serum levels of those markers often vary. We investigated the association between the initial biomarker levels and prognosis. We retrospectively reviewed 445 patients with advanced NSCLC and their baseline serum CEA and CYFRA 21-1 levels. Patients were divided into four groups according to the initial levels of those markers: the NN, HN, NH, and HH group. Kaplan-Meier survival analysis with Log-rank test and Cox proportional hazards regression analysis were performed. The 5-year overall survival (OS) rate in the HN group was the highest (32.2%). Multivariate analyses indicated that the HN group (HR 0.520, 95% CI 0.309-0.878, P= 0.014), female sex (HR 0.685, 95% CI 0.498-0.944, P= 0.021), serum CRP level (HR 1.057, 95% CI 1.034-1.080, P< 0.001), chemotherapy (HR 0.324, 95% CI 0.228-0.460, P< 0.001), and chemotherapy/radiotherapy (HR 0.266, 95% CI 0.171-0.414, P< 0.001) were independent prognostic factors for overall survival. In advanced NSCLC, patients with baseline high serum CEA but low CYFRA 21-1 level have a significant longer overall survival regardless of clinical stage.

Co-production of lipids, eicosapentaenoic acid, fucoxanthin, and chrysolaminarin by Phaeodactylum tricornutum cultured in a flat-plate photobioreactor under varying nitrogen conditions

The marine diatom Phaeodactylum tricornutum is a polymorphological, ecologically significant, and well-studied model of unicellular microalga. This diatom can accumulate diverse important metabolites. Herein, we cultured P. tricornutum in an internally installed tie-piece flat-plate photobioreactor under 14.5 m mol L−1 (high nitrogen, HN) and 2.9 m mol L−1 (low nitrogen, LN) of KNO3 and assessed its time-resolved changes in biochemical compositions. The results showed that HN was inductive to accumulate high biomass (4.1 g L−1). However, the LN condition could accelerate lipid accumulation in P. tricornutum. The maximum total lipid (TL) content under LN was up to 42.5% of biomass on day 12. Finally, neutral lipids (NLs) were 63.8% and 75.7% of TLs under HN and LN, respectively. The content of EPA ranged from 2.3% to 1.5% of dry weight during the growth period under the two culture conditions. Peak volumetric lipid productivity of 128.4 mg L−1d−1 was achieved in the HN group (on day 9). The highest volumetric productivity values of EPA, chrysolaminarin, and fucoxanthin were obtained in the exponential phase (on day 6) under HN, which were 9.6, 93.6, and 4.7 mg L−1d−1, respectively. In conclusion, extractable amounts of lipids, EPA, fucoxanthin, and chrysolaminarin could be obtained from P. tricornutum by regulating the culture conditions.

Modifying oxygen tension affects bone marrow stromal cell osteogenesis for regenerative medicine.

AIMTo establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells (MSCs) using osteogenic matrix cell sheets (OMCSs).METHODSRat MSCs were cultured in osteogenic media under one of four varying oxygen conditions: Normoxia (21% O2) for 14 d (NN), normoxia for 7 d followed by hypoxia (5% O2) for 7 d (NH), hypoxia for 7 d followed by normoxia for 7 d (HN), or hypoxia for 14 d (HH). Osteogenesis was evaluated by observing changes in cell morphology and calcium deposition, and by measuring osteocalcin secretion (ELISA) and calcium content. In vivo syngeneic transplantation using OMCSs and β-tricalcium phosphate discs, preconditioned under NN or HN conditions, was also evaluated by histology, calcium content measurements, and real-time quantitative PCR.RESULTSIn the NN and HN groups, differentiated, cuboidal-shaped cells were readily observed, along with calcium deposits. In the HN group, the levels of secreted osteocalcin increased rapidly from day 10 as compared with the other groups, and plateaued at day 12 (P < 0.05). At day 14, the HN group showed the highest amount of calcium deposition. In vivo, the HN group showed histologically prominent new bone formation, increased calcium deposition, and higher collagen type I messenger RNA expression as compared with the NN group.CONCLUSIONThe results of this study indicate that modifying oxygen tension is an effective method to enhance the osteogenic ability of MSCs used for OMCSs.

Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats.

Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10% O2), one kept at normothermia (HN) (37°C) and the other under deep hypothermia (HH) (central body temperature of 21-22°C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4-HNE protein adduct amounts were significantly lower in the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia.

"Immunonutrition" Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents.

BackgroundImmunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs) or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats.DesignRats were fed with enteral Peptamen® HN (HN group), Peptamen® AF containing n-3 PUFAs (AF group) or Peptamen® AF enriched with L-arginine (AFA group). On day 4, peritonitis by cecal ligation and puncture (CLP) was performed. Rats were resuscitated (H18) once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed.ResultsCompared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05). AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-κB (0.40±0.15 in CLP-AF and 0.69±0.06 in CLP-AFA vs. 0.09±0.03 in SHAM rats and 0.30±0.06 in CLP-HN, ß-actin ratio, p<0.05) and pIκB expression (0.60±0.03 in CLP-AF and 0.94±0.15 in CLP-AFA vs. 0.04±0.01 in SHAM rats and 0.56±0.07 in CLP-HN, ß-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats.ConclusionsAlthough n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore, mortality was higher after L-arginine supplementation.

Robot-assisted laparoscopic management of duplex renal anomaly: Comparison of surgical outcomes to traditional pure laparoscopic and open surgery

Surgical management of duplex renal anomaly (DRA) is complex because of individual anatomic variation, competing priorities of vesicoureteral reflux (VUR) and ureteral obstruction present in the same child, the varied differential function of the different renal moieties, and the presence of voiding dysfunction and recurrent urinary tract infection (UTI). Robot-assisted laparoscopic (RAL) surgical management has been under-reported in this group of children but is becoming a viable alternative to traditional open surgery. The aim was to report the surgical outcomes of a series of children with DRA who had RAL surgery and compare these outcomes to historical cohorts of open and laparoscopic surgery. This was a retrospective analysis of a prospective series of children who had RAL surgery for DRA over an 8-year period. Forty-five RAL surgeries were performed in 47 children. RAL heminephrectomy (RAL HN) was performed in 19 children for poorly or non-functional renal moiety. One had staged bilateral RAL HN. RAL ureteroureterostomy (RAL UU) was performed in 14 children for upper pole ureteral obstruction. Thirteen RAL common sheath ureteral reimplants (RAL csUN) with or without ureteral tapering were performed in 12 children with VUR and UTI. Diagnosis and demographics, results of preoperative imaging, intraoperative time stamps, perioperative complications, success rate, and renal outcomes were recorded. Low-grade VUR present preoperatively in the RAL UU group all resolved within the follow-up period. Four (25%) children in the RAL HN group developed de novo VUR after surgery, which resolved in two (50%) and required surgery in two (50%). Grade I VUR after RAL csUR that occurred in two (14.3%) children was asymptomatic and observed when off preventative antibiotics. Most children with DRA who need surgical treatment can be offered RAL surgery. We report good outcomes and improved operative times for RAL HN and UU that approach historical open and pure laparoscopic cohorts. However, RAL csUR, especially with ureteral tapering, is more complex and inherently susceptible to complications, and has not met the outcomes of the open gold standard. The limits of this study are that selection bias is present, and there is no study control cohort. This report achieves its aim to report surgical outcomes of children who had RAL surgery for DRA.

