OBJECTIVES: Mèniére's disease is one of the most common causes of episodic vestibular syndrome that shows symptom complexes of recurrent vertigo, hearing loss, tinnitus and ear fullness. Isosorbide (Isobide) is a osmotic diuretics which has been used for Meniere's disease to reduce the endolymphatic pressure. The purpose of this study was to evaluate the efficacy of isosorbide in the treatment of Mèniére's disease by comparing the combined therapy of isosorbide and betahistine (Meniace) to betahistine only. METHODS: Among 220 patients enrolled with Mèniére's disease from 9 centers, 187 patients completed this clinical study. Patients were randomly subjected either to betahistine alone therapy at dose of 6 mg three times a day (n=97) or to combined therapy with isosorbide (dose of 30 mL three times a day) and betahistine (n=90) for 12 weeks. Two groups were compared at 4 and 12 weeks after treatment on frequency of vertigo, hearing level (pure tone audiometry, speech audiometry), electocochleography (ECoG), tinnitus (Tinnitus Handicap Inventory, THI) and quality of life (Korean functional level scale, Korean dizziness handicap inventory). RESULTS: During first 4 weeks after treatment, the frequency of vertigo was not reduced in either betahistine alone therapy group or combined therapy group. However, between 8 and 12 weeks, the frequency of vertigo was significantly reduced in either group, and in the combined group frequency of vertigo was more significantly reduced than in the betahistine alone therapy group (p=0.041). The hearing level, ECoG, tinnitus and quality of life was not significantly different between two groups. CONCLUSION: Isosorbide and betahistine combined therapy were more effective for vertigo control than betahistine alone therapy. Isosorbide is an effective diuretic in vertigo control in definite Mèniére's disease.
Audiometry, Speech ; Betahistine ; Clinical Study ; Diuretics, Osmotic ; Dizziness ; Ear ; Hearing ; Hearing Loss ; Humans ; Isosorbide ; Meniere Disease ; Quality of Life ; Tinnitus ; Vertigo

OBJECTIVES: The aims of this study were to investigate the feasibility of isosorbide delivery into perilymph through the round window membrane (RWM), and to compare the intracochlear isosorbide concentration in perilymph after oral administration (PO) versus that after round window perfusion (RWP). METHODS: Sixteen male guinea pigs (32 ears) were used. Isosorbide, an osmotic diuretic, was administered via RWP or PO. First, to investigate the optimal perfusion time, perilymph sampling of scala tympani from the RWM was performed after RWP for 15, 30, or 60 minutes. Second, to compare the drug concentration after RWP versus that after PO, perilymph was aspirated at 3 and 6 hours after administration. Intracochlear concentration of isosorbide was analyzed by high-performance liquid chromatography coupled to refractive index detection. RESULTS: Isosorbide passed through the RWM into perilymph after RWP. After RWP for 15, 30, and 60 minutes, mean isosorbide concentrations in perilymph were 116.27+/-44.65, 245.48+/-112.84, and 279.78+/-186.32 mM, respectively. The intracochlear concentration after RWP for 30 minutes was higher than that after RWP for 15 minutes (P=0.043). At 3 and 6 hours after PO, isosorbide concentrations in perilymph were 28.88+/-4.69 and 12.67+/-2.28 mM, respectively. In contrast, the corresponding concentrations after RWP were 117.91+/-17.70 and 75.03+/-14.82 mM at 3 and 6 hours, respectively. Isosorbide concentrations in perilymph following RWP were significantly higher than those following PO at both 3 and 6 hours (P=0.025 and P=0.034, respectively). CONCLUSION: Isosorbide can rapidly pass through the RWM after RWP in guinea pigs, and 30 minutes of perfusion is considered to be appropriate. In addition, over a 6-hour period, RWP can deliver higher concentrations of isosorbide into perilymph than those achieved with PO.
Administration, Oral* ; Animals ; Chromatography, Liquid ; Diuretics, Osmotic ; Guinea Pigs* ; Humans ; Isosorbide* ; Male ; Membranes ; Meniere Disease ; Perfusion* ; Perilymph* ; Refractometry ; Scala Tympani

