Myocardial perfusion imaging (MPI) is valuable for the diagnosis, prognosis, and management of coronary artery disease (CAD). The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic agents. However, these agents have contraindications and may cause adverse effects in some patients. Thus, other stress agents feasible for more patients are required. Higenamine (HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial infarction. It also has a promising value in MPI for the detection of CAD in preclinical and clinical studies. This review summarizes the application of HG on MPI, including its mechanism of action, stress protocol, efficacy, and safety.
Humans ; Coronary Artery Disease ; Myocardial Perfusion Imaging/methods* ; Tetrahydroisoquinolines ; Alkaloids ; Coronary Angiography/methods*

Pictet-Spenglerases (P-Sases) catalyze the Pictet-Spengler (P-S) reactions and exhibit high stereoselectivity and regioselectivity under mild conditions. The typical P-S reaction refers to the condensation and recyclization of β-arylethylamine with aldehyde or ketone under acidic conditions to form tetrahydroisoquinoline and β-carboline alkaloid derivatives. The related enzymatic products of P-Sases are the backbones of various bioactive compounds, including clinical drugs: morphine, noscapine, quinine, berberine, ajmaline, morphine. Furthermore, the activity of P-Sases in stereoselective and regioselective catalysis is also valuable for chemoenzymatic synthesis. Therefore, this review summarizes the research progress in the discovery, functional identification, biological characteristics and catalytic applications of P-Sases, which provide the useful theoretical reference in future P-Sases research and development.
Alkaloids/chemistry* ; Catalysis ; Enzymes/metabolism* ; Research/trends* ; Tetrahydroisoquinolines/chemistry*

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.
Biomedical Research/*trends ; Breast Neoplasms/therapy ; Combined Modality Therapy ; Dioxoles ; Endometrial Neoplasms/therapy ; Female ; Genital Neoplasms, Female/genetics/*therapy ; Humans ; Immunotherapy ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Ovarian Neoplasms/prevention & control/therapy ; Papillomavirus Vaccines ; Precision Medicine ; Tetrahydroisoquinolines ; Uterine Cervical Neoplasms/prevention & control/therapy/virology ; Uterine Neoplasms/therapy

Epithelial ovarian cancer (OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer (ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.
Antineoplastic Agents, Alkylating ; therapeutic use ; Clinical Trials as Topic ; DNA Damage ; Dioxoles ; administration & dosage ; pharmacology ; therapeutic use ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Neoplasm Recurrence, Local ; drug therapy ; Neoplasms, Glandular and Epithelial ; drug therapy ; Ovarian Neoplasms ; drug therapy ; Polyethylene Glycols ; administration & dosage ; Tetrahydroisoquinolines ; administration & dosage ; pharmacology ; therapeutic use ; Tumor Microenvironment

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) act by irreversibly binding to the H+-K+-ATPase of the proton pump in parietal cells and may possibly affect the vacuolar H+-ATPase in osteoclasts. METHODS: We investigated the effect of 8 weeks of PPI treatment on the parameters of bone turnover and compared PPI with revaprazan, which acts by reversibly binding to H+-K+-ATPase in proton pumps. This study was a parallel randomized controlled trial. For 8 weeks, either a PPI or revaprazan was randomly assigned to patients with gastric ulcers. The parameters of bone turnover were measured at the beginning of and after the 8-week treatment period. RESULTS: Twenty-six patients (PPI, n=13; revaprazan, n=13) completed the intention-to-treat analysis. After the 8-week treatment period, serum calcium and urine deoxypyridinoline (DPD) were increased in the PPI group (serum calcium, p=0.046; urine DPD, p=0.046) but not in the revaprazan group. According to multivariate linear regression analysis, age > or =60 years was an independent predictor for the changes in serum calcium and urine DPD. CONCLUSIONS: In elderly patients, administering a PPI for 8 weeks altered bone parameters. Our study suggested that PPIs might directly alter bone metabolism via the vacuolar H+-ATPase in osteoclasts.
Aged ; Amino Acids/drug effects/urine ; Bone Remodeling/*drug effects ; Bone and Bones/*metabolism ; Calcium/blood ; Female ; Humans ; Intention to Treat Analysis ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Osteoclasts/*metabolism ; Prospective Studies ; Proton Pump Inhibitors/*pharmacology ; Pyrimidinones/*pharmacology ; Tetrahydroisoquinolines/*pharmacology

Abstract: Fifteen novel ligustrazine-tetrahydroisoquinoline derivatives were designed and synthesized according to the association principle of pharmaceutical chemistry. The structures were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by ADP and AA have been measured by Bron method. Preliminary pharmacological results showed that compounds 7g, 7h and 7n had potent inhibitory activity against platelet aggregation induced by AA, and the compound 7o showed significant inhibitory activity against platelet aggregation induced by ADP.
Drug Design ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; Pyrazines ; chemical synthesis ; chemistry ; Tetrahydroisoquinolines ; chemical synthesis ; chemistry

OBJECTIVETo evaluate the efficacy and safety of the combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia (BPH) with overactive bladder (OAB).

METHODSWe randomly divided 166 patients with BPH and concomitant OAB into a mild obstruction symptom group (n = 88) and a moderate obstruction symptom group (n =78), 48 of the former group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 40 with 0. 2 mg tamsulosin; 36 of the latter group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 42 with 0. 2 mg tamsulosin, all administered once daily for 12 weeks. We obtained the International Prostate Symptom Score (IPSS), urine storage period symptom score (USPSS), voiding symptom score (VSS), Qmax, residual urine volume, OAB symptom score (OABSS) and adverse reactions, and compared them among different

RESULTSAmong the patients with mild obstruction symptoms, the combination of tamsulosin and solifenacin achieved remark-groups. able improvement in IPSS, USPSS, Qmax and OABSS as compared with the baseline (P < 0.05), but made no significant difference in the residual urine volume (P > 0. 05) , while tamsulosin improved IPSS only (P < 0.05). The combination therapy exhibited an obvious superiority over tamsulosin alone in improving IPSS (9.7 micro 3.0 vs 15.8 micro 3.3), USPSS (8. 1 micro 1.7 vs 12.3 micro 3.1), Qmax ([18.6 micro 2.3] ml/s vs [14.2 micro 2.3] ml/s ), and OABSS (5.3micro 1.3 vs 9.7 micro 2.7) (P < 0.05), but there were no obvious differences in residual urine, urine routine test results and adverse events between the two therapies ( P > 0. 05). In those with moderate obstruction symptoms, the combination therapy significantly improved IPSS, VSS, Qmax and OABSS (P < 0.05) but not the residual urine (P > 0. 05) in comparison with the baseline. The tamsulosin therapy achieved obvious improvement in IPSS, VSS, Qmax, OABSS and residual urine. The combination therapy showed a better effect than tamsulosin only in OABSS (4. 8 +/-1.5 vs 6.5 +/-2.5, P < 0.05), but no significant differences from the latter in IPSS, Qmax, VSS, routine urine test results, and adverse

CONCLUSIONCombination therapy of tamsulosin and solifenacin is obviously safe and efficacious in the treatment (P > 0.05). events of both mild and moderate BPH with concomitant OAB, and it is superior to tamsulosin alone.

Aged ; Drug Therapy, Combination ; Humans ; Male ; Middle Aged ; Prospective Studies ; Prostatic Hyperplasia ; complications ; drug therapy ; Quinuclidines ; administration & dosage ; therapeutic use ; Solifenacin Succinate ; Sulfonamides ; administration & dosage ; therapeutic use ; Tetrahydroisoquinolines ; administration & dosage ; therapeutic use ; Urinary Bladder, Overactive ; complications ; drug therapy

BACKGROUNDOveractive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB.

METHODSThis was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated.

RESULTSAt baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy.

CONCLUSIONSWe showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Prospective Studies ; Quality of Life ; Quinuclidines ; therapeutic use ; Solifenacin Succinate ; Tetrahydroisoquinolines ; therapeutic use ; Treatment Outcome ; Urinary Bladder, Overactive ; drug therapy

PURPOSE: To evaluate how much the improvement of lower urinary tract symptoms (LUTS) affects sexual function and which storage symptoms or voiding symptoms have the greatest effect on sexual function. MATERIALS AND METHODS: A total of 187 patients were enrolled in this study. Patients were randomly assigned to receive either tamsulosin 0.2 mg (group A) or tamsulosin 0.2 mg and solifenacin 5 mg (group B). At 4 weeks and 12 weeks, the LUTS and sexual function of the patients were evaluated by use of the International Index of Erectile Function-5 (IIEF5), International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS) questionnaire, uroflowmetry, and bladder scan. RESULTS: Both groups A and B showed statistically significant improvements in IPSS, OABSS, and quality of life (QoL). Group A showed improved maximum flow rate, mean flow rate, and residual urine volume by time. Group B did not show an improvement in flow rate or residual urine volume but total voiding volume increased with time. The IIEF5 score was not improved in either group. In group A, the IIEF5 score dropped from 13.66+/-4.97 to 11.93+/-6.14 after 12 weeks (p=0.072). Group B showed a decline in the IIEF5 score from 13.19+/-5.91 to 12.45+/-6.38 (p=0.299). Although group B showed a relatively smaller decrease in the IIEF5 score, the difference between the two groups was not significant (p=0.696). CONCLUSIONS: Tamsulosin monotherapy and combination therapy with solifenacin did not improve erectile function despite improvements in voiding symptoms and QoL. The improvement in storage symptoms did not affect erectile function.
Aged ; Drug Therapy, Combination/methods ; Erectile Dysfunction/*drug therapy/etiology ; Humans ; Lower Urinary Tract Symptoms/complications/*drug therapy ; Male ; Middle Aged ; Quality of Life ; Questionnaires ; Quinuclidines/*administration & dosage ; Rheology ; Sulfonamides/*administration & dosage ; Tetrahydroisoquinolines/*administration & dosage ; Treatment Outcome ; Urological Agents/*administration & dosage

PURPOSE: To evaluate how much the improvement of lower urinary tract symptoms (LUTS) affects sexual function and which storage symptoms or voiding symptoms have the greatest effect on sexual function. MATERIALS AND METHODS: A total of 187 patients were enrolled in this study. Patients were randomly assigned to receive either tamsulosin 0.2 mg (group A) or tamsulosin 0.2 mg and solifenacin 5 mg (group B). At 4 weeks and 12 weeks, the LUTS and sexual function of the patients were evaluated by use of the International Index of Erectile Function-5 (IIEF5), International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS) questionnaire, uroflowmetry, and bladder scan. RESULTS: Both groups A and B showed statistically significant improvements in IPSS, OABSS, and quality of life (QoL). Group A showed improved maximum flow rate, mean flow rate, and residual urine volume by time. Group B did not show an improvement in flow rate or residual urine volume but total voiding volume increased with time. The IIEF5 score was not improved in either group. In group A, the IIEF5 score dropped from 13.66+/-4.97 to 11.93+/-6.14 after 12 weeks (p=0.072). Group B showed a decline in the IIEF5 score from 13.19+/-5.91 to 12.45+/-6.38 (p=0.299). Although group B showed a relatively smaller decrease in the IIEF5 score, the difference between the two groups was not significant (p=0.696). CONCLUSIONS: Tamsulosin monotherapy and combination therapy with solifenacin did not improve erectile function despite improvements in voiding symptoms and QoL. The improvement in storage symptoms did not affect erectile function.
Aged ; Drug Therapy, Combination/methods ; Erectile Dysfunction/*drug therapy/etiology ; Humans ; Lower Urinary Tract Symptoms/complications/*drug therapy ; Male ; Middle Aged ; Quality of Life ; Questionnaires ; Quinuclidines/*administration & dosage ; Rheology ; Sulfonamides/*administration & dosage ; Tetrahydroisoquinolines/*administration & dosage ; Treatment Outcome ; Urological Agents/*administration & dosage