Abstract 903: Comparison of the citrus flavonoid naringenin and metformin for effects on breast cancer in obese ovariectomized mice

Abstract Metformin has been shown to decrease breast cancer incidence in diabetic women, suggesting that improvement of metabolic status may be a useful approach to decrease breast cancer risk. As the putative cellular target of metformin, AMP-activated protein kinase (AMPK) not only regulates energy metabolism in liver, muscle, and adipose tissue but also inhibits protein synthesis and induces cell cycle arrest and apoptosis. Naringenin is a flavonoid abundant in citrus fruits that may have beneficial effects on metabolic health and tumorigenesis. Our in vitro data showed that naringenin inhibited proliferation of E0771 murine breast cancer cells, increased AMPK activity, and reduced expression of cell cycle regulatory proteins Cyclin D1 and anti-apoptotic Bcl-2 protein. In this study, we evaluated whether dietary naringenin acts like metformin to suppress mammary tumor growth in a mouse model of postmenopausal obesity. Ovariectomized female C57BL/6J mice were fed a high-fat diet (60% energy as fat) for 3 weeks to induce obesity. Then mice were randomized to experimental diets of HF (continued the high-fat diet), LN (high fat + 1% wt/wt naringenin in diet), HN (high fat + 3% wt/wt naringenin in diet), and Met (high fat + 180 mg/kg metformin in water) for 5 weeks. After 2 weeks of treatment, 5 × 10(5) E0771 cells were injected into one thoracic mammary fat pad. Mice were maintained on study diets for another 3 weeks. For all mice tumor weight correlated with weight gain in the first 5 weeks prior to cell inoculation (r = 0.51, p &amp;lt; 0.01). There was no difference in fasting glucose levels among the groups on week 8. No difference was observed between the HF and LN groups regarding final body weight, food intake, tissue weights, and tumor mass. HN significantly decreased final body weight, food intake, and adipose depot mass. mRNA expression of two inflammatory cytokines, interleukin 6 and monocyte chemoattractant protein-1 were decreased in perigonadal fat of the HN group. Although tumor growth (cm2) decreased over time in HN mice, there was no significant difference in tumor mass between HF and HN groups at necropsy (p = 0.4). HN did not affect AMPK activity in tumor tissue, but decreased Bcl-2 protein expression. Additionally, dietary naringenin resulted in a dose ­dependent accumulation in plasma, tumor, and mammary fat. In comparison to naringenin enriched diets, metformin significantly reduced tumor growth and final tumor weight, without affecting body weight, food intake, and tissue weights. Metformin decreased protein expression of Cyclin D1 in mammary tumors. However, we did not observe AMPK activation and changes in Bcl-2 protein levels in tumors. Taken together, these data suggest that metformin may inhibit mammary tumor growth without affecting metabolic status as assessed by body weight, adiposity, and fasting glucose. There may be different mechanisms of action for naringenin and metformin to alter mammary tumorigenesis. Citation Format: Jia-Yu Ke, Yung-Hsuan Hsiao, Shana R. Straka, Lisa D. Yee, Martha A. Belury. Comparison of the citrus flavonoid naringenin and metformin for effects on breast cancer in obese ovariectomized mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 903. doi:10.1158/1538-7445.AM2015-903

Effect of hydrogen-saline on lung injury and heme oxygenase-1 expression in the lung tissue of acute paraquat-intoxicated mice

To investigate the effect of Hydrogen-saline on Lung Injury and HO-1 Expression in The Lung Tissue of Acute Paraquat-intoxicated mice. 108 male clean-grade mice were divided randomly into 3 groups: normal control group (n = 8), PQ group (n = 50) and PQ HN group (n = 50), PQ group were lavaged with 20% PQ (50 mg/kg). PQ+Hyclrogen saline group were intxaperitoneal injected with 5 ml/kg saturated hydragen saline after lavaged, 2 times/d. We observe its performance after the poisoning, The lung tissue were taken to HE stained, MDA and SOD activity of lung tissue homogenate were detected, HO-1 activity were observed by immunohistochemistry and western method at 6 h, 1 d, 3 d, 7 d and 14 d. mice came to shortness of breath, exhaustion and death after poisoned. PQ+hydrogen saline group was more alleviative than PQ group. The lung MDA of PQ group was markedly increased at 6 h and 24 h and SOD was decreased at 6 h, 24 h, 3 d, 7 d, 14 d than normal control group. In Comparison with PQ group, the lung MDA was decreased at 24 h and SOD was increased at 24 h and 3 d (P < 0.05). HO-1 expression trend and distribution in PQ+hydrogen saline group are similar with PQ group, but were significantly higher than that of PQ group and the control group each time point (P < 0.05). Oxidative stress plays important roles in lung injury caused by paraquat. Hydrogen-saline may increase expression of HO-1 and alleviate oxidative stress damage in lung.

