Glycerol Trinitrate Research Articles

Glycerol Trinitrate Acts Downstream of Calcitonin Gene-Related Peptide in Trigeminal Nociception-Evidence from Rodent Experiments with Anti-CGRP Antibody Fremanezumab.

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been recognized as important mediators in migraine but their mechanisms of action and interaction have not been fully elucidated. Monoclonal anti-CGRP antibodies like fremanezumab are successful preventives of frequent migraine and can be used to study CGRP actions in preclinical experiments. Fremanezumab (30 mg/kg) or an isotype control monoclonal antibody was subcutaneously injected to Wistar rats of both sexes. One to several days later, glyceroltrinitrate (GTN, 5 mg/kg) mimicking nitric oxide (NO) was intraperitoneally injected, either once or for three consecutive days. The trigeminal ganglia were removed to determine the concentration of CGRP using an enzyme-linked immunosorbent assay (ELISA). In one series of experiments, the animals were trained to reach an attractive sugar solution, the access to which could be limited by mechanical or thermal barriers. Using a semi-automated registration system, the frequency of approaches to the source, the residence time at the source, and the consumed solution were registered. The results were compared with previous data of rats not treated with GTN. The CGRP concentration in the trigeminal ganglia was generally higher in male rats and tended to be increased in animals treated once with GTN, whereas the CGRP concentration decreased after repetitive GTN treatment. No significant difference in CGRP concentration was observed between animals having received fremanezumab or the control antibody. Animals treated with GTN generally spent less time at the source and consumed less sugar solution. Without barriers, there was no significant difference between animals having received fremanezumab or the control antibody. Under mechanical barrier conditions, all behavioral parameters tended to be reduced but animals that had received fremanezumab tended to be more active, partly compensating for the depressive effect of GTN. In conclusion, GTN treatment seems to increase the production of CGRP in the trigeminal ganglion independently of the antibodies applied, but repetitive GTN administration may deplete CGRP stores. GTN treatment generally tends to suppress the animals' activity and increase facial sensitivity, which is partly compensated by fremanezumab through reduced CGRP signaling. If CGRP and NO signaling share the same pathway in sensitizing trigeminal afferents, GTN and NO may act downstream of CGRP to increase facial sensitivity.

Study on Synthesis and Performance of Methyl Diphenyl Urea Stabilizer

Diphenylamine (DPA), formyl chloride, and sodium hydride (NaH) as raw materials synthesize methyldiphenylurea stabilizer by alkylation reaction. The physical and chemical properties of methyldiphenylurea were characterized by nuclear magnetic resonance hydrogen spectrum (1HNMR), X-ray energy spectrum (EDS), Fourier transforms infrared spectroscopy (FT-IR) and differential thermal analysis (DTA). Thermal Decomposition Experiment of Nitrate Propellant Containing Stabilizer by Thermogravimetric Analysis (TGA), exploring the Effect of Different Stabilizers. The molecular surface electrostatic potential energy of methyl diphenyl urea, triphenylamine ( TPA ), dimethyl diphenyl urea (C2), and glycerol trinitrate were calculated by Materials Studio software. The interaction between the stabilizer and glycerol trinitrate molecule was studied. The results showed that the weight loss rate of methyl diphenyl urea was less than 0.1 % within 30 days, and the chemical stability was good. And its negative electrostatic potential energy is larger than that of C2 and TPA, its intermolecular binding ability with glycerol trinitrate is stronger, and its inhibition of nitrate decomposition stability is the best.

Theoretical Kinetic Studies on Thermal Decomposition of Glycerol Trinitrate and Trimethylolethane Trinitrate in the Gas and Liquid Phases.

