Rakesh P Patel

Publications (109)573.65 Total impact

• Dataset: Prime PNAS 2009

  Tracy A Prime, Frances H Blaikie, Cameron Evans, Sergiy M Nadtochiy, Andrew M James, Christina C Dahm, Dario A Vitturi, Rakesh P Patel, C Robin Hiley, Irina Abakumova, Raquel Requejo, Edward T Chouchani, Thomas R Hurd, John F Garvey, Cormac T Taylor, Paul S Brookes, Robin A J Smith, Michael P Murphy
• Dataset: Prime PNAS 2009

  Tracy A Prime, Frances H Blaikie, Cameron Evans, Sergiy M Nadtochiy, Andrew M James, Christina C Dahm, Dario A Vitturi, Rakesh P Patel, C Robin Hiley, Irina Abakumova, Raquel Requejo, Edward T Chouchani, Thomas R Hurd, John F Garvey, Cormac T Taylor, Paul S Brookes, Robin A J Smith, Michael P Murphy
• Article: Targeting endothelial adhesion molecule mRNA to control inflammation: novel insights into potential anti-inflammatory effects of IL-19.

  David W Scott, Rakesh P Patel
  [show abstract] [hide abstract]
  ABSTRACT: N/A.
  AJP Cell Physiology 05/2013; · 3.54 Impact Factor
• Article: Endothelial heterogeneity and adhesion molecules N-glycosylation: implications in leukocyte trafficking in inflammation.

  David W Scott, Rakesh P Patel
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  ABSTRACT: Inflammation is a major contributing element to a host of diseases with the interaction between leukocytes and the endothelium being a key in this process. Much is understood about the nature of the adhesion molecule proteins expressed on any given leukocyte and endothelial cell that modulates adhesive interactions. Although it is appreciated that these proteins are heavily glycosylated, relatively little is known about the roles of these post-translational modifications and whether they are regulated, and if so how during inflammation. Herein we suggest that a paucity in this understanding is one major reason for the lack of successful therapies to date for modulating leukocyte-endothelial interactions in human inflammatory disease and discuss developing paradigms of i) how endothelial adhesion molecule glycosylation (with a focus on N-glycosylation) maybe a critical element in understanding endothelial heterogeneity between different vascular beds and species, ii) how adhesion molecule N-glycosylation may be under distinct, and as yet, unknown modes of regulation during inflammatory stress to affect the inflammatory response in a vascular bed and disease specific manner (analogous to a "zip code" for inflammation), and finally iii) to underscore the concept that a fuller appreciation of the role of adhesion molecule glycoforms is needed to provide foundations for disease and tissue specific targeting of inflammation.
  Glycobiology 02/2013; · 3.58 Impact Factor
• Article: Effects of erythrocyte aging on Nitric oxide and nitrite metabolism.

  Benjamin Y Owusu, Ryan Stapley, Jaideep Honavar, Rakesh P Patel
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  ABSTRACT: Aims: Recent studies have suggested that in addition to oxygen transport, red blood cells (RBC) are key regulators of vascular function by both inhibiting and promoting nitric oxide (NO)-mediated vasodilation. Most studies assume RBC are homogenous, but in fact they are comprised of cells of differing morphology and biochemical composition dependent on their age, parameters that control NO-reactions. We tested the hypothesis that distinct RBC populations will have differential effects on NO-signaling. Results: Young and old RBC were separated by density gradient centrifugation. Consistent with previous reports, old RBC had decreased levels of surface N-acetyl neuraminic acid and increased oxygen binding affinities. Competition kinetic experiments showed that older RBCs scavenged NO ≈2-fold faster compared to younger RBC, which also translated to a more potent inhibition of both acetylcholine and NO-donor dependent vasodilation of isolated aortic rings. Moreover, nitrite oxidation kinetics were faster with older RBC compared to younger RBC, whereas no differences in nitrite-reduciton kinetics were observed. This translated to increased inhibitory effect of older RBC to nitrite-dependent vasodilation under oxygenated and deoxygenated conditions. Finally, leukodepleted RBC storage also resulted in more dense RBC, which may contribute to the greater NO-inhibitory potential of stored RBC. Innovation: These results suggest a key element in vascular NO-homeostasis mechanisms is the distribution of RBC ages across the physiological spectrum (0-120d) and suggest a novel mechanism for inhibited NO-bioavailability in diseases characterized by a shift to an older RBC phenotype. Conclusion: Older RBC inhibit NO-bioavailability by increase NO- and nitrite scavenging.
  Antioxidants & Redox Signaling 01/2013; · 8.20 Impact Factor
• Article: Role of the b93cys, ATP and adenosine in red cell dependent hypoxic vasorelaxation.

