Publications by authors named "Jichuan Wu"

15 Publications

  • Page 1 of 1

HDAC inhibition improves cardiopulmonary function in a feline model of diastolic dysfunction.

Sci Transl Med 2020 01;12(525)

Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.

Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on cardiopulmonary structure, function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysfunction common to human HFpEF. Male domestic short-hair felines ( = 31, aged 2 months) underwent a sham procedure ( = 10) or loose aortic banding ( = 21), resulting in slow-progressive pressure overload. Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, = 8), a Food and Drug Administration-approved pan-HDAC inhibitor, or vehicle (b + veh, = 8) for 2 months. Echocardiography at 4 months after banding revealed that b + SAHA animals had significantly reduced left ventricular hypertrophy (LVH) ( < 0.0001) and left atrium size ( < 0.0001) versus b + veh animals. Left ventricular (LV) end-diastolic pressure and mean pulmonary arterial pressure were significantly reduced in b + SAHA ( < 0.01) versus b + veh. SAHA increased myofibril relaxation ex vivo, which correlated with in vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, compliance, blood oxygenation, and reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar capillary stress failure. Acetylation proteomics revealed that SAHA altered lysine acetylation of mitochondrial metabolic enzymes. These results suggest that acetylation defects in hypertrophic stress can be reversed by HDAC inhibitors, with implications for improving cardiac structure and function in patients.
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http://dx.doi.org/10.1126/scitranslmed.aay7205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065257PMC
January 2020

β-Defensins Coordinate In Vivo to Inhibit Bacterial Infections of the Trachea.

Vaccines (Basel) 2018 Aug 28;6(3). Epub 2018 Aug 28.

Department of Oral Biology, Rutgers New Jersey Dental School, Newark, NJ 07103, USA.

β-defensins are predicted to play an important role in innate immunity against bacterial infections in the airway. We previously observed that a type III-secretion product of inhibits the NF-κB-mediated induction of a β-defensin in airway epithelial cells in vitro. To confirm this in vivo and to examine the relative roles of other β-defensins in the airway, we infected wild-type C57BL/6 mice and mice with a deletion of the mBD-1 gene with wild-type strain, RB50 and its mutant strain lacking the type III-secretion system, WD3. The bacteria were quantified in the trachea and the nasal tissue and mRNA levels of mouse β-defensin-3 (mBD-3) were assessed after 24 h. Infection with the wild-type bacterial strain resulted in lower mBD-3 mRNA levels in the trachea than in mice infected with the type III-deficient strain. Furthermore, we observed an increase in bacterial numbers of RB50 only in the tracheas of mBD-1-deficient mice. Neutrophils were also more abundant on the trachea in RB50 infected WT mice but not in the bronchiolar lavage fluid (BAL), compared with WD3 infected WT and mBD-1 mice, indicating that the coordination of β-defensin chemotactic effects may be confined to tracheal epithelial cells (TEC). RB50 decreased the ability of mice to mount an early specific antibody response, seven days after infection in both WT and mBD-1 mice but there were no differences in titers between RB50-infected WT and mBD-1 mice or between WD3-infected WT and mBD-1 mice, indicating mBD-1 was not involved in induction of the humoral immune response to the . Challenge of primary mouse TEC in vitro with RB50 and WD3, along with IL-1β, further corroborated the in vivo studies. The results demonstrate that at least two β-defensins can coordinate early in an infection to limit the growth of bacteria in the trachea.
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http://dx.doi.org/10.3390/vaccines6030057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161282PMC
August 2018

A Feline HFpEF Model with Pulmonary Hypertension and Compromised Pulmonary Function.

Sci Rep 2017 11 29;7(1):16587. Epub 2017 Nov 29.

Temple University Lewis Katz School of Medicine, Cardiovascular Research Center, Philadelphia, PA, United States.

