Clinical review: beyond immediate survival from resuscitation-long-term outcome considerations after cardiac arrest

A substantial body of literature concerning resuscitation from cardiac arrest now exists. However, not surprisingly, the greater part concerns the cardiac arrest event itself and optimising survival and outcome at relatively proximal time points. The aim of this review is to present the evidence base for interventions and therapeutic strategies that might be offered to patients surviving the immediate aftermath of a cardiac arrest, excluding components of resuscitation itself that may lead to benefits in long-term survival. In addition, this paper reviews the data on long-term impact, physical and neuropsychological, on patients and their families, revealing a burden that is often underestimated and underappreciated. As greater numbers of patients survive cardiac arrest, outcome measures more sophisticated than simple survival are required.     

Interventional radiological removal of a foreign body from a peripheral bronchus

We describe the extraction of an impacted tooth from a bronchiole of a ventilated, critically ill patient. Following failed attempts using flexible and rigid bronchoscopy a radiological approach was explored. The successful method described below used guiding catheters, an extraction basket and an occlusion balloon, deployed under fluoroscopic guidance.     

The effect of exogenous cholesterol and lipid-modulating agents on enterocytic amyloid-beta abundance

Dietary cholesterol may influence Alzheimer's disease risk, because it regulates the synthesis of amyloid-beta. It was recently demonstrated in enterocytes of wild-type mice that intracellular amyloid-beta expression is enhanced in response to a high-fat diet made up of SFA and cholesterol. Intestinally derived amyloid-beta may be associated with postprandial lipoproteins in response to dietary fats and could be a key regulator in chylomicron metabolism. The present study was designed to investigate the role of cholesterol in modulating amyloid-beta abundance in enterocytes. Wild-type mice were fed a low-fat diet supplemented with 2 % (w/w) cholesterol. The effects of cholesterol absorption inhibition and cholesterol biosynthesis inhibition utilising ezetimibe and atorvastatin, respectively, were also studied. Quantitative immunohistochemistry was utilised to determine enterocytic amyloid-beta homeostasis. We found that enterocytic amyloid-beta concentration was significantly attenuated in mice fed the 2 % (w/w) cholesterol diet. However, blocking cholesterol absorption reversed the cholesterol-feeding effect. Consistent with a suppressive effect of cholesterol on enterocytic amyloid-beta abundance, atorvastatin, an inhibitor of cholesterol biosynthesis, enhanced amyloid-beta. However, providing exogenous cholesterol abolished the atorvastatin-induced effect. In contrast to the suppression of enterocytic amyloid-beta by dietary cholesterol, mice fed a diet enriched in SFA had markedly greater abundance. Collectively, the findings suggest that exogenous and endogenous cholesterol reduce amyloid-beta concentration in enterocytes by suppressing production, or enhancing secretion associated with postprandial lipoproteins. Intestinally derived amyloid-beta will contribute to the pool of plasma protein and may influence cerebral amyloid homeostasis by altering the bi-directional transfer across the blood-brain barrier.     

Colocalisation of plasma derived apo B lipoproteins with cerebral proteoglycans in a transgenic-amyloid model of Alzheimer's disease

Alzheimer's disease (AD) is characterized by cerebral proteinaceous deposits comprised of amyloid beta (Aβ). Evidence suggests that enhanced blood-to-brain delivery of Aβ occurs when plasma concentration is increased, exacerbating amyloidosis. In blood, significant Aβ is associated with apolipoprotein (apo) B lipoproteins. In this study, immunofluorescent microscopy was utilised to explore if there is an association between apo B lipoproteins and proteoglycan expression within Aβ-rich plaques in transgenic-amyloid mice. Focal accumulation of apo B was found with Aβ-plaque in APP/PS1 mice. There was enrichment in the proteoglycans, agrin, perlecan, biglycan and decorin within the core of dense Aβ-plaque. Perlecan, biglycan and decorin were positively associated with apo B lipoprotein abundance within amyloid plaque consistent with a cause-for-retention effect. These findings show that proteoglycans are an integral component of Aβ deposits in APP/PS1 mice. This study suggests that some proteoglycans contribute to Aβ retention, whilst other proteoglycans have different functions in the aetiology of AD.     

Antinociceptive Activities of Aqueous and Ethanol Extracts of Piper betle. Leaves in Rats

Abstract

Leaves of Piper betle. Linn (Piperaceae) possess a broad spectrum of pharmacological and therapeutic properties. However, its antinociceptive activity has not been investigated so far. The aim of this study therefore, was to examine the antinociceptive activity of hot water extract (HWE) and cold ethanol extract (CEE) of P. betle. leaves using rats and three models of nociception (tail flick, hot plate, and formalin tests). Different concentrations of HWE (125, 200, 300, 500 mg/kg) and CEE (125, 200, 300, 500 mg/kg) were made and orally administrated to rats, and the reaction times were determined. The results showed that the extracts have marked antinociceptive activity when evaluated in the hot plate and the formalin tests but not in the tail-flick test. The overall antinociceptive effect of CEE was higher than that of HWE. The antinociceptive effect was mediated via opioid mechanisms.     

Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats

Leaves of Piper betle (Piperaceae) possess several bioactivities and are used in traditional medicinal systems. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study therefore, was to investigate the antidiabetic activity of Piper betle leaves. This was tested in normoglycaemic and strepozotocin (STZ)-induced diabetic rats using oral administration of hot water extract (HWE) and cold ethanolic extract (CEE). In normoglycaemic rats, both HWE and CEE significantly lowered the blood glucose level in a dose-dependent manner. In glucose tolerance test, both extracts markedly reduced the external glucose load. The antidiabetic activity of HWE is comparable to that of CEE. Moreover, HWE failed to inhibit the glucose absorption from the small intestine of rats. Both extracts were found to be non-toxic and well tolerated after following chronic oral administration (no overt signs of toxicity, hepatotoxicity or renotoxicity). However, the weight of the spleen had increased in treated groups possibly indicating lymphoproliferative activity. It is concluded that HWE and CEE of Piper betle leaves possess safe and strong antidiabetic activity.     

Amyloid-β colocalizes with apolipoprotein B in absorptive cells of the small intestine

Background  

Amyloid-β is recognized as the major constituent of senile plaque found in subjects with Alzheimer's disease. However, there is increasing evidence that in a physiological context amyloid-β may serve as regulating apolipoprotein, primarily of the triglyceride enriched lipoproteins. To consider this hypothesis further, this study utilized an in vivo immunological approach to explore in lipogenic tissue whether amyloid-β colocalizes with nascent triglyceride-rich lipoproteins.     

Alpinia calcarata Roscoe: a potent antiinflammatory agent

Aim of the study

Alpinia calcarata Roscoe (Family: Zingiberaceae) rhizomes are often used in Sri Lankan traditional systems of medicine as a remedy for bronchitis, cough, respiratory ailments, diabetics, asthma and arthritis. Generally drugs that are used for arthritis have antinociceptive and antiinflammatory properties. However, validity of the antiinflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the antiinflammatory potential of Alpinia calcarata rhizomes using hot water extract (AWE) and hot ethanolic extract (AEE).

Materials and Methods

The antiinflammatory activity of Alpinia calcarata was evaluated by use of the carrageenan-induced paw oedema model in rats. In addition, the mechanism/s by which Alpinia calcarata is mediated the antinflammatory activity was assessed by determining its effects on (a) membrane stabilizing, (b) antihistamine and (c) prostaglandin synthesis inhibition activity.

Results

All the tested doses of AWE and AEE (250, 500, 750, and 1000 mg/kg) produced a significant (P ≤ 0.05) inhibition of the inflammation, most pronounced at 4 h after the injection of carrageenan. The antiinflammatory effect induced by 500 mg/kg of AEE was superior than the reference drug, indomethacin at 4 h. Inhibition of histamine and prostaglandin synthesis production is probable mechanisms by which Alpinia calcarata mediates its antiinflammatory action.

Conclusion

These findings rationalize the traditional usage of Alpinia calcarata as an antiinflammatory agent for the first time.     

Clinical review: Beyond immediate survival from resuscitation – long-term outcome considerations after cardiac arrest

A substantial body of literature concerning resuscitation from cardiac arrest now exists. However, not surprisingly, the greater part concerns the cardiac arrest event itself and optimising survival and outcome at relatively proximal time points. The aim of this review is to present the evidence base for interventions and therapeutic strategies that might be offered to patients surviving the immediate aftermath of a cardiac arrest, excluding components of resuscitation itself that may lead to benefits in long-term survival. In addition, this paper reviews the data on long-term impact, physical and neuropsychological, on patients and their families, revealing a burden that is often underestimated and underappreciated. As greater numbers of patients survive cardiac arrest, outcome measures more sophisticated than simple survival are required.     

A method to remove the influence of fixative concentration on postmortem T2 maps using a kinetic tensor model

Formalin fixation has been shown to substantially reduce T₂ estimates, primarily driven by the presence of fixative in tissue. Prior to scanning, post‐mortem samples are often placed into a fluid that has more favourable imaging properties. This study investigates whether there is evidence for a change in T₂ in regions close to the tissue surface due to fixative outflux into this surrounding fluid. Furthermore, we investigate whether a simulated spatial map of fixative concentration can be used as a confound regressor to reduce T₂ inhomogeneity. To achieve this, T₂ maps and diffusion tensor estimates were obtained in 14 whole, formalin‐fixed post‐mortem brains placed in Fluorinert approximately 48 hr prior to scanning. Seven brains were fixed with 10% formalin and seven brains were fixed with 10% neutral buffered formalin (NBF). Fixative outflux was modelled using a proposed kinetic tensor (KT) model, which incorporates voxelwise diffusion tensor estimates to account for diffusion anisotropy and tissue‐specific diffusion coefficients. Brains fixed with 10% NBF revealed a spatial T₂ pattern consistent with modelled fixative outflux. Confound regression of fixative concentration reduced T₂ inhomogeneity across both white and grey matter, with the greatest reduction attributed to the KT model versus simpler models of fixative outflux. No such effect was observed in brains fixed with 10% formalin. Correlations between the transverse relaxation rate R ₂ and ferritin/myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between R ₂ and PLP for the two fixative types after KT correction.