Glycerol trinitrate (NG) and trimethylolethane trinitrate (TMETN), as typical nitrate esters, are important energetic plasticizers in solid propellants. With the aid of high-precision quantum chemical calculations, the Rice-Ramsperger-Kassel-Marcus (RRKM)/master equation theory and the transition state theory have been employed to investigate the decomposition kinetics of NG and TMETN in the gas phase (over the temperature range of 300-1000 K and pressure range of 0.01-100 atm) and liquid phase (using water as the solvent). The continuum solvation model based on solute electron density (SMD) was used to describe the solvent effect. The thermal decomposition mechanism is closely relevant to the combustion properties of energetic materials. The results show that the RO-NO2 dissociation channel overwhelmingly favors other reaction pathways, including HONO elimination for the decomposition of NG and TMETN in both the gas phase and liquid phase. At 500 K and 1 atm, the rate coefficient of gas phase decomposition of TMETN is 5 times higher than that of NG. Nevertheless, the liquid phase decomposition of TMETN is a factor of 5835 slower than that of NG at 500 K. The solvation effect caused by vapor pressure and solubility can be used to justify such contradictions. Our calculations provide detailed mechanistic evidence for the initial kinetics of nitrate ester decomposition in both the gas phase and liquid phase, which is particularly valuable for understanding the multiphase decomposition behavior and building detailed kinetic models for nitrate ester.

The Anti-CGRP Antibody Fremanezumab Lowers CGRP Release from Rat Dura Mater and Meningeal Blood Flow.

Monoclonal antibodies directed against the neuropeptide calcitonin gene-related peptide (CGRP) belong to a new generation of therapeutics that are effective in the prevention of migraine. CGRP, a potent vasodilator, is strongly implicated in the pathophysiology of migraine, but its role remains to be fully elucidated. The hemisected rat head preparation and laser Doppler flowmetry were used to examine the effects on CGRP release from the dura mater and meningeal blood flow of the subcutaneously injected anti-CGRP monoclonal antibody fremanezumab at 30 mg/kg, when compared to an isotype control antibody. Some rats were administered glycerol trinitrate (GTN) intraperitoneally to produce a migraine-like sensitized state. When compared to the control antibody, the fremanezumab injection was followed by reduced basal and capsaicin-evoked CGRP release from day 3 up to 30 days. The difference was enhanced after 4 h of GTN application. The samples from the female rats showed a higher CGRP release compared to that of the males. The increases in meningeal blood flow induced by acrolein (100 µM) and capsaicin (100 nM) were reduced 13–20 days after the fremanezumab injection, and the direct vasoconstrictor effect of high capsaicin (10 µM) was intensified. In conclusion, fremanezumab lowers the CGRP release and lasts up to four weeks, thereby lowering the CGRP-dependent meningeal blood flow. The antibody may not only prevent the released CGRP from binding but may also influence the CGRP release stimulated by noxious agents relevant for the generation of migraine pain.

Forensic science deals with safety armour during warfare explosives

Forensic analysis of explosives includes analysis of post-explosion residues, and detection and identification of traces of explosives on suspects’ hands, on clothing, and on other related items. Preliminary field tests may be used for screening the debris on the explosion site. They include commercially available explosive vapor detectors and chemical color tests. Like post-explosion residues, personal items suspected to contain traces of explosives and hand-swabs, are often heavily contaminated. It is therefore of major importance that the analytical procedures have to include good screening, clean-up, and extraction methods. The main explosives dealt with in this chapter include nitroaromatic explosives, such as 2,4,6-trinitrotoluene (TNT) and 2,4,6, N-tetranitro-N-methyl aniline (tetryl), nitrate esters, such as ethylene glycol dinitrate (EGDN), glycerol trinitrate (nitroglycerin, NG), and pentaerythritol tetranitrate (PETN), and nitramine explosives, such as 1,3,5- trinitro-1,3,5-triazacyclohexane, (RDX) and 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX), as well as mixtures containing one or more of these explosives. Additional explosives include triacetone triperoxide (TATP) and ammonium nitrate (AN), NH4NO3.

Impaired endothelium-dependent and endothelium-independent systemic vasodilatory reserve in pulmonary hypertension regardless the clinical group: A generalized dysfunction beyond the pulmonary arteries?

