Nitrite Group Research Articles

Abstract 221: Pharmacokinetics and Brain Bioavailability of Nitrite Therapy After Ventricular Fibrillation Cardiac Arrest in Rats

Introduction: Nitrite (NO 2- ) reduces neurological damage and myocardial dysfunction after cardiac arrest (CA), likely through a nitric oxide (NO) or S-nitrosothiol mechanism. The pharmacokinetics (PK) and blood brain barrier (BBB) penetration and elimination of nitrite therapy after CA are unknown but have important implications for clinical translation. Prior reports support optimal cytoprotection at blood levels of 10-20 μM. We tested the hypothesis that exogenous nitrite rapidly crosses the BBB and is taken up by tissues, increasing levels in cerebrospinal fluid (CSF), brain and heart. Methods: Rats (total n=23) were subjected to 5 min VF CA followed by 1.5 min CPR/defibrillation. Rats received either 1 ml placebo or nitrite (8μM) intravenously between 5-10 min resuscitation time (RT). Shams (n=6) with or without nitrite treatment were also analyzed. Nitrite blood levels were measured at various times up to 60 min. At 16 min RT (n=13), CSF was obtained, animals perfused with nitrite-free saline and brain, and heart removed. Separate placebo-controlled experiments (n=6) measured blood nitrite clearance during the initial hour RT. Tissue nitrite concentrations were calculated based on wet tissue weight. Results: Blood nitrite levels were 57.14±10.82 μM at 11 min RT in the nitrite groups, respectively, vs. 0.94±0.58 μM in placebo (p<0.001). Blood nitrite rapidly declined in the initial 2 min after dosing (distribution) reaching 73% of peak values with a more gradual elimination (beta t ½ = 25 min) subsequently. Nitrite rapidly crossed the BBB and was present in CSF at 17.1±1.1 min RT in levels comparable to plasma. Heart and brain had more modest 2-3 fold increases. Conclusions: Nitrite given after CA rapidly crosses the BBB and the PK data suggest significant tissue uptake. These data provide a biological basis for potential cytoprotection including the brain and will inform clinical trials regarding optimal dosing.

GW24-e1015 Nitrate improves postresuscitation myocardial dysfunction and the involvement of nitric oxide and phospholamban protein

ObjectivesThe abnormality of Sarcoplasmic reticulum (SR) Ca2+ handling proteins was shown to be essential in myocardial dysfunction after acute reperfusion injury, which might be attenuated by NO therapy. Cardiac arrest...

Poppers-Makulopathie

Poppers are a common drug belonging to the alkyl nitrite group and in use for several decades. They can be legally purchased for air freshening, but are illegal to buy for inhalation. Abuse is associated with maculopathy and visual loss as a rare side effect. A case series of 27 male, homosexual patients with poppers abuse presenting to a single eye clinic in Berlin, Germany, is described. Four patients with visual impairment and maculopathy associated with the inhalation of poppers were found. Four patients experienced subacute visual loss over 2-6 months, one patient can no longer read without a magnifying glass. The median age is 40.25 years (28-45 years). Three patients are HIV-positive (known since 10-22 years, HAART), a patient is also hepatitis C-positive. No other ocular and systemic diseases are known. Poppers have been inhaled for about 1.5, 12, 15 and 25 years (3-4 ×/week); all patients have a mixed use with the brands Jungle Juice, Rush and Amsterdam. Three patients noticed a simultaneous change in colour and shade. Clinical signs on fundoscopy ranged from normal foveal appearance to yellowish, dull macula. Optical coherence tomography (HD-OCT) showed varying degrees of disruption of the presumed inner segment/outer segment (IS/OS) junction; 3 cases bilaterally symmetrical. Although poppers have been in use for several decades, in 2007 in England, the popper composition was changed by law from isobutyl nitrite to isopropyl nitrite. It is hard to distinguish whether a specific nitrite group triggers the maculopathy or whether it is the dose level, thus suggesting the existence of a cumulative dose-response relationship. We postulate that a major factor of the manifestation of maculopathy is the individual limit of vulnerability. Despite decades of use, the majority of our series does not present any pathology. Limits of our patient population represents the HIV disease: three maculopathies of our series are HIV-associated and controlled by antiretroviral therapy, so that a clear distinction to the disease is absent. Poppers were earlier regarded to cause an AIDS-defining disease of viral aetiology: Kaposi sarcoma. We are well aware of that association and postulate that the observed maculopathies are not causally related to HIV disease and antiretroviral therapy. Considering the cultural background of our patients (multiple partners, frequent sex) and the disinhibiting effect of poppers, an increased risk of HIV disease is found. Since this disease is a rare disorder, patients should be asked specifically about poppers abuse. Further study of the effect of poppers on maculopathy is needed.

Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI)

BackgroundWhilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial.Methods and outcomesThe aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6–8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6–8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6–8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6–8 days and six months.Funding, ethics and regulatory approvalsThis study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26).Trial registrationClinicalTrials.gov: NCT01388504 and Current Controlled Trials: ISRCTN57596739

Abstract 297: Chronic Antihypertensive Effects of Sodium Nitrite in L-name-induced Hypertension in Rats

Dietary nitrite and nitrate have been recently implicated as an important source of nitric oxide with antihypertensive effects. We have previously shown acute antihypertensive effects exerted by a single oral dose of sodium nitrite (NaNO 2 ) in renovascular hypertension. However, the possible chronic antihypertensive effects of NaNO 2 have not been examined yet. We evaluated the effects of NaNO 2 on L-NAME (Nω-Nitro-L-arginine methyl ester)-induced hypertension in Wistar rats. METHODS: Rats received vehicle (tap water) or L-NAME (1g/L) in their drinking water. After two weeks of treatment, the rats received NaNO 2 (15 mg/kg/day by gavage) or vehicle for 4 weeks. Systolic blood pressure (SBP) was evaluated by pletismography weekly. Plasma levels of nitrate and nitrite were assessed by Griess reaction and ozone-based chemiluminescence, respectively. Dihydroethidium (DHE) was used in aortic sections to evaluate reactive oxygen species (ROS) production by fluorescence microscopy. Results: while NaNO 2 treatment induced no changes on SBP in vehicle-treated rats (p>0.05), this treatment significantly reduced SBP in L-NAME-treated rats (192±2 mmHg in L-NAME + vehicle group versus 164±2 mmHg in L-NAME + nitrite group; P<0.05). At the end of treatment, we found lower plasma nitrite levels in L-NAME rats compared with normotensive controls (148±14 nM versus 445±97; P<0.05). NaNO 2 treatment increased plasma nitrite levels in both normotensive controls and in L-NAME-treated rats (P<0.05). While no significant changes were found in plasma nitrate levels in L-NAME-treated rats when compared with controls (903±157 nM versus 995±145; p>0.05), NaNO 2 treatment induced significant increases in plasma nitrate levels in both normotensive and hypertensive rats (191±13 nM and 199±17 respectively; p<0.05 when compared to the controls). When compared to the control groups, higher ROS levels were found in the aortic rings from L-NAME treated rats (4091±249 A.U. versus 5709±598 A.U.; p<0.05) but treatment did not affect this increase (p>0.05). Conclusion: Our results show for the first time that NaNO 2 has relevant chronic antihypertensive effects in L-NAME hypertension. However, was unable to reverse the oxidative stress associated with L-NAME-induced hypertension.

Heterometallic Complexes of Ruthenium and Lanthanides (Ce, Pr, Nd, Eu) with NO2 Bridges – Synthesis, Structures, Properties

AbstractFive new heterometallic complexes with a {Ln[RuNO(μ‐NO2)4(μ3‐OH)]2Ln} (Ln = Ce, Pr, Nd, Eu) core were prepared by reaction of Na2[RuNO(NO2)4OH] and lanthanide nitrates in the presence of pyridine. The crystal structures of the obtained compounds were determined by single‐crystal X‐ray analysis. In all complexes, Ru and Ln atoms are connected by N,O‐bridging nitrite groups and OH groups. The coordination environment of Ln3+ is completed by oxygen atoms of nitrate ions and water molecules and by nitrogen atoms of pyridine molecules. Magnetic interactions between lanthanide atoms become apparent at temperatures lower than 40–50 K, and at temperatures higher than 100 K, the dependencies of the magnetic susceptibilities of the complexes are well explained by the presence of two noninteracting paramagnetic centers. Thermal decomposition of the investigated complexes in an inert atmosphere results in a mixture of metallic ruthenium and the corresponding lanthanide oxide. Formation of mixed oxide phases RuPrOx was also detected after decomposition of the praseodymium complex.