  Yanping Liu, Chiao-Wang Sun, Jaideep Honavar, Tim Townes, Rakesh P Patel
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  ABSTRACT: Two of the proposed mechanisms by which red blood cells (RBC) mediate hypoxic vasorelaxation by coupling hemoglobin deoxygenation to the activation of nitric oxide signaling involve ATP-release from RBC and S-nitrosohemoglobin (b93C(SNO)Hb) dependent bioactivity. However, different studies have reached opposite conclusions regarding the aforementioned mechanisms. Using isolated vessels, hypoxic vasorelaxation induced by human, C57BL/6 or mouse RBC which exclusively express either native human hemoglobin (HbC93) or human hemoglobin in which the conserved b93cys was replaced with Ala (HbC93A) were compared. All RBCs stimulated hypoxic vasodilation to similar extents suggesting the b93cys is not required for this RBC-mediated function. Hypoxic vasorelaxation was inhibited by co-incubation of ATP-pathway blockers including L-NAME (eNOS inhibitor) and Apyrase. Moreover, we tested if modulation of adenosine-dependent signaling affected RBC-dependent vasorelaxation using pan- or subtype specific adenosine receptor blockers, or adenosine deaminase (ADA). Interestingly, ADA and adenosine A2 receptor blockade, but not A1 receptor blockade, inhibited HbC93, HbC93A dependent hypoxic vasorelaxation. Equivalent results were obtained with human RBC. These data suggest that using isolated vessels, RBC do not require the presence of the b93cys to elicit hypoxic vasorelaxation and mediate this response via ATP- and a novel adenosine-dependent mechanism.
  International Journal of Physiology, Pathophysiology and Pharmacology 01/2013; 5(1):21-31.
• Article: Antioxidant functions for the hemoglobin β93 cysteine residue in erythrocytes and in the vascular compartment in vivo.

  Dario A Vitturi, Chiao-Wang Sun, Victoria M Harper, Bessy Thrash-Williams, Nadiezhda Cantu-Medellin, Balu K Chacko, Ning Peng, Yanying Dai, J Michael Wyss, Tim Townes, Rakesh P Patel
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  ABSTRACT: The β93 Cysteine (β93Cys) residue of hemoglobin is conserved in vertebrates but its function in the red blood cell (RBC) remains unclear. Since this residue is present at concentrations more than two orders of magnitude higher than enzymatic components of the RBC antioxidant network, a role in the scavenging of reactive species was hypothesized. Initial studies utilizing mice that express human hemoglobin with either Cys (B93C) or Ala (B93A) at the β93 positions, demonstrated that loss of the β93Cys did not affect activities nor expression of established components of the RBC antioxidant network (catalase, superoxide dismutase, peroxiredoxin-2, glutathione peroxidase, GSH:GSSG ratios). Interestingly, exogenous addition to RBC of reactive species that are involved in vascular inflammation demonstrated a role for the β93Cys in hydrogen peroxide and chloramine consumption. To simulate oxidative stress and inflammation in vivo, mice were challenged with LPS. Notably, LPS induced a greater degree of hypotension and lung injury in B93A versus B93C mice, which was associated with greater formation of RBC reactive species and accumulation of DMPO-reactive epitopes in the lung. These data suggest that the β93Cys is an important effector within the RBC antioxidant network contributing to the modulation of tissue injury during vascular inflammation.
  Free radical biology & medicine 11/2012; · 5.42 Impact Factor
• Source

  Available from: Jason Hellmann

  Dataset: eNOS and High Fat

  Brian E Sansbury, Timothy D Cummins, Yunan Tang, Jason Hellmann, Candice R Holden, Matthew A Harbeson, Yang Chen, Rakesh P Patel, Matthew R Spite, Aruni Bhatnagar, Bradford G Hill
• Source

  Available from: Timothy D. Cummins

  Article: Overexpression of endothelial nitric oxide synthase prevents diet-induced obesity and regulates adipocyte phenotype.

