Carbazoles ; therapeutic use ; Child, Preschool ; Heart Failure ; complications ; drug therapy ; Humans ; Male ; Propanolamines ; therapeutic use ; Takayasu Arteritis ; complications ; drug therapy ; Vasodilator Agents ; therapeutic use

OBJECTIVEEndocardial fibroelastosis (EFE), a common pediatric cardiovascular disease, often results in chronic heart failure (CHF) and death. Clinical trials have shown that the regimen of combining beta-adrenoreceptor blocker with traditional medicines against CHF can improve left ventricular function and prevent the ventricle from remodeling in patients with CHF. The present study aimed to observe the effect of carvedilol on concentration of plasma brain-type natriuretic peptide (BNP), and safety in children with EFE.

METHODSTwenty-one children with EFE were randomly divided into two groups: (1) treated with traditional regimen (digoxin, prednisone and/or diuretics) (n = 10); (2) treated with carvedilol plus traditional regimen (n = 11). Measurement of plasma concentration of BNP by ELISA, cardiac function by ultrasound were performed before and after 6 months of treatment. The changes in clinical symptom, heart rate, heart function, side effect and maximal tolerance dose after treatment with carvedilol were observed.

RESULTSPlasma concentration of BNP was much higher in the group of patients with EFE [(865 +/- 702) ng/L] than that of control group [(154 +/- 78) ng/L] (P < 0.01), and there was a positive correlation between plasma concentration of BNP and cardiac function classification, and cardiac function grades II, III, and IV corresponded to plasma concentration of BNP (286 +/- 125) ng/L, (437 +/- 386) ng/L, (1673 +/- 859) ng/L respectively in children with EFE. Compared with the group treated with traditional medicines, plasma concentration of BNP [(403 +/- 216) ng/L vs. (219 +/- 87) ng/L] significantly decreased, the clinical symptom was significantly improved, cardio-thoracic ratio (CTR) (0.60 +/- 0.05 vs. 0.54 +/- 0.06) (P < 0.05) and heart rate [(115 +/- 20) bpm vs. (90 +/- 14) bpm] (P < 0.01) decreased, ejection fraction (EF) (46.6% +/- 13.4% vs. 54.5% +/- 12.9%), fractional shortening (21.6% +/- 8.1% vs. 24.1% +/- 7.5%), mean velocity of circumferential fiber shortening [(0.8 +/- 0.5) cir/s vs. (0.9 +/- 0.4) cir/s] were significantly increased (P < 0.01), left ventricular end-systolic dimension [(34.0 +/- 8.6) mm vs. (32.2 +/- 9.1) mm] (P < 0.05), left ventricular mass [(65.9 +/- 34.1) g vs. (65.9 +/- 34.1) g], interventricular septal thickness at end-systole [(6.0 +/- 1.0) mm vs (5.5 +/- 1.1) mm] were notably decreased (P < 0.01) after treatment with carvedilol.

CONCLUSIONThese data indicated that plasma concentration of BNP significantly increased in children with EFE, carvedilol can decrease plasma concentration of BNP, inhibit the remodeling of ventricle, significantly improve the cardiac function in children with EFE. Carvedilol is effective and safe in treatment of children with EFE.

Adrenergic beta-Antagonists ; therapeutic use ; Carbazoles ; therapeutic use ; Child ; Child, Preschool ; Endocardial Fibroelastosis ; drug therapy ; Female ; Humans ; Infant ; Male ; Natriuretic Peptide, Brain ; blood ; Propanolamines ; therapeutic use ; Treatment Outcome

Lung cancer is a malignant tumor with high incidence rate and mortality rate in China and even the whole world, of which non-small cell lung cancer accounts for about 80%. Anaplastic lymphoma kinase (ALK) gene mutation accounts for about 5%. Alectinib, ALK-tyrosine kinase inhibitor (ALK-TKI), has great performance in clinical. The early detection and treatment of adverse drug reactions can greatly improve clinical benefits. This paper reports a patient of ALK positive non-small cell lung cancer was admited to Baotou Central Hospital in April 2020. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed.
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Anaplastic Lymphoma Kinase/genetics* ; Antineoplastic Agents/therapeutic use* ; Carbazoles/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/secondary* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Piperidines/therapeutic use* ; Pleural Neoplasms/secondary* ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVETo detect the serum autoantibodies against the cardiac beta(1)-adrenergic receptor and observe the clinical characteristics and response to carvedilol use in patients with chronic heart failure (CHF).