Abstract 8626: Multi Detector CT Accurately Defines Infarct Size, but not Microvascular Obstruction Post Myocardial Infarction, and Sodium Nitrite Increases Microvascular Obstruction Region Blood Flow Without Affecting CT Hypoenchancement Area

(a) Purpose To determine what areas of hyperenchancement and hypoenhancement on multi-detector CT (MDCT) represent in terms of infarct size and myocardial regional blood flow (RBF), and the effect of nitrite on RBF and MDCT contrast patterns. (b) Materials and Methods MDCT contrast-defined I, MVO, and non-infarct remote (R) areas in vivo were compared to matched areas defined ex vivo by triphenyltetrazolium chloride (TTC) staining (infarct area) and Thioflavin S exclusion (TSE) (area of MVO), and their RBF by fluorescent microspheres and flow cytometry, in 16 female Landrace pigs who underwent mid-LAD myocardial infarction (MI) (90 minutes ischemia, 120 minutes reperfusion), and treated with saline (n=8) or nitrite (n=8). All analyses were performed by at least two blinded observers. (c) Results There was a correlation between infarct area on CT and that defined by TTC (r 2 =0.75). There was a poor correlation between MVO on CT and MVO by TSE (r 2 =0.46). TTC and TSE identified distinct differences in flow within R (1.2 ± 0.19 ml/min/g), I (0.62 ± 0.11 ml/min/g), and MVO (0.3 ± 0.04 ml/min/g) areas, respectively. Despite increased RBF in remote (+45%) and MVO (+80 %) regions in nitrite group compared to saline, there was no corresponding change in MDCT contrast patterns. Two animals died in each group. (d) Conclusion MDCT is a reliable predictor of infarct size but not microvascular obstruction at 24 hours post infarction. Sodium nitrite increased RBF to MVO regions, but this was not detected by MDCT.

Tolerated nitrite therapy in experimental intracerebral hemorrhage: Rationale of nitrite therapy in a broad range of hyperacute strokes

Nitrite therapy is more effective in cerebral ischemia when administered earlier. It would be beneficial during the hyperacute stages of stroke if the nitrite effect is demonstrated in intracerebral hemorrhage (ICH). When nitrite is injected intravenously 3 h after ICH induction in rats, most doses of nitrite provided no beneficial effects on behavioral deficits, brain edema and hematoma volumes. A high dose of nitrite, however, decreased hematoma volume, but not brain edema. Peri-hematomal apoptosis and inflammation were similar between the control and nitrite groups. Nitrite therapy may be considered a therapeutic option in hyperacute stroke because nitrite therapy is tolerated in ICH as well.

Nitrite Therapy Positively Augments Arteriogenesis in a Murine Model of Hind Limb Ischemia

Objective The objective of this study was to test the hypothesis that delayed sodium nitrite therapy in the femoral artery ligation (FAL) mediated hind limb ischemia model stimulates collaterization and ischemic tissue reperfusion. Methods Permanent hind limb ischemia was induced by FAL in C57BL/6J mice. Mice were randomly assigned to four experimental group; control, sodium nitrite, sodium nitrite with cPTIO, or cPTIO alone. The various treatments were administered twice daily and began 5 days post-surgical ligation and continued to 23 days post-ischemia. Tissue blood perfusion was measured using laser Doppler and SPY imaging (angiographic contrast). Vessel diameter and branches were measured by microfil vascular casting and morphometric analysis. Number of capillaries and mature arterioles were also counted. Result Blood perfusion was significantly increased in the nitrite therapy group compared to PBS. Sodium nitrite therapy with concomitant cPTIO treatment significantly blunted ischemic tissue reperfusion. The number of visible collaterals as seen by angiographic SPY imaging was significantly higher in sodium nitrite group compared to PBS. Arterial branches, diameter, and vascular density were all enhanced by sodium nitrite therapy in an NO dependent manner. Sodium nitrite therapy also significantly increased arteriole SMA staining in an NO dependent manner. Conclusion Sodium nitrite therapy during established tissue ischemia quickly augments blood perfusion in the FAL hind limb model by stimulating arteriogenesis in an NO dependent manner. These data suggest that sodium nitrite may be useful in stimulating therapeutic arteriogenesis. Supported by NIH grants HL80482, HL94021, and DK43785

(Nitrato-κ2O,O′)(nitrito-κ2O,O′)(0.25/1.75)]bis(1,10-phenanthroline-κ2N,N′)cadmium(II)

The reaction of cadmium nitrate and sodium nitrite in the presence of 1,10-phenanthroline yields the mixed nitrate–nitrite title complex, [Cd(NO2)1.75(NO3)0.25(C12H8N2)2]. The metal ion is bis-chelated by two N-heterocycles as well as by the nitrate/nitrite ions in a distorted dodeca­hedral CdN4O4 coordination environment. One nitrite group is ordered; the other is disordered with respect to a nitrate group (ratio 0.75:0.25) concerning the O atom that is not involved in bonding to the metal ion.

