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)     

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.     

Can losartan improve cardiac performance during the treadmill exercise test in hypertensive subjects?

Systolic blood pressure (SBP) normally increases during exercise. This increase is frequently exaggerated in hypertensive individuals. The aim of our study was to evaluate the antihypertensive effects of losartan at peak exercise and on cardiac performance during the treadmill test in individuals with essential hypertension. Forty subjects with a mean age of 44.2 +/- 12.4 years and with mild-to-moderate essential hypertension were enrolled. After a 14-day washout period, all selected subjects were given a treadmill exercise test using the modified Bruce protocol for exercise. The test was performed at the end of the washout period (step 0), again after 1 month (step 1), after 3 months (step 2) and after 6 months (step 3) of losartan administration (50 mg/daily per oral). Heart rate, SBP and diastolic blood pressure (DBP) were measured at rest and at maximal exercise. Exercise duration and double product were also recorded. In all patients who completed the study, a significant reduction from baseline in SBP at rest was found at 3 and 6 months (p < 0.05). No significant reduction from baseline in SBP at peak exercise was observed. No significant changes from baseline were found in double product, DBP, heart rate or exercise time. The results of our study suggest that losartan is effective in reducing blood pressure only at rest but is unable to improve exercise BP response or cardiac performance in subjects with mild-to-moderate essential hypertension.     

Immunologic effects of exposure to low levels of inorganic mercury

OBJECTIVE: The immune system is a target for the toxic effects of inorganic mercury, both in humans and animals. In humans it has been observed that occupational and environmental exposure to inorganic mercury may cause both clinical (autoimmunity, hypersensitivity) and subclinical effects (cellular and humoral immunologic variable modifications). To obtain a better definition of these effects with respect to the exposure levels, a multicentre study was performed on 117 workers exposed to very low doses of inorganic mercury and 172 subjects from the general population of the same geographical area with environmental exposure to mercury from dental amalgams and dietary fish intake. RESULTS: The white blood cell count was included in the normality range for all subjects and there was no difference between exposed and non exposed subjects. The immunologic variables studied showed an increase of the CD4+ and CD8+ number in exposed workers compared to non-exposed subjects, with a statistically significance only for CD4+, while no difference was observed regarding CD4+, CD8+, NK+ percentage and CD4+/CD8+ ratio. A significative decrease of serum IL-8 and an inverse correlation between serum levels of this cytokine and HgU were observed in exposed workers compared to non exposed subjects. No association between immunologic variables and both dental amalgams and dietary fish intake was found in subjects not occupationally exposed to inorganic mercury. DISCUSSION: The decrease in IL-8 serum levels observed in exposed workers might suggest an immunosuppressive effect of occupational exposure to very low doses of inorganic mercury. This result suggests the need to revise of current HgU BEI after further definition of its prognostic significance.