This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Tryptophan ; Arachidonic Acid/metabolism* ; Mice, Inbred C57BL ; Colon ; Cytokines/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Metabolomics ; Purines/therapeutic use* ; Dextran Sulfate/metabolism* ; Disease Models, Animal ; Colitis/chemically induced*

OBJECTIVETo investigate the effect of Bushengzhuyang Fang (Yangjing Capsule, YJC) on penile erectile function and its action mechanisms in rats.

METHODSFifty-six male SD rats were randomly divided into seven groups of equal number: blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The rats in the blank control group were treated intragastrically with normal saline and those in the other groups with daidzein at the dose of 100 mg per kg per day for 30 days. Then the last five groups received additionally testosterone (4 mg per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26 mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed the apomorphine-induced spontaneous erectile response and pathological changes in the corpus cavernosum of the rats, recorded the number of penile erection and erectile incubation period, and determined the serum levels of testosterone (T) and luteinizing hormone (LH).

RESULTSAt 30 days of treatment, the number of apomorphine-induced erections was decreased, the erectile incubation period prolonged, and the serum levels of T and LH reduced remarkably in all groups of rats (P < 0.05). Compared with the findings at 30 days, the number of penile erections was significantly decreased at 60 days in the daidzein group (1.39 ± 0.42 vs 2.67 ± 0.33, P < 0.05) and daidzein + low-dose YJC group (1.33 ± 0.49 vs 2.83 ± 0.61, P < 0.05); the erectile incubation period was markedly ex- tended ([16.33 ± 3.11] vs [8.50 ± 0.93] min and [15.50 ± 3.21] vs [8.63 ± 1.54] min, P < 0.05); and the serum levels of T ([5.34 ± 0.89] vs [1.24 ± 0.30] ng/ml and [5.28 ± 1.12] vs [2.07 ± 0.76] ng/ml, P < 0.05) and LH ([3.62 ± 0.37] vs [2.09 ± 0.12] ng/ml and [3.79 ± 0.28] vs [2.17 ± 0.33] ng/ml, P < 0.05) were significantly reduced in the daidzein and daidzein + low-dose YJC groups, respectively. Pathological examination revealed slightly decreased cavernous sinuses and blood vessels in the corpus cavernosum of the rats in the daidzein + testosterone, daidzein + sildenafil, daidzein + medium-dose YJC, and daidzein + high-dose YJC groups as compared with those in the blank control group.

CONCLUSIONHigh-dose Yangjing Capsule is efficacious for the recovery of erectile function in rats, especially for phytoestrogen-induced erectile dysfunction.

Animals ; Apomorphine ; pharmacology ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; chemically induced ; drug therapy ; Humans ; Isoflavones ; pharmacology ; Luteinizing Hormone ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; drug effects ; pathology ; Phytoestrogens ; Phytotherapy ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfonamides ; therapeutic use ; Testosterone ; therapeutic use ; Vasodilator Agents ; therapeutic use

CAL-101 is a selective inhibitor of the phosphatidylinositol-3 kinase (PI3K), it inhibits the survival, proliferation and migration of tumor cells by directly inducing apoptosis and inhibiting micro-environmental interactions. It has been determined that the P110δ isoforms of PI3K expressed primarily in cells of hematopoietic lineage, such as B and T cells. This review focuses on the target, mechanism of action, the use and prospect of CAL-101 in tumors of blood and lymph systems.
Animals ; Class Ia Phosphatidylinositol 3-Kinase ; antagonists & inhibitors ; Hematologic Neoplasms ; drug therapy ; Humans ; Purines ; pharmacology ; therapeutic use ; Quinazolinones ; pharmacology ; therapeutic use ; Signal Transduction ; drug effects

OBJECTIVETo observe the clinical efficacy and safety of sildenafil in the treatment of high altitude heart disease associated with severe pulmonary arterial hypertension (PAH) in children.

METHODSFifty children (aged 2 months to 2 years) with high altitude heart disease associated with severe PAH, who were continuously transferred to the Intensive Care Unit between January 2011 and October 2013, were randomly assigned to observation and control groups. The control group was given conventional treatment, while the observation group received oral sildenafil [1 mg/(kg . d)] three times daily for 7-10 days in addition to the conventional treatment. Before and after treatment, hemodynamics, blood gas, routine blood parameters, and blood biochemical parameters were recorded.

RESULTSAfter treatment, the observation group had a significantly higher decrease in mean pulmonary artery pressure and significantly higher increases in arterial partial pressure of oxygen, cardiac output, cardiac index, and oxygenation index compared with the control group (P<0.05). In the observation group, there were no significant changes in mean arterial pressure, routine blood parameters and blood biochemical parameters (P>0.05), and no obvious adverse reactions were found.

CONCLUSIONSFor children with high altitude heart disease associated with severe PAH, sildenafil can effectively reduce pulmonary artery pressure and improve cardiac function and does not cause adverse reactions. This therapy has good safety according to the preliminary evaluation.