Mononuclear and dinuclear bromide–nitrite cadmium(II) complexes with related 1,4-diazabicyclo[2.2.2]octane ligands

The title compounds, di-μ-bromido-bis[bromido(1-carboxymethyl-4-aza-1-azoniabicyclo[2.2.2]octane-κN(4))(nitrito-κ(2)O,O')cadmium(II)] dihydrate, [Cd(2)Br(4)(C(8)H(15)N(2)O(2))(2)(NO(2))(2)]·2H(2)O, (I), and aquabromido(1-cyanomethyl-4-aza-1-azoniabicyclo[2.2.2]octane-κN(4))bis(nitrito-κ(2)O,O')cadmium(II) monohydrate, [CdBr(C(8)H(14)N(3))(NO(2))(2)(H(2)O)]·H(2)O, (II), are two-dimensional hydrogen-bonded metal-organic hybrid complexes. In (I), the complex is situated on a centre of inversion so that each symmetry-related Cd(II) atom is coordinated by two bridging Br atoms, one monodentate Br atom, one chelating nitrite ligand and one organic ligand, yielding a significantly distorted octahedral geometry. The combination of O-H···O and O-H···Br hydrogen bonds produces centrosymmetric R(6)(6)(16) ring motifs, resulting in two-dimensional layers parallel to the ab plane. In contrast, the complex molecule in (II) is mononuclear, with the Cd(II) atom seven-coordinated by two bidentate nitrite groups, one N atom from the organic ligand, one monodentate Br atom and a water O atom in a distorted pentagonal-bipyramidal environment. The combination of O-H···O and O-H···Br hydrogen bonds produces R(5)(4)(14) and R(3)(3)(8) rings which lead to two-dimensional layers parallel to the ac plane.

Effects of long term nitrite therapy on functional recovery in experimental ischemia model

Our data have shown that nitrite therapy can rescue the ischemic brain when injected <3h after cerebral ischemic-reperfusion (I/R) injury and its effects can be prolonged to 4.5h in combination with memantine. We investigated whether or not long-term nitrite therapy is beneficial in ischemic brains. Sodium nitrite (1–100μg/kgip) or saline were administered to rats subjected to focal I/R injury for 7days beginning 24h after I/R. Behavioral tests for 5weeks revealed better functional recovery in the high-dose nitrite group than the control group. Other nitrite groups with relatively low doses showed no functional benefits. Hemispheric atrophy was attenuated by approximately 30% in the high-dose nitrite group. High-dose nitrite therapy also reduced inflammatory cytokine levels and caspase activity in the subacute period, and increased BrdU+MAP2+ and BrdU+laminin+ cells, and vascular density in the 5-week ischemic brain. Long-term nitrite therapy, when initiated 24h after I/R, corrected the subacute hostile environment, induced tissue and vascular regeneration, and improved functional recovery. Early and subsequent long term nitrite therapy may be effective in the management for ischemic stroke patients.

Catena-Poly[[(1,10-phenanthroline-κ2N,N′)lead(II)]-μ-azido-κ2N1:N3-μ-nitrito-κ3O,O′:O′-[(1,10-phenanthroline-κ2N,N′)lead(II)]-di-μ-azido-κ4N1:N1

The title coordination polymer, [Pb2(N3)3(NO2)(C12H8N2)2]n, has as the repeat unit a centrosymmetric dinuclear mol­ecule having azide and nitrite groups that bridge adjacent heterocycle-coordinated metal centers. One of the azide group uses its terminal ends to bridge whereas the nitrite group chelates to one metal atom and uses one of its O atoms to bridge. The azide and nitrite groups are disordered with respect to each other in a 1:1 ratio. Adjacent dinuclear mol­ecules are further bridged by the other two azide groups, generating a linear chain motif parallel to [010]. Half of the Pb atoms show a Ψ-dodeca­hedral coordination and the other half show a Ψ-penta­gonal-bipyramidal coordination.

