Feed aggregator

Non-continuous measurement of intraocular pressure in laboratory animals.

Recent Research Articles from UNTHSC - Tue, 02/09/2016 - 07:29
Related Articles

Non-continuous measurement of intraocular pressure in laboratory animals.

Exp Eye Res. 2015 Dec;141:74-90

Authors: Millar JC, Pang IH

Abstract
Glaucoma is a leading cause of blindness, which is treatable but currently incurable. Numerous animal models therefore have both been and continue to be utilized in the study of numerous aspects of this condition. One important facet associated with the use of such models is the ability to accurately and reproducibly measure (by cannulation) or estimate (by tonometry) intraocular pressure (IOP). At this juncture there are several different approaches to IOP measurement in different experimental animal species, and the list continues to grow. We feel therefore that a review of this subject matter is timely and should prove useful to others who wish to perform similar measurements. The general principles underlying various types of tonometric and non-tonometric techniques for non-continuous determination of IOP are considered. There follows discussion of specific details as to how these techniques are applied to experimental animal species involved in the research of this disease. Specific comments regarding anesthesia, circadian rhythm, and animal handling are also included, especially in the case of rodents. Brief consideration is also given to possible future developments.

PMID: 25933714 [PubMed - indexed for MEDLINE]

Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles.

Recent Research Articles from UNTHSC - Sun, 02/07/2016 - 07:29

Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles.

J Control Release. 2016 Feb 2;

Authors: Pham K, Li D, Guo S, Penzak S, Dong X

Abstract
The aim of this study was to develop a nanotechnology to formulate a fixed-dose combination of poorly water-soluble drugs in a children-friendly, flexible solid dosage form. For diseases like HIV, pediatric patients are taking multiple drugs for effective treatments. Fixed-dose combinations could reduce pill burdens and costs as well as improving patient adherence. However, development of fixed-dose combinations of poorly water-soluble drugs for pediatric formulations is very challenging. We discovered a novel nanotechnology that produced in situ self-assembly nanoparticles (ISNPs) when the ISNP granules were introduced to water. In this study, antiretroviral drug granules, including lopinavir (LPV) ISNP granules and a fixed-dose combination of LPV/ritonavir (RTV) ISNP granules, were prepared using the ISNP nanotechnology, which spontaneously produced drug-loaded ISNPs in contact with water. Drug-loaded ISNPs had particle size less than 158nm with mono-dispersed distribution, over 95% entrapment efficiency for both LPV and RTV and stability over 8h in simulated physiological conditions. Drug-loaded ISNP granules with about 16% of LPV and 4% of RTV were palatable and stable at room temperature over 6months. Furthermore, LPV/RTV ISNP granules displayed a 2.56-fold increase in bioavailability and significantly increased LPV concentrations in tested tissues, especially in HIV sanctuary sites, as compared to the commercial LPV/RTV tablet (Kaletra®) in rats. Overall, the results demonstrated that the novel ISNP nanotechnology is a promising platform to manufacture palatable, "heat" stable, and flexible pediatric granules for fixed-dose combinations that can be used as sachets and sprinkles. To the best of our knowledge, this is the first report on this kind of novel nanotechnology for pediatric fixed-dose combinations of poorly water-soluble drugs.

PMID: 26849919 [PubMed - as supplied by publisher]

Massively parallel sequencing of forensic STRs: Considerations of the DNA commission of the International Society for Forensic Genetics (ISFG) on minimal nomenclature requirements.

Recent Research Articles from UNTHSC - Fri, 02/05/2016 - 07:29

Massively parallel sequencing of forensic STRs: Considerations of the DNA commission of the International Society for Forensic Genetics (ISFG) on minimal nomenclature requirements.

Forensic Sci Int Genet. 2016 Jan 21;22:54-63

Authors: Parson W, Ballard D, Budowle B, Butler JM, Gettings KB, Gill P, Gusmão L, Hares DR, Irwin JA, King JL, Knijff P, Morling N, Prinz M, Schneider PM, Neste CV, Willuweit S, Phillips C

