A sensitive and specific ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was deve-loped for analysis of rutaecarpine(Ru), evodiamine(Ev), rutaevine(Rv), limonin(Li), ginsendside Rb_1(Rb_1), ginsendside Re(Re) in rat plasma and brain tissues of nitroglycerin-induced migraine rats. Male healthy Sprague-Dawley(SD) rats were orally given multiple dose of optimized(OS) and un-optimized Wuzhuyu Decoction(UNOS), and their blood samples and brainstem were collected at different time points after injection of nitroglycerin(10 mg·kg~(-1)) into the frontal region. The drug concentrations of the 6 analytes in plasma and brainstem were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma were calculated by using Phoenix WinNolin 5.2.1 software. The methodological test showed that all of analytes in both plasma and brainstem homogenate exhibited a good linearity within the concentration range(r>0.994 7). The intra-day and inter-day accuracy, precision, matrix effect, stability of the investigated components meet the requirements for biopharmaceutical analysis. The developed method was successfully applied in pharmacokinetic studies on abovementioned ingredients in rat plasma and brain stem. The plasma pharmacokinetic parameters of active ingredients in two different Wuzhuyu Decoction group were compared, it was found that Rb_1 had higher t_(1/2), T_(max), C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. Meanwhile, Ev had higher t_(1/2) and T_(max) but lower C_(max), AUC_(0-24 h) and AUC_(0-∞), Ru has higher t_(1/2 )but lower C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. The brain tissue distribution of each component were compared between the two groups, the component with higher content in OS, such as Ru at 30 min and 2 h after administration, Ev at 30 min, Rb_1 at 30 min and Rb_1 at 2 h after administration have lower brain tissue distribution than those in UNOS group, while the component with higher content in UNOS, such as Rv at 30 min, 2 h and 12 h after administration had higher brain tissue distribution than those in OS group.
Administration, Oral ; Animals ; Brain/drug effects* ; Brain Chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Migraine Disorders/drug therapy* ; Nitroglycerin ; Plasma/chemistry* ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry

Prinzmetal's variant angina describes chest pain secondary to reversible coronary artery vasospasm in the context of both diseased and non-diseased coronary arteries. Symptoms typically occur when the patient is at rest and are associated with transient ST-segment elevation. Acute episodes respond to glyceryl trinitrate, but myocardial infarction and other potentially fatal complications can occur, and long-term management can be challenging. Although it is not well understood, the underlying mechanism appears to involve a combination of endothelial damage and vasoactive mediators. In this case, a 35-year-old woman with myocardial infarction secondary to coronary artery vasospasm experienced recurrent chest pain. Coronary angiography revealed severe focal stenosis in the mid left anterior descending artery, which completely resolved after administration of intracoronary glyceryl trinitrate. The patient was discharged on nitrates and calcium channel blockers. The patient re-presented with another myocardial infarction, requiring up-titration of medical therapy.
Adult ; Angina Pectoris, Variant ; complications ; drug therapy ; Constriction, Pathologic ; drug therapy ; pathology ; Coronary Angiography ; Coronary Vasospasm ; Coronary Vessels ; physiopathology ; Electrocardiography ; Female ; Humans ; Myocardial Infarction ; complications ; drug therapy ; pathology ; Nitroglycerin ; therapeutic use ; Recurrence ; Vasodilator Agents ; therapeutic use

OBJECTIVETo evaluate the clinical efficacy and safety of glyceryl trinitrate (GTN) ointment in the treatment of anal fissure.

METHODSIn this multi-center, randomized, double-blind and placebo-controlled trial, 240 chronic anal fissure patients from 7 clinical centers were randomized to receive eight-week treatment with GTN ointment (treatment group) or vaseline ointment (control group) respectively. Healing rate, visual analogue score (VAS), maximum anal resting pressure (MARP) and adverse reactions were recorded and compared.

RESULTSA total of 221 patients (92.1%) finished the trial, including 114 patients in treatment group (95.0%, 114/120) and 107 in control group (89.2%, 107/120). At the endpoint of treatment (56 d), 90 patients in treatment group (78.9%, 90/114) healed completely compared to 31 patients in control group (29.0%, 31/107), and decrease rates of VAS in the two groups were (94.8±15.7)% and (61.2±35.7)% respectively, both differences were statistically significant (P<0.01). MARP after first administration was (20.2±18.5) mm Hg in treatment group (n=12) and (7.1±14.7) mm Hg in control group (n=6), which was not significantly different (P=0.152). Adverse reaction incidence was higher in treatment group (42.1% vs. 9.3%, P<0.05), while these adverse reactions were mainly headache and fullness in head, which were self-limiting.

CONCLUSIONGTN ointment can effectively promote healing and relieve pain in anal fissure with safety and tolerance.

Adult ; Double-Blind Method ; Female ; Fissure in Ano ; drug therapy ; Humans ; Male ; Middle Aged ; Nitroglycerin ; therapeutic use ; Treatment Outcome

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

OBJECTIVETo assess the clinical efficacy of danlou tablet (DT) in treating coronary heart disease angina (CHDA) patients of phlegm and stasis mutual obstruction syndrome (PSMOS).