METHODSCardiac function was examined by echocardiography and levels of autoantibodies against cardiac beta(1)-adrenergic receptor were detected in 65 patients with CHF by means of enzyme linked immune assay. Carvedilol was added on ACEI, diuretics and digitalis regimen for a target dose of 50 mg/d. All patients were followed up for 6 months.

RESULTSAutoantibodies against cardiac beta(1)-adrenergic receptor were detected in 30 patients (group 1) and not detected in the remaining 35 patients (group 2). The achieved target dose of carvedilol was significantly higher in group 1 than that in group 2 [(36.25 +/- 14.31) mg/d vs. (25.97 +/- 8.83) mg/d, P < 0.01]. Heart rate was significantly higher in group 1 compared to group 2 [(94.19 +/- 14.46) beats/min vs. (86.56 +/- 15.88) beats/min, P < 0.05] before treatment and heart rate and blood pressure of both groups decreased significantly (P < 0.01) and there was no significant difference between two group (P > 0.05) after 6 months treatment. LVEDD and LVESD were significantly larger while LVEF significantly lower in group 1 patients than those in group 2 patients (all P < 0.05) before treatment and LVEDD and LVESD decreased and LVEF increased significantly in both groups (all P < 0.01 vs. before treatment) and there was on significant difference in LVEDD, LVESD and LVEF between two groups (all P > 0.05) post 6 months treatment. Moreover, average titer of autoantibodies against the cardiac beta(1)-adrenergic receptors significantly decreased after 6 months treatment (1:119.35 vs. 1:72.21, P < 0.01).

CONCLUSIONThe detection of autoantibodies against the cardiac beta(1)-adrenergic receptors is related to severer cardiac dysfunction and autoantibodies title decrease was found with improved cardiac function after standard therapy (ACEI, digitalis, betablocker) in patients with CHF.

Adrenergic beta-Antagonists ; therapeutic use ; Adult ; Aged ; Autoantibodies ; blood ; Carbazoles ; therapeutic use ; Female ; Follow-Up Studies ; Heart Failure ; blood ; immunology ; physiopathology ; Humans ; Male ; Middle Aged ; Propanolamines ; therapeutic use ; Receptors, Adrenergic, beta-1 ; immunology

OBJECTIVETo investigate the effects of carvedilol on neurohormone and magnesium metabolism in patients with chronic heart failure (CHF).

METHODSFifty-seven patients with CHF were divided into two groups randomly: received conventional treatment alone or combined with carvedilol for 8 weeks, respectively. Urine magnesium excretion (UME), plasma levels of magnesium (PMC), norepinephrine (NE), angiotensin-II (Ang-II), aldosterone (ALD), plasma renin activity (PRA) and peripheral monocyte magnesium content (MMC) were measured before and after treatments. Twenty-six health persons were selected as normal subjects.

RESULTSThere was a significant increase in UME and plasma concentrations of NE, ALD, Ang-II and PRA, and a significant decrease in MMC in patients with CHF, compared with the control group (P < 0.01). UME was positively correlated with ALD, Ang-II, PRA r = 0.41, 0.42, 0.38, respectively (P < 0.01). These parameters significantly improved after carvedilol (P < 0.05).

CONCLUSIONCarvedilol decreases significantly plasma concentrations of neurohormone and urine magnesium excretion, and increases cell magnesium content in patients with CHF.

Adrenergic beta-Antagonists ; therapeutic use ; Adult ; Aged ; Aldosterone ; blood ; Angiotensin II ; blood ; Carbazoles ; therapeutic use ; Female ; Heart Failure ; blood ; drug therapy ; Humans ; Magnesium ; blood ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Norepinephrine ; blood ; Propanolamines ; therapeutic use

OBJECTIVETo investigate the effect of prostaglandin D2 receptor antagonists on the airway inflammation in rats with asthma.

METHODSForty male SD rats were randomly divided into four groups: Group A (normal control), Group B (asthma group), Group C (CRTH2 antagonist BAYu3405 treatment group), Group D (DP1 antagonist BWA868C treatment group). Asthma was induced by ovalbumin (OVA) challenge. The rats in each group were sacrificed 24 h after the last challenge of OVA.DP1/CRTH2 receptors on eosinophils (EOS) were measured by radiological binding assay (RBA). The left lungs were used for histological examinations and bronchoalveolar lavage fluid (BALF) was collected from the right lungs. The total cell numbers, EOS absolute count and differential cell counts in BALF were performed. Serum concentrations of IL-4, 5 and IFN-gamma were measured by ELISA.