Abstract
The DNA Commission of the International Society for Forensic Genetics (ISFG) is reviewing factors that need to be considered ahead of the adoption by the forensic community of short tandem repeat (STR) genotyping by massively parallel sequencing (MPS) technologies. MPS produces sequence data that provide a precise description of the repeat allele structure of a STR marker and variants that may reside in the flanking areas of the repeat region. When a STR contains a complex arrangement of repeat motifs, the level of genetic polymorphism revealed by the sequence data can increase substantially. As repeat structures can be complex and include substitutions, insertions, deletions, variable tandem repeat arrangements of multiple nucleotide motifs, and flanking region SNPs, established capillary electrophoresis (CE) allele descriptions must be supplemented by a new system of STR allele nomenclature, which retains backward compatibility with the CE data that currently populate national DNA databases and that will continue to be produced for the coming years. Thus, there is a pressing need to produce a standardized framework for describing complex sequences that enable comparison with currently used repeat allele nomenclature derived from conventional CE systems. It is important to discern three levels of information in hierarchical order (i) the sequence, (ii) the alignment, and (iii) the nomenclature of STR sequence data. We propose a sequence (text) string format the minimal requirement of data storage that laboratories should follow when adopting MPS of STRs. We further discuss the variant annotation and sequence comparison framework necessary to maintain compatibility among established and future data. This system must be easy to use and interpret by the DNA specialist, based on a universally accessible genome assembly, and in place before the uptake of MPS by the general forensic community starts to generate sequence data on a large scale. While the established nomenclature for CE-based STR analysis will remain unchanged in the future, the nomenclature of sequence-based STR genotypes will need to follow updated rules and be generated by expert systems that translate MPS sequences to match CE conventions in order to guarantee compatibility between the different generations of STR data.

PMID: 26844919 [PubMed - as supplied by publisher]

Evaluation of Xpert MTB/RIF to identify pulmonary tuberculosis in tuberculosis suspects from low and higher prevalence settings compared to acid fast smear and culture.

Recent Research Articles from UNTHSC - Thu, 02/04/2016 - 07:29

Evaluation of Xpert MTB/RIF to identify pulmonary tuberculosis in tuberculosis suspects from low and higher prevalence settings compared to acid fast smear and culture.

Clin Infect Dis. 2016 Feb 2;

Authors: Firnhaber C, Kendall MA, Wu X, Mazurek GH, Benator DA, Tuberculosis Trials Consortium, Arduino R, Fernandez M, Guy E, Johnson P, Metchock B, Sattler F, Telzak E, Wang YF, Weiner M, Swindells S, Sanne IM, Havlir DV, Grinsztejn B, Alland D, ACTG A5295 and TBTC Study 34 teams

Abstract
BACKGROUND:  Xpert MTB/RIF(Xpert) is a rapid nucleic acid amplification test widely used in high tuberculosis(TB) prevalence settings to detect tuberculosis as well as rpoB mutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation.
METHODS:  Xpert was compared to two sputa, each evaluated with AFB smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary TB from the US, Brazil, and South Africa.
RESULTS:  Of 992 participants enrolled with evaluable results, 22% had culture-confirmed TB. In 638(64%) US participants, one Xpert demonstrated sensitivity of 85.2%(96.7% in participants with AFB smear-positive(AFB+) sputum, 59.3% with AFB- sputum),specificity of 99.2%, NPV 97.6%, and PPV 94.9%. Results did not differ between higher and low prevalence settings. A second Xpert increased overall sensitivity to 91.1%(100% if AFB+, 71.4% if AFB-), with specificity of 98.9%. In US participants, a single negative Xpert predicted the absence of AFB+/culture+ tuberculosis with an NPV of 99.7%; NPV of two Xperts was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected TB DNA and mutations associated with rifampin resistance in five of seven participants with rifampin-resistant, culture+ tuberculosis. Specificity for rifampin resistance was 99.5%,NPV was 98.9%.
CONCLUSIONS:  In the US, Xpert testing performed comparably to two higher TB prevalence settings. These data support the use of Xpert in the initial evaluation of TB suspects and in algorithms assessing need for respiratory isolation.

PMID: 26839383 [PubMed - as supplied by publisher]

Neural Control of Blood Pressure in Chronic Intermittent Hypoxia.

Recent Research Articles from UNTHSC - Thu, 02/04/2016 - 07:29

Neural Control of Blood Pressure in Chronic Intermittent Hypoxia.

Curr Hypertens Rep. 2016 Mar;18(3):19

Authors: Shell B, Faulk K, Cunningham JT

Abstract
Sleep apnea (SA) is increasing in prevalence and is commonly comorbid with hypertension. Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in SA, and through this paradigm, the mechanisms that underlie SA-induced hypertension are becoming clear. Cyclic hypoxic exposure during sleep chronically stimulates the carotid chemoreflexes, inducing sensory long-term facilitation, and drives sympathetic outflow from the hindbrain. The elevated sympathetic tone drives hypertension and renal sympathetic activity to the kidneys resulting in increased plasma renin activity and eventually angiotensin II (Ang II) peripherally. Upon waking, when respiration is normalized, the sympathetic activity does not diminish. This is partially because of adaptations leading to overactivation of the hindbrain regions controlling sympathetic outflow such as the nucleus tractus solitarius (NTS), and rostral ventrolateral medulla (RVLM). The sustained sympathetic activity is also due to enhanced synaptic signaling from the forebrain through the paraventricular nucleus (PVN). During the waking hours, when the chemoreceptors are not exposed to hypoxia, the forebrain circumventricular organs (CVOs) are stimulated by peripherally circulating Ang II from the elevated plasma renin activity. The CVOs and median preoptic nucleus chronically activate the PVN due to the Ang II signaling. All together, this leads to elevated nocturnal mean arterial pressure (MAP) as a response to hypoxemia, as well as inappropriately elevated diurnal MAP in response to maladaptations.