Endothelium-dependent (ED) and endothelium-independent (EI) flow-mediated vasodilatation (FMD) have been used as measures of systemic arterial vasodilatory reserve. In this study, we aimed to assess both ED-FMD and EI-FMD in different groups with pulmonary hypertension (PH), and to investigate the relationship of these measures with clinical, echocardiographic, and invasive parameters of diseases severity and targeted treatment status. Our study population comprised 41 patients with PH [28 (68.2%) women, age 46.3±19.6 years] including idiopathic pulmonary arterial hypertension, Eisenmenger syndrome, and chronic thromboembolic PH in whom diagnosis were confirmed in accordance with current guidelines and 17 age and sex-matched healthy controls. The brachial artery (BA) was used for assessment of FMD with Duplex ultrasound, and serial changes in diameter were recorded at baseline, 1, and 3 minutes after termination of 2-minute external occlusive compression for ED-FMD, and after sublingual intake of glycerol trinitrate for EI-FMD, respectively. Compared with controls, overall the PH group showed significantly lower ED-FMD (0.65±0.21 vs. 0.30±0.23 and 0.65±0.18 vs. 0.24±0.21) and EI-FMD (0.67±0.15 vs. 0.37±0.25 and 0.75±0.20 vs. 0.32±0.24) responses at 1st and 3rd min (p<0.001 for all). All these changes in the values of ED-FMD and EI-FMD were comparable among the PH subgroups. Neither ED-FMD nor EI-FMD were correlated with measures of PH severity and targeted therapy (TT) status (p>0.05). Our results suggest an impaired BA vasodilatory reserve in patients with PH regardless of the clinical subgroup. Although these findings seem to be consistent with systemic dysfunction, acute FMD may not reflect the severity of PH and cannot be used as a potential surrogate for outcome in this setting.

Biotransformation of organic nitrates by glutathione S-transferases and other enzymes: An appraisal of the pioneering work by William B. Jakoby

Organic nitrates (R–ONO2; R, organic residue) such as nitroglycerin are used as drugs in part for more than a century. Their pharmacological use is associated with clinically relevant tolerance which is reportedly known since 1888. The underlying mechanisms of both, the mechanisms of action and the main pharmacological effect, which is vasodilatation and reduction of blood pressure, and the development of tolerance, which means increasing need of drug amount in sustained long-term therapy, are still incompletely understood. William B. Jakoby and associates were the first to report the biotransformation of organic nitrates, notably including nitroglycerin (i.e., glycerol trinitrate; GTN), by glutathione S-transferase (GST)-catalyzed conjugation of glutathione (GSH) to the nitrogen atom of one of the three nitrate groups of GTN to generate glutathione sulfenyl nitrite (glutathione thionitrate, S-nitroglutathione; GSNO2). Jakoby's group was also the first to suggest that GSNO2 reacts with a second GSH molecule to produce inorganic nitrite (ONO−) and glutathione disulfide (GSSG) without the catalytic involvement of GST. This mechanism has been adopted by others to the biotransformation of GTN by mitochondrial aldehyde dehydrogenase (mtALDH-(CysSH)2) which does not require GSH as a substrate. The main difference between these reactions is that mtALDH forms an internal thionitrate (mtALDH-(CysSH)-CysSNO2) which releases inorganic nitrite upon intra-molecular reaction to form mtALDH disulfide (mtALDH-(CysS)2). Subsequently, ONO− and GSNO2 are reduced by several proteins and enzymes to nitric oxide (NO) which is a very potent activator of soluble guanylyl cyclase to finally relax the smooth muscles thus dilating the vasculature. GSNO2 is considered to rearrange to GSONO which undergoes further reactions including GSNO and GSSG formation. The present article is an appraisal of the pioneering work of William B. Jakoby in the area of the biotransformation of organic nitrates by GST. The two above mentioned enzymatic reactions are discussed in the context of tolerance development to organic nitrates, still a clinically relevant pharmacological concern.

To the Question of Detonation of Multicomponent Energetic Condensed Systems by a Nanosecond Electron Beam

An experimental study was made of the initiation of detonation of a polymer-bonded energetic condensed system containing glycerol trinitrate, ammonium perchlorate, and aluminum powder by a nanosecond relativistic electron beam with a flux density of 200 J/cm2. It has been found that the velocity of dispersion of gas–plasma formations from the surface of the energetic condensed system is ∼22 km/s. It has been shown that the detonation of the studied energetic condensed system by the nanosecond relativistic electron beam is reached at much lower pressures than in the case of initiation by an explosive charge.

Nitration of glycerol-A byproduct of biodiesel production

Production of biodiesel is a renewable and pollution free source but it increases co-product i.e. crude glycerol. This paper demonstrates applications of the side product in an efficient and cost effective manner. The crude glycerol hence produced can be utilized in varied industries and can be used as precursor for the production of various products having better economic significance. The majority of crude glycerol is used as feedstock for production of other value-added chemicals. The utilization of glycerol in production of Glycerol trinitrate, Tartronic acid and Glyceric acid has been reported successfully.

