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Potential Biochemical Mechanisms of Lung Injury in Diabetes.

Recent Research Articles from UNTHSC - Fri, 02/17/2017 - 07:32
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Potential Biochemical Mechanisms of Lung Injury in Diabetes.

Aging Dis. 2017 Feb;8(1):7-16

Authors: Zheng H, Wu J, Jin Z, Yan LJ

Abstract
Accumulating evidence has shown that the lung is one of the target organs for microangiopathy in patients with either type 1 or type 2 diabetes mellitus (DM). Diabetes is associated with physiological and structural abnormalities in the diabetic lung concurrent with attenuated lung function. Despite intensive investigations in recent years, the pathogenic mechanisms of diabetic lung injury remain largely elusive. In this review, we summarize currently postulated mechanisms of diabetic lung injury. We mainly focus on the pathogenesis of diabetic lung injury that implicates key pathways, including oxidative stress, non-enzymatic protein glycosylation, polyol pathway, NF-κB pathway, and protein kinase c pathway. We also highlight that while numerous studies have mainly focused on tissue or cell damage in the lung, studies focusing on mitochondrial dysfunction in the diabetic lung have remained sketchy. Hence, further understanding of mitochondrial mechanisms of diabetic lung injury should provide invaluable insights into future therapeutic approaches for diabetic lung injury.

PMID: 28203478 [PubMed]

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

Recent Research Articles from UNTHSC - Fri, 02/17/2017 - 07:32
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Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

Am J Physiol Regul Integr Comp Physiol. 2017 Feb 15;:ajpregu.00120.2016

Authors: Lalley PM, Mifflin SW

Abstract
μ-Opioid receptors are distributed widely in the brainstem respiratory network, and opioids with selectivity for μ-type receptors slow in-vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and inter-spike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brainstem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid mediated disinhibition and postsynaptic enhancement of NMDA receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brainstem respiratory network to override opioid blunting of CO2/pH chemosensitivity.

PMID: 28202437 [PubMed - as supplied by publisher]

Managing Spaghetti Syndrome in Critical Care With a Novel Device: A Nursing Perspective.

Recent Research Articles from UNTHSC - Thu, 02/16/2017 - 10:37
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Managing Spaghetti Syndrome in Critical Care With a Novel Device: A Nursing Perspective.

Crit Care Nurse. 2015 Dec;35(6):38-45

Authors: Haynes J, Bowers K, Young R, Sanders T, Schultz KE

Abstract
BACKGROUND: Managing "spaghetti syndrome," the tangle of therapeutic cables, tubes, and cords at patients' bedsides, can be challenging.
OBJECTIVES: To assess nurses' perceptions of the effectiveness of a novel banding device in management of spaghetti syndrome.
METHODS: A simple color-coded elastomeric banding strap with ribbed flaps was attached to bed rails of adult critical care patients to help organize therapeutic cables, tubes, wires, and cords. Nurses were surveyed before and after use of the bands and after the nursing shift to assess the burden of spaghetti syndrome and the effectiveness of using the bands.
RESULTS: Use of the bands decreased the time spent untangling cords, reduced the frequency of contact of tubing with the floor, and diminished disruptions in care.
CONCLUSIONS: Use of a simple flexible latex-free elastomeric band may help organize therapeutic tubing at patients' bedsides and may promote improvements in nursing care.

PMID: 26628544 [PubMed - indexed for MEDLINE]

FRET study in oligopeptide-linked donor-acceptor system in PVA matrix.

Recent Research Articles from UNTHSC - Tue, 02/14/2017 - 07:32

FRET study in oligopeptide-linked donor-acceptor system in PVA matrix.

Methods Appl Fluoresc. 2016 Dec 13;4(4):047002

Authors: Shah S, Mandecki W, Li J, Gryczynski Z, Borejdo J, Gryczynski I, Fudala R

Abstract
An oligopeptide: Lys-Gly-Pro-Arg-Ser-Leu-Ser-Gly-Lys-NH2, cleaved specifically by a matrix metalloproteinase 9 (MMP-9) at the Ser-Leu bond, was labeled on the ε-NH2 groups of lysine with donor (5, 6 TAMRA) and acceptor (HiLyte647) dye. The donor control was a peptide labeled with 5, 6 TAMRA only on the C-terminal lysine, and the acceptor control was free HiLyte647. Following three products were studied by dissolving in 10% (w/w) poly(vinyl alcohol) and dried on glass slides forming 200 micron films. Absorption spectra of the films show full additivity of donor and acceptor absorptions. A strong Fluorescence Resonance Energy Transfer (FRET) with an efficiency of about 85% was observed in the fluorescence emission and excitation spectra. The lifetime of the donor was shorter and heterogeneous compared with the donor control.