Heart Failure with preserved Ejection Fraction (HFpEF) represents a major public health problem. The causative mechanisms are multifactorial and there are no effective treatments for HFpEF, partially attributable to the lack of well-established HFpEF animal models. We established a feline HFpEF model induced by slow-progressive pressure overload. Male domestic short hair cats (n = 20), underwent either sham procedures (n = 8) or aortic constriction (n = 12) with a customized pre-shaped band. Pulmonary function, gas exchange, and invasive hemodynamics were measured at 4-months post-banding. In banded cats, echocardiography at 4-months revealed concentric left ventricular (LV) hypertrophy, left atrial (LA) enlargement and dysfunction, and LV diastolic dysfunction with preserved systolic function, which subsequently led to elevated LV end-diastolic pressures and pulmonary hypertension. Furthermore, LV diastolic dysfunction was associated with increased LV fibrosis, cardiomyocyte hypertrophy, elevated NT-proBNP plasma levels, fluid and protein loss in pulmonary interstitium, impaired lung expansion, and alveolar-capillary membrane thickening. We report for the first time in HFpEF perivascular fluid cuff formation around extra-alveolar vessels with decreased respiratory compliance. Ultimately, these cardiopulmonary abnormalities resulted in impaired oxygenation. Our findings support the idea that this model can be used for testing novel therapeutic strategies to treat the ever growing HFpEF population.
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http://dx.doi.org/10.1038/s41598-017-15851-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707379PMC
November 2017

Acute right heart failure after hemorrhagic shock and trauma pneumonectomy-a management approach: A blinded randomized controlled animal trial using inhaled nitric oxide.

J Trauma Acute Care Surg 2017 02;82(2):243-251

From the Department of Surgery at Temple University Hospital (A.L.L., L.O.S., A.G., A.P., T.S.), Cardiovascular Research Center (T.E.S., M.W., R.M.B.), Department of Physiology (T.E.S., M.W., R.M.B., L.A.P., J.W., M.R.W.), Department of Thoracic Medicine and Surgery (L.A.P., J.W., M.R.W.), Center for Inflammation, Translational and Clinical Lung Research (L.A.P., J.W., M.R.W.), CENTRe: Collaborative for Environmental and Neonatal Therapeutics Research (L.A.P., J.W., M.R.W.), and Temple Lung Center of Lewis Katz School of Medicine at Temple University Philadelphia, PA (L.A.P., J.W., M.R.W.).

Background: Hemorrhagic shock and pneumonectomy causes an acute increase in pulmonary vascular resistance (PVR). The increase in PVR and right ventricular (RV) afterload leads to acute RV failure, thus reducing left ventricular (LV) preload and output. Inhaled nitric oxide (iNO) lowers PVR by relaxing pulmonary arterial smooth muscle without remarkable systemic vascular effects. We hypothesized that with hemorrhagic shock and pneumonectomy, iNO can be used to decrease PVR and mitigate right heart failure.

Methods: A hemorrhagic shock and pneumonectomy model was developed using sheep. Sheep received lung protective ventilatory support and were instrumented to serially obtain measurements of hemodynamics, gas exchange, and blood chemistry. Heart function was assessed with echocardiography. After randomization to study gas of iNO 20 ppm (n = 9) or nitrogen as placebo (n = 9), baseline measurements were obtained. Hemorrhagic shock was initiated by exsanguination to a target of 50% of the baseline mean arterial pressure. The resuscitation phase was initiated, consisting of simultaneous left pulmonary hilum ligation, via median sternotomy, infusion of autologous blood and initiation of study gas. Animals were monitored for 4 hours.

Results: All animals had an initial increase in PVR. PVR remained elevated with placebo; with iNO, PVR decreased to baseline. Echo showed improved RV function in the iNO group while it remained impaired in the placebo group. After an initial increase in shunt and lactate and decrease in SvO2, all returned toward baseline in the iNO group but remained abnormal in the placebo group.

Conclusion: These data indicate that by decreasing PVR, iNO decreased RV afterload, preserved RV and LV function, and tissue oxygenation in this hemorrhagic shock and pneumonectomy model. This suggests that iNO may be a useful clinical adjunct to mitigate right heart failure and improve survival when trauma pneumonectomy is required.
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http://dx.doi.org/10.1097/TA.0000000000001325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315536PMC
February 2017

Effect of serum 25-hydroxyvitamin D3 on insulin resistance and β-cell function in newly diagnosed type 2 diabetes patients.

J Diabetes Investig 2016 Mar 8;7(2):226-32. Epub 2015 Jul 8.

Department of Endocrinology Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Chengdu Sichuan China.

Aims/introduction: To evaluate serum 25-hydroxyvitamin D3 (25(OH)D3) in newly diagnosed type 2 diabetes patients and to explore the associations of 25(OH)D3 with insulin resistance and β-cell function.