PMID: 26838032 [PubMed - in process]

A weighted U statistic for association analyses considering genetic heterogeneity.

Recent Research Articles from UNTHSC - Wed, 02/03/2016 - 07:29
Related Articles

A weighted U statistic for association analyses considering genetic heterogeneity.

Stat Med. 2016 Feb 1;

Authors: Wei C, Elston RC, Lu Q

Abstract
Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 26833871 [PubMed - as supplied by publisher]

Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Recent Research Articles from UNTHSC - Wed, 02/03/2016 - 07:29
Related Articles

Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Bioorg Med Chem Lett. 2015 Dec 11;

Authors: Acharya S, Rogers P, Krishnamoorthy RR, Stankowska DL, Dias HV, Yorio T

Abstract
Synthesis and bioactivity of novel dual acting nitric oxide releasing and reactive oxygen scavenging hybrid compound SA-2 is described. The hybrid molecule SA-2 significantly increased the superoxide dismutase enzyme level and protected the photoreceptor cells from H2O2 induced oxidative stress. Synthesis of ocular esterase sensitive aceloxy alkyl carbamate prodrug SA-4 with improved aqueous half-life is achieved to aid topical ocular formulation. This class of hybrid molecule and prodrug may have dual potential of improved IOP lowering and neuroprotection in glaucomatous optic neuropathy.

PMID: 26832784 [PubMed - as supplied by publisher]

Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains.

Recent Research Articles from UNTHSC - Wed, 02/03/2016 - 07:29
Related Articles

Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains.

Leg Med (Tokyo). 2016 Jan;18:7-12

Authors: Ambers A, Turnbough M, Benjamin R, Gill-King H, King J, Sajantila A, Budowle B

Abstract
Forensic and ancient DNA samples often are damaged and in limited quantity as a result of exposure to harsh environments and the passage of time. Several strategies have been proposed to address the challenges posed by degraded and low copy templates, including a PCR based whole genome amplification method called degenerate oligonucleotide-primed PCR (DOP-PCR). This study assessed the efficacy of four modified versions of the original DOP-PCR primer that retain at least a portion of the 5' defined sequence and alter the number of bases on the 3' end. The use of each of the four modified primers resulted in improved STR profiles from environmentally-damaged bloodstains, contemporary human skeletal remains, American Civil War era bone samples, and skeletal remains of WWII soldiers over those obtained by previously described DOP-PCR methods and routine STR typing. Additionally, the modified DOP-PCR procedure allows for a larger volume of DNA extract to be used, reducing the need to concentrate the sample and thus mitigating the effects of concurrent concentration of inhibitors.

PMID: 26832369 [PubMed - in process]

Allosteric modulation of nicotinic acetylcholine receptors: the concept and therapeutic trends.

Recent Research Articles from UNTHSC - Wed, 02/03/2016 - 07:29
Related Articles

Allosteric modulation of nicotinic acetylcholine receptors: the concept and therapeutic trends.

Curr Pharm Des. 2016 Jan 31;

Authors: Uteshev VV

Abstract
Expressing functional nicotinic acetylcholine receptors (nAChRs) may be beneficial to central neurons and neuronal networks because activation of nAChRs enhances neuronal resistance to injury, improves attention, cognitive performance, and produces robust anti-inflammatory and analgesic effects in mammals. Although exogenous orthosteric nAChR ligands present valuable tools in treatment of age- and trauma-related neurological deficits, therapeutic approaches that could amplify the brain's innate ability to maintain cholinergic homeostasis and resist injury may serve as intriguing and promising alternatives and have not been fully explored. One of these novel approaches utilizes positive allosteric modulators (PAMs) of nAChRs. Because of the ubiquitous expression of nAChRs in neuronal, glial and immune tissues, highly selective PAMs could amplify multiple endogenous neuroprotective, pro-cognitive, anti-inflammatory and anti-nociceptive cholinergic pathways to offset cholinergic hypofunction and generate therapeutic efficacy by targeting only a single player: i.e., nAChRs activated by endogenous cholinergic tone. In this article, I review the concept of allosteric modulation and current trends in therapeutic applications of nicotinic PAMs.

PMID: 26831463 [PubMed - as supplied by publisher]

Pages