PMID: 28192309 [PubMed - in process]

Fluorescence lifetime imaging with time-gated detection of hyaluronidase using a long lifetime azadioxatriangulenium (ADOTA) fluorophore.

Recent Research Articles from UNTHSC - Tue, 02/14/2017 - 07:32

Fluorescence lifetime imaging with time-gated detection of hyaluronidase using a long lifetime azadioxatriangulenium (ADOTA) fluorophore.

Methods Appl Fluoresc. 2016 Nov 17;4(4):047001

Authors: Chib R, Requena S, Mummert M, Strzhemechny YM, Gryczynski I, Borejdo J, Gryczynski Z, Fudala R

Abstract
A fluorescence lifetime imaging probe with a long lifetime was used in combination with time-gating for the detection of hyaluronidase using hyaluronic acid as the probe template. This probe was developed by heavily labeling hyaluronic acid with long lifetime azadioxatriangulenium fluorophores (ADOTA). We used this probe to image hyaluronidase produced by DU-145 prostate cancer cells.

PMID: 28192308 [PubMed - in process]

Skeletal Muscle Function Deficits in the Elderly: Current Perspectives on Resistance Training.

Recent Research Articles from UNTHSC - Tue, 02/14/2017 - 07:32
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Skeletal Muscle Function Deficits in the Elderly: Current Perspectives on Resistance Training.

J Nat Sci. 2017 Jan;3(1):

Authors: Papa EV, Dong X, Hassan M

Abstract
A variety of changes in skeletal muscle occur with aging. Sarcopenia is the age-associated loss of muscle mass and is one of the main contributors to musculoskeletal impairments in the elderly. Traditional definitions of sarcopenia focused on the size of human skeletal muscle. However, increasing evidence in older adults suggests that low muscle mass is associated with weakness, and weakness is strongly associated with function and disability. In recent years a global trend has shifted toward more encompassing definitions for the loss of muscle mass which include decreases in physical function. This review focuses on skeletal muscle function deficits in the elderly and how these age-associated deficits can be ameliorated by resistance training. We set forth evidence that skeletal muscle deficits arise from changes within the muscle, including reduced fiber size, decreased satellite cell and fiber numbers, and decreased expression of myosin heavy chain (MHC) isoform IIa. Finally, we provide recommendations for clinical geriatric practice regarding how resistance training can attenuate the increase in age-associated skeletal muscle function deficits. Practitioners should consider encouraging patients who are reluctant to exercise to move along a continuum of activity between "no acticity" on one end and "recommended daily amounts" on the other.

PMID: 28191501 [PubMed - in process]

Effects of intermittent pressure imitating rolling manipulation on calcium ion homeostasis in human skeletal muscle cells.

Recent Research Articles from UNTHSC - Tue, 02/14/2017 - 07:32
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Effects of intermittent pressure imitating rolling manipulation on calcium ion homeostasis in human skeletal muscle cells.

