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Purpose: To estimate the overall prevalence of complementary and alternative medicine and specific modalities used among children with asthma, identify predictors of use, and perceived positive or negative effects of therapies., Results: Of the 161 children enrolled in the study, 76.4% had ever used complementary and alternative medicine. Humidifiers, air purifiers, and multivitamins were the most common modalities used. Complementary and alternative medicine use in children was associated with family use, younger child age, and disease severity, indicated by recent asthma exacerbation. The majority of participants perceived benefit from their complementary and alternative medicine use, with very few reporting negative side effects. Only 36.7% of participants reported discussing their complementary and alternative medicine use with the asthma clinic healthcare team., Conclusions: The prevalence of complementary and alternative medicine use in children with asthma is high, with the majority of families perceiving benefit from its use. This study offers clinicians a reference to inform families regarding the subjective helpfulness of various types of complementary and alternative medicine modalities that can facilitate the dialogue between health care professionals and families interested in complementary and alternative medicine use., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Mammalian cells carefully control their cholesterol levels by employing multiple feedback mechanisms to regulate synthesis of cholesterol and uptake of cholesterol from circulating lipoproteins. Most of a cell's cholesterol (~80% of total) is in the plasma membrane (PM), but the protein machinery that regulates cellular cholesterol resides in the endoplasmic reticulum (ER) membrane, which contains a very small fraction (~1% of total) of a cell's cholesterol. How does the ER communicate with PM to monitor cholesterol levels in that membrane? Here, we describe a tool, ALOD4, that helps us answer this question. ALOD4 traps cholesterol at the PM, leading to depletion of ER cholesterol without altering total cell cholesterol. The effects of ALOD4 are reversible. This tool has been used to show that the ER is able to continuously sample cholesterol from PM, providing ER with information about levels of PM cholesterol.

Over the past few decades, the concept of personalized medicine has proved to play an important role in the healthcare sector. Personalized medicine modifies the current dosage forms according to the needs of the patient. Based on this improved concept, we are now able to bring out best treatment options for a particular individual leading to better therapeutic outcomes and decreased adverse effects. It also has the potential to identify the disease at an earlier stage. It links the diseased condition of a person to the basic genetic and molecular profile causing better understanding of the condition of the patient and to pick out better treatment options. This review is to enlighten the past, present, and future perspective of personalized medicine and how the personalized-medicine approach is used as customized drug delivery, as well as the regulatory aspects towards it. Personalized medicine has the potential to modify the way we recognize and manage our health problems and has already proven to have a huge impact on patient care and on clinical research. The impact of personalized medicine is expected to increase with an increased knowledge about the term and related technologies., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Purpose: To estimate the overall prevalence of complementary and alternative medicine use among children with cystic fibrosis, determine specific modalities used, predictors of use and subjective helpfulness or harm from individual modalities., Results: Of 53 children attending the cystic fibrosis clinic in London, Ontario (100% recruitment), 79% had used complementary and alternative medicine. The most commonly used modalities were air purifiers, humidifiers, probiotics, and omega-3 fatty acids. Family complementary and alternative medicine use was the only independent predictor of overall use. The majority of patients perceived benefit from specific modalities for cystic fibrosis symptoms., Conclusions: Given the high frequency and number of modalities used and lack of patient and disease characteristics predicting use, we recommend that health care providers should routinely ask about complementary and alternative medicine among all pediatric cystic fibrosis patients and assist patients in understanding the potential benefits and risks to make informed decisions about its use., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The gravity of the impact of renal failure on human health is well known and as there is no specific pharmacotherapy for renal failure, the current study was undertaken to evaluate the effect of root extract of Azima tetracantha , an ancient medicinal plant used in Siddha and Ayurvedhic systems of medicine. The experiment was done in glycerol-induced acute renal failure in Wistar albino rats. Thirty rats were divided into five groups. Group 1 was given normal saline (10 ml/kg) per oral, group 2 with single dose of hypertonic glycerol (8 ml/kg) by intramuscular injection into the hind limbs, group 3 with glycerol and ethanolic extract of A. tetracantha root (ATR) 250 mg/kg, group 4, glycerol and ATR 500 mg/kg and group 5, 500 mg/kg ATR. Extract was given orally 60 min prior to glycerol injection. 24 h urine output, serum creatinine, blood urea nitrogen, total proteins and albumin were measured for all the groups. Kidneys were examined for histopathological changes. The antioxidant activity of the extract was tested in vitro and in vivo . Rats treated with ATR showed significant improvement in biochemical parameters and histopathological changes compared to glycerol treated group. The protective effect was highly significant at 500 mg/kg. Both in vitro and in vivo assays showed significant antioxidant activity. The in vitro activity was comparable to vitamin-C. The ethanolic extract of ATR has nephroprotective effect in glycerol-induced acute renal failure and the mechanism of action could be the antioxidant effect.