METHODSTotally 66 CHDA patients of PSMOS were recruited from four centers (Beijing Guang'anmen Hospital, Beijing Anzhen Hospital, First Affiliated Hospital of Henan College of Traditional Chinese Medicine, and Hubei Union Hospital). They were assigned to two groups according to the random digit table, the treatment group (treated by DT +Western medicine) and the control group (treated by Western medicine), 33 in each group. All patients took Western medicine. Patients in the treatment group were given DT, 1.5 g each time, twice daily, while those in the control group took DT placebo. The treatment course was 28 days for all. The efficacy of angina, the angina attack frequency, its duration, the score of angina, the numbers of ST segment depression and flat or inversed T wave, the lead number of inversed T wave, the angina relief time after taking nitroglycerin, the amount of nitroglycerin were observed in the two groups. The changes of Chinese medicine (CM) syndrome scores, including the duration and frequency of chest tightness and pain, shortness of breath, fatigue, palpitation, spontaneous sweating, and total syndrome score were compared before and after treatment. The changes of hypersensitive C-reactive protein (hs-CRP), homocysteic acid (HCY), soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and vascular cell adhesion molecular-1 (VCAM-1) were also observed in both groups.

RESULTSThe total effective rate was significantly higher in the treatment group (26/32 cases, 81.2%) when compared with the control group (13/30 cases, 43.3%, P < 0.05). Compared with before treatment in the same group, the duration and frequency of chest tightness and pain, the score of angina, the numbers of ST segment depression and flat or inversed T wave, the lead number of inversed T wave, the angina relief time after taking nitroglycerin, the amount of nitroglycerin, the duration and frequency of chest tightness and pain, hs-CRP, sCD40L, HCY, IL-6, MMP-9, MPO were lowered after treatment in both groups (P < 0.01, P < 0.05). The VCAM-1 level decreased in the treatment group, while it increased in the control group, showing statistical difference (P < 0.01, P < 0.05). Compared with the control group after treatment, the duration and frequency of chest tightness and pain, the score of angina, the angina relief time after taking nitroglycerin, the amount of nitroglycerin, the duration and frequency of chest tightness and pain, fatigue, the total syndrome score, the levels of hs-CRP, sCD40L, HCY, IL-6, MMP-9, MPO, and VCAM-1 were lowered in the treatment group after treatment (P < 0.01, P < 0.05).

CONCLUSIONDT could improve CHDA patients' clinical symptoms, inhibit the inflammation reaction, showing plaque stabilizing and anti-oxidization effects.

Adult ; Aged ; Angina Pectoris ; drug therapy ; Coronary Disease ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Nitroglycerin ; therapeutic use ; Phytotherapy ; Treatment Outcome

Native coronary artery spasm after coronary artery bypass grafting (CABG) is scarce. It frequently causes disastrous circulatory collapse. We report a 72-yr-old male, who experienced native coronary artery spasm and grafted artery spasm following CABG, which was successfully treated with coronary angiography and intracoronary injection of nitroglycerine.
Aged ; Coronary Angiography ; Coronary Artery Bypass/*adverse effects ; Coronary Vasospasm/drug therapy/*etiology ; *Coronary Vessels/drug effects/physiopathology/surgery ; Humans ; Male ; Nitroglycerin/therapeutic use ; Treatment Outcome ; Vasodilator Agents/therapeutic use

OBJECTIVETo investigate the effect of controlled hypotension using different drugs on gastrointestinal perfusion and bleeding volume in nasal endoscopic surgery.

METHODSThirty ASA class I or II patients scheduled for nasal endoscopic surgery were randomized into three groups, including a routine general anesthesia group (group A) and two controlled hypotension groups (groups B and C). After anesthesia induction, anesthesia was maintained with 1%-2% isoflurane and vecuronium. ECG, mean arterial blood pressure (MAP), heart rate (HR), SpO(2) and PETCO(2) were continuously monitored. TRIP tonometry catheter 14 F was inserted into the stomach and connected to Tonocap (Datex-Ohmeda, Finland ). In groups B and C, hypotension was induced with isoflurane (1%-2%) and sodium nitroprusside (0.3-3 microg.kg(-1).min(-1)), and with isoflurane (1%-2%) and glonoine (0.5-5 microg.kg(-1).min(-1)), respectively, and the MAP was reduced to 50-55 mmHg in 10-15 min. In groups B and C, blood samples were taken for blood gas analysis after anesthesia (T(0)), after acute hypervolemic hemodilution (T(1)), at 30 and 60 min after controlled hypotension (T(2) and T(3)), and 30 min after recovery from hypotension (T(4)). In group A, blood samples were taken at different time points in the perioperative period.

RESULTSThe patients in groups B and C had smaller bleeding volume than those in group A. HR was decreased after moderate acute hypervolemic hemodilution, and increased after controlled hypotension (T(2) and T(3)) in comparison with that at T(1) to a level similar to that at T(0). No significant changes were found in pHi at T(2) and T(3) in comparison with that at T(1) in the three groups.