  Brian E Sansbury, Timothy D Cummins, Yunan Tang, Jason Hellmann, Candice R Holden, Matthew A Harbeson, Yang Chen, Rakesh P Patel, Matthew Spite, Aruni Bhatnagar, Bradford G Hil
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  ABSTRACT: Rationale: Endothelial dysfunction is a characteristic feature of diabetes and obesity in animal models and humans. Deficits in nitric oxide production by endothelial nitric oxide synthase (eNOS) are associated with insulin resistance, which is exacerbated by high-fat diet. Nevertheless, the metabolic effects of increasing eNOS levels have not been studied. Objective: The current study was designed to test whether overexpression of eNOS would prevent diet-induced obesity and insulin resistance. Methods and Results: In db/db mice and in high-fat diet-fed wild-type C57BL/6J mice, the abundance of eNOS protein in adipose tissue was decreased without significant changes in eNOS levels in skeletal muscle or aorta. Mice overexpressing eNOS (eNOS transgenic mice) were resistant to diet-induced obesity and hyperinsulinemia, although systemic glucose intolerance remained largely unaffected. In comparison with wild-type mice, high-fat diet-fed eNOS transgenic mice displayed a higher metabolic rate and attenuated hypertrophy of white adipocytes. Overexpression of eNOS did not affect food consumption or diet-induced changes in plasma cholesterol or leptin levels, yet plasma triglycerides and fatty acids were decreased. Metabolomic analysis of adipose tissue indicated that eNOS overexpression primarily affected amino acid and lipid metabolism; subpathway analysis suggested changes in fatty acid oxidation. In agreement with these findings, adipose tissue from eNOS transgenic mice showed higher levels of PPAR-α and PPAR-γ gene expression, elevated abundance of mitochondrial proteins, and a higher rate of oxygen consumption. Conclusions: These findings demonstrate that increased eNOS activity prevents the obesogenic effects of high-fat diet without affecting systemic insulin resistance, in part, by stimulating metabolic activity in adipose tissue.
  Circulation Research 08/2012; 111(9):1176-89. · 9.49 Impact Factor
• Article: Administration of nitrite after chlorine gas exposure prevents lung injury: Effect of administration modality.

  Andrey A Samal, Jaideep Honavar, Angela Brandon, Kelley M Bradley, Stephen Doran, Yanping Liu, Chad Dunaway, Chad Steele, Edward M Postlethwait, Giuseppe L Squadrito, Michelle V Fanucchi, Sadis Matalon, Rakesh P Patel
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  ABSTRACT: Cl(2) gas toxicity is complex and occurs during and after exposure, leading to acute lung injury (ALI) and reactive airway syndrome (RAS). Moreover, Cl(2) exposure can occur in diverse situations encompassing mass casualty scenarios, highlighting the need for postexposure therapies that are efficacious and amenable to rapid and easy administration. In this study, we assessed the efficacy of a single dose of nitrite (1mg/kg) to decrease ALI when administered to rats via intraperitoneal (ip) or intramuscular (im) injection 30min after Cl(2) exposure. Exposure of rats to Cl(2) gas (400ppm, 30min) significantly increased ALI and caused RAS 6-24h postexposure as indexed by BAL sampling of lung surface protein and polymorphonucleocytes (PMNs) and increased airway resistance and elastance before and after methacholine challenge. Intraperitoneal nitrite decreased Cl(2)-dependent increases in BAL protein but not PMNs. In contrast im nitrite decreased BAL PMN levels without decreasing BAL protein in a xanthine oxidoreductase-dependent manner. Histological evaluation of airways 6h postexposure showed significant bronchial epithelium exfoliation and inflammatory injury in Cl(2)-exposed rats. Both ip and im nitrite improved airway histology compared to Cl(2) gas alone, but more coverage of the airway by cuboidal or columnar epithelium was observed with im compared to ip nitrite. Airways were rendered more sensitive to methacholine-induced resistance and elastance after Cl(2) gas exposure. Interestingly, im nitrite, but not ip nitrite, significantly decreased airway sensitivity to methacholine challenge. Further evaluation and comparison of im and ip therapy showed a twofold increase in circulating nitrite levels with the former, which was associated with reversal of post-Cl(2) exposure-dependent increases in circulating leukocytes. Halving the im nitrite dose resulted in no effect in PMN accumulation but significant reduction of BAL protein levels, indicating a distinct nitrite dose dependence for inhibition of Cl(2)-dependent lung permeability and inflammation. These data highlight the potential for nitrite as a postexposure therapeutic for Cl(2) gas-induced lung injury and also suggest that administration modality is a key consideration in nitrite therapeutics.
  Free radical biology & medicine 08/2012; 53(7):1431-9. · 5.42 Impact Factor
• Article: Erythrocyte storage increases rates of NO and nitrite scavenging: implications for transfusion-related toxicity.