RESULTSRats in BAYu3405 treatment group showed profoundly decreased infiltrates of EOS and lymphocytes in the wall of bronchus when compared with those of asthma group and BWA868C treatment group. Serum concentrations of IFN-gamma in rats of BAYu3405 treatment group increased, but IL-4 and IL-5 decreased significantly when compared with those in rats of asthma group and BWA868C treatment group (P<0.01), and BALF EOS count was decreased significantly (P<0.01). Peripheral blood EOS count was higher than that in rats of normal control group, but was not significantly different from that in rats of asthma group and BWA868C treatment group. The combining capacity of CRTH2 and DP total combining capacity on EOS in asthma group, BAYu3405 treatment group and BWA868C treatment group were significantly higher than those in Group A (P<0.01). There was no significant difference in DP1 among all the groups (P>0.05).

CONCLUSIONCRTH2, but not DP1 antagonist can effectively ameliorate airway inflammation in rats with asthma.

Animals ; Asthma ; chemically induced ; drug therapy ; pathology ; Bronchi ; immunology ; pathology ; Carbazoles ; pharmacology ; therapeutic use ; Inflammation ; drug therapy ; Male ; Ovalbumin ; Prostaglandin D2 ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Immunologic ; antagonists & inhibitors ; Receptors, Prostaglandin ; antagonists & inhibitors ; Sulfonamides ; pharmacology ; therapeutic use

OBJECTIVETo assess the association of T190C polymorphism of β3 adrenergic receptor gene (β3-AR) with chronic heart failure (CHF), and to evaluate the effect of this polymorphism on clinical response to β-AR blockade among patients with CHF.

METHODSThree hundred and thirty patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 5 months after the maximal tolerated dose of carvedilol was reached, all indices including heart rate (HR), blood pressure (BP), left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) level, 6 min walk distance were measured and compared with the indices of those with a T190C genotype. Distribution of the T190C polymorphisms in the control group and CHF group was compared.

RESULTSThe frequencies of T190C genotypes of the β3-AR gene have fit with the Hardy-Weinberg equilibrium. No significant difference was found between the frequencies of T190C alleles and genotypes between the two groups (P > 0.05). Compared with CC-homozygotes, TT-homozygous patients showed substantially greater improvement in LVEF and BNP (all P < 0.01).

CONCLUSIONNo difference has been detected in the prevalence of the three genotypes between healthy and CHF subjects. The T190C variation of the β3-AR gene was not associated with increased risk for CHF. CHF patients with a T allele have greater response to carvedilol than those carrying a C allele in ethnic Han Chinese.

Adult ; Carbazoles ; therapeutic use ; Chronic Disease ; Female ; Heart Failure ; drug therapy ; genetics ; physiopathology ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Propanolamines ; therapeutic use ; Receptors, Adrenergic, beta-3 ; genetics ; Ventricular Function, Left

OBJECTIVETo examine serum B-type natriuretic peptide (BNP) levels and BNP expression of protein and mRNA in the right ventricular myocardium in juvenile rats with right heart failure (RHF) and the effects of beta-adrenergic receptor blocker carvedilol on serum and myocardial BNP levels in order to investigate the role of BNP in the diagnosis and treatment of RHF.

METHODSFifty-one four-week-old Sprague-Dawley rats were randomly assigned to 5 groups: RHF 1, RHF 2, carvedilol-treated RHF, control 1 and control 2. RHF was developed 4 weeks after an intraperitoneal injection of monocrotaline in the RHF 1, RHF 2 and carvedilol-treated RHF groups. The rats in the RHF 1 and the control 1 groups were sacrificed after the RHF event for observing pathological changes in the myocardium. After the RHF event, the carvedilol-treated group was given intragastric administration of carvedilol (3.5 mg/kg/d) for 2 weeks. The RHF 2 and the control 2 groups were given distilled water of equal dose instead. The rats were sacrificed 2 weeks after carvedilol or distilled water administration. Serum BNP levels were measured using ELISA. BNP protein and mRNA expression in the right ventricular myocardium were measured by immunohistochemistry and RT-PCR, respectively. Haemodynamics and some physiological indexes were measured.