In order to understand the clinical characteristics of patients with coronary heart disease (CHD) in real world and provide reference for clinical prevention and treatment, this study analyzed informations of patient with CHD in hospital information system. Data from 17 national hospitals were collected. Select patients with coronaryheart disease in diagnosis of the first place in 17 hospitals, general informations and traditional Chinese medicine (TCM) syndrome, complications, medicine were analyzed using frequency method and association rules. This study included 84 697 patients with CHD, the majority of men and in the elderly. The average age of patients was 71 years. The proportion of men to women was about 1. 45: 1. Hospital stay time ranged from 8 to 14 d. The most common total hospitalization cost distribution was 5 000-20 000 RMB. Young patients have a rising trend year by year. The death of patients increased with increasing age. Common complications were hypertension, diabetes, cerebral infarction and hyperlipidemia, 57.24 percent of the CHD patient complicated with hypertension, 21.94 percent patients complicated with diabetes. Among TCM syndrome types, Qi-Yin deficiency and qi deficiency blood stasis were the most common syndromes. Blood stasis was the highest syndrome elements, accounted for 79.97%, followed by Qi deficiency, phlegm, Yin deficiency, and so on. The most common western medicine was aspirin, followed with isosorbide dinitrate, clopidogrel. The most common used traditional Chinese medicine was danhong injection, followed by shuxuetong injection. Combined with removing blood stasis drugs has been more common at present clinical treatment, there were 43.46 percent of patients combined with anti-platelet western drug and injection of removing blood stasis.
Adult ; Aged ; Aged, 80 and over ; Aspirin ; therapeutic use ; Coronary Disease ; complications ; drug therapy ; epidemiology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Isosorbide Dinitrate ; therapeutic use ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Ticlopidine ; analogs & derivatives ; therapeutic use

The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan (ACS). This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan's side chain. The structure of ACS was confirmed by FT-IR, 1H NMR and element analysis. In addition, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum corneurn. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Hacat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.
Administration, Cutaneous ; Animals ; Arginine ; chemical synthesis ; chemistry ; pharmacology ; Aspirin ; administration & dosage ; pharmacokinetics ; Cell Line ; Cell Survival ; drug effects ; Cell-Penetrating Peptides ; chemical synthesis ; chemistry ; pharmacology ; Chitosan ; chemical synthesis ; chemistry ; pharmacology ; Drug Carriers ; Humans ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Keratinocytes ; cytology ; Male ; Mice ; Prazosin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Skin Absorption ; drug effects

OBJECTIVEBased on real world research the circumstances of the clinical use of usual drugs combined with salvianolate injection are surveyed.

METHODDescriptive statistics on the use of salvianolate injection in 18 general hospitals in China.

RESULTIn 1 605 patients with coronary heart disease (CHD), salvianolate injection was most frequently (51%) combined with clopidogrel and isosorbide dinitrate. In addition this combination showed a higher clinical effectiveness as compared with other drug combinations.

CONCLUSIONIn the real world, salvianolate injection combined with usual treatment was found to be more effective than other treatment combinations. In addition practice conformed to the clinical treatment of coronary heart disease (CHD) guidelines for drug use. However, liver and kidney function, routine blood tests and the blood's coagulation function require ongoing monitoring.

Aged ; Aged, 80 and over ; Coronary Disease ; drug therapy ; mortality ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hospital Information Systems ; statistics & numerical data ; Humans ; Isosorbide Dinitrate ; therapeutic use ; Male ; Middle Aged ; Plant Extracts ; administration & dosage ; Pragmatic Clinical Trials as Topic ; Propensity Score ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Treatment Outcome

OBJECTIVETo understand the clinical circumstances for the use of parenterally administered Shenfu in the treatment of coronary heart disease, in order to provide a reference guide for its clinical use.

METHODInformation was extracted and summarized on the treatment of coronary heart disease patients, who received parenterally administered Shenfu, from 20 nationwide general hospitals HIS data. Descriptive statistical methods were used to analyze the usage and dosage. Correlation analysis was adopted to analyze information including drug combinations, and outcomes were compared with other combinations.

RESULTReal world HIS data showed that the drug delivery method for parenterally administered Shenfu was intravenous infusion. Treatment courses were from 3 to7 days, at a dosage of 60 mL. The drug combination was mostly with chemical drugs. The most common combinations were Shenfu plus clopidogrel, aspirin and isosorbide dinitrate.

CONCLUSIONParenterally administered Shenfu is a common drug used in the treatment of coronary heart disease. Most of the usage was in accordance with instructions. The chemical combination drugs were mainly clopidogrel, aspirin and isosorbide dinitrate.

Adult ; Aged ; Aged, 80 and over ; Aspirin ; therapeutic use ; Coronary Disease ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Hospital Information Systems ; statistics & numerical data ; Humans ; Infusions, Parenteral ; Isosorbide Dinitrate ; therapeutic use ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Pragmatic Clinical Trials as Topic

Coronary artery spasm is an uncommon, but well recognized, etiology for acute myocardial infarction. However, cardiogenic shock with myocardial infarction resulting from simultaneous multiple coronary artery spasm has been rarely reported, and not in Korea. Recently, we experienced such a case in a 50-year-old Korean man without previous diagnosis of variant angina. The patient, hospitalized for blood sugar control, developed severe chest pain accompanying ST-segment elevation in multiple leads. The patient immediately received cardiac catheterization because of cardiogenic shock. Coronary angiogram revealed the severe and simultaneous spasm of three major epicardial arteries, which was promptly relieved by an intracoronary administration of isosorbide dinitrate. This case highlights the need to rule out the potential mechanism of coronary spasm even in the most severe episodes of acute coronary syndrome.
Acute Coronary Syndrome ; Arteries ; Blood Glucose ; Cardiac Catheterization ; Cardiac Catheters ; Chest Pain ; Coronary Vasospasm ; Coronary Vessels ; Humans ; Isosorbide Dinitrate ; Korea ; Middle Aged ; Myocardial Infarction ; Myocardial Ischemia ; Shock, Cardiogenic ; Spasm

BACKGROUNDGlucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.