  Ryan Stapley, Benjamin Y Owusu, Angela Brandon, Marianne Cusick, Cilina Rodriguez, Marisa B Marques, Jeffrey D Kerby, Scott R Barnum, Jordan A Weinberg, Jack R Lancaster, Rakesh P Patel
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  ABSTRACT: Storage of erythrocytes in blood banks is associated with biochemical and morphological changes to RBCs (red blood cells). It has been suggested that these changes have potential negative clinical effects characterized by inflammation and microcirculatory dysfunction which add to other transfusion-related toxicities. However, the mechanisms linking RBC storage and toxicity remain unclear. In the present study we tested the hypothesis that storage of leucodepleted RBCs results in cells that inhibit NO (nitric oxide) signalling more so than younger cells. Using competition kinetic analyses and protocols that minimized contributions from haemolysis or microparticles, our data indicate that the consumption rates of NO increased ~40-fold and NO-dependent vasodilation was inhibited 2-4-fold comparing 42-day-old with 0-day-old RBCs. These results are probably due to the formation of smaller RBCs with increased surface area: volume as a consequence of membrane loss during storage. The potential for older RBCs to affect NO formation via deoxygenated RBC-mediated nitrite reduction was also tested. RBC storage did not affect deoxygenated RBC-dependent stimulation of nitrite-induced vasodilation. However, stored RBCs did increase the rates of nitrite oxidation to nitrate in vitro. Significant loss of whole-blood nitrite was also observed in stable trauma patients after transfusion with 1 RBC unit, with the decrease in nitrite occurring after transfusion with RBCs stored for >25 days, but not with younger RBCs. Collectively, these data suggest that increased rates of reactions between intact RBCs and NO and nitrite may contribute to mechanisms that lead to storage-lesion-related transfusion risk.
  Biochemical Journal 06/2012; 446(3):499-508. · 4.90 Impact Factor
• Source

  Available from: Wayne Orr

  Article: Role of endothelial N-glycan mannose residues in monocyte recruitment during atherogenesis.

  David W Scott, Jie Chen, Balu K Chacko, James G Traylor, Anthony W Orr, Rakesh P Patel
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  ABSTRACT: Upregulated expression of endothelial adhesion molecules and subsequent binding to cognate monocytic receptors are established paradigms in atherosclerosis. However, these proteins are the scaffolds, with their posttranslational modification with sugars providing the actual ligands. We recently showed that tumor necrosis factor-α increased hypoglycosylated (mannose-rich) N-glycans on the endothelial surface. In the present study, our aim was to determine whether (1) hypoglycosylated N-glycans are upregulated by proatherogenic stimuli (oscillatory flow) in vitro and in vivo, and (2) mannose residues on hypoglycosylated endothelial N-glycans mediate monocyte rolling and adhesion. Staining with the mannose-specific lectins concanavalin A and lens culinaris agglutinin was increased in human aortic endothelial cells exposed to oscillatory shear or tumor necrosis factor-α and at sites of plaque development and progression in both mice and human vessels. Increasing surface N-linked mannose by inhibiting N-glycan processing potentiated monocyte adhesion under flow during tumor necrosis factor-α stimulation. Conversely, enzymatic removal of high-mannose N-glycans, or masking mannose residues with lectins, significantly decreased monocyte adhesion under flow. These effects occurred without altering induced expression of adhesion molecule proteins. Hypoglycosylated (high mannose) N-glycans are present on the endothelial cell surface at sites of early human lesion development and are novel effectors of monocyte adhesion during atherogenesis.
  Arteriosclerosis Thrombosis and Vascular Biology 06/2012; 32(8):e51-9. · 6.37 Impact Factor
• Article: Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.