Vapor Pressure of Linear Nitrate Esters Determined by Transpiration Method in Combination with VO‐GC/MS

AbstractGas phase detection of explosives is an ongoing trend in the detection sciences. The conception of gas phase detection devices requires knowledge about gas phase concentration of the target analytes. Nitrate esters are well performing explosives with a high potential for misuse in improvised explosive devices that need to be detected at vulnerable infrastructures. With respect to this the six nitrate esters, ethyl nitrate (1), ethylene glycol dinitrate (2), glycerol trinitrate (3), meso‐erythritol tetranitrate (4), d‐mannitol hexanitrate (5) and pentaerythritol tetranitrate (6) were investigated in terms of detectability by vacuum outlet‐GC/MS as potential components in improvised explosive devices. All compounds besides 5 could be detected using vacuum outlet GC/MS and their limits of detection were determined according to DIN 32645 : 2008. The vapor pressure of 2–4 was measured using the transpiration method. It was observed that the introduction of a CHONO2 unit lowers the vapor pressure of the nitrate esters by about two orders of magnitude. For compound 4 the saturation concentration (73 ng L−1) was compared with a vapor pressure based estimation of its concentration in diffusion equilibrium (0.385 pg L−1).

Dielecric Relaxation in Energy Condensed Systems on the Basis of Polyefirretane Elastomer. II. Temperature Dependence and Ignition

This paper describes the effect of the composition of energy condensed systems, containing glycerol trinitrate, aluminum powder, ammonium perchlorate, and HMX, on their ignition in an electric field with a frequency of 50 Hz. Conditions under which energy condensed systems ignite in an alternating electric field with a frequency of 50 Hz are determined experimentally. Temperature changes of their dielectric characteristics in a frequency range from 20 Hz to 1 MHz are established. The possibilities of an electric breakdown and heating of the samples are theoretically estimated. It is revealed that electrical luminescence is observed in a polymer binder based on glycerol trinitrate and polyetherurethane.

Abstract TP108: The Impact of Aggressive Blood Pressure Management in the Post-Thrombolysis Setting

Introduction: High blood pressure post-thrombolysis has been associated with an increased rate of bleeding and poorer outcome. Aiming for a maximum systolic blood pressure (SBP) of 180 mmHG often fails to adequately maintain SBP &lt;180 mmHg due to unavoidable treatment delays. We tested whether a more aggressive target of SBP &lt;160mmHg would result in fewer protocol violations, a lower rate of sICH and improved patient outcomes off-setting any potential harm relating to a potentially higher risk of hypotensive events resulting in cerebral hypoperfusion. Methods: In late 2014 a new blood pressure (BP) protocol was introduced, aiming for SBP &lt;160mmHg post thrombolysis with a low threshold for using a glycerine trinitrate infusion (GTN). Patients were prospectively captured in a thrombolysis register and registry data was supplemented by retrospective chart review, comparing patients thrombolysed during the 12 months before and 12 months following the introduction of the new protocol, allowing for a 6 month transition period. Results were adjusted for baseline function and stroke severity using regression analysis. Results: During the 12 months preceding and the 12 months following the transition to the new protocol 68 and 100 patients were thrombolysed respectively. Baseline characteristics were similar between groups including age, pre-stroke level of independence and stroke severity at presentation. There was a trend for a lower rate of SBPs &gt;180mmHg (adjusted OR 0.49; 95% CI 0.31-1.1; p=0.097) and a significantly higher rate of SBPs &lt;120mmHg (adjusted OR 3.06; 95% CI 1.52-6.17; p=0.002) in the aggressive BP protocol group; although events of extreme SBPs (&gt;200 and &lt;100 mmHg) were similar between groups. Favourable outcomes (mRS = 0-2) at 3 months were not significantly more common in the aggressive BP protocol group (adjusted OR 1.27; 95% CI 0.58-2.8; p=0.56), nor was there a reduced rate of sICH (adjusted OR 1.26; 95% CI 0.28-5.7; p=0.76). However, model fit was improved by adding study group to the model. Conclusions: The introduction of a more aggressive post-thrombolysis BP protocol successfully shifted the SBP range into a potentially safer zone, however, this was not conclusively associated with improved patient outcomes.