RESULTSSerum BNP levels and BNP protein and mRNA expression in the right ventricular myocardium were significantly higher in the RHF 1 group than those in the control 1 group (p<0.01). Serum BNP levels and BNP protein and mRNA expression in the right ventricular myocardium increased more significantly in the RHF 2 group. There was a positive correlation between serum BNP levels and myocardial BNP protein expression in the RHF group (r=0.698, p<0.01). Serum BNP levels and BNP protein and mRNA expression in the carvedilol-treated RHF group were significantly reduced when compared with the RHF 2 group (p<0.05). Carvedilol treatment also resulted in improved hemodynamics and relieved right ventricular hypertrophy.

CONCLUSIONSBNP may serve an index for the diagnosis of RHF and the evaluation of severity in children with RHF. Carvedilol shows protections against RHF caused by pressure load.

Adrenergic beta-Antagonists ; pharmacology ; Animals ; Carbazoles ; pharmacology ; therapeutic use ; Heart Failure ; blood ; drug therapy ; pathology ; physiopathology ; Natriuretic Peptide, Brain ; blood ; genetics ; Propanolamines ; pharmacology ; therapeutic use ; RNA, Messenger ; analysis ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring anticancer drugs have gained increasing attention because of their potential effectiveness and safety. Fruits and vegetables are promising sources of anticancer remedy. Clausena (family Rutaceae) is a genus of flowering plants and includes several kinds of edible fruits and vegetables. Phytochemical and pharmacological studies show that carbazole alkaloids and coumarins from Clausena plants exhibit anticancer activity. This review summarizes research progresses made in the anticancer properties of plants belonging to Clausena; in particular, compounds with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune potentiation effects are discussed. This review reveals the potential use of plants from Clausena in preventing and treating cancer and provides a basis for development of relevant therapeutic agents.
Alkaloids ; chemistry ; pharmacology ; therapeutic use ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Carbazoles ; chemistry ; pharmacology ; therapeutic use ; Cell Cycle Checkpoints ; drug effects ; Clausena ; chemistry ; Coumarins ; chemistry ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Humans ; Plants, Medicinal ; chemistry

OBJECTIVETo study the effects of carvedilol combined with perindopril on Ca(2+) pump activity and the density of Ca(2+)-release channel ryanodine receptor (RyR2) in the myocardial sarcoplasmic reticulum (SR) in rats with chronic heart failure caused by myocardial infarction.

METHODSRat models of chronic heart failure established by left coronary artery ligation were divided into different groups and treated with carvedilol (6 mg.kg(-1).d(-1)), perindopril (4 mg.kg(-1).d(-1)), terazosin (2 mg.kg(-1).d(-1)), or the combination of carvedilol (6 mg.kg(-1).d(-1)) and perindopril (4 mg.kg(-1).d(-1)) for 9 weeks. Another 12 rats with sham operation served as the sham-operated group. The hemodynamic parameters, activity of SR Ca(2+) pump, and RyR2 density were determined.

RESULTSCompared with shame-operated group, the rats with chronic heart failure showed significantly increased left ventricular end-diastolic pressure (LVEDP) (P<0.01) and decreased +dP/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Both monotherapies with carvedilol and perindopril attenuated the increment of LVEDP, and significantly increased +dp/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Combined treatment even further enhanced the therapeutic effects, whereas terazosin produced no obvious effect. The activity of SR Ca(2+) pump was strongly correlated to +dp/dtmax and -dp/dtmax (r=0.596 and 0.684, respectively, P<0.01).

CONCLUSIONProlonged treatment with beta-blocker carvedilol in combination with ACE inhibitor perindopril may improve the hemodynamic parameters, enhance Ca(2+) pump activity and increase the density of RyR2 of myocardial SR more effectively than either monotherapy in preventing and treating chronic heart failure following myocardial infarction.

Animals ; Calcium ; metabolism ; Carbazoles ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Heart Failure ; drug therapy ; etiology ; metabolism ; Male ; Myocardial Infarction ; complications ; metabolism ; Perindopril ; pharmacology ; therapeutic use ; Propanolamines ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Ryanodine Receptor Calcium Release Channel ; drug effects ; Sarcoplasmic Reticulum ; drug effects ; metabolism