  Stacey S Kelpke, Bo Chen, Kelley M Bradley, Xinjun Teng, Phillip Chumley, Angela Brandon, Brett Yancey, Brandon Moore, Hughston Head, Liliana Viera, John A Thompson, David K Crossman, Molly S Bray, Devin E Eckhoff, Anupam Agarwal, Rakesh P Patel
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  ABSTRACT: Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.
  Kidney International 04/2012; 82(3):304-13. · 6.61 Impact Factor
• Article: Single-dose pharmacokinetics of different oral sodium nitrite formulations in diabetes patients.

  Frank L Greenway, Benjamin L Predmore, Douglas R Flanagan, Tony Giordano, Yang Qiu, Angela Brandon, David J Lefer, Rakesh P Patel, Christopher G Kevil
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  ABSTRACT: Diabetic foot ulcers, although associated with macrovascular disease and neuropathy, have a microvascular disease causing ischemia not amenable to surgical intervention. Nitrite selectively releases nitric oxide in ischemic tissues, and diabetes subjects have low nitrite levels that do not increase with exercise. This study explores the safety and pharmacokinetics of a single dose of sodium nitrite in subjects with diabetic foot ulcers. Using a blinded, randomized crossover study design, 12 subjects with diabetes mellitus and active or healed foot ulcers received a single dose of sodium nitrite on two occasions 7-28 days apart, once with an immediate release (IR) formulation and once with an enteric-coated (EC) formulation for delayed release. Serum nitrite, nitrate, methemoglobin, sulfhemoglobin, blood pressure, pulse rate, complete blood count, chemistry panel, electrocardiogram, and adverse events were followed for up to 6 h after each dose. The IR and EC nitrite levels were analyzed by one-way analysis of variance and by pharmacokinetic modeling. The IR formulation elevated nitrite levels between 0.25 and 0.75 h (P<0.05). The EC formulation did not elevate nitrite levels significantly, but both formulations gave plasma nitrite levels previously suggested to be therapeutic (approximately 2-5 μM). The IR formulation gave an asymptomatic blood pressure drop of 10/6 mm Hg (P<0.003), and two subjects experienced mild flushing. There was no elevation of methemoglobin or other safety concerns. Pharmacokinetic modeling of plama nitrite levels gave r(2) values of 0.81 and 0.97 for the fits for IR and EC formulations, respectively. Oral sodium nitrite administration is well tolerated in diabetes patients.
  Diabetes Technology &amp Therapeutics 04/2012; 14(7):552-60. · 1.93 Impact Factor
• Article: Metabolic and cardiac signaling effects of inhaled hydrogen sulfide and low oxygen in male rats.