Materials And Methods: A total of 97 newly diagnosed type 2 diabetes patients and 69 healthy controls were recruited. Serum 25(OH)D3 was determined using high-pressure liquid chromatography. Insulin resistance was measured using a homeostasis model assessment of insulin resistance (HOMA-IR). β-Cell function was determined using the HOMA β-cell function index (HOMA-β), early-phase insulin secretion index (ΔI30/ΔG30) and area under the insulin curve (AUCins). Correlation analysis was carried out using Pearson's correlation and multiple stepwise regression analysis.

Results: Serum 25(OH)D3 was much lower in patients with newly diagnosed type 2 diabetes (t = -13.00, P < 0.01), and the prevalence of hypovitaminosis 25(OH)D3 was 62.9% (61/97) in diabetic patients. Among the diabetic patients, patients with hypovitaminosis 25(OH)D3 showed higher glycosylated hemoglobin and AUCglu (P < 0.01) as well as lower HOMA-β, ΔI30/ΔG30 and AUCins. Serum 25(OH)D3 was independently positively correlated with ΔI30/ΔG30 and AUCins (P < 0.05), but was not significantly correlated with either HOMA-IR or HOMA-β. Only triglycerides, glycosylated hemoglobin and ΔI30/ΔG30 emerged as independent factors associated with serum 25(OH)D3 in both diabetes patients and the health control group.

Conclusions: The present results further showed a low serum 25(OH)D3 concentration in patients with newly diagnosed type 2 diabetes. 25(OH)D3 deficiency is associated with disturbances in glucose metabolism and lipid metabolism. Serum 25(OH)D3 is not correlated with basal insulin resistance or β-cell function, but is significantly positively correlated with glucose-stimulated insulin secretion and β-cell function.
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http://dx.doi.org/10.1111/jdi.12381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773668PMC
March 2016

A Novel Approach for Ovine Primary Alveolar Epithelial Type II Cell Isolation and Culture from Fresh and Cryopreserved Tissue Obtained from Premature and Juvenile Animals.

PLoS One 2016 21;11(3):e0152027. Epub 2016 Mar 21.

Department of Thoracic Medicine and Surgery, Katz School of Medicine at Temple University, Philadelphia, PA, United States of America.

The in vivo ovine model provides a clinically relevant platform to study cardiopulmonary mechanisms and treatments of disease; however, a robust ovine primary alveolar epithelial type II (ATII) cell culture model is lacking. The objective of this study was to develop and optimize ovine lung tissue cryopreservation and primary ATII cell culture methodologies for the purposes of dissecting mechanisms at the cellular level to elucidate responses observed in vivo. To address this, we established in vitro submerged and air-liquid interface cultures of primary ovine ATII cells isolated from fresh or cryopreserved lung tissues obtained from mechanically ventilated sheep (128 days gestation-6 months of age). Presence, abundance, and mRNA expression of surfactant proteins was assessed by immunocytochemistry, Western Blot, and quantitative PCR respectively on the day of isolation, and throughout the 7 day cell culture study period. All biomarkers were significantly greater from cells isolated from fresh than cryopreserved tissue, and those cultured in air-liquid interface as compared to submerged culture conditions at all time points. Surfactant protein expression remained in the air-liquid interface culture system while that of cells cultured in the submerged system dissipated over time. Despite differences in biomarker magnitude between cells isolated from fresh and cryopreserved tissue, cells isolated from cryopreserved tissue remained metabolically active and demonstrated a similar response as cells from fresh tissue through 72 hr period of hyperoxia. These data demonstrate a cell culture methodology using fresh or cryopreserved tissue to support study of ovine primary ATII cell function and responses, to support expanded use of biobanked tissues, and to further understanding of mechanisms that contribute to in vivo function of the lung.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152027PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801353PMC
July 2016

Biodistribution and Efficacy of Targeted Pulmonary Delivery of a Protein Kinase C-δ Inhibitory Peptide: Impact on Indirect Lung Injury.

J Pharmacol Exp Ther 2015 Oct 4;355(1):86-98. Epub 2015 Aug 4.