BMC Complement Altern Med. 2016 Aug 26;16(1):314

Authors: Zhang H, Liu H, Lin Q, Zhang G, Mason DC

Abstract
BACKGROUND: Homeostasis imbalance of intracellular Ca(2+) is one of the key pathophysiological factors in skeletal muscle injuries. Such imbalance can cause significant change in the metabolism of Ca(2+)-related biomarkers in skeletal muscle, such as superoxide dismutase (SOD), malondialdehyde (MDA) and creatine kinase (CK). Measurements of these biomarkers can be used to evaluate the degree of damage to human skeletal muscle cells (HSKMCs) injury. Rolling manipulation is the most popular myofascial release technique in Traditional Chinese Medicine. The mechanism of how this technique works in ameliorating muscle injury is unknown. This study aimed to investigate the possible Ca(2+) mediated effects of intermittent pressure imitating rolling manipulation (IPIRM) of Traditional Chinese Medicine in the injured HSKMCs.
METHODS: The normal HSKMCs was used as control normal group (CNG), while the injured HSKMCs were further divided into five different groups: control injured group (CIG), Rolling manipulation group (RMG), Rolling manipulation-Verapamil group (RMVG), static pressure group (SPG) and static pressure-Verapamil group (SPVG). RMG and RMVG cells were cyclically exposed to 9.5-12.5 N/cm(2) of IPIRM at a frequency of 1.0 Hz for 10 min. SPG and SPVG were loaded to a continuous pressure of 12.5 N/cm(2) for 10 min. Verapamil, a calcium antagonist, was added into the culture mediums of both RMVG and SPVG groups to block the influx of calcium ion.
RESULT: Compared with the CNG (normal cells), SOD activity was remarkably decreased while both MDA content and CK activity were significantly increased in the CIG (injured cells). When the injured cells were treated with the intermittent rolling manipulation pressure (RMG), the SOD activity was significantly increased and MDA content and CK activity were remarkably decreased. These effects were suppressed by adding the calcium antagonist Verapamil into the culture medium in RMVG. On the other hand, exposure to static pressure in SPG and SPVG affected neither the SOD activity nor the MDA content and CK activity in the injured muscle cells regardless of the presence of verapamil or not in the culture medium.
CONCLUSION: These data suggest that the intermittent rolling pressure with the manipulation could ameliorate HSKMCs injury through a Ca(2+) dependent pathway. Static pressure did not lead to the same results.

PMID: 27561948 [PubMed - indexed for MEDLINE]

Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia.

Recent Research Articles from UNTHSC - Sun, 02/12/2017 - 07:47

Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia.

Neurochem Int. 2017 Feb 08;:

Authors: Dalwadi DA, Kim S, Schetz JA

Abstract
Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047. This effect could be antagonized by a selective concentration of the S1R antagonist BD1063. Haloperidol is known to have high affinity interactions with the S1R, yet it was unable to facilitate BDNF release. Remarkably, however, two metabolites of haloperidol, haloperidol I and haloperidol II (reduced haloperidol), were discovered to facilitate BDNF secretion and this effect was antagonized by BD1063. Neither 4-PPBP, nor either of the haloperidol metabolites affected the level of BDNF mRNA as assessed by qPCR. These results demonstrate for the first time that haloperidol metabolites I and II facilitate the secretion of BDNF from astrocytes by acting as functionally selective S1R agonists.

PMID: 28188803 [PubMed - as supplied by publisher]

Transethnic genome-wide scan identifies novel Alzheimer's disease loci.

Recent Research Articles from UNTHSC - Sun, 02/12/2017 - 07:47
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Transethnic genome-wide scan identifies novel Alzheimer's disease loci.

Alzheimers Dement. 2017 Feb 06;:

Authors: Jun GR, Chung J, Mez J, Barber R, Beecham GW, Bennett DA, Buxbaum JD, Byrd GS, Carrasquillo MM, Crane PK, Cruchaga C, De Jager P, Ertekin-Taner N, Evans D, Fallin MD, Foroud TM, Friedland RP, Goate AM, Graff-Radford NR, Hendrie H, Hall KS, Hamilton-Nelson KL, Inzelberg R, Kamboh MI, Kauwe JS, Kukull WA, Kunkle BW, Kuwano R, Larson EB, Logue MW, Manly JJ, Martin ER, Montine TJ, Mukherjee S, Naj A, Reiman EM, Reitz C, Sherva R, St George-Hyslop PH, Thornton T, Younkin SG, Vardarajan BN, Wang LS, Wendlund JR, Winslow AR, Alzheimer's Disease Genetics Consortium, Haines J, Mayeux R, Pericak-Vance MA, Schellenberg G, Lunetta KL, Farrer LA

Abstract
BACKGROUND: Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood.
METHODS: We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset.
RESULTS: Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 × 10(-8)) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the APOE ɛ4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10(-6)) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10(-6)).
DISCUSSION: Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

PMID: 28183528 [PubMed - as supplied by publisher]

Δ(9)-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats.

Recent Research Articles from UNTHSC - Sun, 02/12/2017 - 07:47
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Δ(9)-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats.