  Asaf Stein, Zhengkuan Mao, Joanna P Morrison, Michelle V Fanucchi, Edward M Postlethwait, Rakesh P Patel, David W Kraus, Jeannette E Doeller, Shannon M Bailey
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  ABSTRACT: Low concentrations of inhaled hydrogen sulfide (H(2)S) induce hypometabolism in mice. Biological effects of H(2)S in in vitro systems are augmented by lowering O(2) tension. Based on this, we hypothesized that reduced O(2) tension would increase H(2)S-mediated hypometabolism in vivo. To test this, male Sprague-Dawley rats were exposed to 80 ppm H(2)S at 21% O(2) or 10.5% O(2) for 6 h followed by 1 h recovery at room air. Rats exposed to H(2)S in 10.5% O(2) had significantly decreased body temperature and respiration compared with preexposure levels. Heart rate was decreased by H(2)S administered under both O(2) levels and did not return to preexposure levels after 1 h recovery. Inhaled H(2)S caused epithelial exfoliation in the lungs and increased plasma creatine kinase-MB activity. The effect of inhaled H(2)S on prosurvival signaling was also measured in heart and liver. H(2)S in 21% O(2) increased Akt-P(Ser473) and GSK-3β-P(Ser9) in the heart whereas phosphorylation was decreased by H(2)S in 10.5% O(2), indicating O(2) dependence in regulating cardiac signaling pathways. Inhaled H(2)S and low O(2) had no effect on liver Akt. In summary, we found that lower O(2) was needed for H(2)S-dependent hypometabolism in rats compared with previous findings in mice. This highlights the possibility of species differences in physiological responses to H(2)S. Inhaled H(2)S exposure also caused tissue injury to the lung and heart, which raises concerns about the therapeutic safety of inhaled H(2)S. In conclusion, these findings demonstrate the importance of O(2) in influencing physiological and signaling effects of H(2)S in mammalian systems.
  Journal of Applied Physiology 03/2012; 112(10):1659-69. · 3.75 Impact Factor
• Article: Encapsulation of hemoglobin inside liposomes surface conjugated with poly(ethylene glycol) attenuates their reactions with gaseous ligands and regulates nitric oxide dependent vasodilation.

  Shahid Rameez, Nicole Guzman, Uddyalok Banerjee, Jorge Fontes, Michael E Paulaitis, Andre F Palmer, Rakesh P Patel, Jaideep Honavar
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  ABSTRACT: Acellular hemoglobin (Hb)-based O2 carriers (HBOCs) are being investigated as red blood cell (RBC) substitutes for use in transfusion medicine. However, commercial acellular HBOCs elicit both vasoconstriction and systemic hypertension which hampers their clinical use. In this study, it is hypothesized that encapsulation of Hb inside the aqueous core of liposomes should regulate the rates of NO dioxygenation and O2 release, which should in turn regulate its vasoactivity. To test this hypothesis, poly(ethylene glycol) (PEG) conjugated liposome-encapsulated Hb (PEG-LEHs) dispersions were prepared using human and bovine Hb. In this study, the rate constants for O2 dissociation, CO association, and NO dioxygenation were measured for free Hb and PEG-LEH dispersions using stopped-flow UV-visible spectroscopy, while vasoactivity was assessed in rat aortic ring strips using both endogenous and exogenous sources of NO. It was observed that PEG-LEH dispersions had lower O2 release and NO dioxygenation rate constants compared with acellular Hbs. However, no difference was observed in the CO association rate constants between free Hb and PEG-LEH dispersions. Furthermore, it was observed that Hb encapsulation inside vesicles prevented Hb dependent inhibition of NO-mediated vasodilation. In addition, the magnitude of the vasoconstrictive effects of Hb and PEG-LEH dispersions correlated with their respective rates of NO dioxygenation and O2 release. Overall, this study emphasizes the pivotal role Hb encapsulation plays in regulating gaseous ligand binding/release kinetics and the vasoactivity of Hb.
  Biotechnology Progress 02/2012; 28(3):636-45. · 2.34 Impact Factor
• Article: ABO Blood Group Is Associated with Response to Inhaled Nitric Oxide in Neonates with Respiratory Failure.

  George T El-Ferzli, Mackenzie Dreher, Rakesh P Patel, Namasivayam Ambalavanan
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  ABSTRACT: Inhaled nitric oxide (iNO) reduces death or need for extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). However, the response to iNO is variable and only 50-60% of infants demonstrate a response to iNO. It is not known why only some infants respond to iNO. Adults and children with blood groups B or AB do not respond as well to iNO as those with blood groups O/A. To determine if blood group was associated with iNO response in newborn infants, a retrospective medical record review was done of infants admitted to a regional NICU from 2002-9 with a diagnosis of PPHN. Data were collected during the first twelve hours post-initiation of treatment. Of 86 infants diagnosed with PPHN, 23 infants had blood group A [18 received iNO], 21 had group B [18 with iNO], 40 had group O [36 with iNO], and 2 had group AB [both received iNO]. Change in PaO(2)/FiO(2) was less in infants with blood group A, of whom less than half were responders (ΔPaO(2)/FiO(2)>20%) at 12 h versus 90% of infants with either O or B. Race, sex, birth weight, gestational age, Apgar scores at 1 and 5 minutes, and baseline PaO(2)/FiO(2) were similar among groups. Outcomes including need for ECMO, death, length of ventilatory support, length of iNO use, and hospital stay were statistically not different by blood groups. Our results indicate that blood group influences iNO response in neonates. We hypothesize that either there is genetic linkage of the ABO gene locus with vasoregulatory genes, or that blood group antigens directly affect vascular reactivity.
  PLoS ONE 01/2012; 7(9):e45164. · 4.09 Impact Factor
• Source