Center for Inflammation, Clinical and Translational Lung Research (M.J.M., P.A.K., J.W., M.K., S.T.B., M.R.W., L.E.K.), Department of Physiology (M.J.M., P.A.K., J.W., S.T.B., M.R.W., L.E.K.), Sol Sherry Thrombosis Research Center (M.J.M., L.C.K., L.E.K.), Departments of Pediatrics and Medicine (M.R.W.), and Department of Radiology (L.C.K.), Temple University School of Medicine, Philadelphia, Pennsylvania

Sepsis and sepsis-induced lung injury remain a leading cause of death in intensive care units. We identified protein kinase C-δ (PKCδ) as a critical regulator of the acute inflammatory response and demonstrated that PKCδ inhibition was lung-protective in a rodent sepsis model, suggesting that targeting PKCδ is a potential strategy for preserving pulmonary function in the setting of indirect lung injury. In this study, whole-body organ biodistribution and pulmonary cellular distribution of a transactivator of transcription (TAT)-conjugated PKCδ inhibitory peptide (PKCδ-TAT) was determined following intratracheal (IT) delivery in control and septic [cecal ligation and puncture (CLP)] rats to ascertain the impact of disease pathology on biodistribution and efficacy. There was negligible lung uptake of radiolabeled peptide upon intravenous delivery [<1% initial dose (ID)], whereas IT administration resulted in lung retention of >65% ID with minimal uptake in liver or kidney (<2% ID). IT delivery of a fluorescent-tagged (tetramethylrhodamine-PKCδ-TAT) peptide demonstrated uniform spatial distribution and cellular uptake throughout the peripheral lung. IT delivery of PKCδ-TAT at the time of CLP surgery significantly reduced PKCδ activation (tyrosine phosphorylation, nuclear translocation and cleavage) and acute lung inflammation, resulting in improved lung function and gas exchange. Importantly, peptide efficacy was similar when delivered at 4 hours post-CLP, demonstrating therapeutic relevance. Conversely, spatial lung distribution and efficacy were significantly impaired at 8 hours post-CLP, which corresponded to marked histopathological progression of lung injury. These studies establish a functional connection between peptide spatial distribution, inflammatory histopathology in the lung, and efficacy of this anti-inflammatory peptide.
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http://dx.doi.org/10.1124/jpet.115.224832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576664PMC
October 2015

The diagnosis of diabetic acute complications using the glucose-ketone meter in outpatients at endocrinology department.

Int J Clin Exp Med 2014 15;7(12):5701-5. Epub 2014 Dec 15.

Department of Endocrinology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospita Sichuan, China.

Objective: To determine urine ketone and blood β-hydroxybutyrate acid (β-HBA) in outpatients of endocrinology department and to investigate the association between urine ketone or blood β-HBA and diabetic ketosis (DK) or diabetic ketoacidosis (DKA).

Methods: Urine ketone, blood β-HBA, body mass index (BMI) and glycosylated hemoglobin (HbA1c) were determined in 134 patients with blood glucose ≥ 13.9 mmol/L.

Results: In 134 patients with severe hyperglycemia, there were 30 patients (22.4%) with acute complications of diabetes, including 24 patients (17.9%) diagnosed with DK and 6 patients (4.5%) diagnosed with DKA. Among them, 6 patients (20%) were withdrawal, 2 (6.7%) were infected, and 19 (63.3%) were not treated. When there was a negative urine ketone, 10% patients would have had blood β-HBA ≥ 0.3 mmol/L. When there was a positive urine ketone (+ to +++), 22.62% patients would have had blood β-HBA < 0.3 mmol/L.

Conclusions: Blood β-HBA had a positive correlation with blood glucose (r = 0.34, P < 0.001). Complications of severe hyperglycemia could be diagnosed quickly and accurately by analyzing blood β-HBA using the glucose-ketone meter.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307541PMC
February 2015

High flow nasal cannula (HFNC) with Heliox decreases diaphragmatic injury in a newborn porcine lung injury model.

Pediatr Pulmonol 2014 Dec 5;49(12):1214-22. Epub 2014 Feb 5.

Neonatology, Alfred I. duPont Hospital for Children, Wilmington, Delaware; Neonatology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

Background: High flow nasal cannula (HFNC) improves ventilation by washing out nasopharyngeal dead space while delivering oxygen. Heliox (helium-oxygen gas mixture), a low-density gas mixture, decreases resistance to airflow, reduces the work of breathing, and facilitates distribution of inspired gas. Excessive lung work and potential injury increases the workload on the immature diaphragm predisposing the muscle to fatigue, and can lead to inflammatory and oxidative stress, thereby contributing to impaired diaphragmatic function. We tested the hypothesis that HFNC with Heliox will decrease the work of breathing thereby unloading the neonatal diaphragm, and potentially reducing diaphragmatic injury.

