Imatinib mesylate has been commonly used in the treatment of patients with chronic myeloid leukemia (CML). However, a significant number of CML patients treated with imatinib developed thrombocytopenia, oligocythemia, granulocytopenia. It has been confirmed that imatinib not only inhibits BCR-ABL mutations, but also suppresses other tyrosine kinase receptor genes such as PDGFR, JAK2V617F and C-KIT mutations, providing an important potential of targeted therapy for myeloproliferative disease. As the PDGFR, JAK2 and C-KIT play important roles in the regulation of hematopoiesis, suggesting that imatinib may block the phosphorylation of PDGFR, JAK2V617F and C-KIT receptors, interrupt the signal transduction cascades, disrupt cell differentiation and proliferation. In this review, the application and the potential molecular mechanism of imatinib in the treatment of thrombocythemia and other myeloproliferative diseases are discussed.
Benzamides ; therapeutic use ; Humans ; Imatinib Mesylate ; Myeloproliferative Disorders ; drug therapy ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Thrombocytosis ; drug therapy

This paper reviewed the efficacy and safety of vardenafil, a highly selective phosphodiesterase type 5 (PDE 5) inhibitor, in men with erectile dysfunction who were difficult to treat. Several large-scale studies indicated vardenafil was effective and safe in the treatment of these difficult-to-treat ED patients, including ED with depression or diabetes, ED after radical retropubic prostatectomy, ED caused by spinal cord injury, and sildenafil nonresponders. Vardenafil provides a rational treatment alternative.
Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; therapeutic use ; Male ; Middle Aged ; Phosphodiesterase Inhibitors ; therapeutic use ; Piperazines ; therapeutic use ; Sulfones ; therapeutic use ; Treatment Outcome ; Triazines ; therapeutic use ; Vardenafil Dihydrochloride

Child ; Humans ; Hypertension, Pulmonary ; drug therapy ; Phosphodiesterase Inhibitors ; therapeutic use ; Piperazines ; administration & dosage ; therapeutic use ; Purines ; administration & dosage ; therapeutic use ; Sildenafil Citrate ; Sulfones ; administration & dosage ; therapeutic use

The therapeutic efficacy of sildenafil for the treatment of erectile dysfunction is correlative with the pharmacokinetics of the drug and the time of sexual behavior. More and more researches on the time effect window of sildenafil for the treatment of erectile dysfunction have elucidated the least time to achieve sufficient penile hardness for intercourse and to reach the best erectile state after the drug administration, as well as the therapeutic effect of the long-term treatment with the drug.
Erectile Dysfunction ; drug therapy ; Humans ; Male ; Phosphodiesterase Inhibitors ; pharmacokinetics ; therapeutic use ; Piperazines ; pharmacokinetics ; therapeutic use ; Purines ; pharmacokinetics ; therapeutic use ; Sildenafil Citrate ; Sulfones ; pharmacokinetics ; therapeutic use ; Time Factors

In recent years, more and more attention has been drawn to the role of phosphodiesterase 5 (PDE5) in penile erection. The cyclic nucleotide (cGMP) signaling pathway mediates the smooth-muscle relaxing effect of nitric oxide necessary for normal erectile function. Down-regulation of this pathway is the pathological pivot of many forms of erectile dysfunction (ED) and leads to the development of some chronic diseases. Therapeutic outcomes have shown that vardenafil is effective and safe in the treatment of ED associated with dyslipidemia, hypertension, depression, diabetes, radical retropubic prostatectomy, spinal cord injury, sildenafil failure, renal transplantation, chronic prostatitis and that accompanied by premature ejaculation. Vardenafil provides a reasonable therapeutic alternative for these refractory ED patients. In addition, vardenafil can prolong erectile duration of ED patients.
Cyclic Nucleotide Phosphodiesterases, Type 5 ; therapeutic use ; Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; therapeutic use ; Male ; Phosphodiesterase Inhibitors ; therapeutic use ; Piperazines ; therapeutic use ; Sulfones ; therapeutic use ; Triazines ; therapeutic use ; Vardenafil Dihydrochloride ; Vasodilator Agents ; therapeutic use

OBJECTIVETo evaluate phosphodiesterase type 5 (PDE5) inhibitors in the management of temporary penile erectile dysfunction (ED) in patients undergoing assisted reproductive technology (ART).

METHODSThis study included 75 male patients that experienced ejaculation failure due to temporary ED during ART treatment. We treated the patients with PDE5 inhibitors sildenafil, tadanafil and vardenafil, and then evaluated the hardness of penile erection using Erection Hardness Score (EHS) and analyzed the end-point efficacy.

RESULTSSildenafil was administered to 28 of the patients, tadanafil to 25, and vardenafil to 22. Of the total number of patients, 61 (81.3%) achieved effective erection, but no significant differences were observed in the rate of effectiveness among the sildenafil (24 cases, 85.7%), tadanafil (20 cases, 80.0%) and vardenafil (17 cases, 77.3%) groups (P > 0.05). After medication, 53 (70.7%) of the patients successfully ejaculated, but there were no remarkable differences in the success rate among the sildenafil (21 cases, 75.0%), tadanafil (17 cases, 68.0%) and vardenafil (15 cases, 68.2%) groups (P > 0.05). Of the 75 patients, 37 received the recommended initial dose and 38 the maximum recommended dose of PDE5 inhibitors, but no significant differences were found in the rate of successful sperm retrieval between the former (28 cases, 75.7%) and the latter group (25 cases, 65.8%) (P > 0.05). Mild adverse events, including transient flush and dizziness, occurred in 5 cases (6.7%).

