Versatile magnetic microdiscs for the radio enhancement and mechanical disruption of glioblastoma cancer cells

This study describes the use of highly versatile, lithographically defined magnetic microdiscs. Gold covered magnetic microdiscs are used in both radiosensitizing cancer cells, acting as intracellular emitters of secondary electrons during radiotherapy, and as well as inducing mechanical damage by exerting a mechanical torque when exposed to a rotating magnetic field. This study reveals that lithographically defined microdiscs with a uniform size of 2 microns in diameter highly increase the DNA damage and reduce the glioblastoma colony formation potential compared to conventional radiation therapy. Furthermore, the addition of mechanical disruption mediated by the magnetic component of the discs increased the efficiency of brain cancer cell killing.

First study demonstrating the use of physically engineered magnetic particles that display two functionalities for cancer treatment.     

Multiplex analysis of genetic polymorphisms within UGT1A9, a gene involved in phase II of Δ9-THC metabolism

We present a novel multiplex assay for the simultaneous detection of 12 polymorphisms within the UGT1A9 sequence, which codes for enzymes involved in phase II biotransformation. The assay combines a multiplexed amplification step with single-base extension sequencing. The method described here is fast, cost-effective, and easy-to-use, combining the relevant features of screening methods for research and diagnostics in pharmacogenetics. To validate the assay, we tested reproducibility and sensitivity and analysed allele frequencies of 110 Caucasian individuals. Furthermore, we describe combining genetic information of individuals consuming Cannabis sativa products with respective plasma concentrations of a metabolite.

     

Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients

Neurological Sciences - Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for...     

Circulating SIRT1 Increases After Intragastric Balloon Fat Loss in Obese Patients

Background

Sirtuins (SIRTs), ubiquitous deacetylases, are main regulators of energy homeostasis and metabolism. SIRT1 has a positive impact on obesity, diabetes mellitus, liver steatosis, and other metabolic disorders. Lean subjects have higher expression of SIRT1 in the adipose tissue compared to obese. However, it is not known whether weight loss associates with changes in blood SIRT1. We evaluated the effect of weight loss on circulating SIRT1, metabolic parameters, and body composition.

Methods

Thirty-two obese subjects were studied before and 6 months after BioEnterics® Intragastric Balloon (BIB®) [22 patients, BMI 41.82?±?6.28 kg/m²] or hypocaloric diet [10 patients, BMI 38.95?±?6.90 kg/m²]. Plasma SIRT1, body composition, measures of metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure, HDL cholesterol, triglycerides), and inflammation markers (ESR, CRP, fibrinogen) were recorded.

Results

SIRT1 levels showed a significant increase, together with a significant reduction of BMI, excess body weight, and total fat mass either after BIB or diet intervention. The percent excess body weight loss was 33.73?±?19.06 and 22.08?±?11.62 % after BIB and diet, respectively, a trend toward a metabolic and inflammatory amelioration was observed with both treatments. Negative correlation between SIRT1 and % fat mass (BIB, ρ?=??0.537, p?=?0.017; diet, ρ?=??0.638, p?=?0.047) was also seen.

Conclusions

The reduction of fat mass associates with increased plasma SIRT1 indicating that, besides tissue levels, circulating SIRT1 is stimulated by a negative caloric balance. The rise of plasma SIRT1 may represent a parameter associating with fat loss rather than weight lowering regardless of the weight reduction system method used.

     

Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation

Rhythmic and effective cardiac contraction depends on appropriately timed generation and spread of cardiac electrical activity. The basic cellular unit of such activity is the action potential, which is shaped by specialized proteins (channels and transporters) that control the movement of ions across cardiac cell membranes in a highly regulated fashion. Cardiac disease modifies the operation of ion channels and transporters in a way that promotes the occurrence of cardiac rhythm disturbances, a process called "arrhythmogenic remodeling." Arrhythmogenic remodeling involves alterations in ion channel and transporter expression, regulation and association with important protein partners, and has important pathophysiological implications that contribute in major ways to cardiac morbidity and mortality. We review the changes in ion channel and transporter properties associated with three important clinical and experimental paradigms: congestive heart failure, myocardial infarction, and atrial fibrillation. We pay particular attention to K+, Na+, and Ca2+ channels; Ca2+ transporters; connexins; and hyperpolarization-activated nonselective cation channels and discuss the mechanisms through which changes in ion handling processes lead to cardiac arrhythmias. We highlight areas of future investigation, as well as important opportunities for improved therapeutic approaches that are being opened by an improved understanding of the mechanisms of arrhythmogenic remodeling.     

Modulation of 2B4 (CD244) activity and regulated SAP expression in human NK cells

The adapter protein SAP is important for the signal transduction of the family of SLAM-related receptors (SRR), which have important immune-modulating functions. The importance of SAP and SRR for a functional immune reaction becomes obvious in patients suffering from X-linked lymphoproliferative disease, which is characterized by non-functional SAP. Here we investigate the regulation of SAP expression in human NK cells. We demonstrate that SAP mRNA expression and protein levels are low in freshly isolated resting NK cells. IL-2 stimulation leads to an up-regulation of SAP expression, which can be enhanced by IL-12, the stimulation of TLR3 by polyinosinic-polycytidylic acid (poly(I:C))and to a lesser extent by IFN-alpha. EAT-2, a SAP-related adapter protein, is already detectable in resting NK cells and does not change its expression after IL-2 stimulation. The regulation of SAP has functional consequences for the stimulation of NK cell cytotoxicity by 2B4. In resting NK cells, 2B4 stimulation can only enhance NK cell lysis when co-triggered with other activating NK cell receptors. In IL-2-activated NK cells with high SAP expression the triggering of 2B4 alone is sufficient to induce NK cell cytotoxicity, demonstrating a correlation between the regulated SAP expression and the function of 2B4.     