Methods: Spontaneously breathing neonatal pigs were randomized to Nitrox (nitrogen-oxygen gas mixture) or Heliox, and studied over 4 hr following oleic acid injury. Gas exchange, pulmonary mechanics indices, and systemic markers of inflammation were measured serially. Diaphragm inflammation biomarkers and histology for muscle injury were assessed at termination.

Results: Heliox breathing animals demonstrated decreased respiratory load and work of breathing with lower pressure-rate product, lower labored breathing index, and lower levels of diaphragmatic inflammatory markers, and muscle injury score as compared to Nitrox.

Conclusion: These results suggest that HFNC with Heliox is a useful adjunct to attenuate diaphragmatic fatigue in the presence of lung injury by unloading the diaphragm, resulting in a more efficient breathing pattern, and decreased diaphragm injury.
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http://dx.doi.org/10.1002/ppul.23000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122654PMC
December 2014

Real-time rendering of drug injection and interactive simulation of vessel deformation using GPU.

Annu Int Conf IEEE Eng Med Biol Soc 2013 ;2013:4569-72

Developing patient specific model for the simulation of chemotherapy drug injection is important in medical application. This paper proposed a two-phase fluidic method to simulate chemotherapy drug injection and an improved lumped element method to simulate deformation of vessel at real-time by using GPU for general computing. Firstly, a three-dimensional (3-D) model of hepatic vessels is reconstructed from clinical CT-images using multi-layer method. A 3-D thinning algorithm based on Valence Driven Spatial Median (VDSM) is applied to generate unit-width skeleton of the vessel tree. The two-phase flow simulation of drug injection is based on Hagen-Poiseuille model by introducing a friction factor using bubbly flow Reynolds number. The improved lumped element method achieves good simulation realism at high computational speed to simulate deformable object. Real-time rendering and interaction of vessel deformation, self collision, and surface tearing has been realized and demonstrated in a virtual experiment.
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http://dx.doi.org/10.1109/EMBC.2013.6610564DOI Listing
July 2015

Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS.

Pediatr Res 2012 Oct 20;72(4):375-83. Epub 2012 Jul 20.

Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.

Background: Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants.

Methods: Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination.

Results: SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or beractant.

Conclusion: These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant.
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http://dx.doi.org/10.1038/pr.2012.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888789PMC
October 2012

Perfluorochemical liquid-adenovirus suspensions enhance gene delivery to the distal lung.

Pulm Med 2011 18;2011:918036. Epub 2011 Aug 18.

The Cardiopulmonary Research Institute and Departments of Medicine and Pediatrics, SUNY Stony Brook School of Medicine, Winthrop University Hospital, Mineola, NY 11507, USA.

WE COMPARED LUNG DELIVERY METHODS OF RECOMBINANT ADENOVIRUS (RAD): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined using A549 cells, a murine model using luciferase bioluminescence, and histological analyses. Relative to saline, a 4X increase in transduction efficiency was observed in A549 cells exposed to PFC-rAd for 2-4 h. rAd transgene expression was improved in alveolar epithelial cells, and the level and distribution of luciferase expression when delivered in PFC-rAd suspensions consistently peaked at 24 h. These results demonstrate that PFC-rAd suspensions improve distribution and enhance rAd-mediated gene expression which has important implications in improving lung function by gene therapy.
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http://dx.doi.org/10.1155/2011/918036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159382PMC
November 2011

Prototype hybrid systems for neonatal warming: in vitro comparisons to standard of care devices.

Biomed Instrum Technol 2010 Nov-Dec;44(6):523-7

Department of Physiology, Temple University, Philadelphia, PA, USA.

