In vitro release of lectins by Phallusia mamillata hemocytes.

-Lactose specific lectins are released from Phallusia mamillata hemocytes during short-term cultures. The molecular weight of the subunits, the immunological cross-reaction and the sugar specificity suggest that the released lectins are similar to those isolated from the sonicated hemocytes. Because lectin release appears to take place independently of active protein synthesis, the possibility exists that lectins are pre-formed, stored in hemocytes and released when in vitro conditions stimulate the cells.     

Effect of obesity on left ventricular function studied by radionuclide angiocardiography

Several studies have shown a significant association of obesity with cardiovascular morbidity and mortality. The present study was carried out to investigate central and systemic haemodynamics in overweight and moderate obese, but otherwise healthy subjects, and in a lean control group to determine whether obesity can influence left ventricular performance per se. In this study an attempt has been made to eliminate misleading factors, such as diabetes, lipid abnormalities and hypertension. A total of 67 subjects, 44 with overweight or moderate obesity and 23 lean healthy subjects, were included. Patients were divided into three groups according to BMI levels and Garrow's criteria as follows: lean control group (BMI less than 25 kg/m2); overweight (BMI from 25 to 30 kg/m2); moderate obese (BMI greater than 30 less than 40 kg/m2). Overweight and moderate obese subjects were further subgrouped according to duration of obesity (DO) in subgroup A (DO less than 98 months) and in subgroup B (DO greater than 98 months). Haemodynamic assessment was performed using first pass radionuclide angiocardiography. When compared with lean subjects, overweight and moderate obese subjects were characterized by a significant increase in cardiac output (CO), stroke volume (SV), end diastolic volume (EDV), end systolic volume (ESV), total blood volume (TBV) and total plasma volume (TPV) and by a significant decrease in left ventricular ejection fraction (EF); some of these changes appeared to be related to the degree of obesity. In overweight and moderate obese subjects, total peripheral resistance (TPR) was lower than in lean controls, but this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhaltsstoffe von Fagaceae (Cupuliferae), 19. Mitt.: Triterpensaponine und Acylflavonoide aus Quercus robur var. stenocarpa Beck.

Constituents of Fagaceae (Cupuliferae), XIX: Triterpene Saponins and Acylated Flavonoids from Quercus robur L. var. stenocarpa Beck. In addition to four known glycosides from leaves of Quercus robur L. var. stenocarpa Beck. a new triterpene saponin has been isolted and identified as 28-β-d-glucopyranosyl ester of the 2α,3β,19α-trihydroxy-olean-12-ene-24,28-dioic acid ( I ).     

Beta-Blockers and Ivabradine in Chronic Heart Failure: From Clinical Trials to Clinical Practice

Beta-blockers have become one of the cornerstones of treatment of patients with heart failure (HF) and depressed left ventricular function, but in clinical practice only 30–35 % of patients achieve the therapeutic target dose as established in randomized clinical trials. Moreover, high resting heart rate (HR) has emerged as a simple but relevant risk factor for cardiovascular events, including coronary artery disease and HF; also, it was found to have an independent prognostic value in patients with HF. Evidence that HR could be considered a good parameter to evaluate the quality of treatment in patients with HF has been suggested; of note, many patients maintain a resting HR ≥70 beats per minute despite optimal beta-blocker therapy. In recent years, a new drug able to reduce HR, ivabradine, has been introduced in clinical practice, and its use in the clinical setting of HF patients has been recommended by current European Society of Cardiology (ESC) guidelines. Here we review the evidence of the prognostic role of HR in systolic HF and the potential relationship between HR lowering and the beneficial effects of beta-blockers; we will also analyze the reasons why an appropriate use of these drugs is seldom achieved in clinical practice, and review the evidence for the use of ivabradine in systolic HF in the clinical setting.     

Beyond HbA1c and Glucose: the Role of Nontraditional Glycemic Markers in Diabetes Diagnosis,Prognosis, and Management

Erectile dysfunction (ED) is highly prevalent affecting at least 50 % of men with diabetes mellitus (DM). DM may cause ED through a number of pathophysiological pathways. These include neuropathy, endothelial dysfunction, cavernosal smooth muscle structural/functional changes, and hormonal changes. Lifestyle changes, diabetes control, and treatment of hypogonadism are important as the first step in ED management since there is no curative treatment for ED. Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment option. Intracavernous administration of vasoactive drugs is commonly used as a second-line medical treatment when PDE5i have failed. Alprostadil is the most widely used drug in this second-line setting. The combination of papaverine, phentolamine, and alprostadil represents the most efficacious intracavernous pharmacologic treatment option that may save non-responders to alprostadil. Penile prosthesis implantation can be considered in treatment refractory cases, with excellent functional and safety results in the properly informed patients.     

Locating binding poses in protein-ligand systems using reconnaissance metadynamics

A molecular dynamics-based protocol is proposed for finding and scoring protein-ligand binding poses. This protocol uses the recently developed reconnaissance metadynamics method, which employs a self-learning algorithm to construct a bias that pushes the system away from the kinetic traps where it would otherwise remain. The exploration of phase space with this algorithm is shown to be roughly six to eight times faster than unbiased molecular dynamics and is only limited by the time taken to diffuse about the surface of the protein. We apply this method to the well-studied trypsin-benzamidine system and show that we are able to refind all the poses obtained from a reference EADock blind docking calculation. These poses can be scored based on the length of time the system remains trapped in the pose. Alternatively, one can perform dimensionality reduction on the output trajectory and obtain a map of phase space that can be used in more expensive free-energy calculations.     

Antiproliferative oleanane saponins from Meryta denhamii

Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.     

Docetaxel and oxaliplatin combination in second-line treatment of patients with advanced gastric cancer

Background In advanced gastric cancer few data are available on the efficacy or safety of new drug combination regimens after progression following first-line chemotherapy. Methods Patients with histologically confirmed advanced gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than 2, progressing after first-line chemotherapy, were eligible. Patients were treated with docetaxel 75 mg/m² on day 1 and oxaliplatin 80 mg/m² on day 2, every 3 weeks, until progression or unacceptable toxicity. Results Between May 2002 and April 2005, 38 patients were enrolled. Men accounted for 73.7% of the patients and the median age was 59 years. The primary tumor was not resected in 47.4% of the patients; the peritoneum was the most frequent metastatic site (60.5%). The first-line treatment was cisplatin, epirubicin, and infusional 5-fluorouracil (ECF) in 81.5% of the patients and cisplatin and infusional 5-fluorouracil (CF) in 15.7%. The median number of cycles was 4.3. The treatment was well tolerated, with no toxic deaths. National Cancer Institute (NCI) grade III-IV neutropenia was frequent (26.3%), but no febrile neutropenia was reported. Severe asthenia (15.7%) and severe nausea (15.7%) required dose reductions in 2 patients and treatment discontinuation in another. The overall response rate was 10.5%, and 18 patients (47.3%) experienced disease stabilization (7 of them with significant clinical benefit). Median time to progression was 4.0 months (range, 2–8 months) and median overall survival was 8.1 months (range, 3–26 months). Thirteen patients (34.2%) also received third-line chemotherapy, with an irinotecan-containing regimen, and their median overall survival was higher than that of the other patients (16.3 vs 6.0 months) Conclusion The combination of oxaliplatin and docetaxel shows only marginal activity as second-line treatment, but it has a good tolerability profile. This suggests that there is room for optimizing the schedule as well as for planning sequential treatments in gastric cancer.