Eight new bibenzyl derivatives from Dendrobium candidum

Eight bibenzyl derivatives, namely dendrocandins J–Q (1–8), were isolated from the stems of Dendrobium candidum. Their structures were elucidated by 1D and 2D NMR experiments and mass spectrometry. Compounds 1–8 were examined for antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay, and the IC₅₀ values were 36.8, 70.2, 45.0, 60.5, 87.6, 50.4, 22.3, and 30.3 μM, respectively.     

Direct renin inhibition: an evaluation of the safety and tolerability of aliskiren

ABSTRACT

Background: Aliskiren, an antihypertensive drug approved in the United States and Europe, is the first in a new class known as direct renin inhibitors. Aliskiren has been evaluated for safety and tolerability in more than 6400 patients. It has demonstrated a favorable safety and tolerability profile alone or in combination with other drugs.

Objective: This article reviews the currently available safety and tolerability data for aliskiren.

Methodology: Using the search term aliskiren, MEDLINE (no timeframe set) and major cardiovascular congresses (2005–2008) were searched. Articles and abstracts with safety and drug interaction data were included.

Findings: Aliskiren may share common adverse effects observed with angiotensin-converting enzyme (ACE)-inhibitor and angiotensin receptor blocker (ARB) therapy. In placebo-controlled trials, those commonly reported for aliskiren at the approved dosage were headache, diarrhea, and fatigue, with incidences similar to those of placebo. Aliskiren has been well tolerated in black, geriatric, diabetic, or obese patients and patients with renal or hepatic impairment. Aliskiren neither inhibits nor induces the cytochrome P450 system; it does not inhibit P-glycoprotein, but is a substrate for this drug transporter. Adding a direct renin inhibitor to another renin–angiotensin–aldosterone system (RAAS) inhibitor may further improve cardiovascular outcomes, renal outcomes, or both, without increasing the incidence of adverse effects.

Conclusions: Aliskiren is well tolerated, has an adverse effect profile comparable to that of placebo, and has a low potential for drug interactions. Data from ongoing trials evaluating the effects of aliskiren on surrogate markers, morbidity, and mortality will further define the role of direct renin inhibition in the antihypertensive armamentarium.     

Impact of Temporal Lobe Epilepsy on Phonological Processing and Reading: A Case Study of Identical Twins

In order to evaluate the possible consequences of temporal lobe epilepsy on reading acquisition, we first compared the reading skills and phonological awareness abilities in a set of 13-year-old identical twins, one of whom is affected by temporal lobe epilepsy (LB). We then compared their performances to those of an age- and IQ-matched control group. Both siblings have an intellectual quotient above average as well as normal memory and linguistic abilities. Results showed that the reading age of LB (assessed by the Lefabvrais French reading test) was more than two years behind expectations whereas that of her sister was above average. Further, in contrast to her sister and healthy control subjects, LB exhibited specific deficits in elaborate metaphonological awareness abilities (non-word repetition, rhyme production, phonemic segmentation and syllabic inversion). These could be linked to temporal lobe dysfunction, thus confirming the important role of the temporal lobes in reading acquisition.     

Solubilization of flurbiprofen into aptamer-modified PEG–PLA micelles for targeted delivery to brain-derived endothelial cells in vitro

Abstract

Novel aptamer-functionalized polyethylene glycol–polylactic acid (PEG–PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer’s disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients.     

Pharmacokinetics,tissue distribution and excretion study of a furostanol glycoside-based standardized fenugreek seed extract in rats

Abstract

The furostanol glycoside isolated from the seed of fenugreek (SFSE-G) has an array of pharmacological activities. To date, no validated high-performance liquid chromatography (HPLC) method has been reported for quantification of SFSE-G in biological samples. Hence, the aim of the present study was to study the pharmacokinetics, tissue distribution and excretion profiles of SFSE-G after oral administration in rats. A rapid, sensitive, selective, robust and reproducible HPLC method has been developed for determination of SFSE-G in the rat biological samples. The chromatographic separation was accomplished on a reversed-phase C18 column using formic acid and acetonitrile (80:20) as mobile phase at a flow rate of 1.0?mL/min and 274?nm as a detection wavelength. The assay was linear for SFSE-G with the correlation coefficients (R²) >0.996. The analytes were stable during samples storage and handling, and no matrix effects were observed. After oral dosing of SFSE-G at a dose of 200?mg/kg, the elimination half-life was app. 40.10?h. It showed relatively slowly distribution and eliminated in urine and feces after 24?h, and could be detected until 108?h post-dosing. Following oral single dose (200?mg/kg), SFSE-G was detected in lung and brain which indicated that it could cross the blood–brain barrier. It is a major route of elimination is excretion through urine and feces. In conclusion, oral administration of SFSE-G showed slow distribution to tissues, such as lung and brain, but showed fast renal elimination.     

Neurological and humoral control of blood pressure

There is a relationship between arterial blood pressure, cardiac output and vascular resistance which can be described mathematically, and helps us to understand the short-term control of blood pressure in the terms of a hydraulic system. The sensors in this system are the arterial baroreceptors which mediate changes in the hydraulic system though control of the autonomic nervous system, which in turn influences heart rate, inotropy and vascular tone. Altering the distribution of blood between the arterial and venous systems compensates for acute changes in total blood volume. The total blood volume is controlled predominantly by the kidney, with the renin–angiotensin–aldosterone system acting as both the ‘sensor’ of blood pressure/volume (via renin release in the juxtaglomerular apparatus) and the ‘effector’ of blood pressure/volume (via aldosterone secretion by the adrenal cortex). Overall control is shared; the baroreceptors being responsible for mediating short-term changes, and renal mechanisms determining the long-term control of blood pressure. These systems have to be adaptable in order to deal with physiological variation in the delivery of blood to tissues from rest to exercise, and with the large shifts in blood volume seen in acute haemorrhage. Pathophysiological changes in these systems lead to maladaptive responses, with systemic hypertension the most commonly seen.     

The pediatric surgeon–patient relationship

Though technical aspects of surgical practice are commonly emphasized, communication is the most frequent “procedure” employed by surgeons. A good patient–physician relationship enhances the quality of surgical care by improving outcomes and patient and family satisfaction. There are general principles that can enhance communication with all children and families. Employing a developmentally sensitive approach that adjusts communication style based on a child's cognitive abilities and emotional concerns can further enhance the relationship with children of different ages. These communication skills can be learned and are improved by practice and self-reflection.     

Components of variance

Components of variance have a long history and find application in all areas of scientific investigation. This review introduces components of variance and their importance firstly by examples on blood pressure, proteomic data, breath analysers and esophageal pH monitoring devices. We then present an intuitive geometric representation of analysis of variance and explain how the components of variance can be estimated from the analysis of variance table. We conclude by suggesting practice points for studies which incorporate components of variance, and recommend commonly used statistical software to undertake such analysis.     

Assessment of collateral blood flow in patients with distal branch occlusion of the middle cerebral artery

Purpose

Aim of this study was to evaluate the collateral blood flow between more distal branches of the middle cerebral artery (MCA) in the case of peripheral MCA branch occlusion on dynamic 4D angiograms. We sought to individually predict the finally resulting infarction volume with regard to the extent of collateral blood flow.