Experience of using an individual approach in the anal fissures treatment

To objectify the criteria for choosing the method of treatment of anal fissures, to determine the indications for surgery and sphincterotomy. The results of treatment of 206 patients with chronic and acute anal fissures between the ages of 17 to 75 years are analyzed. The posterior anal fissure was detected in 175 (84.9%) patients, the front - in 18 (8.7%), the combination of fissures was noted 13 (6.3%) times. The history of the disease - from 1 month to 12 years. The examination included analysis of clinical data, indicators of pre- and postoperative anorectal manometry, endorectal ultrasound. The period of postoperative monitoring is from 6 to 12 months, control examinations with a functional study of the anal sphincters were carried out 1 and 2 months after healing. Concomitant hemorrhoids were noted in 65 (31.5%) patients, of which 20 (9.7%) patients were simultaneously hemorrhoidectomized. In 11 (5.3%) patients, simultaneous operations were performed in the presence of paraproctitis, rectal fistula. In 77.8% of patients with acute fissures, the use of conservative therapy, which included myotropic antispasmodics and local application of glycerol trinitrate made it possible to achieve healing of fissures without surgery. Operated 185 (89.8%) patients. With an increase in the basal anal pressure at the level of the internal sphincter, an increase in the average pressure in the anal canal, a decrease in the amplitude and duration of the rectoanal reflex, the indications for dosed sphincterotomy were determined in 167 patients. At the same time, in 117 persons, the excision of fissures was supplemented with a lateral 'closed' sphincterotomy, in 50 cases the posterior 'open' dosed sphincterotomy was performed. In 18 (9.7% of the operated ones) patients in the absence of sphincter hypertonus, the fissures were excised without sphincterotomy. The best functional results were obtained after performing the lateral 'closed' subcutaneous sphincterotomy. It was noticed that in the absence of characteristic complaints and clinical manifestations of incontinence, in 14 patients there was a decrease in the average pressure in the anal canal at rest and with volitional contraction. At the same time, 6 patients out of 14 belonged to the older age groups, and in 9 women there was a rectocele, pelvic floor prolapse. Postoperative incontinence was not observed. Recovery with complete epithelialization of the anoderm defect and the absence of complaints was achieved in 191 (92.7%) patients, satisfactory results (healing of fissures in the presence of pain or proctitis) - in 8 (3.9%) and in 7 (3.4%) patients relapse of the disease was noted with the ineffectiveness of therapy. The ineffectiveness of complex conservative treatment for more than two weeks, with a history of more than 3 months, is an indication for surgical treatment. Preoperative functional and clinical and physiological examination of patients allows the formation of surgical tactics. A differentiated approach to the choice of treatment method, as well as individual determination of indications for surgery and sphincterotomy can improve long-term results. The technique of simultaneous operations with the combination of anal fissure and other proctological diseases needs to be improved.

Topical Nitroglycerine Versus Lateral Sphincterectomy for Fissure in Ano: A Hospital Based Comparative Study

Background: Anal fissure is a common benign condition presenting as severe pain, constipations and bleeding per rectum. It is defined as longitudinal tear or defect in anal canal skin. Surgical treatment of this conditions requires hospital admission and complications, like bleeding, infection and to its severe extent continence disturbances. That warrants a new treatment modality as pharmacological sphincterotomy i. e topical GTN (glycerine trinitrate) whose effects are reversible, cost effective and simple.&#x0D; Objective: The objective is to compare the effectiveness of topical GTN over lateral sphincterotomy in terms of pain management and healing of fissure.&#x0D; Method: This was a comparative study carried out in the department of Surgery at Nepalgunj Medical College, Teaching Hospital. Two groups were created and 25 patients in each group were put randomly. First group (Group 1) used topical GTN whereas second group(Group 2) underwent lateral sphincterotomy for treatment of fissure. The two groups were reassessed at 4 and 8 weeks for pain and fissure healing.&#x0D; Result: Total number of patients was 50. Each group consisted of 25 patients. The male to female ratio in group 1 was 1:1.5 and in group 2 it was 1: 1.8. In group 1 patients after 4 weeks of application of GTN pain reduced from the mean of 80±15 at the time of presentation to 50±9.27. When these patients were seen after 8 weeks, the pain reduction on VAS was nil in 21 patients out of 25. In group 2 the mean score fell from 75±15 to 20±10 after 4 weeks and at 8weeks 23 out of 25 patients didn't have any pain. It was observed that the pain reduction and healing were faster in group 2 patients when evaluated after 4 weeks (p=0.0029). but at the end of 8 weeks both group patients were similar in terms of pain reduction and healing of fissure (p=.28).&#x0D; Conclusion: According to study local GTN application is as effective as lateral sphincterotomy with cost effectiveness, simple with tolerable side effect and no continence disturbances.