Preterm infants lack necessary thermoregulation. An ideal incubator should maintain a uniform and constant thermal environment. We compared the effectiveness of a supplemental heating blanket to improve the heating characteristics of two different incubator warming devices using assessment of their respective function alone as controls. Device A and device B, with and without a heating blanket (Harvard Apparatus), were instrumented with a distribution matrix of multiple temperature (n = 11) and humidity probes. These data were serially measured during warm up to 37.5 °C and through a series of open-door perturbations. The time constant, temperature variation, and change in air temperature were calculated. Data were analyzed for significance by 2-factor ANOVA for each respective incubator either turned on or off with either the heating blanket turned on or off. Device A warms faster (33.87% ; p < 0.05) than device B, but has a greater (37.27% ; p < 0.05) temperature variation during warmup. The heating blanket enhances the thermal response of device A during warmup, but does not alter those of device B. With the side door open, device A shows a smaller (-16.5% ; p < 0.05) temperature variation than device B; the heating blanket attenuates the temperature change in both devices. These results demonstrate that the use of a supplemental heating blanket, as well as device-related differences, may impact clinical control of a thermal environment.
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http://dx.doi.org/10.2345/0899-8205-44.6.523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888790PMC
February 2011

Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population.

BMC Med Genet 2010 Jun 15;11:97. Epub 2010 Jun 15.

Center for Human Molecular Biology & Genetics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.

Background: At least twenty genes/loci were shown to be associated with type 2diabetes in European original populations. Five of these genes were shown to be associated with type 2 diabetes (T2D) in Chinese populations. The purpose of this study was to replicate the association of genetic vairants in the eight diabetes-related genes/loci with type 2 diabetes in a Han Chinese cohort from western part of China. Nineteen single nucleotide polymorphisms (SNPs) from the eight genes/loci including TCF7L2, HHEX, CDKAL1, SLC30A8, PPARG, IGF2BP2, KCNJ11, and CDKN2A/CDKN2B were genotyped in 1,529 cases and 1,439 controls in a Han Chinese population using the ABI SNaPshot method. The meta-analysis of the association between rs7903146 in TCF7L2 gene and T2D in the Han Chinese was performed.

Results: Among the eight genes/loci examined, we found that four were significantly associated with T2D. Although previous studies showed that the association between the SNP rs7903146 in the TCF7L2 gene and T2D was controversial within the Han Chinese population, we have confirmed the significant association between the SNP rs7903146 in the TCF7L2 gene and T2D in both this study and the meta-analysis in the population. In addition, we also confirmed that three SNPs (rs1111875, rs7923837 and rs5015480) in HHEX , one SNP (rs10946398) in CDKAL1, and three SNPs (rs13266634, rs3802177 and rs11558471) in SLC30A8 were significantly associated with T2D in the population being studied.

Conclusions: We demonstrated that the variants in TCF7L2, CDKAL1, HHEX, and SLC30A8 genes are associated with T2D in a Han Chinese population.
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http://dx.doi.org/10.1186/1471-2350-11-97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894791PMC
June 2010

Intranasal perfluorochemical spray for preferential brain cooling in sheep.

Neurocrit Care 2008 ;8(3):437-47

Department of Physiology & Pediatrics, Temple University School of Medicine, 3420 N Broad Street, Philadelphia, PA 19140, USA.

Introduction: Hypothermic brain protection has been linked to how rapidly cooling is initiated and how quickly and uniformly the therapeutic hypothermic zone (THZ) is reached. The nasopharyngeal (NP) approach is uniquely suited for preferential brain cooling due to anatomic proximity to the cerebral circulation, cavernous sinus, and carotid arteries. This study explores a novel NP cooling approach employing evaporative characteristics of aerosolized perfluorochemical (PFC).

Methods: Anesthetized, normotensive sheep (n = 30) were instrumented with temperature probes and vascular catheters, then randomized to NP approach (NP-PFC: PFC spray device; n = 24) or whole body surface (WBS: n = 6) cooling. Regional temperatures, vital signs, and blood chemistries were assessed serially. Two animals were exposed to double PFC flow rates and PFC was measured in blood during NP-PFC cooling to assess PFC uptake and elimination. Cooling rates were evaluated (ANOVA) as a function of method (NP-PFC versus WBS) and time to reach the brain THZ (i.e., < or =-3.5 degrees C below baseline).

Results: Independent of region, brain cooling was faster during NP-PFC versus WBS (P < 0.001). During NP-PFC, brain > vascular > rectal cooling rates (P < 0.001), brain to systemic temperature gradients were maintained, the brain THZ was reached within 15 min, and the NP epithelial surface appeared histologically intact. During WBS, brain versus systemic cooling rates were not significantly different and the brain THZ could not be reached within 2 h.

Conclusions: The NP-PFC procedure more rapidly induced preferential brain cooling as compared to WBC without adverse effects.
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http://dx.doi.org/10.1007/s12028-008-9064-0DOI Listing
September 2008