Suppression effects of negative pressure on the proliferation and metastasis in human pancreatic cancer cells.

The aim was to explore the effect of negative pressure on the proliferation and metastasis of human pancreatic cancer SW1990 cells. Three groups were conducted in the work: normal control group (NC group, 0 mm Hg), low negative pressure group (LN group, -300 mm Hg), and high negative pressure group (HN group, -600 mm Hg). Cell morphological assay was conducted using an inverted Nikon TE2000-S microscope. Cell viability was assayed using cell counting kit-8 solution. Cell apoptosis was evaluated with flow cytometry. Cell migration was investigated using transwell assay. Compared to LN and HN groups, SW1990 cells in NC group grew quite well, showing a higher density. The NC group represented the highest cell viability. The HN group represented the lowest cell viability, which was lower than that of the LN group (P < 0.01). The apoptosis rate in NC group, LN group and HN group was 1.91% ± 0.13%, 2.31% ± 0.06% and 15.22% ± 0.81%, respectively (P < 0.05). The average number of migration cells in NC group was 53.60 ± 4.14 (× 200), which was decreased to 18.93 ± 3.67 and 11.07 ± 3.01 in LN group and HN group, respectively (P < 0.01). The negative pressure shows suppression effects on the proliferation and metastasis of human pancreatic cancer SW1990 cells. It is indicated that negative pressure may be involved in the development of human pancreatic cancer by influencing cell biological characteristics.

Melanocortin 4 Receptor Is Involved in the Development of Morphine Tolerance

Background: Prolonged morphine treatment usually results in the development of analgesic tolerance. Melanocortin 4 receptor (MC4R) is involved in the development of morphine tolerance. The aim of this study was to examine the effects of an MC4R antagonist, HS014, on MC4R-mediated hyperalgesia and on microglia and cytokine expression in the spinal cord of rat during morphine tolerance.Methods: Thirty rats were assigned randomly to the N group, M group, HM group, NM group and HN group (N=6 in each group). Rats received 5-day treatment with saline (N group) or morphine (M group). Rats were given an intrathecal injection (i.t.) of HS014 (HM group) or saline (NM group) at 15 minutes prior to the morphine challenge. In the HN group, rats were injected with HS014 at 15 minutes prior to the saline. To observe the effect of HS014 on the development of morphine tolerance, morphine-tolerant rats were assigned to M1 group, M2 group, M3 group and N group on day 6 (N=6 in each group). The morphine-tolerant rats in M1 group, M2 group and M3 group received morphine (10 mg/kg, i.p.), HS014 (5 μg, i.t.) and HS014 (5 μg, i.t.) followed 15 minutes later by injection of morphine (10 mg/kg, i.p.), respectively. Control rats (N group, N=6) were injected with saline under identical conditions.Results: Morphine treatment (10 mg/kg, i.p. twice daily) over 5 days induced tolerance as reflected by a significant reduction of withdrawal latency from 29.67 ± 1.81 s to 8.67 ± 1.70 seconds in the hot-plate test. Repeated HS014 injection prior to morphine administration inhibited the development of morphine tolerance. Furthermore, a single administration of HS014 restored morphine analgesic potency in morphine-tolerant rats. Immunohistochemical staining showed that the administration of HS014 during the induction of morphine tolerance inhibited the activation of microglia, reduced the expression of proinflammatory cytokines, such as interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α, and increased the expression of anti-inflammatory cytokines (IL-10) at the L5 lumbar spinal cord.Conclusions: HS014 attenuates the development of antinociceptive tolerance following chronic administration of morphine by inhibiting microglial activation and reducing the expression of IL-1, IL-6 and TNF-α. Citation: Hong-Mei Xu, Ze-Jun Niu, Hai-Chen Chu, Xue-Feng Zhang. Melanocortin 4 receptor is involved in the development of morphine tolerance. J Anesth Perioper Med 2014; 1: 90-6. doi: 10.24015/JAPM.2014.0014This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

