Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma

AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for diffe...     

Early intravenous beta-blockers in patients with acute coronary syndrome—A meta-analysis of randomized trials

Background

Intravenous (IV) beta-blockade is currently a Class IIa recommendation in early management of patients with acute coronary syndromes (ACS) without obvious contraindications.

Methods

We searched the PubMed, EMBASE and the Cochrane Register for Controlled Clinical Trials for randomized clinical trials from 1965 through December, 2011, comparing intravenous beta-blockers administered within 12 hours of presentation of ACS with standard medical therapy and/or placebo. The primary outcome assessed was the risk of short-term (in-hospital mortality-with maximum follow up duration of 90 days) all-cause mortality in the intervention group versus the comparator group. The secondary outcomes assessed were ventricular tachyarrhythmias, myocardial reinfarction, cardiogenic shock, and stroke. Pooled treatment effects were estimated using relative risk with Mantel–Haenszel risk ratio, using a random-effects model.

Results

Sixteen studies enrolling 73,396 participants met the inclusion ⁄ exclusion criteria. In- hospital mortality was reduced 8% with intravenous beta-blockers, RR = 0.92 (95% CI, 0.86–1.00; p = 0.04) when compared with controls. Moreover, intravenous beta-blockade reduced the risk of ventricular tachyarrhythmias (RR = 0.61; 95 % CI 0.47–0.79; p = 0.0003) and myocardial reinfarction (RR = 0.73, 95 % CI 0.59–0.91; p = 0.004) without increase in the risk of cardiogenic shock, (RR = 1.02; 95% CI 0.77–1.35; p = 0.91) or stroke (RR = 0.58; 95 % CI 0.17–1.98; p = 0.38).

Conclusions

Intravenous beta-blockers early in the course of appropriate patients with ACS appears to be associated with significant reduction in the risk of short-term cardiovascular outcomes, including a reduction in the risk of all-cause mortality.     

Hospital mortality prognostication in sepsis using the new biomarkers suPAR and proADM in a single determination on ICU admission

Purpose

The soluble form of the urokinase-type plasminogen activator receptor (suPAR) and proadrenomedullin (proADM) are two new and promising sepsis biomarkers. We assessed the prognostic value of a single determination of proADM and suPAR, comparing them with C-reactive protein (CRP) and procalcitonin (PCT), and evaluating whether their addition to severity scores (APACHE II and SOFA) could improve their prognostic accuracy.

Methods

A single-centre prospective observational study conducted in an adult intensive care department at Marques de Valdecilla University Hospital in Spain. APACHE II and SOFA scores, CRP, PCT, suPAR and proADM levels on the day of ICU admission were collected.

Results

A total of 137 consecutive septic patients were studied. The best area under the curve (AUC) for the prediction of in-hospital mortality was for APACHE II (0.82) and SOFA (0.75) scores. The ROC curve for suPAR yielded an AUC of 0.67, higher than proADM (0.62), CRP (0.50) and PCT (0.44). Significant dose-response trends were found between hospital mortality and suPAR (OR Q4 = 4.83, 95 % CI 1.60–14.62) and pro-ADM (OR Q4 = 3.00, 95 % CI 1.06–8.46) quartiles. Non-significant associations were found for PCT and CRP. The combination of severity scores and each biomarker did not provide superior AUCs.

Conclusions

SuPAR and, to a lesser extent, proADM levels on ICU admission were better tools in prognosticating in-hospital mortality than CRP or PCT. However, neither of the two new biomarkers has been demonstrated to be excessively useful in the current setting. The prognostic accuracy was better for severity scores than for any of the biomarkers.     

