Search

Introduction: The role of the chloride anion on the deleterious effects of excessive consumption of salt (NaCl) and whether its effects are independent each other of the presence of sodium remains to date, unknown and unclear. Objective: To demonstrate that both a chloride overload and a sodium overload in the diet produce deleterious effects, by different mechanisms, on systolic blood pressure (SBP), renal function and markers of oxidative stress in the kidney. Materials and Methods: Male Wistar rats were divided into four groups (n = 8 / group) and fed with different diets for three weeks: C: control (standard diet), and diets: NaCl: hypersodic-hyperchloric; Na: hypersodic without chloride and Cl: hyperchloric without sodium. Systolic blood pressure (SBP) and renal function were determined, and the production of thiobarbituric acid reactive species (TBARS) and the activity and expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes were evaluated in renal cortex tissue. Results: SBP increased (*) in the two groups fed with chloride. The fractional excretion of sodium and chloride increased (*) in the NaCl and Na groups. increased (*) in the renal cortex with the three diets. No changes were observed in the activity and expression of SOD and CAT. GPx activity increased (*) in the two groups that received chloride; (* p

Background: In our laboratory, we have developed subcutaneous implants of carvedilol capable of maintaining stable concentrations of the β-blocker during 3 weeks. Objective: The aim of this study was to evaluate the in vivo release and the cardioprotective efficacy of subcutaneous implants of carvedilol developed with poly-epsilon-caprolactone (PCL) and Soluplus (SP) polymers in spontaneously hypertensive rats (SHR). Methods: Twelve spontaneously hypertensive male rats (250-300 g) underwent placement of subcutaneous implant of PCL:SP 100:50 mg (control group, n=6) or carvedilol:PCL:SP (100mg:100mg:50mg) (carvedilol group, n=6), every 3 weeks. The plasma profile of each implant and its effect on systolic blood pressure (SBP) was evaluated for 62 days. At the end of treatment, echocardiographic parameters were determined, and direct SBP and direct mean blood pressure (MBP) were measured. Results: The group that received the implant containing 100 mg of carvedilol presented plasma concentrations of the drug in the range of 100- 500 ng/mL throughout 62 days of treatment, after which the SBP was 20 mmHg lower than in the control group (217±3 mm Hg vs. 237±6 mm Hg; p

Additional file 1.

Additional file 3.

Additional file 2.

The present review will focus on the role of chloride anion in cardiovascular disease, with special emphasis in the development of hypertensive disease and vascular inflammation. It is known that acute and chronic overload of sodium chloride increase blood pressure and have pro-inflammatory and pro-fibrotic effects on different target organs, but it is unknown how chloride may influence these processes. Chloride anion is the predominant anion in the extracellular fluid and its intracellular concentration is dynamically regulated. As the queen of the electrolytes, it is of crucial importance to understand the physiological mechanisms that regulate the cellular handling of this anion including the different transporters and cellular chloride channels, which exert a variety of functions, such as regulation of cellular proliferation, differentiation, migration, apoptosis, intracellular pH and cellular redox state. In this article, we will also review the relationship between dietary, serum and intracellular chloride and how these different sources of chloride in the organism are affected in hypertension and their impact on cardiovascular disease. Additionally, we will discuss the approach of potential strategies that affect chloride handling and its potential effect on cardiovascular system, including pharmacological blockade of chloride channels and non-pharmacological interventions by replacing chloride by another anion.

Aim: Despite the rise in cancer survivorship, few reviews have examined the quality of studies of cancer pain management and practices around the globe. With a void in trials spanning multiple geographical settings, this review evaluates the quality of cancer trials across three continents. Materials & methods: A literature review and search of established databases was conducted to identify eligible studies. The Cochrane method, the Jadad Score and a cancer pain-specific ad hoc tool were used to evaluate quality of studies. Results: Eighteen studies representing a total of 4693 individuals were included in the review. Study quality correlated positively with study sample size and palliative care index. Trials in all three continents were prone to use opioids for pain management, whereas trials in Europe and North America utilized other adjuvant therapies such as antidepressants and steroids. Conclusion: This review underscores the need for better multidimensional quality assessment tools for cancer pain trials.

We aimed to investigate the efficacy and tolerability of empagliflozin, an oral, potent, and selective inhibitor of sodium-glucose co-transporter 2, in patients with type 2 diabetes who had not received drug treatment in the preceding 12 weeks.In our multicentre, randomised, placebo-controlled, phase 3 trial, we enrolled adults (aged ≥18 years) who had not received oral or injected anti-diabetes treatment in the previous 12 weeks. Eligible patients had HbA1c concentrations of 7-10%. We randomly allocated patients (1:1:1:1) with a computer-generated random sequence, stratified by region, HbA1c, and estimated glomerular filtration rate at screening, to placebo, empagliflozin 10 mg, empagliflozin 25 mg, or sitagliptin 100 mg once daily for 24 weeks. Patients and investigators were masked to treatment assignment. The primary endpoint was change from baseline in HbA1c at week 24 by ANCOVA in all randomly allocated patients who were treated with at least one dose of study drug and had a baseline HbA1c value. This study is completed and registered with ClinicalTrials.gov, number NCT01177813.Between Aug 12, 2010, and March 19, 2012, we randomly allocated 228 patients to receive placebo, 224 to receive empagliflozin 10 mg, 224 to receive empagliflozin 25 mg, and 223 to receive sitagliptin. Compared with placebo, adjusted mean differences in change from baseline HbA1c at week 24 were -0·74% (95% CI -0·88 to -0·59; p0·0001) for empagliflozin 10 mg, -0·85% (-0·99 to -0·71; p0·0001) for empagliflozin 25 mg, and -0·73% (-0·88 to -0·59; p0·0001) for sitagliptin. 140 (61%) patients in the placebo group reported adverse events (four [2%] severe and six [3%] serious), as did 123 (55%) patients in the empagliflozin 10 mg group (eight [4%] severe and eight [4%] serious), 135 (60%) patients in the empagliflozin 25 mg group (seven [3%] severe and five [2%] serious), and 119 (53%) patients in the sitagliptin group (five [2%] severe and six [3%] serious).Empagliflozin provides a tolerable and efficacious strategy to reduce HbA1c in patients with type 2 diabetes who had not previously received drug treatment.Boehringer Ingelheim and Eli Lilly.

Most microfluidic devices developed to date for the analysis of live cells incorporate channels with relatively simple constant rectangular or semi-circular cross-sections, relying on complex channel network geometries rather than alteration of the shapes of the channels themselves for development of diverse functional fluidic controls, e.g., spatial gradients of bioactive ligands. In this study we describe a simple alternative method to create highly defined and predictable gradients of surface bound molecules. This method relies on the generation of a considerable variation in the spatial distribution of flow velocities within a channel with a triangular cross-section. The triangular shape can be easily implemented by using bulk wet etching and polydimethylsiloxane (PDMS) replica molding techniques. By analytical modeling and simulation, we predict that the deposition of the solute onto a channel boundary depends on the local flow rate values, yielding gradient spanning the whole width of the channel. This prediction was validated by direct visualization of the flow rate and fibronectin-rhodamine deposition in a fabricated microchannel. Using this experimental platform, we assessed cell migration in response to a fibronectin gradient deposited in the microchannels. We find that this gradient could induce robust haptotaxis of Chinese Hamster Ovary (CHO) cells towards the areas of higher fibronectin surface density. We propose that the described simple gradient generation method can help to avoid complexity present in many current device designs, allowing to introduce more easily other potentially useful design features.