Psychopharmacology (Berl). 2016 05;233(10):1901-10

Authors: Gatch MB, Forster MJ

Abstract
RATIONALE: Novel cannabinoid compounds continue to be marketed as "legal" marijuana substitutes, even though little is known about their molecular and behavioral effects.
OBJECTIVES: Six of these compounds (ADBICA, ADB-PINACA, THJ-2201, RCS-4, JWH-122, JWH-210) were tested for in vitro and in vivo cannabinoid-like effects to determine their abuse liability.
METHODS: Binding to and functional activity at CB1 cannabinoid receptors was tested. Locomotor activity in mice was tested to screen for behavioral activity and to identify behaviorally active dose ranges and times of peak effect. Discriminative stimulus effects of the six compounds were tested in rats trained to discriminate Δ(9)-tetrahydrocannabinol (Δ(9)-THC).
RESULTS: ADBICA, ADB-PINACA, THJ-2201, RCS-4, JWH-122, and JWH-210 showed high affinity binding at the CB1 receptor at nanomolar affinities (0.59 to 22.5 nM), and all acted as full agonists with nanomolar potencies (0.024 to 111 nM) when compared to the CB1 receptor full agonist CP 55940. All compounds depressed locomotor activity below 50 % of vehicle responding, with depressant effects lasting 1.5 to nearly 4 h. All compounds fully substituted (<80 % Δ(9)-THC-appropriate responding) for the discriminative stimulus effects of Δ(9)-THC. 3,4-Methylenedioxy-methamphetamine (MDMA) was tested as a negative control and did not substitute for Δ(9)-THC (11 % Δ(9)-THC-appropriate responding).
CONCLUSIONS: All six of the compounds acted at the CB1 receptor and produced behavioral effects common to abused cannabinoid compounds, which suggest that these compounds have substantial abuse liability common to controlled synthetic cannabinoid compounds.

PMID: 26875756 [PubMed - indexed for MEDLINE]

Can ceftazidime/avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae?

Recent Research Articles from UNTHSC - Thu, 02/09/2017 - 07:34
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Can ceftazidime/avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae?

Antimicrob Agents Chemother. 2017 Feb 06;:

Authors: Marshall S, Hujer AM, Rojas LJ, Papp-Wallace KM, Humphries RM, Spellberg B, Hujer KM, Marshall EK, Rudin SD, Perez F, Wilson BM, Wasserman RB, Chikowski L, Paterson DL, Vila AJ, van Duin D, Kreiswirth BN, Chambers HF, Fowler VG, Jacobs MR, Pulse ME, Weiss WJ, Bonomo RA

Abstract
Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram negative bacteria, we tested the effectiveness of the combination of ceftazidime/avibactam (CAZ/AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk-diffusion and agar based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ/AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ/AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ/AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥ 21 mm. All isolates demonstrated a reduction in CAZ/AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥ 4 log10 CFU decrease for all groups that had CAZ/AVI plus ATM (8 μg/ml) added, compared to the CAZ/AVI alone group. In the murine neutropenic thigh infection model, an almost 4 log10 reduction in CFUs was noted at 24 h for CAZ/AVI (32 mg/kg q8h) plus ATM (32 mg/kg q8h) vs. CAZ/AVI (32 mg/kg q8h) alone. The data presented herein, requires us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae.

PMID: 28167541 [PubMed - as supplied by publisher]

Dexamethasone-Induced Ocular Hypertension in Mice: Effects of Myocilin and Route of Administration.

Recent Research Articles from UNTHSC - Thu, 02/09/2017 - 07:34
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Dexamethasone-Induced Ocular Hypertension in Mice: Effects of Myocilin and Route of Administration.

Am J Pathol. 2017 Feb 03;:

Authors: Patel GC, Phan TN, Maddineni P, Kasetti RB, Millar JC, Clark AF, Zode GS

Abstract
Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious adverse effect of prolonged GC therapy that can lead to iatrogenic glaucoma and permanent vision loss. An appropriate mouse model can help us understand precise molecular mechanisms and etiology of GC-induced OHT. We therefore developed a novel, simple, and reproducible mouse model of GC-induced OHT. GC-induced myocilin expression in the trabecular meshwork (TM) has been suggested to play an important role in GC-induced OHT. We further determined whether myocilin contributes to GC-OHT. C57BL/6J mice received weekly periocular conjunctival fornix injections of a dexamethasone-21-acetate (DEX-Ac) formulation. Intraocular pressure (IOP) elevation was relatively rapid and significant, and correlated with reduced conventional outflow facility. Nighttime IOPs were higher in ocular hypertensive eyes compared to daytime IOPs. DEX-Ac treatment led to increased expression of fibronectin, collagen I, and α-smooth muscle actin in the TM in mouse eyes. No changes in body weight indicated no systemic toxicity associated with DEX-Ac treatment. Wild-type mice showed increased myocilin expression in the TM on DEX-Ac treatment. Both wild-type and Myoc(-/-) mice had equivalent and significantly elevated IOP with DEX-Ac treatment every week. In conclusion, our mouse model mimics many aspects of GC-induced OHT in humans, and we further demonstrate that myocilin does not play a major role in DEX-induced OHT in mice.

PMID: 28167045 [PubMed - as supplied by publisher]

Correlation of Lipid Profile and Risk of Developing Type 2 Diabetes Mellitus in 10-14 Year Old Children.

Recent Research Articles from UNTHSC - Thu, 02/09/2017 - 07:34
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Correlation of Lipid Profile and Risk of Developing Type 2 Diabetes Mellitus in 10-14 Year Old Children.

Cell Physiol Biochem. 2016;39(5):1695-1704

Authors: Habiba NM, Fulda KG, Basha R, Shah D, Fernando S, Nguyen B, Xiong Y, Franks SF, Matches SJ, Magie RD, Bowman WP

Abstract
BACKGROUND/AIMS: The role of lipid profile in predicting the risk of Type 2 diabetes mellitus (T2DM) in children is not clearly established. Our aim is to screen non-diabetic children aged 10-14 years for risk of developing T2DM and evaluate the association of abnormal lipids and socioeconomic status (SES).
METHODS: Data on race/ethnicity, family history, body mass index percentile, blood pressure and presence of neck pigmentation (acanthosis nigricans) were collected from 149 non-diabetic children. Using these factors, children were classified into low risk (<3 risk factors) and high risk (>3 risk factors) groups. Logistic regression model and chi-square tests were used to evaluate the association of blood lipid profile and demographic variables. Independent t-test was used to compare the ratio of Total Cholesterol (TC) and High Density Lipids (HDL) with T2DM risk.
RESULTS: 60% of children were at high risk for developing T2DM. HDL (p<0.001), triglycerides (p=0.02) and TC/HDL ratio (p<.001) were significantly abnormal in high risk group. Low SES showed a marginal association with high risk group. There were no gender or age differences between high and low risk groups.
CONCLUSIONS: The significant determinants associated with high risk group were modifiable factors providing an opportunity for early intervention and prevention.

PMID: 27642750 [PubMed - indexed for MEDLINE]

Role of RAGE in Alzheimer's Disease.

Recent Research Articles from UNTHSC - Tue, 02/07/2017 - 07:32
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Role of RAGE in Alzheimer's Disease.

Cell Mol Neurobiol. 2016 May;36(4):483-95

Authors: Cai Z, Liu N, Wang C, Qin B, Zhou Y, Xiao M, Chang L, Yan LJ, Zhao B

Abstract
Receptor for advanced glycation end products (RAGE) is a receptor of the immunoglobulin super family that plays various important roles under physiological and pathological conditions. Compelling evidence suggests that RAGE acts as both an inflammatory intermediary and a critical inducer of oxidative stress, underlying RAGE-induced Alzheimer-like pathophysiological changes that drive the process of Alzheimer's disease (AD). A critical role of RAGE in AD includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles, failure of synaptic transmission, and neuronal degeneration. The steady-state level of Aβ depends on the balance between production and clearance. RAGE plays an important role in the Aβ clearance. RAGE acts as an important transporter via regulating influx of circulating Aβ into brain, whereas the efflux of brain-derived Aβ into the circulation via BBB is implemented by LRP1. RAGE could be an important contributor to Aβ generation via enhancing the activity of β- and/or γ-secretases and activating inflammatory response and oxidative stress. However, sRAGE-Aβ interactions could inhibit Aβ neurotoxicity and promote Aβ clearance from brain. Meanwhile, RAGE could be a promoting factor for the synaptic dysfunction and neuronal circuit dysfunction which are both the material structure of cognition, and the physiological and pathological basis of cognition. In addition, RAGE could be a trigger for the pathogenesis of Aβ and tau hyper-phosphorylation which both participate in the process of cognitive impairment. Preclinical and clinical studies have supported that RAGE inhibitors could be useful in the treatment of AD. Thus, an effective measure to inhibit RAGE may be a novel drug target in AD.