Altitude ; Familial Primary Pulmonary Hypertension ; Female ; Heart Diseases ; drug therapy ; Humans ; Hypertension, Pulmonary ; complications ; physiopathology ; Infant ; Male ; Piperazines ; adverse effects ; therapeutic use ; Purines ; adverse effects ; therapeutic use ; Sildenafil Citrate ; Sulfones ; adverse effects ; therapeutic use ; Vasodilator Agents ; adverse effects ; therapeutic use

Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of Controlled Trials, Korea med and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. The outcomes were the exercise capacity and adverse events. Four randomized controlled trials involving 109 subjects were included in the analysis. Two trials involved bosentan, one sildenafil and one beraprost. The studies varied in duration of treatment from 3 to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8). COPD with overt PH significantly improved the exercise capacity (mean difference, 111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference, 26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a significant effect in improving exercise capacity in COPD with overt PH.
Anoxia ; Antihypertensive Agents/adverse effects/*therapeutic use ; Clinical Trials as Topic ; Databases, Factual ; Epoprostenol/adverse effects/analogs & derivatives/therapeutic use ; Humans ; Hypertension, Pulmonary/complications/*drug therapy ; Piperazines/adverse effects/therapeutic use ; Pulmonary Disease, Chronic Obstructive/*etiology ; Purines/adverse effects/therapeutic use ; Questionnaires ; Risk Factors ; Sulfonamides/adverse effects/therapeutic use ; Sulfones/adverse effects/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

OBJECTIVETo sum up the experience in administering oral tadalafil on alternate days for the treatment of erectile dysfunction (ED) that fails to respond to on-demand medication.

METHODSWe retrospectively analyzed the clinical data of 15 cases of ED treated with oral tadalafil on alternate days from September 2010 to March 2012. All the patients had failed to respond to on-demand medication of sildenafil previously.

RESULTSAfter 4 weeks of tadalafil treatment, 11 (73.3%) of the cases were remarkably improved, with significant difference in IIEF-5 scores before and after treatment (P < 0.05). Transient adverse reactions were observed in the other 4 cases, including mild headache in 2, slight backache in 1, and facial flush in 1.

CONCLUSIONOral tadalafil on alternate days is safe and effective in the treatment of ED that fails to respond to on-demand medication of sildenafil.

Administration, Oral ; Adult ; Carbolines ; administration & dosage ; therapeutic use ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Phosphodiesterase Inhibitors ; administration & dosage ; therapeutic use ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Retrospective Studies ; Sildenafil Citrate ; Sulfones ; therapeutic use ; Tadalafil ; Treatment Failure ; Treatment Outcome

Adult ; Carbolines ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Middle Aged ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Semen ; Sildenafil Citrate ; Specimen Handling ; Sulfones ; therapeutic use ; Tadalafil

OBJECTIVETo investigate the protective effect of L-carnitine (LC) combined with sildenafil on the reproductive endocrine function of male rats with diabetes mellitus (DM).

METHODSA total of 40 male SD rats were randomly divided into five groups, group A taken as normal controls, and groups B, C, D and E made into DM models by injection of streptozotocin at 65 mg/kg. Then the rats in groups A and B were treated with normal saline, C with sildenafil at 5 mg per kg per d, D with LC at 300 mg per kg per d, and E with sildenafil at 5 mg per kg per d plus LC at 300 mg per kg per d, all via gastric gavage for 6 weeks, followed by determination of the levels of testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum of the rats.

RESULTSAfter 6 weeks of treatment, the T, FSH and LH levels were (25.25 +/- 2.67) nmol/L, (5.78 +/- 0.61) IU/L and (625.21 +/- 43.45) ng/L in group A, (9.63 +/- 1.71) nmol/L, (1.98 +/- 0.42) IU/L and (479.89 +/- 27.62) ng/L in group B, (18.98 +/- 3.07) nmol/L, (5.08 +/- 0.33) IU/L and (586.57 +/- 31.72) ng/L in group C, (16.18 +/- 2.65) nmol/L, (4.63 +/- 0.30) IU/L and (540.78 +/- 25.52) ng/L in group D, and (23.65 +/- 2.66) nmol/L, (5.59 +/- 0.48) IU/L and (621.53 +/- 36. 40) ng/L in group E. The three parameters were significantly lower in B than in the other four groups (P < 0.01), and so were they in C and D than in A and E (P < 0.05), but showed no significant differences either between C and D (P > 0. 05) or between A and E (P > 0.05).

CONCLUSIONSix-week medication of either sildenafil or LC alone could increase the levels of T, FSH and LH in the serum of DM rats, but the combination of the two had an even more obvious increasing effect, which indicates a still better protective effect on the reproductive endocrine function of diabetic male rats.

Animals ; Carnitine ; adverse effects ; therapeutic use ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Drug Therapy, Combination ; Follicle Stimulating Hormone ; blood ; Luteinizing Hormone ; blood ; Male ; Piperazines ; administration & dosage ; therapeutic use ; Purines ; administration & dosage ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfones ; administration & dosage ; therapeutic use ; Testosterone ; blood

Sildenafil (Viagra) citrate has been well accepted by physicians and patients for its reliable efficacy and safety in the treatment of erectile dysfunction (ED) ever since its introduction into clinical andrology in China 10 years ago. It has been proved effective for various ED subgroups, regardless of causes, severity and age. Recent studies show that sildenafil also benefits patients with premature ejaculation, either used alone or in combination with other therapies.
China ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Piperazines ; therapeutic use ; Premature Ejaculation ; drug therapy ; Purines ; therapeutic use ; Sildenafil Citrate ; Sulfones ; therapeutic use