HN, NH, CA, CB and methyl group assignments of Filamin C two Ig-domain fragment FLNc4-5

HN, NH, CA, CB and methyl group assignments of Filamin C two Ig-domain fragment FLNc4-5

HN, NH, Cα, Cβ, and methyl group assignments of filamin multidomain fragments IgFLNc4–5 and IgFLNa3–5

Filamins regulate the actin cytoskeleton by cross-linking actin filaments, linking the cytoskeleton to the cell membrane, and through interaction with numerous binding partners such as intracellular signalling molecules, ion channels, receptors, enzymes and transcription factors. The rod region of filamins consists of 24 immunoglubulin (Ig)-like repeats, for some of which the functional unit is a domain pair. Our aim is to study filamin Ig domain-domain interactions and quaternary arrangement as well as to locate peptide binding sites on domain assemblies. We report here the H(N), N(H), C(α), C(β), and methyl group assignments of filamin A three-domain fragment IgFLNa3-5 and filamin C two-domain fragment IgFLNc4-5.

Effects of Menstrual Cycle and Neuroticism on Emotional Responses of Healthy Women

Women experience dramatic fluctuations in progesterone and estradiol during menstrual cycles, which will likely influence their mood. The subjective experience and neural responses towards emotional stimuli of women who suffer from premenstrual syndrome(PMS) seemed to differ across menstrual cycles. However, it remains unknown that if women without PMS will have mood swings during a menstrual cycle. Additionally, some studies argued that neuroticism was closely associated with PMS. But it is still unclear whether neurotic women without PMS would have different responses towards emotional stimuli in different phases of menstrual cycle like women with PMS. The current study was designed to investigate the influence of neuroticism on the subjective experience and physiological responses towards emotional stimuli in the non-PMS sample across a menstrual cycle. We hypothesized that neurotic women would have more intense subjective experience and physiological responses towards emotional stimuli, especially in the premenstrual phase. Forty-one right-handed female with regular menstrual cycle took part voluntarily in this within-subject study. The results of Eysenck Personality Questionnaire(EPQ) divided this sample into the high neuroticism group(HN group, n = 16) and the low neuroticism group(LN group, n = 25). Each participant performed a film watching and evaluating task three times during mid-late luteal, menstrual and late ovulation phases respectively. 12 film clips were selected. Among them, nine 3-minute film clips were supposed to evoke amusement, sadness, and anger(3 clips for each emotion) and 3 film clips were neutral. For each visit, the participant would watch 4 film clips randomly selected from 12 film clips, one for each emotion and a neutral one, and the order of clips was counter-balanced. Each time the participant came to the lab and relaxed for 3 minutes(baseline), then she watched a film clip and completed the emotion inventory to evaluate how they felt about the clip. She was then asked to relax for another 3 minutes to recover from the emotional arousal. The physiological responses including heart rate, galvanic skin response(GSR) and respiratory rate were recorded at this time. This procedure was repeated until all 4 film clips(one for each emotion and a neural film) were viewed. The results showed that there was a significant interaction between menstrual cycle and group membership for self-reported anger and disgust in response to angry films. The HN group scored lower in self-reported anger and disgust than the LN group only in the mid-late luteal phase, and there was a significant effect of menstrual cycle in HN group but not in LN group for self-reported anger. We calculated rate of change for the analysis of heart rate and found a significant effect of menstrual cycle for the HN group but not for the LN group when they were watching neutral and sad films. The rate of change in the LN group was significantly greater than that in the HN group in the mid-late luteal phase, but not in the other two phases. We also calculated rate of change for the analysis of respiration rate and found that the change of rate is significantly greater for the HN group than that for the LN group, but only in the menstrual phase. Taken together, the subjective experience and physiological responses towards negative emotion during menstrual cycles seem to be more influential for neurotic women than for those who are low in neuroticism. Furthermore, neurotic women seemed to be less vulnerable to negative emotion during their mid-late luteal phase than during other phases. Sensitive response of neurotic women to the fluctuation of progesterone during menstrual cycles may be one of the reasons that account for their mood change.