Prevalence of diabetes in france and drug use: study based on the French pharmacovigilance database

AIM: The aim of this study was to investigate the use of the French Pharmacovigilance Database to estimate characteristics of drug utilization in specific diseases. MATERIALS AND METHOD: We identified diabetic patients from the French Pharmacovigilance Database between 2002 and 2005. In this population, we studied demographic characteristics, and the patterns of drug use, particularly hypoglycemiant drug use and other drug exposure. In order to validate this approach, we compared our data to a population of patients with diabetes identified from the French Health Insurance System claims database in one French area. RESULTS: The estimation of prevalence of diabetes was very close in the sources: 2.7% in the French Pharmacovigilance Database and 3.2% in the French Health Insurance System claims database. We found similar results as well for demographic characteristics as for hypoglycemiant drug use and other drug exposure. CONCLUSION: These results suggest that the French Pharmacovigilance Database may be used to investigate drug utilization patterns.     

Influence of circadian rhythm on mortality after myocardial infarction: data from a prospective cohort of emergency calls

Myocardial infarction (MI) occurs more frequently in the morning as a result of the concomitant unfavorable timing of several physiological parameters and/or biochemical conditions. However, little is known about the possible influence of this circadian pattern on prognosis. To evaluate whether the time of symptom onset could potentially influence mortality from acute MI, this prospective study considered all consecutive MIs admitted to the ED of Ferrara, Italy, after a call to the Emergency Coordinating Unit from January 1, 1998, to December 31, 2001. The total sample consisted of 442 MIs (mean age, 68.7 years; males, 72%). Eighty patients (males, 82.5%) died in the ED; the remaining 362 were admitted to the hospital. Of these, 50 (males, 60%) died during their hospital stay. Based on the timing of their symptom onset, cases were categorized both into 24 1-hour intervals and four 6-hour intervals (midnight to 5:59 am, 6:00 am to 11:59 am, noon to 5:59 pm, and 6:00 pm to 11:59 pm), and the circadian distributions of fatal versus nonfatal MIs were compared. The circadian variation of MI peaked between 6:00 am and noon (P < .001), and in this period, there was a trend toward a higher frequency of fatal cases (41.5% vs. 35.2%; chi(2) = 1.911, P = .167). To verify whether this higher frequency of fatal events in the morning hours could be related to possible higher severity of cases observed in that hours, a further separate analysis considering age, infarct site, and peak levels of MB was made. Again, no significant temporal differences among the four 6-hour intervals were found between fatal and nonfatal Mis, although a trend toward older age was observed in morning MIs. Not only the frequency, but also the mortality, of acute MI could be increased in the morning hours. This could be of practical interest for emergency doctors and could have significant implications for acute treatment, because several studies have reported a lowered efficacy of thrombolytic drugs in the morning hours.     

Counter incision is a safe and effective method for alternative reservoir placement during inflatable penile prosthesis surgery

BackgroundAlternative reservoir placement is increasingly popular during inflatable penile prosthesis (IPP) surgery to prevent intraperitoneal positioning, bowel, bladder, or vascular injury in patients with prior pelvic surgeries. Counter incision (CI) can be used for submuscular reservoir placement in high risk patients, however series exploring the safety remain limited.MethodsA database of IPP surgeries was queried for use of a CI during reservoir placement to compare 90-day clinical outcomes in a retrospective case-control study. Primary outcome was device infections, with secondary outcomes including reservoir herniation, hematoma, device malfunction rates, and operative times. Groups were compared using Kruskal-Wallis and Chi-Squared tests, with multivariate logistic regression models to identify predictors of infectious complications.ResultsA total of 534 cases met criteria, of which 51 (9.6%) used a CI for reservoir placement. The CI cohort included significantly more removal and replacements, 45.1% vs. 20.9% (P<0.001). Thirty-one CI patients (61.0%) had undergone prior prostatectomy compared to 134 (27.7%) non-CI patients (P=0.001). The most common reasons for CI were prior prostatectomy and inguinal hernia repair. Median operative time was 17 minutes longer in the CI group (74 vs. 57 minutes, P<0.001). Device infection rates were similar (2.0% vs. 4.1%, P=0.71), as were rates of hematoma (5.9% vs. 2.7%, P=0.19), and device malfunction (0.0% vs. 1.4% P=1.00).ConclusionsComplication rates were similar between CI and non-CI cohorts, even in a subset where approximately half the cases were removal and replacements. For physicians not comfortable with alternative placement through a penoscrotal or infrapubic incision, this offers a reasonable alternative and permits use of three-piece devices in patients with a hostile pelvis.