Humans ; Leukemia, Large Granular Lymphocytic/drug therapy* ; Aminopyridines ; Benzamides

Aminopyridines are potassium channel blockers that increase the excitability of nerve cells and axons; therefore, they are widely used to treat different neurological disorders. Here we present a patient with idiopathic downbeat nystagmus and lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia who was treated with the sustained-release form of 4-aminopyridine (4-AP). During treatment with 4-AP, the LUTS improved. This improvement was monitored by using uroflowmetry and the International Prostate Symptom Score. A significant improvement of symptoms was observed in relation to the voided volume. This included an improved emptying of the bladder without an increase in residual urine. In animal studies, both nonselective K+ channel blockade and selective voltage-sensitive potassium blockade by 4-AP resulted in increased contraction on rat detrusor strips. To our knowledge, this is the first clinical observation of the mode of action of 4-AP in urological symptoms in humans.
4-Aminopyridine* ; Aminopyridines ; Animals ; Axons ; Drug Therapy ; Humans ; Lower Urinary Tract Symptoms* ; Nervous System Diseases ; Neurons ; Potassium ; Potassium Channel Blockers ; Prostate ; Prostatic Hyperplasia* ; Rats ; Urinary Bladder ; Urinary Bladder, Neurogenic

OBJECTIVE: To investigate the effects of chidamide combined with anti-myeloma drugs on the proliferation and apoptosis of myeloma cells. METHODS: The proliferation inhibition of the cells was detected by CCK-8 method, and flow cytometry was used to detected the apoptosis of the cells. RESULTS: Chidamide could inhibit the proliferation of myeloma cells and promote the apoptosis of primary myeloma plasma cells in a time- and dose-dependent manner (P<0.05). In NCI-H929 cell line, chidamide combined with low-dose bortezomib and lenalidomide showed synergistic effect, while combined with dexamethasone and pomalidomide showed additive effect. In MM.1s cell line, chidamide combined with bortezomib, dexamethasone, lenalidomide and pomalidomide all showed synergistic effects. CONCLUSION Chidamide inhibits proliferation of myeloma cells in a time- and dose-dependent manner and promotes apoptosis of primary myeloma plasma cells. Furthermore, it can enhance the inhibitory effect of anti-myeloma drugs.
Aminopyridines ; Apoptosis ; Benzamides ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma ; Pharmaceutical Preparations

Aminopyridines ; Benzamides ; Humans ; Programmed Cell Death 1 Receptor ; Sezary Syndrome/drug therapy* ; Skin Neoplasms/drug therapy*

BACKGROUND: The aims of this study were to test if amrinone or milrinone reverses cardiac depression induced by the exposure to isoflurane in the isolated heart and to determine whether amrinone or milrinone dilates the coronary artery directly. METHODS: Using the isolated Sprague-Dawley rat hearts, heart rate, left ventricular pressure, dp/dt (differentiated rate of pressure development), O2 delivery(DO2), myocardial oxygen consumption(MVO2), and percent O2 extraction were measured. After the isolated hearts were exposed to isoflurane at 1.2 vol% during 10 min, amrinone(10, 50, 100 M) or milrinone(1, 5, 10 M) was separately given to six groups. RESULTS: Amrinone and milrinone reversed, not statistically significant, the depression of cardiac contractility induced by isoflurane, while the isoflurane-induced bradycardia substantially returned to normal by amrinone 100 M. And amrinone and milrinone elevated coronary flow, DO2, MVO2, while isoflurane increased in coronary flow and DO2, except MVO2. CONCLUSIONS: These results suggest that amrinone and milrinone did not counteract the isoflurane-induced cardiac depression and indirectly increased in coronary blood flow through the elevation of cardiac work.
Amrinone* ; Animals ; Bradycardia ; Coronary Vessels ; Depression ; Heart Rate ; Heart* ; Isoflurane ; Milrinone* ; Myocardium* ; Oxygen ; Rats* ; Rats, Sprague-Dawley ; Ventricular Pressure