Near Infrared Fluorescence Imaging to Assess Breast Flap Perfusion and Prevention of Ischemia: Case Report

Introduction: Breast skin flap ischemia and necrosis is a serious consequence of breast reconstruction with reported incidence of 10% to 15%. Current clinical method of assessing breast skin flap perfusion includes combination of skin color, temperature, dermal edge bleeding, and capillary refill. Given the high incidence of ischemia and the presence of certain cohort of patient with greater risk, there is a need for an objective method of assessing the skin flap perfusion. Near infrared fluorescence imaging using indocyanine green is a new technique of assessing skin flap perfusion. We present a first reported case where breast skin flap ischemia was objectively identified intraoperatively by NIRF imaging, and this ischemia was reversed through active intra- and postoperative measures, which was objectively again identified by NIRF imaging. Case presentation: A 36-year-old female patient underwent bilateral nipple sparing mastectomies with immediate reconstruction using tissue expanders. Clinical assessment of the breast skin flap was equivocal. NIRF imaging using SPY imaging system (Novadaq Technologies Inc, Toronto, ON, Canada) showed poor perfusion in the periareolar region. As a result, it was decided to completely deflate the expander, actively warm the skin flap and encourage cutaneous perfusion through use of topical glycerin trinitrate patch. A repeat NIRF imaging 48 hours showed 10-fold increase in perfusion in the skin flap. Conclusion: NIRF imaging is a useful tool in assessing breast skin perfusion and to predict potential ischemia, which can aid in surgeon's management of patient.

Surgical management of anal fissure versus Glyceryl Trinitrate ointment: a comparative prospective study

Background: Anal fissure is common condition in general population which cause severe pain at the anal region while defecation and associated with bleeding. These symptoms cause reduction in quality of life with considerable morbidity. The objective of this study was to compare the difference in outcome between open lateral anal sphincterotomy and application of topical 0.2% nitroglycerin ointment for the treatment of chronic anal fissure and their individual efficacy.Methods: 68 cases with a clinical diagnosis of anal fissure were recruited in the study. All selected patients met with inclusion criteria. Thus, selected cases were assigned to one of the other groups by odd and even method. Group A was managed conservatively using topical 0.2% nitroglycerin ointment, whereas Group B underwent open lateral anal sphincterotomy. Both groups were followed up at 3 week, 6 weeks, and 12 weeks, after the treatment.Results: Among all the 68 patients, all patients had come with complaint of pain whereas 31 patients had bleeding per rectum along with pain. On clinical examination, hypertonic anal sphincter elicited in 47 patients, sentinel skin tag was noted in the 23 patients. Group A included 34 patients treated with topical 0.2% nitroglycerin ointment and group B included 34 patients who underwent lateral internal sphincterotomy. In group A, 25 (73.5%) patients treated successfully, 9 (26.4%) patients were uncured who underwent lateral anal sphincterotomy, with no fresh complaints during follow up. By contrast, all patients in group B were successfully treated and only one (0.03%) patient came with unexplained discomfort and one patient suffered from flatus incontinency.Conclusions: This prospective study, demonstrates that open lateral internal sphincterotomy is superior to topical nitroglycerin application in the treatment of anal fissure with good symptomatic relief, high rate of healing with very low rate of early incontinence. Patients who are not willing to undergo surgery the glycerin trinitrate ointment can be used as medical line for fissure in ano.

The crystal structure of XdpB, the bacterial old yellow enzyme, in an FMN-free form.

