The Impact of Rotigotine on Cardiovascular Autonomic Function in Early Parkinson's Disease

Dysautonomia can occur in early stages of Parkinson's disease (PD) influencing tolerance to dopaminergic therapies. Rotigotine, a non-ergot dopamine agonist, has recently been developed as an effective alternative antiparkinsonian drug, but its influence on the autonomic nervous system was not investigated. Twenty subjects out of 34 consecutive de novo PD patients were submitted to full assessment of cardiovascular autonomic function before and after reaching a stable rotigotine regimen [6 mg/24 h (n = 3) or 8 mg/24 h (n = 17)]. Patients reached significant clinical improvement (-27% on the Unified Parkinson's Disease Rating Scale part III) and did not show significant differences in cardiovascular tests compared to baseline data. However, an unexpected trend towards increasing systolic blood pressure after head-up tilt test was detected. Our study demonstrates that rotigotine does not influence cardiovascular autonomic responses in early de novo PD patients. Consequently, it may represent a well-tolerated and efficacious therapeutic option in newly diagnosed PD subjects.     

The fungicide mancozeb induces toxic effects on mammalian granulosa cells

The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects oocyte meiotic spindle morphology and impairs fertilization rate even when used at very low concentrations. We evaluated the toxic effects of mancozeb on the mouse and human ovarian somatic granulosa cells. We examined parameters such as cell morphology, induction of apoptosis, and p53 expression levels. Mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of their morphology, and acquired the ability to migrate but not to proliferate. The expression level of p53, in terms of mRNA and protein content, decreased significantly in comparison with unexposed cells, but no change in apoptosis was recorded. Toxic effects could be attributed, at least in part, to the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was found in culture medium. Human granulosa cells also showed dose-dependent morphological changes and reduced p53 expression levels after exposure to mancozeb. Altogether, these results indicate that mancozeb affects the somatic cells of the mammalian ovarian follicles by inducing a premalignant-like status, and that such damage occurs to the same extent in both mouse and human GC. These results further substantiate the concept that mancozeb should be regarded as a reproductive toxicant.     

Potential protective role of linezolid against Clostridium difficile infection

Clostridium difficile infection (CDI) is one of the main causes of diarrhoea associated with antimicrobial therapy. Antibiotics with good ‘in vitro’ activity against C. difficile could protect patients from developing CDI. In this study, the potential of linezolid to protect patients with ventilator-associated pneumonia (VAP) from developing CDI was assessed. Over a 4-year period, a cohort of patients who developed VAP following major heart surgery (MHS) in Gregorio Marañón General Hospital (Madrid, Spain) was retrospectively analysed. Patients were divided into those who developed CDI in the post-operative period and those who did not. Variables associated with the development of CDI were analysed, including the role of antimicrobial therapy. Overall, 1934 patients underwent MHS; 90 patients were excluded due to intra-operative or early post-operative (first 48 h) death, leaving a study population of 1844 patients, of which 105 cases had VAP. Complete clinical data were available in 91 cases. CDI occurred in 22 patients (24.2%). When comparing VAP cases with and without CDI, EuroSCORE and overall antibiotics prescribed were not significantly different. Patients with chronic renal failure (CRF) were more prone to develop CDI than those without CRF (32% vs. 13%; P = 0.04), and patients with CDI received more doses of linezolid than those without CDI [12.4 ± 9.7 defined daily doses (DDDs) vs. 6.7 ± 4.0 DDDs; P = 0.007]. Multivariate analysis confirmed that receiving more DDDs of linezolid protects from developing CDI (hazard ratio = 0.908, 95% confidence interval 0.83–0.99; P = 0.04). This work is retrospective and addresses a very particular population, but it is the first to suggest the potential impact of linezolid against CDI.     

Inflammation in Peripheral Arterial Disease (PAD)

Peripheral arterial disease (PAD) affects a large number of individuals over the age of 55 years old, and data from studies has shown a relationship between inflammation, and PAD. Many researchers have not only focused on the role played by inflammatory biomarkers and the progression of PAD, but also on the efficiency of biomarkers in monitoring medical, surgical and interventional strategies in PAD patients. In this review, Authors aim to demonstrate that biomarkers play a key role in the pathophysiology of PAD, and consequently they could be screened to highlight individuals showing these crucial pathophysiological signs. Based on a large debate about phlogosis, it is now considered to be a relevant objective in reducing the prevalence and consequences of atherosclerotic diseases such as PAD. Finally, efforts must be made towards addressing this very important objective, and consequently a greater number of studies need to be made in combatting phlogosis, especially among PAD patients.     

In Vitro and In Vivo Study of Solid Lipid Nanoparticles Loaded with Superparamagnetic Iron Oxide

Solid Lipid Nanoparticles (SLN) are already under investigation as a pharmaceutical tool able to change the pharmacokinetic and biodistribution of carried molecules. SLN are able to target drugs to lymph after duodenal administration and to overcome the Blood Brain Barrier (BBB). In this study, superparamagnetic SLN have been prepared, have colloidal size, in vitro analysis showed relaxometric properties similar to Endorem_®. In vivo Magnetic Resonance Imaging (MRI) of the central nervous system (CNS) with both SLN and Endorem_® showed that superparamagnetic SLN have slower blood clearance than Endorem_®. MRI data are consistent with CNS uptake of SLN lasting up to the end of the experiment (135 min). These findings confirm the ability of SLN to overcome the BBB; SLN might be used as a CNS MRI contrast agent.     

High-sensitivity gamma-glutamyltransferase fraction pattern in alcohol addicts and abstainers

BackgroundFour fractions of gamma-glutamyltransferase (GGT) with different molecular weight (b-, m-, s-, and f-GGT) are present in human plasma. Differential GGT fraction pattern is found in non-alcoholic liver disease (NAFLD) and chronic viral hepatitis, characterized by normal or decreased b-GGT/s-GGT (b/s) ratio, respectively.MethodsChromatographic fractional GGT analysis was performed on plasma obtained from 51 subjects: 27 alcoholics (mean (SD), age 45 (9) years; 23 males; 14 positive for viral infection), 24 abstinents from at least 1 month (43 (12) years; 20 males; 6 positive for viral infection). Twenty-seven blood donors matched for age and gender (44 (9) years; 23 males) were selected as controls.ResultsAll fractions were significantly increased in alcoholics (P < 0.001), s-GGT showing the largest increase, while only m-GGT and s-GGT were elevated in abstainers (P < 0.01), in comparison with controls. The b/s ratio was significantly lower in both alcoholics and abstainers than in controls (median (25th–75th perc.): 0.10 (0.07–0.15), 0.16 (0.10–0.24), 0.35 (0.29–0.53), respectively, P < 0.001). Viral infection did not significantly changes absolute values of individual GGT fractions in alcoholics, but the b/s ratio was significantly lower in virus positive than in virus negative subjects (0.08 (0.05–0.12), 0.14 (0.09–0.20), respectively, P < 0.01).ConclusionsThe fraction pattern analysis might increase the specificity of GGT as biomarker of alcohol abuse, especially concerning the differential diagnosis between alcoholism and NAFLD, a common cause of elevated GGT level in the general population.     

Antifungal Agents in Current Pediatric Practice

Invasive fungal infections are an important cause of morbidity and mortality in immunocompromised children. Increases in the incidence of systemic mycoses have been observed during the last 2 decades. Treatment of invasive fungal infections has improved through a better knowledge and application of current treatment strategies and through the development of new antifungal compounds. The purpose of this review is to provide antifungal treatment recommendations for pediatric patients that can help clinicians find the most suitable treatment for each specific case.