Fe Promoted NOx Storage Materials: Structural Properties and NOx Uptake

Fe promoted NOx storage materials were synthesized in the form of FeOx/BaO/Al2O3 ternary oxides with varying BaO (8 and 20 wt %) and Fe (5 and 10 wt %) contents. Synthesized NOx storage materials were investigated via TEM, EELS, BET, FTIR, TPD, XRD, XPS, and Raman spectroscopy, and the results were compared with the conventional BaO/Al2O3 NOx storage system. Our results suggest that the introduction of Fe in the BaO/Al2O3 system leads to the formation of additional NOx storage sites which store NOx mostly in the form of bidentate nitrates. NO2 adsorption experiments at 323 K via FTIR indicate that, particularly in the early stages of the NOx uptake, the NOx storage mechanism is significantly altered in the presence of Fe sites where a set of new surface nitrosyl and nitrite groups were detected on the Fe sites and the surface oxidation of nitrites to nitrates is significantly hindered with respect to the BaO/Al2O3 system. Evidence for the existence of both Fe3+ as well as reduced Fe2+/(3−x)+ sites on the ...

Dinuclear alkoxo-bridged copper(II) coordination polymers: Syntheses, structural and magnetic properties

The alkoxo-bridged dinuclear copper(II) complexes [Cu2(ap)2(NO2)2] (1), [Cu2(ap)2(C6H5COO)2] (2) and [Cu2(ap)2μ-1,3-C6H4(COO)2(dmso)2]·dmso (3) (ap = 3-aminopropanolato and dmso = dimethyl sulfoxide) have been synthesized via self-assembly from copper(II) perchlorate, 3-aminopropanol as main chelating ligand and nitrite and isophthalate anions as spacers and benzoate anion as auxiliary ligand. Complexes 1 and 3 crystallize as 2D and 1D coordination polymers, respectively, and their structures consist of dinuclear [Cu2(ap)2]2+ units connected with nitrite and isophthalate ligands. The adjacent dinuclear units of 2 and 1D polymers of 3 are further connected by hydrogen bonds resulting in the formation of 2D layers. The variable temperature crystallographic measurements of 1 at 100, 173 and 293 K indicate the static Jahn–Teller distortion with librational disorder in the nitrite group. Experimental magnetic studies showed that complexes 1–3 exhibit strong antiferromagnetic couplings. The values of the magnetic exchange coupling constant for 1–3 are well reproduced by the theoretical calculations.

Hydroxocobalamin and Sodium Thiosulfate Versus Sodium Nitrite and Sodium Thiosulfate in the Treatment of Acute Cyanide Toxicity in a Swine (Sus scrofa) Model

Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate. Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance. Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar. Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.

96 The Structure and Function of the Gastro-Esophageal Junction in Health and Reflux Disease Assessed By Magnetic Resonance Imaging and High Resolution Manometry

nitrate, and during acid reflux, generation of NO is shifted to the distal esophagus. We have demonstrated that high concentrations of luminal NO can impair the gastric mucosal barrier function by disrupting the tight junction (Gut 2008). We hypothesized that NO generated luminally during acid reflux could disrupt the esophageal barrier function and provoke DIS. Aim: To investigate the direct effects of luminal NO on the esophageal barrier function using an ex vivo chamber model. Design and Setting: A chamber model in which the rat esophageal mucosal membrane was mounted between the two halves of a chamber was designed to simulate the microenvironment of the lumen and the adjacent mucosa of the esophagus. On the mucosal side of the chamber, NO was generated by the acidification of physiologic concentrations of sodium nitrite. The epithelial barrier function was evaluated by electrophysiological transmembrane resistance (R) and membrane permeability with 3H-mannitol flux in four groups; Krebs buffer, acid alone (pH 1.5), acid + sodium nitrite 5.0 mM, and acid + sodium nitrite 1.0 mM. Intercellular space diameters were measured on transmission electron microscopy photomicrographs. Results: In all groups except for Krebs buffer, the R decreased rapidly within the initial 15 minutes, followed by gradual decrease thereafter. At 180 minutes, the R decreased by 34% in acid alone group, by 39% in acid + nitrite 1.0 mM group, by 45% in acid + nitrite 5.0 mM group by 55%. Consequently, the administration of acidified nitrite (1.0 mM or 5.0 mM) to the mucosal side significantly decreased the R compared with that of the acid alone (p<0.01). While epithelial permeability with 3Hmannitol slightly increased at 180 minutes in acid alone group, it remarkably increased in acid + nitrite 5.0 mM group. Thus, the administration of acidified nitrite to the mucosal side significantly increased epithelial permeability compared with the acid alone group (p<0.05). DIS was observed in the nitrite groups but not in the acid alone group. Conclusions: The NO generated luminally via acidification of nitrite disrupted the barrier function of the esophageal epithelium and provoked DIS, suggesting that NO generated luminally contributes to DIS observed in GERD patients and plays an important role in the pathophysiology of GERD.