CONCLUSIONWhen appropriate measures are taken, induced hypotension at 50-55 mmHg does not necessarily produce disturbance in gastrointestinal perfusion. Induced hypotension with glonoin can decrease the bleeding volume better than sodium nitroprusside in nasal endoscopic surgery.

Adolescent ; Adult ; Blood Loss, Surgical ; prevention & control ; Endoscopy ; Female ; Hemodilution ; methods ; Humans ; Hypotension, Controlled ; methods ; Intestines ; blood supply ; Male ; Middle Aged ; Nitroglycerin ; therapeutic use ; Nitroprusside ; therapeutic use ; Paranasal Sinuses ; surgery ; Young Adult

This study investigated whether trinitroglycerine (TNG) as nitric oxide (NO) releasing agent had anti-leishmanial effects and mediated pathology in BALB/c mice infected with Leishmania major. Cutaneous leishmaniasis (CL), a zoonotic infection caused by leishmania protozoa is still one of the health problems in the world and in Iran. NO is involved in host immune responses against intracellular L. major, and leishmania killing by macrophages is mediated by this substance. Moreover, application of CL treatment with NO-donors has been recently indicated. In our study, TNG was used for its ability to increase NO and to modify CL infection in mice, in order to evaluate NO effects on lesion size and formation, parasite proliferation inside macrophages, amastigote visceralization in target organs, and NO induction in plasma and organ suspensions. Data obtained in this study indicated that TNG increased plasma and liver-NO, reduced lesion sizes, removed amastigotes from lesions, livers, spleens, and lymph nodes, declined proliferation of amastigotes, hepatomegaly, and increased survival rate. However, TNG reduced spleen-NO and had no significant effects on spelenomegaly. The results show that TNG therapy reduced leishmaniasis and pathology in association with raised NO levels. TNG had some antiparasitic activity by reduction of positive smears from lesions, livers, spleens, and lymph nodes, which could emphasize the role of TNG to inhibit visceralization of L. major in target organs.
Animal Structures/parasitology ; Animals ; Antiprotozoal Agents/chemistry/*therapeutic use ; Female ; Leishmania major/*drug effects/immunology ; Leishmaniasis, Cutaneous ; Macrophages/parasitology ; Mice ; Mice, Inbred BALB C ; Nitric Oxide/blood/metabolism/*pharmacology ; Nitroglycerin/*analogs & derivatives/*therapeutic use ; Severity of Illness Index ; Skin/pathology ; Survival Analysis

OBJECTIVETo compare the therapeutic effect of recombinant human brain natriuretic peptide (rhBNP) and nitroglycerin on acute decompensated heart failure (ADHF).

METHODSFifty ADHF patients were randomly divided into rhBNP group and nitroglycerin group. In all the patients, dyspnea and global clinical status were assessed before and at 30 min, 6 h and 24 h after drug administration, and the volume of fluid intake and urine along with hemodynamic parameters was recorded 24 h after drug administration. In the nitroglycerin group, the patients received an initial nitroglycerin dose of 5 microg/min, with subsequent dose increment of 5 microg/min every 3 to 5 min; the dose was adjusted individually according to the hemodynamics of the patients. The patients in rhBNP group were given rhBNP at the initial dose of 1.5 microg/kg by with an intravenous bolus injection followed by infusion at the rate of 0.0075 microg.kg(-1).min(-1) for 72 h.

RESULTSAt 30 min and 6 h after drug administration, the patients in the rhBNP group showed significant greater improvement of dyspnea (P=0.042 and 0.019) and global clinical status (P=0.018 and 0.044) than those in the nitroglycerin group, but 24 h after drug administration, no significant difference was noted between the two groups (P=0.192 and 0.179). Twenty-four hours after drug administration, the mean urine volume was significantly greater in rhBNP group than in nitroglycerin group (1513.8-/+242.9 vs 1341.2-/+239.7 ml, P=0.015), and the ejection fraction increased and pulmonary arterial pressure and systolic blood pressure decreased at greater amplitude in the former group (P=0.001,0.000 and 0.002, respectively). At 72 h, the numbers of premature ventricular contraction and couplets premature beats and onset of paroxysmal ventricular tachycardia were significantly reduced in rhBNP group as compared with the nitroglycerin group (P=0, 0.001 and 0.002, respectively).

CONCLUSIONRhBNP promotes urine excretion, decreases pulmonary arterial pressure and increases left ventricular ejection fraction to improve dyspnea and global clinical status and reduce the onset of ventricular arrhythmia in ADHF patients.

Aged ; Aged, 80 and over ; Blood Pressure ; drug effects ; Female ; Heart Failure ; drug therapy ; pathology ; physiopathology ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; administration & dosage ; genetics ; therapeutic use ; Nitric Oxide Donors ; administration & dosage ; therapeutic use ; Nitroglycerin ; administration & dosage ; therapeutic use ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Treatment Outcome