Chronic obstructive pulmonary disease (COPD) shows a high mortality as well as a high prevalence around the world. Recent large-scale clinical studies showed that inhaled long-acting anticholinergics, inhaled long-acting beta2-agonists, and inhaled corticosteroid have beneficial effects on patients suffered from COPD. In addition, the combination of the two or three inhalers above shows more beneficial effects. The beneficial effects are the improvement of symptom, lung function, and quality of life as well as the reduction of exacerbation and possibly death. These beneficial effects are true not only for the patients with severe and very severe COPD but also for the patients with moderate COPD. Clinical studies also showed that mucolytics and roflumilast, a new anti-inflammatory drug have beneficial effects on the patients with COPD. According to these beneficial results proven by the recent clinical studies, the guidelines for the management of COPD might be revised to promote the usage of the beneficial drugs for the patients with COPD. The promoted usage of the COPD drugs would help the COPD patients to overcome their symptom, limitation of airflow and frequent exacerbation and also to improve their quality of life.
Aminopyridines ; Benzamides ; Cholinergic Antagonists ; Cyclopropanes ; Expectorants ; Humans ; Lung ; Nebulizers and Vaporizers ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; Quality of Life

OBJECTIVE: To investigate the efficacy and safety of combination chidamide and hematopoietic stem cell transplantation (HSCT) in the treatment of childhood acute T lymphoblastic leukemia (T-ALL). METHODS: Seven children with acute T lymphoblastic leukemia received hematopoietic stem cell transplantation in SUN Yat-Sen Memorial Hospital of SUN Yat-Sen University were selected. 7 cases of T-ALL were divided into 2 groups: HSCT plus chidamide-treated group (4 cases) and traditional HSCT-treated group (3 cases) as control. The incidence of GVHD and other related complications, as well as implantation, recurrence and survival were compared between the two groups, and the side effects of chidamide were observed. All the patients were follow-up until January 2019. RESULTS: All the 7 patients were alive and, there was no difference in the incidence of acute GVHD between the HSCT plus chidamides treated group and the traditional HSCT-treated group. The implantation rate of HSCT was 100%, and there were no recurrence occurred. During the application of chidamide, 3 cases showed adverse reactions, of which 2 cases had adverse reactions of grade 3 or higher, and 2 cases were hematological adverse reactions (neutropenia, thrombocytopenia), other adverse reactions were non-hematologic adverse reactions (transaminase elevation, fatigue, nausea, vomiting), there were no serious adverse reactions occurred. In the HSCT plus chidamide-treated group, 2 cases were found that mature lymphocytes were not expressed by tumors, during examing for minimal redidaul disease (MRD). Compared with the immunophenotype and TCR rearrangement at first diagnosis, the results did not support the source of residual T-ALL tumor cells. During the review of MRD, it was found that the abnormal T cells showed an increasing trend, indicating that chidamide might induce leukemia cell differentiation through some pathways. CONCLUSION Hematopoietic stem cell transplantation is still an effective method to cure children's T-ALL. In some cases, abnormal T-cell nonclonal amplification occurs during the application of chidamide, and the children with T-ALL can tolerable adverse reactions of chidamide.
Aminopyridines ; Benzamides ; Child ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Recurrence ; Transplantation, Homologous

Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Lymphoma, Non-Hodgkin/drug therapy* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols

Aminopyridines ; Antineoplastic Combined Chemotherapy Protocols ; Benzamides ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Lymphoma, T-Cell, Peripheral/drug therapy*

OBJECTIVEThis study was aimed to explore the effect of a novel histone deacetylase inhibitor Chidamide on apoptosis of human multiple myeloma(MM) cells and its relevance to DNA damage response(DDR).

METHODSThe cell proliferation was detected by MTT method, apoptosis and cell cycle distribution were analyzed by flow cytometry, the expression levels of targeted proteins were detected by Western blot, the DNA damage response was blocked by ATM kinase inhibitor KU-55933.

RESULTSChidamide inhibited RPMI 8226 cell proliferation in dose- and time-dependent manner and its IC50 values of 24,48,72 h were 9.6, 6 and 2.8 µmol/L respectively. Chidamide induced cell cycle arrest of RPMI 8226 cells in G0/G1 phase by upregulating the expression of P21. Chidamide triggered caspase-3 dependent apoptosis and upregulated expression of DDR-related proteins including γH2AX, pATM in RPMI 8226 cells. Pretreatment with ATM kinase inhibitor KU-55933 down-regulated expression of DDR related proteins induced by chidamide, thereby inhibiting DNA damage response and finally resulting in suppression of apoptotic cell death.

CONCLUSIONProliferative inhibtion, cell cycle arrest and apoptosis of multiple myeloma cells induced by chidamide involve DDR.

Aminopyridines ; Apoptosis ; Benzamides ; Caspase 3 ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; DNA Damage ; Down-Regulation ; Flow Cytometry ; Histone Deacetylase Inhibitors ; Humans ; Morpholines ; Multiple Myeloma ; Pyrones