A 12-week placebo-controlled study of rupatadine 10 mg once daily compared with cetirizine 10 mg once daily, in the treatment of persistent allergic rhinitis

Background:  With the current increasing incidence of allergies worldwide, new treatments showing efficacy and long term safety are needed for chronic conditions such as persistent allergic rhinitis (PER). New generation H1-antihistamines have demonstrated anti-allergic properties, which could possibly enhance their effectiveness in long-term periods of treatment.
Objective:  To investigate the efficacy of rupatadine, in controlling symptoms of PER over a 12-week period.
Methods:  A randomized, double blind, parallel-group, placebo-controlled study was carried out in patients aged older than 12 years with PER. Main inclusion criteria were: instantaneous total symptom score (i6TSS) ≥45, nasal obstruction score ≤12, and overall assessment of PER ≥2 as moderate during the first visit. The primary efficacy endpoint was the 12-week average change from baseline of the patients' i6TSS.
Results:  In all, 736 patients were selected. Of them, 543 (73.8%) were randomized in three different groups: placebo ( n  = 185), cetirizine ( n  = 175) and rupatadine ( n  = 183). Rupatadine ( P  = 0.008) but not cetirizine ( P  = 0.07) statistically reduced the baseline i6TSS vs placebo (47.8%, 44.7% and 38.8%, respectively), after 12 weeks. Onset of action was observed at the first 24 h for both treatments (rupatadine vs placebo, P  = 0.013; cetirizine vs placebo, P  = 0.015). Furthermore, instantaneous total nasal symptoms score (iTNSS) (including nasal blockage) mean change from baseline showed a significant reduction with rupatadine 10 mg in comparison with placebo, along all treatment duration of 12 weeks. Study treatments were well tolerated.
Conclusion:  Rupatadine significantly relieves symptoms of PER, providing a rapid onset of action and maintains its effects over a long period of 12-weeks.     

How photoperiods affect the immature development of forensically important blowfly species Chrysomya albiceps (Calliphoridae)

The purpose of this study was to verify the influence of different photoperiods on larval body weight, post-embryonic development, and viability of Chrysomya albiceps. The bioassays were performed in acclimatized chamber at 27?±?1?°C and 60?±?10?% relative humidity regulated by three different light and dark cycles for a period of 24?h-12:12, 24:00, and 00:24. Four replications with 50 newly hatched larvae each were used per photoperiod. The larvae were placed in container containing bovine ground meat (50?g). When mature larvae spontaneously abandoned the diet, they were individually weighed and separated into glass tubes until emergence. The larvae that did not abandon the diet were not weighed. The larvae from 24?h of photophase did not abandon the diet and pupated inside, so these larvae were not weighed and the larval and pupal developments were not registered. The mean of larval body weight did not vary between the 24?h scotophase and 12?h photophase. The mean duration of larval developmental time varied significantly when comparing the 24?h scotophase and the 12?h photophase, and the pupal developmental time also varied for the same photoperiods; in both stages, the duration of development was faster in the 24?h scotophase. The developmental time of neo-larvae to adult was verified in all photoperiods and gradually increased as photophase increased. There was a trend to augment of viability with the reduction of photophase length.     

Importance of the distal airway in COPD

Chronic obstructive pulmonary disease (COPD) is characterized by inflammation causing airflow obstruction. However, the initial histological lesion of COPD occurs in the respiratory bronchiole and spirometry is unable to detect involvement of this area until the disease is advanced. Major advances have been made in characterizing the inflammatory process in the small airways. However, in clinical practice, a non-invasive marker of small airways involvement, which would allow injury and the effect of treatment to be monitored, is lacking. To date, the combination of bronchodilators and inhaled corticosteroids is recommended for the most severe cases, although the effects of this therapeutic option on the small airways are not well known. New treatments that reach the distal airways and novel techniques to assess the small airways will allow a more complete approach to this disease.     

Systemic fibrinolysis through intraosseous vascular access in ST-segment elevation myocardial infarction

In emergency situations, intraosseous cannulation represents an alternative route of vascular access when peripheral vein insertion is difficult. We present the first documented case of intraosseous systemic fibrinolysis in a patient with ST-segment elevation myocardial infarction. In this case, repetitive episodes of ventricular fibrillation occurred soon after first contact with emergency care providers. Given that the patient had difficult peripheral venous access, an intraosseous catheter was inserted. Fibrinolytics and antiarrhythmic drugs were administered though this line, resulting in resolution of coronary ischemia and electrical instability, without complications. Intraosseous cannulation represents a novel route for administration of systemic fibrinolysis in cases of difficult peripheral venous access in the out-of-hospital setting.