METHODSEighty hospitalized patients (average age (59.0 +/- 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment.

RESULTSImmunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.

CONCLUSIONSBoth the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.

Aged ; Blotting, Western ; Coronary Disease ; drug therapy ; metabolism ; Female ; Humans ; Isosorbide Dinitrate ; therapeutic use ; Lovastatin ; therapeutic use ; Male ; Metoprolol ; therapeutic use ; Middle Aged ; Nifedipine ; therapeutic use ; Receptors, Glucocorticoid ; metabolism

BACKGROUND: Multi-vessel off-pump coronary bypass surgery (OPCAB) imposes cumulative myocardial ischemia/reperfusion injury, which may be attenuated by continuous infusion of nitrate. However, nitrate infusion and consequent decrease in preload may be hazardous during heart displacement which causes restrictive filling of the ventricles. Therefore, we evaluated the effect of nitrate infusion on myocardial protection and hemodynamics in patients undergoing OPCAB, in a prospective, randomized and controlled trial. METHODS: Fifty patients with stable angina and left ventricular ejection fraction >40% undergoing elective, isolated, multivessel OPCAB were enrolled. Patients were randomized equally to either continuous infusion of isosorbide dinitrate 0.5microg/kg/min or same amount of normal saline during the surgery. Operative data including hemodynamic variables, intraoperative ST segment changes and postoperative cardiac enzyme release (creatine kinase-MB, troponin T) were compared. RESULTS: Patients characteristic and operative data including ST segment changes and use of vasopressors were similar between the groups except the total amount of infused crystalloid during the surgery which was significantly higher in the nitrate group. Postoperative variables including cardiac enzyme release were also similar between the groups. CONCLUSIONS: Prophylactic continuous infusion of nitrate during OPCAB exerted no additional benefit in terms of myocardial protection. It also, was not associated with accentuated decrease in cardiac output during heart displacement, and the decrease in preload seems to have been nullified by modest increase in fluid therapy.
Angina, Stable ; Cardiac Output ; Displacement (Psychology) ; Fluid Therapy ; Heart ; Hemodynamics ; Humans ; Isosorbide ; Isosorbide Dinitrate ; Isotonic Solutions ; Myocardial Ischemia ; Prospective Studies ; Stroke Volume ; Troponin

The aim of present study is to investigate the cardioprotective effect of a new compound acetyl ferulaic isosorbide (AFI), composed of ferulaic acid (FA) and isosorbide mononitrate (ISMN) by esterification in myocardial ischemia/reperfusion (MI/R). Male Sprague-Dawley rats, subjected to 30 minutes of myocardial ischemia and 3 hours of reperfusion, randomly received one of the following treatments separately: SHAM, I/R (MI/R + solvent), SF (MI/R+SF, 40 mg x kg(-1), ig), ISMN (MI/R + ISMN, 30 mg x kg(-1), ig), SF + ISMN (MI/R + SF + ISMN, 40 mg x kg(-1) + 30 mg x kg(-1), ig) and AFI (MI/R + AFI, 10 mg x kg(-1), ig). Left ventricle developed pressures (LVDP) and the maximal first derivative of developed pressure ( +/-dP / dtmax) were monitored throughout the experiments. Myocardial infarction size, serum creatine kinase (CK) activity, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) production were determined at the end of reperfusion. Compared with SF, ISMN or SF + ISMN treatment groups, AFI treatment decreased infarction size (n=8, P < 0.01), improved cardiac function as evidenced by increased LVDP and +/- dP/dtmax (n=8, P < 0.05), increased serum SOD activity, reduced serum CK and LDH activities, H2O2 and MDA production (n=8, P < 0.05). The new compound AFI showed a stronger cardioprotective effect against MI/R injury than SF, ISMN or their combined administration did.
Animals ; Cardiotonic Agents ; chemical synthesis ; chemistry ; pharmacology ; Creatine Kinase ; blood ; Electrocardiography ; Hydrogen Peroxide ; blood ; Isosorbide Dinitrate ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; L-Lactate Dehydrogenase ; blood ; Male ; Malondialdehyde ; blood ; Myocardial Reperfusion Injury ; blood ; pathology ; physiopathology ; prevention & control ; Myocardium ; pathology ; Nitric Oxide ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood