Progress in cardiac pacing

This review summarizes recent scientific developments in ambulatory monitoring and its legal implications in appropriately selected patients. It also considers how new cardiac pacing devices can be used in the clinical monitoring of atrial fibrillation, sleep apnea and, in transplant patients, heart failure and transplant rejection. In addition, the system of accreditation for cardiac pacing services in Spain is outlined, with a focus on process development and quality indicators. Finally, the scientific articles on cardiac pacing that made the greatest impact in 2007 are summarized.     

Progesterone modulates cadmium-induced oxidative stress and inflammation in hepatic tissues of Wistar rats

In recent times, there has been an increased risk of human exposure to cadmium especially in developing countries. We studied the role of progesterone as an anti-inflammatory and antioxidant agent in cadmium induced toxicity. Cadmium toxicity was induced with cadmium chloride (30 mg/kg) per oral while the control group was given distilled water. The Cd group was given CdCl₂ only, P₄ group; progesterone only (10 mg/kg intraperitoneally) and Cd+P₄ group; CdCl₂ and progesterone. All treatments lasted for 21 days. Following sacrifice, liver function tests and antioxidant status were assessed using standard kits; TNFα was immunolocalized across the study groups and the staining intensity measured using Image J software. Cadmium administration induced oxidative stress by a significant elevation in MDA and GC6P levels and a significant reduction in SOD, CAT, and GSH. These were attenuated by progesterone administration. While cadmium exposure caused an increase in serum ALT, AST, and ALP activities, progesterone significantly alleviated these effects. Inflammation shown by significant immunoreactivity in the TNFα positive cells in the liver in the cadmium group was reversed by progesterone. We conclude that cadmium toxicity induces oxidative stress that was attenuated by progesterone.     

T‐705‐modified ssRNA in complex with Lassa virus nucleoprotein exhibits nucleotide splaying and increased water influx into the RNA‐binding pocket

Lassa virus infection is clinically characterized by multiorgan failure in humans. Without an FDA‐approved vaccine, ribavirin is the frontline drug for the treatment but with attendant toxicities. 6‐Fluoro‐3‐hydroxy‐2‐pyrazinecarboxamide (T‐705) is an emerging alternative drug with proven anti‐Lassa virus activity in experimental model. One of the mechanisms of action is its incorporation into nascent single‐strand RNA (ssRNA) which forms complex with Lassa nucleoprotein (LASV‐NP). Here, using molecular dynamics simulation, the structural and electrostatics changes associated with LASV‐NP‐ssRNA complex have been studied when none, one, or four of its bases has been substituted with T‐705. The results demonstrated that glycosidic torsion angle χ (O4′‐C1′‐N1‐C2) rotated from high‐anti‐ (?110° and ?60°) to the syn‐ conformation (+30) with increased T‐705 substitution. Similarly, increased T‐705 substitution resulted in increased splaying (55°–70°), loss of ssRNA‐LASV‐NP H‐bond interaction, increased water influx into the ssRNA‐binding pocket, and decreased electrostatic potentials of ssRNA pocket. Furthermore, strong positively correlated motion observed between α6 residues (aa: 128–145) and its contact ssRNA bases (5–7) is weakened in Apo biosystem and transitioned into anticorrelated motions in ssRNA‐bound LASV‐NP biosystem. Finally, LASV genome may become more accessible to cellular ribonuclease access with T‐705 incorporation due to loss of NP interaction.     

The Effect of Amino Acids on Wound Healing: A Systematic Review and Meta-Analysis on Arginine and Glutamine

Under stress conditions, the metabolic demand for nutrients increases, which, if not met, may slow down or indeed stop the wound from healing, thus, becoming chronic wounds. This study aims to perform a systematic review and meta-analysis of the effect of arginine and glutamine supplementation on wound healing. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for the systematic review and ten electronic databases were used. Five and 39 human studies met the inclusion criteria for arginine and glutamine, respectively. The overall meta-analysis demonstrated a significant effect of arginine supplementation on hydroxyproline content (MD: 4.49, 95% CI: 3.54, 4.45, p < 0.00001). Regarding glutamine supplementation, there was significant effect on nitrogen balance levels (MD: 0.39, 95% CI: 0.21, 0.58, p < 0.0001), IL-6 levels (MD: −5.78, 95% CI: −8.71, −2.86, p = 0.0001), TNFα levels (MD: −8.15, 95% CI: −9.34, −6.96, p < 0.00001), lactulose/mannitol (L/M) ratio (MD: −0.01, 95% CI: −0.02, −0.01, p < 0.00001), patient mortality (OR: 0.48, 95% CI: 0.32, 0.72, p = 0.0004), C-reactive protein (CRP) levels (MD: −1.10, 95% CI: −1.26, −0.93, p < 0.00001) and length of hospital stay (LOS) (MD: −2.65, 95% CI: −3.10, −2.21, p < 0.00001). Regarding T-cell lymphocytes, a slight decrease was observed, although it failed to reach significance (MD: −0.16, 95% CI: −0.33, 0.01, p = 0.07). Conclusion: The wound healing might be enhanced in one or at various stages by nutritional supplementation in the right dose.     

Determination of the nutraceutical, glucosamine hydrochloride, in raw materials, dosage forms and plasma using pre-column derivatization with ultraviolet HPLC

A selective and specific high performance liquid chromatography method was developed to quantitate glucosamine hydrochloride in raw materials, dosage forms and plasma. Reverse phase chromatography using pre-column derivatization with phenylisothiocyanate, and ultraviolet detection (lambda = 254 nm) was used to quantify the eluate. The mobile phase consisted of MeOH/H2O/CH3COOH (10:89.6:0.04) and was pumped at a flow rate of 1.2 ml/min. The standard curves for glucosamine hydrochloride showed linearity (r > or = 0.99) over the selected concentration range from 6.65 to 16.63 microg/ml for raw materials and dosage forms. The precision of the dosage form assay, expressed as the % relative standard deviation (R.S.D.), was < 5% at all concentrations. The intra-day and inter-day accuracy, as indicated by the relative error (R.E.), ranged from - 2.54 to 2.70% for glucosamine hydrochloride. For the plasma assay, beagle dog plasma was used to prepare standard curves in the concentration range of 1.25-20 microg/ml. Precipitation of plasma proteins was accomplished with acetonitrile to separate interfering endogenous products from the compound of interest. The supernatant was derivatized using phenylisocyanate in phosphate buffer (pH = 8.3) and subsequently evaporated to dryness under a nitrogen stream at 42 degrees C. The residue was dissolved in 250 microl mobile phase and injected onto the chromatographic system. The assay was linear in concentration ranges of 1.25-20 microg/ml (r > or = 0.999). Intra- and inter-day precision was < or = 5.23 and 5.65%, respectively and the intra- and inter-day accuracy, indicated by R.E., ranged from - 8.6 to 10.35%. The method was found to be specific and with excellent linearity, accuracy and precision and is well suited for the quantitation of glucosamine hydrochloride in raw materials, dosage forms, and pharmacokinetic studies.