Animal cells strictly control the distribution of cholesterol in their organelle membranes. This regulation requires an efficient machinery to transport insoluble cholesterol between organelles. In the present study, we generate an (125)I-labeled mutant version of Perfringolysin O (PFO), a cholesterol-binding protein, and use it to measure cholesterol in the plasma membrane of intact cells. We also purify plasma membranes from the same cells, which allows us to directly relate cholesterol concentration to (125)I-PFO binding. We show that cholesterol is organized in the plasma membrane in a manner that makes it inaccessible to PFO until its concentration exceeds a threshold of 35 mol% of total lipids. This 35% threshold is in striking contrast to the 5% threshold previously found for PFO binding to endoplasmic reticulum membranes. The (125)I-PFO probe also proved useful in monitoring the movement of LDL-derived cholesterol from lysosomes to plasma membranes. Using three different mutant cell lines, we show that this transport requires receptor-mediated uptake of LDL, hydrolysis of LDL-cholesteryl esters in lysosomes, and transfer of the liberated cholesterol to the plasma membrane.

Egress of lipoprotein-derived cholesterol from lysosomes requires two lysosomal proteins, polytopic membrane-bound Niemann-Pick C1 (NPC1) and soluble Niemann-Pick C2 (NPC2). The reason for this dual requirement is unknown. Previously, we showed that the soluble luminal N-terminal domain (NTD) of NPC1 (amino acids 25-264) binds cholesterol. This NTD is designated NPC1(NTD). We and others showed that soluble NPC2 also binds cholesterol. Here, we establish an in vitro assay to measure transfer of [(3)H]cholesterol between these two proteins and phosphatidylcholine liposomes. Whereas NPC2 rapidly donates or accepts cholesterol from liposomes, NPC1(NTD) acts much more slowly. Bidirectional transfer of cholesterol between NPC1(NTD) and liposomes is accelerated >100-fold by NPC2. A naturally occurring human mutant of NPC2 (Pro120Ser) fails to bind cholesterol and fails to stimulate cholesterol transfer from NPC1(NTD) to liposomes. NPC2 may be essential to deliver or remove cholesterol from NPC1, an interaction that links both proteins to the cholesterol egress process from lysosomes. These findings may explain how mutations in either protein can produce a similar clinical phenotype.

Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.

Animal cell membranes pose conceptual problems related to the physical chemistry of liquids. An avenue to the solution of some of these problems has been opened by the discovery of liquid-liquid immiscibility in synthetic membranes composed of cholesterol and phospholipids. This discovery has led to the development of a thermodynamic model involving condensed complexes. In this model, the phospholipids with longer fatty-acid chains react reversibly with cholesterol to form complexes. The complexes themselves can have a repulsive interaction with other phospholipids, leading to immiscibility. A striking example of this effect is revealed in the phase diagrams of ternary mixtures of cholesterol, a saturated phosphatidylcholine (or sphingomyelin), and an unsaturated phosphatidylcholine. As found by a number of investigators, all binary pairs are miscible in bilayers, whereas the ternary mixture can form two liquid phases. The model of condensed complexes accounts for this effect. Condensed complexes also have a major effect on the chemical activity of cholesterol and on the ordering of phospholipid acyl chains both in the presence and absence of phase separations. Model calculations of phospholipid order parameters account for several features of the deuterium NMR spectra of labeled phospholipid molecules in bilayer mixtures with cholesterol.

The polytopic membrane protein SCAP transports sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi, thereby activating cholesterol synthesis. Cholesterol accumulation in the ER membranes changes SCAP to an alternate conformation in which it binds ER retention proteins called Insigs, thereby terminating cholesterol synthesis. Here, we show that the conserved Asp-428 in the sixth transmembrane helix of SCAP is essential for SCAP's dissociation from Insigs. In transfected hamster cells, mutant SCAP in which Asp-428 is replaced by alanine (D428A) remained in an Insig-binding conformation when cells were depleted of sterols. As a result, mutant SCAP failed to dissociate from Insigs, and it failed to carry SREBPs to the Golgi. These data identify an important functional residue in SCAP, and they provide genetic evidence that the conformation of SCAP dictates the rate of cholesterol synthesis in animal cells.