Conformers and Photochemistry of Propyl Nitrites: A Matrix Isolation Study

The infrared spectra of both constitutional isomers (n and i) of propyl nitrite have been recorded in an Ar matrix. Conformational analysis and assignments of the vibrational transitions have been carried out on the basis of quantum chemical calculations. Assignment of spectral lines to different conformers was also aided experimentally, by utilizing the different rate of photodecomposition of the conformers, as well as by employing conformational cooling using a supersonic jet as the inlet source for matrix deposition. The rate of photodecomposition is primarily determined by the steric alignment of the nitrite group, whereas jet cooling affects mainly the conformation of the alkyl tail. On the basis of these experimental observations and computational predictions two to three conformers of isopropyl nitrite and eight conformers of n-propyl nitrite were identified. After broadband ultraviolet-visible (UV-vis) photolysis of isopropyl nitrite in the matrix, HNO, acetone, HNO.acetone complex, acetaldehyde, and nitrosomethane were identified as the main products. Furthermore, in a small amount, NO and possibly the isopropoxy radical were also present in the matrix. Photolysis of n-propyl nitrite yielded HNO, propanal, and their 1:1 complex as the main products together with a small amount of NO and cis-1-nitrosopropanol.

Picric Acid Degradation in Sediments from the Louisiana Army Ammunition Plant

Picric acid is an explosive historically produced and disposed at the Louisiana Army Ammunition Plant (LAAP) in northern Louisiana. The potential for natural degradation of picric acid was investigated by creating picric-acid slurries with four LAAP sediments of variable composition and monitoring for up to 98 days. The concentrations of picric acid decreased rapidly in all slurries during the first day, attributed to adsorption, followed by slower decreases in some samples due to degradation. Degradation in unsterilized slurries was nearly complete within 80 days for two of the four sediments. Increases in nitrite and nitrate concentration over time were proportional to the loss of picric acid and indicate that at least two of the three nitrite groups were removed from the picric acid molecule. The absence of significant concentrations of compounds with a mass greater than 100 amu in the final solutions suggests that all three nitrite groups were removed. No correlation was found between the degree of degradation and grain size, clay content, organic content, carbonate content, or a suite of element concentrations in the sediment. Degradation in sterilized samples was minimal for all sediment slurries, indicating microbial activity as the primary mechanism of degradation.

Vibrational analysis of n-butyl, isobutyl, sec-butyl and tert-butyl nitrite

Raman and infrared spectra of n-butyl, isobutyl, sec-butyl and tert-butyl nitrite are reported. Density functional theory and Møeller–Plesset calculations with 6-31G * and 6-311G * basis sets were used to determine ground state molecular geometries and vibrational frequencies of these compounds. Calculations and spectral data of these molecules were used to perform partial vibrational mode assignments for the observed transitions. In agreement with previous investigations of alkyl nitrites, cis and trans rotational conformers of n-butyl, isobutyl and sec-butyl nitrite were observed in the gas phase infrared spectra and the condensed phase Raman and infrared spectra. Among the several predicted geometries of these compounds, the cis– trans geometry ( cis with respect to the C–O–N O dihedral angle and trans with respect to the C–C–O–N dihedral) was calculated to be the most stable conformer of n-butyl and isobutyl nitrite, while the cis– gauche conformer was found to be the most stable geometry of sec-butyl nitrite. The cis-type structures of these three molecules are favored due to formation of a pseudo hydrogen bond between the nitrite group and the α-carbon hydrogen atoms. Hindrance with the alkyl moiety, however, causes the trans conformer ( trans with respect to the C–O–N O dihedral) of tert-butyl nitrite to lie lower than its cis conformer, a result that was supported by our spectroscopic measurements. The characteristic N O stretch frequency for the trans conformers of all the compounds examined was observed to decrease with increasing branching at the α-carbon, while the same mode for the cis conformers shows no change among the primary and secondary nitrites. Evidence is also provided that suggests that the relative number of cis conformers to trans conformers decreases as the α-carbon branching increases