  Available from: John D Lang

  Article: The hepatoprotective effect of sodium nitrite on cold ischemia-reperfusion injury.

  Wei Li, Zihui Meng, Yuliang Liu, Rakesh P Patel, John D Lang
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  ABSTRACT: Liver ischemia-reperfusion injury is a major cause of primary graft non-function or initial function failure post-transplantation. In this study, we examined the effects of sodium nitrite supplementation on liver IRI in either Lactated Ringer's (LR) solution or University of Wisconsin (UW) solution. The syngeneic recipients of liver grafts were also treated with or without nitrite by intra-peritoneal injection. Liver AST and LDH release were significantly reduced in both nitrite-supplemented LR and UW preservation solutions compared to their controls. The protective effect of nitrite was more efficacious with longer cold preservation times. Liver histological examination demonstrated better preserved morphology and architecture with nitrite treatment. Hepatocellular apoptosis was significantly reduced in the nitrite-treated livers compared their controls. Moreover, liver grafts with extended cold preservation time of 12 to 24 hours demonstrated improved liver tissue histology and function post-reperfusion with either the nitrite-supplemented preservation solution or in nitrite-treated recipients. Interestingly, combined treatment of both the liver graft and recipient did not confer protection. Thus, nitrite treatment affords significant protection from cold ischemic and reperfusion injury to donor livers and improves liver graft acute function post-transplantation. The results from this study further support the potential for nitrite therapy to mitigate ischemia-reperfusion injury in solid organ transplantation.
  Journal of Transplantation 01/2012; 2012:635179.
• Source

  Available from: Christoph Geisler

  Article: Program and abstracts for the 2011 Meeting of the Society for Glycobiology.

  M Tony Hollingsworth, Gerald W Hart, James C Paulson, Elizabeth Stansell, Kevin Canis, I-Cheuh Huang, Maria Panico, Howard Morris, Stuart Haslam, Michael Farzan, [......], Kazunori Hamamura, Takenosuke Yoshida, Kaoru Akita, Tetsuya Okajima, Keiko Furukawa, Takeshi Urano, Koichi Furukawa, L Renee Ruhaak, Suzanne Miyamoto, Carlito B Lebrilla
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  ABSTRACT: Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine kinases and other cell surface receptors, and engage in signal transduction in order to communicate information regarding conditions at the cell surface to the nucleus. In that context, the MUC1 cytoplasmic tail (MUC1CT) receives phosphorylation signals from receptor tyrosine kinases and serine/threonine kinases, which enables its association with different signaling complexes that conduct these signals to the nucleus and perhaps other subcellular organelles. We have detected the MUC1CT at promoters of over 500 genes, in association with several different transcription factors, and have shown that promoter occupancy can vary under different growth factor conditions. However, the full biochemical nature of the nuclear forms of MUC1 and its function at these promoter regions remain undefined. I will present evidence that nuclear forms of the MUC1CT include extracellular and cytoplasmic tail domains. In addition, I will discuss evidence for a hypothesis that the MUC1CT possesses a novel catalytic function that enables remodeling of the transcription factor occupancy of promoters, and thereby engages in regulation of gene expression.
  Glycobiology 11/2011; 21(11):1454-531. · 3.58 Impact Factor
• Article: Losing control over adenosine 5'-triphosphate release: implications for the red blood cell storage lesion.

  Rakesh P Patel
  Critical care medicine 11/2011; 39(11):2573-4. · 6.37 Impact Factor