PMID: 26175217 [PubMed - indexed for MEDLINE]

Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery.

Recent Research Articles from UNTHSC - Mon, 02/06/2017 - 07:34
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Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery.

J Neuroimmune Pharmacol. 2017 Feb 03;:

Authors: Joshi CR, Labhasetwar V, Ghorpade A

Abstract
Neurological diseases and disorders (NDDs) present a significant societal burden and currently available drug- and biological-based therapeutic strategies have proven inadequate to alleviate it. Gene therapy is a suitable alternative to treat NDDs compared to conventional systems since it can be tailored to specifically alter select gene expression, reverse disease phenotype and restore normal function. The scope of gene therapy has broadened over the years with the advent of RNA interference and genome editing technologies. Consequently, encouraging results from central nervous system (CNS)-targeted gene delivery studies have led to their transition from preclinical to clinical trials. As we shift to an exciting gene therapy era, a retrospective of available literature on CNS-associated gene delivery is in order. This review is timely in this regard, since it analyzes key challenges and major findings from the last two decades and evaluates future prospects of brain gene delivery. We emphasize major areas consisting of physiological and pharmacological challenges in gene therapy, function-based selection of a ideal cellular target(s), available therapy modalities, and diversity of viral vectors and nanoparticles as vehicle systems. Further, we present plausible answers to key questions such as strategies to circumvent low blood-brain barrier permeability and most suitable CNS cell types for targeting. We compare and contrast pros and cons of the tested viral vectors in the context of delivery systems used in past and current clinical trials. Gene vector design challenges are also evaluated in the context of cell-specific promoters. Key challenges and findings reported for recent gene therapy clinical trials, assessing viral vectors and nanoparticles are discussed from the perspective of bench to bedside gene therapy translation. We conclude this review by tying together gene delivery challenges, available vehicle systems and comprehensive analyses of neuropathogenesis to outline future prospects of CNS-targeted gene therapies.

PMID: 28160121 [PubMed - as supplied by publisher]

The Effects of Performance Fatigability on Postural Control and Rehabilitation in the Older Patient.

Recent Research Articles from UNTHSC - Mon, 02/06/2017 - 07:34
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The Effects of Performance Fatigability on Postural Control and Rehabilitation in the Older Patient.

Curr Geriatr Rep. 2016 Sep;5(3):172-178

Authors: Papa EV, Hassan M, Bugnariu N

Abstract
Fatigue is common in older adults and has a significant effect on quality of life. Despite the high prevalence of fatigue in older individuals, several aspects are poorly understood. It is important to differentiate subjective fatigue complaints from fatigability of motor performance because the two are independent constructs with potentially distinct consequences on mobility. Performance fatigability is the magnitude of change in a performance criterion over a given time of task performance. Performance fatigability is a compulsory element of any strength training program, yet strength training is an important component of rehabilitation programs for older adults. The consequences of fatigability for older adults suggest that acute exercise of various types may result in acute impairments in postural control. The effects of performance fatigability on postural control in older adults are evaluated here to aid the rehabilitation clinician in making recommendations for evaluation of fall risks and exercise prescription.

PMID: 28154794 [PubMed - in process]

Potential Problems With Systematic Reviews and Meta-Analyses.

Recent Research Articles from UNTHSC - Mon, 02/06/2017 - 07:34
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Potential Problems With Systematic Reviews and Meta-Analyses.

J Pain. 2017 Feb;18(2):228-229

Authors: Gatchel RJ, Licciardone JC

PMID: 28153422 [PubMed - in process]

Non-Gradient Blue Native Polyacrylamide Gel Electrophoresis.

Recent Research Articles from UNTHSC - Fri, 02/03/2017 - 16:52

Non-Gradient Blue Native Polyacrylamide Gel Electrophoresis.

Curr Protoc Protein Sci. 2017 Feb 02;87:19.29.1-19.29.12

Authors: Luo X, Wu J, Jin Z, Yan LJ

Abstract
Gradient blue native polyacrylamide gel electrophoresis (BN-PAGE) is a well established and widely used technique for activity analysis of high-molecular-weight proteins, protein complexes, and protein-protein interactions. Since its inception in the early 1990s, a variety of minor modifications have been made to this gradient gel analytical method. Here we provide a major modification of the method, which we call non-gradient BN-PAGE. The procedure, similar to that of non-gradient SDS-PAGE, is simple because there is no expensive gradient maker involved. The non-gradient BN-PAGE protocols presented herein provide guidelines on the analysis of mitochondrial protein complexes, in particular, dihydrolipoamide dehydrogenase (DLDH) and those in the electron transport chain. Protocols for the analysis of blood esterases or mitochondrial esterases are also presented. The non-gradient BN-PAGE method may be tailored for analysis of specific proteins according to their molecular weight regardless of whether the target proteins are hydrophobic or hydrophilic. © 2017 by John Wiley & Sons, Inc.