Significance of the serum carcinoembryonic antigen level during the follow-up of patients with completely resected non-small-cell lung cancer

The purpose of this study was to elucidate the detectability of recurrence and the prognostic significance of the serum carcinoembryonic antigen (CEA) levels in patients with completely resected non-small-cell lung cancer (NSCLC). Five hundred and eighteen NSCLC patients who underwent complete resection at Aichi Cancer Center between April 2001 and March 2006 were enrolled in this study. The patient characteristics were as follows: the median age was 63 years; 331 tumours were classified as pathological stage I, 88 tumours were pathological stage II and 99 tumours were pathological stage III; 140 tumours were adenocarcinomas with epidermal growth factor receptor (EGFR) mutations, 268 tumours were adenocarcinomas with EGFR wild-type mutations and 110 tumours were other NSCLCs. The patients were divided into three groups: those with a normal CEA level before and 1-3 months after surgery (N group, n = 380), those with an elevated CEA level before surgery and a normal CEA level 1-3 months after surgery (HN group, n = 105) and those with an elevated CEA level 1-3 months after surgery regardless of the preoperative CEA level (H group, n = 33). The correlations between the changes in the serum CEA levels and the clinical outcomes were analysed. Recurrence developed in 122 patients (32%) in the N group, 49 patients (47%) in the HN group and 19 patients (58%) in the H group (P = 0.001). The sensitivity and specificity of an elevated serum CEA level during the follow-up period for detecting recurrence were 30 and 98% in the N group and 82 and 73% in the HN group, respectively. Twenty-seven asymptomatic recurrent tumours combined with an elevated serum CEA level were detected in the HN group. In the multivariate Cox regression analysis, the serum CEA level 1-3 months after surgery had prognostic value for overall survival. In completely resected NSCLC patients, measuring the serum CEA level during the follow-up period is useful in patients in whom an elevated level normalizes after surgery, and the serum CEA level 1-3 months after surgery is considered to have prognostic significance regarding survival.

Prognostic significance of postoperative serum carcinoembryonic antigen levels in patients with completely resected pathological-stage I non-small cell lung cancer

BackgroundUntil date, there are no clear recommendations for regular perioperative measurements of serum CEA levels for lung cancer in any guidelines. The purpose in the present study is to evaluate the prognostic significance of perioperative serum carcinoembryonic antigen (CEA) levels in patients with pathological-stage I non-small cell lung cancer (NSCLC).MethodsWe retrospectively reviewed 263 completely resected pathological-stage I NSCLC patients whose preoperative and postoperative serum CEA levels were measured. Patients were subdivided according to the perioperative change of CEA levels: continuously normal CEA levels (NN group), continuously high CEA levels (HH group), and high preoperative CEA levels that returned to normal levels post-operation (HN group). The clinicopathological factors and overall survival (OS) among these 3 groups were compared. Univariate and multivariate analyses of the correlation between clinicopathological factors and OS were performed.ResultsHigh preoperative CEA levels significantly correlated with men aged >70 years with smoking history, high serum CYFRA 21–1 levels, greater tumor diameter, presence of visceral pleural invasion (VPI), and moderate-to-poor differentiation. Five-year OS rates in the NN and HH groups were 95.5% and 59.3%, respectively. Four-year OS rate in the HN group was 85.5%. Multivariate analyses indicated tumor diameter of more than 30 mm, presence of VPI, and the HH group were independent unfavorable prognostic factors.ConclusionsA high postoperative CEA level was an independent unfavorable prognostic factor in pathological-stage I NSCLC patients. Patients with high postoperative CEA levels may benefit from adjuvant chemotherapy.