CONCLUSIONPDE5 inhibitors can help temporary ED patients to achieve penile erection and ejaculation during ART treatment.

Ejaculation ; Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; therapeutic use ; Male ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Reproductive Techniques, Assisted ; Sildenafil Citrate ; Sulfonamides ; therapeutic use ; Sulfones ; therapeutic use ; Triazines ; therapeutic use ; Vardenafil Dihydrochloride

Besides 36 (28 single-tablets and 8 fixed-dose combinations) used antiretroviral drugs clinically, there are a number of investigational antiretroviral agents currently in phase 2-3 clinical trial. Tenofoviralafenamidefumarate (TAF) is a novel nucleoside analogue reverse transcriptase inhibitor that is potent and less toxicity than tenofovir (TDF). Doravirine is a non-nucleoside analogue reverse transcriptase inhibitor that demonstrates activity against NNRTI-resistant viral strains. GSK744 is an integrase inhibitor with a long acting preparation. In addition, several drugs with new mechanisms are also noted, for example, BMS-663 068 is a small molecule CD4 attachment inhibitors and cenicriviroc is a novel CCR5/CCR2 antagonist with antiretroviral activity and anti-inflammatory effects. Several drug classes that target known pathways in HIV latency have being developed, and leading the list are histone deacetylase inhibitors. Other agents include protein kinase C activators, positive transcription elongation factor activators, DNA methyl-transferase inhibitors and histone methyl-transferase inhibitors and so on. This review is focused on the above-mentioned drug candidates that may be used in clinical in next couple of years and those compounds that can reverse latent HIV infections.
Adenine ; analogs & derivatives ; therapeutic use ; Anti-HIV Agents ; therapeutic use ; HIV Infections ; drug therapy ; Humans ; Organophosphates ; therapeutic use ; Organophosphonates ; therapeutic use ; Piperazines ; therapeutic use ; Pyridones ; therapeutic use ; Reverse Transcriptase Inhibitors ; therapeutic use ; Tenofovir

The rate of erectile dysfunction after radical retropubic prostatectomy is from 10% to 100%. The prevalence of erectile dysfunction after nerve-sparing radical prostatectomy is more than one third. In the patients who had undergone bilateral NS, 72% responded to sildenafil, 71.7% and 59.7% responded to 20 mg and 10 mg of vardenafil respectively. For all randomized patients who received tadalafil, the mean percentage of successful penetration attempts was 54% and the mean percentage of successful intercourse attempts was 41%. For the subgroup with evidence of postoperative tumescence these values were 69% and 52%, respectively. No head-to-head trials have been performed with sildenafil, vardenafil and tadalafil in treatment of erectile dysfunction after radical prostatectomy.
Carbolines ; therapeutic use ; Erectile Dysfunction ; drug therapy ; etiology ; Humans ; Imidazoles ; therapeutic use ; Male ; Phosphodiesterase Inhibitors ; therapeutic use ; Piperazines ; therapeutic use ; Prostatectomy ; adverse effects ; Purines ; therapeutic use ; Sildenafil Citrate ; Sulfones ; therapeutic use ; Tadalafil ; Triazines ; therapeutic use ; Vardenafil Dihydrochloride

OBJECTIVETo evaluate the efficacy and safety of sertraline and vardenafil in the treatment of patients with concomitant erectile dysfunction (ED) and premature ejaculation (PE).

METHODSSixty patients with concomitant ED and PE received at our clinic of andrology were randomly divided into a vardenafil group and a sertraline group. The vardenafil group received flexible doses of vardenafil from 10 mg to 20 mg and the sertraline group 50 mg daily, both for 2 months. The differences in IIEF-5 before and after the treatment were recorded and compared, and the results of ED treatment evaluated. Intravaginal ejaculatory latency time (IELT) was recorded to evaluate the outcome of PE treatment.

RESULTSIn the vardenafil group, 24 patients had their ED improved and the efficacy rate was 80%, as compared with 27% in the sertraline group. There was significant difference between the two groups (P < 0.05). Twenty patients had their PE improved in vardenafil group, with an efficacy rate of 67% as compared with 40% in the sertraline group. The difference was significant between the two groups (P < 0.05). In both of the two groups, a significantly higher rate of PE improvement was found in patients with improved ED than in those without. Only mild side effects were recorded, and none withdrew from the treatment.

CONCLUSIONTo patients with concomitant ED and PE, the key to the treatment is to improve their erectile function, and for this purpose, vardenafil works better than sertraline.

Adult ; Ejaculation ; drug effects ; Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; therapeutic use ; Male ; Middle Aged ; Phosphodiesterase Inhibitors ; therapeutic use ; Piperazines ; therapeutic use ; Serotonin Uptake Inhibitors ; therapeutic use ; Sertraline ; therapeutic use ; Sulfones ; therapeutic use ; Treatment Outcome ; Triazines ; therapeutic use ; Vardenafil Dihydrochloride

Gastrointestinal stromal tumor(GIST) originates from interstitial cells of Cajal(ICCs). Tyrosine kinase inhibitors(TKI) such as imatinib and sunitinib, are effective agents besides surgery. However some GIST can become primarily or secondarily resistant to those drugs. The difference in gene mutation types and secondary gene mutation is the main cause. When the GIST is proved to be drug resistance, reasonable personal treatment strategies based on individualized medicine should be made to improve outcomes and quality of life.
Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Drug Resistance, Neoplasm ; genetics ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; Humans ; Imatinib Mesylate ; Indoles ; therapeutic use ; Piperazines ; therapeutic use ; Protein Kinase Inhibitors ; therapeutic use ; Pyrimidines ; therapeutic use ; Pyrroles ; therapeutic use