PMID: 28150881 [PubMed - in process]

Adequate dietary fiber supplement along with TONE concept can help avoid surgery in most patients with advanced hemorrhoids.

Recent Research Articles from UNTHSC - Fri, 02/03/2017 - 16:52
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Adequate dietary fiber supplement along with TONE concept can help avoid surgery in most patients with advanced hemorrhoids.

Minerva Gastroenterol Dietol. 2017 Feb 01;:

Authors: Garg P, Singh P

Abstract
BACKGROUND: The root cause of hemorrhoids are three deranged defecation habits (DDH) - (1) increased straining, (2) prolonged defecation-time and, (3) frequent bowel-motions. These DDH are responsible for development of new hemorrhoids, progression of existing hemorrhoids and hemorrhoidal rupture (bleeding). DDH can be corrected by TONE concept. TONE entails specifying exact treatment goals (T-Three minutes at defecation, O-Once a day defecation- frequency, N-No straining during passing motions, E-Enough fiber). TONE can be implemented by proper counseling and by prescribing fiber supplement appropriately (5-6 teaspoonfuls of psyllium husk with 600 ml of water daily). Corrected DDH would prevent the progression of hemorrhoids and bleeding. An office procedure may be done to further downgrade the hemorrhoids.
METHODS: Patients with advanced hemorrhoids (grade III & IV) who were referred for surgery were prescribed fiber supplement and were counseled to follow TONE. The outcome parameters evaluated were- improvement in prolapse, bleeding episodes, satisfaction levels.
RESULTS: 102 patients (Male/Female: 75/10, age 46.0 ±13.5 years, 17 lost to follow-up) with advanced hemorrhoids (grades: early III-41, late III-38 & IV-6) were included in the study. All patients had symptoms of prolapsed and bleeding was present in 71.8% (61/85) patients. After the follow-up of 40 (12-96) months, 68.2% (58/85) patients were highly satisfied, 12.9% (11/85) were moderately satisfied and 18.9% (16/85) were not satisfied with treatment. Prolapse improved in 56.5%(48/85), didn't progress over time in 25.9(22/85) and continued to progress in 4.7 %(4/85) patients. 12.9% (11/85) underwent operation for hemorrhoids. Bleeding episodes decreased from 71.8% (61/85) to 29.4%(25/85) (p<0.0001,Fischer's).
CONCLUSIONS: Adequate fiber supplement coupled with TONE concept can correct deranged defecation habits and can thus prevent progression of hemorrhoids and bleeding and the need for surgery in most patients with advanced hemorrhoids.

PMID: 28150480 [PubMed - as supplied by publisher]

Primary Cutaneous Diffuse Large B-Cell Lymphoma With a MYC-IGH Rearrangement and Gain of BCL2: Expanding the Spectrum of MYC/BCL2 Double-Hit Lymphomas.

Recent Research Articles from UNTHSC - Wed, 02/01/2017 - 07:34
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Primary Cutaneous Diffuse Large B-Cell Lymphoma With a MYC-IGH Rearrangement and Gain of BCL2: Expanding the Spectrum of MYC/BCL2 Double-Hit Lymphomas.

Am J Dermatopathol. 2016 Oct;38(10):769-74

Authors: Testo N, Olson LC, Subramaniyam S, Hanson T, Magro CM

Abstract
Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma. More recently, MYC rearrangement with multiple copies/gain of BCL2 or multiple copies/gain of MYC with a BCL2 rearrangement have been described and exhibit a very similar clinical course to conventional double-hit lymphomas. We report the seventh case of diffuse large B-cell lymphoma exhibiting this distinct cytogenetic abnormality and the first reported case in the skin. The patient's clinical course was aggressive, succumbing to disease 18 months after his initial presentation.

PMID: 27391453 [PubMed - indexed for MEDLINE]

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