Old Yellow Enzymes (OYEs) are NAD(P)H dehydrogenases of not fully resolved physiological roles that are widespread among bacteria, plants, and fungi and have a great potential for biotechnological applications. We determined the apo form crystal structure of a member of the OYE class, glycerol trinitrate reductase XdpB, from Agrobacterium bohemicum R89-1 at 2.1 Å resolution. In agreement with the structures of the related bacterial OYEs, the structure revealed the TIM barrel fold with an N-terminal β-hairpin lid, but surprisingly, the structure did not contain its cofactor FMN. Its putative binding site was occupied by a pentapeptide TTSDN from the C-terminus of a symmetry related molecule. Biochemical experiments confirmed a specific concentration-dependent oligomerization and a low FMN content. The blocking of the FMN binding site can exist in vivo and regulates enzyme activity. Our bioinformatic analysis indicated that a similar self-inhibition could be expected in more OYEs which we designated as subgroup OYE C1. This subgroup is widespread among G-bacteria and can be recognized by the conserved sequence GxxDYP in proximity of the C termini. In proteobacteria, the C1 subgroup OYEs are typically coded in one operon with short-chain dehydrogenase. This operon is controlled by the tetR-like transcriptional regulator. OYEs coded in these operons are unlikely to be involved in the oxidative stress response as the other known members of the OYE family because no upregulation of XdpB was observed after exposing A. bohemicum R89-1 to oxidative stress.

Pain Relieving Effect of Sublingual Glycerol Trinitrate in Renal Colic: a Randomized Placebo-Controlled Trial.

Introduction:Renal colic is caused by colicky spasms of ureters. As has been shown in previous experiments, glycerol trinitrate (TNG) can inhibit these muscular spasms. Objective:This study was performed to assess the pain relieving effect of TNG among patients referred due to renal colic pain to the emergency department (ED). Methods:This study is a randomized, placebo-controlled study on 60 patients with renal colic who were referred to the ED, who were diagnosed clinically to have renal colic, and their pain was more than 5 based on a visual analogue scale (VAS). The patient's pain was recorded at the moment of clinical diagnosis, and each one received one capsule, either 0.4 mg TNG or placebo, plus a 100 mg indomethacin suppository. The pain score was re-assessed after 5 and 30 min. The values were recorded and compared using SPSS-16 software. Results:Sixty patients with a mean age of 35.75 ± 11.99 years were enrolled (73.3% male). Patients in the two groups were matched for age (p = 0.290), sex (p = 0.559), and the presence of microscopic hematuria (p = 0.292). Pain relief from the start point until the end of the intervention was statistical different in all studied patients (p < 0.05); but the comparison between the two groups showed no significant difference in this regard (p = 0.440). Conclusion:It is likely that adding TNG to an indomethacin suppository had no significant effects on better pain management of patients referred with renal colic to the ED.

Dielectric relaxation in energy condensed systems on the basis of polyefirretane elastomer. I. Frequency dependence

This paper describes the experimental study of dielectric relaxation in energy condensed systems based on ether urethane rubber plasticized by glycerin trinitrate and ammonium perchlorate, HMX, and aluminum powders in the frequency range of the electric field from 40 to 1.2 · 109 Hz. Depending on the field frequency, it was possible to determine relaxation processes caused by dipole polarization, the bulk electrical conductivity of a polymer binder, and the influence of the surface of aluminum particles.

Analysis of Explosives by GC-UV.

A mixture of explosives was analyzed by gas chromatography (GC) linked to ultraviolet (UV) spectrophotometry that enabled detection in the range of 178-330 nm. The gas-phase UV spectra of 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), ethylene glycol dinitrate (EGDN), glycerine trinitrate (NG, nitroglycerine), triacetone triperoxide (TATP), and pentaerythritol tetranitrate (PETN) were successfully recorded. The most interesting aspect of the current application is that it enabled simultaneous detection of both the target analyte and its decomposition products. At suitable elevated temperatures of the transfer line between the GC instrument and the UV detector, a partial decomposition was accomplished. Detection was made in real time and resulted in overlaid spectra of the mother compound and its decomposition product. Hence, the presented approach added another level to the qualitative identification of the explosives in comparison with traditional methods that relies only on the detection of the target analyte. As expected, the decomposition product of EGDN, NG, and PETN was NO, while TATP degraded to acetone. DNT and TNT did not exhibit any decomposition at the temperatures used.