Drug-perturbation-based stratification of blood cancer

Science.gov (United States)

Dietrich, Sascha; Lu, Junyan; Wu, Bian; Hüllein, Jennifer; da Silva Liberio, Michelle; Walther, Tatjana; Wagner, Lena; Rabe, Sophie; Ghidelli-Disse, Sonja; Bantscheff, Marcus; Słabicki, Mikołaj; Mock, Andreas; Oakes, Christopher C.; Wang, Shihui; Oppermann, Sina; Lukas, Marina; Kim, Vladislav; Sill, Martin; Jauch, Anna; Sutton, Lesley Ann; Rosenquist, Richard; Liu, Xiyang; Jethwa, Alexander; Lee, Kwang Seok; Lewis, Joe; Putzker, Kerstin; Lutz, Christoph; Rossi, Davide; Oellerich, Thomas; Herling, Marco; Nguyen-Khac, Florence; Plass, Christoph; von Kalle, Christof; Ho, Anthony D.; Hensel, Manfred; Dürig, Jan; Ringshausen, Ingo; Huber, Wolfgang

2017-01-01

As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care. PMID:29227286

Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

Directory of Open Access Journals (Sweden)

Han-Chung Wu

2010-01-01

Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

[Carrier-mediated Transport of Cationic Drugs across the Blood-Tissue Barrier].

Science.gov (United States)

Kubo, Yoshiyuki

2015-01-01

Studies of neurological dysfunction have revealed the neuroprotective effect of several cationic drugs, suggesting their usefulness in the treatment of neurological diseases. In the brain and retina, blood-tissue barriers such as blood-brain barrier (BBB) and blood-retinal barrier (BRB) are formed to restrict nonspecific solute transport between the circulating blood and neural tissues. Therefore study of cationic drug transport at these barriers is essential to achieve systemic delivery of neuroprotective agents into the neural tissues. In the retina, severe diseases such as diabetic retinopathy and macular degeneration can cause neurological dysfunction that dramatically affects patients' QOL. The BRB is formed by retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB). Blood-to-retina transport of cationic drugs was investigated at the inner BRB, which is known to nourish two thirds of the retina. Blood-to-retinal transport of verapamil suggested that the barrier function of the BRB differs from that of the BBB. Moreover, carrier-mediated transport of verapamil and pyrilamine revealed the involvement of novel organic cation transporters at the inner BRB. The identified transport systems for cationic drugs are sensitive to several cationic neuroprotective and anti-angiogenic agents such as clonidine and propranolol, and the involvement of novel transporters was also suggested in their blood-to-retina transport across the inner BRB.

Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier

OpenAIRE

Strazielle, Nathalie; Ghersi-Egea, Jean-Fran?ois

2016-01-01

The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system dise...

[The blood-brain barrier and drug delivery in the central nervous system].

Science.gov (United States)

Loch-Neckel, Gecioni; Koepp, Janice

2010-08-01

To provide an updated view of the difficulties due to barriers and strategies used to allow the release of drugs in the central nervous system. The difficulty for the treatment of many diseases of the central nervous system, through the use of intra-venous drugs, is due to the presence of barriers that prevent the release of the same: the blood-brain barrier, blood-cerebro-spinal fluid barrier and the blood-arachnoid barrier. The blood-brain barrier is the main barrier for the transport of drugs in the brain that also acts as a immunologic and metabolic barrier. The endothelial cells of the blood-brain barrier are connected to a junction complex through the interaction of transmembrane proteins that protrude from de inside to the outside, forming a connection between the endothelial cells. The transport of substances to the brain depends on the mechanisms of transport present in the barrier and the diffusion of these compounds also depends on the physicochemical characteristics of the molecule. Some diseases alter the permeability of the blood-brain barrier and thus the passage of drugs. Strategies such as the use of methods for drug delivery in the brain have been investigated. Further details regarding the mechanisms of transport across the blood-brain barrier and the changes in neuropathology would provide important information about the etiology of diseases and lead to better therapeutic strategies.

Strategies to improve drug delivery across the blood-brain barrier.

Science.gov (United States)

de Boer, Albertus G; Gaillard, Pieter J

2007-01-01

The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.

Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier

Science.gov (United States)

Strazielle, Nathalie; Ghersi-Egea, Jean-François

2016-01-01

The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates. PMID:27464721

Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

Science.gov (United States)

Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

2013-06-01

In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

Electromembrane extraction of stimulating drugs from undiluted whole blood

DEFF Research Database (Denmark)

Jamt, Ragnhild Elén Gjulem; Gjelstad, Astrid; Eibak, Lars Erik Eng

2012-01-01

For the first time, electromembrane extraction (EME) of six basic drugs of abuse from undiluted whole blood and post mortem blood in a totally stagnant system is reported. Cathinone, methamphetamine, 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-methamphet-amine (MDMA), ketamine and 2...

Effect of buspirone: An anxiolytic drug on blood glucose in humans

OpenAIRE

Ojha, S. K.; Nandave, M.; Sharma, C.

2006-01-01

The present study investigated the effect of an antianxiety drug, buspirone on blood glucose and plasma insulin level concerning the role of 5-HT1A receptors in blood glucose regulation in healthy humans. Twelve healthy male volunteers were administered single oral doses of buspirone (10 mg) or placebo, in a randomized, crossover way, followed by oral glucose load (75 gm in 200 ml) at reported Tmax i.e. the time of peak plasma concentration of the respective administered drug. The blood sampl...

High Blood Pressure

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... normal blood pressure 140/90 or higher is high blood pressure Between 120 and 139 for the top number, ... prehypertension. Prehypertension means you may end up with high blood pressure, unless you take steps to prevent it. High ...

Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood-Brain Barrier.

Science.gov (United States)

Georgieva, Julia V; Hoekstra, Dick; Zuhorn, Inge S

2014-11-17

The blood-brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood-brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier-drug system ("Trojan horse complex") is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain.

Assessment of light stability of drugs in blood and plasma.

Science.gov (United States)

de Vries, Ronald; Diels, Luc; Dillen, Lieve; Sips, Luc; Van Roosbroek, Dirk; Verhaeghe, Tom; Timmerman, Philip

2016-10-01

A procedure was developed for the assessment of photochemical stability of drugs in blood and plasma under standardized conditions. The procedure avoids a variable outcome of photochemical stability experiments and tests relevant worst case conditions so that unnecessary light protection is avoided. Results/methodology: Blood and plasma were spiked with a mixture of drugs and incubated in a Suntest CPS(+), in the laboratory on the bench and near the window on a sunny summer day. The results were compared. No protection from light, limited protection from light and full protection from light are advised for drugs that are stable in plasma in the Suntest CPS(+) at 250 W/m(2) for at least 30 min, for 5-30 min and for <5 min, respectively.

Hypertension (High Blood Pressure)

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... Safe Videos for Educators Search English Español Hypertension (High Blood Pressure) KidsHealth / For Teens / Hypertension (High Blood Pressure) What's ... rest temperature diet emotions posture medicines Why Is High Blood Pressure Bad? High blood pressure means a person's heart ...

Optimization and application of octadecyl-modified monolithic silica for solid-phase extraction of drugs in whole blood samples.

Science.gov (United States)

Namera, Akira; Saito, Takeshi; Ota, Shigenori; Miyazaki, Shota; Oikawa, Hiroshi; Murata, Kazuhiro; Nagao, Masataka

2017-09-29

Monolithic silica in MonoSpin for solid-phase extraction of drugs from whole blood samples was developed to facilitate high-throughput analysis. Monolithic silica of various pore sizes and octadecyl contents were synthesized, and their effects on recovery rates were evaluated. The silica monolith M18-200 (20μm through-pore size, 10.4nm mesopore size, and 17.3% carbon content) achieved the best recovery of the target analytes in whole blood samples. The extraction proceeded with centrifugal force at 1000rpm for 2min, and the eluate was directly injected into the liquid chromatography-mass spectrometry system without any tedious steps such as evaporation of extraction solvents. Under the optimized condition, low detection limits of 0.5-2.0ngmL -1 and calibration ranges up to 1000ngmL -1 were obtained. The recoveries of the target drugs in the whole blood were 76-108% with relative standard deviation of less than 14.3%. These results indicate that the developed method based on monolithic silica is convenient, highly efficient, and applicable for detecting drugs in whole blood samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS)

DEFF Research Database (Denmark)

Bath, Philip M W; Woodhouse, Lisa; Scutt, Polly

2015-01-01

BACKGROUND: High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs......·91-1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90-1·22; p=0·55). INTERPRETATION: In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show...

Effects of aerobic exercise and drug therapy on blood pressure and ...

African Journals Online (AJOL)

EB

Key words: Aerobic exercise, drug therapy, blood pressure, randomised controlled trial. African Health Sciences 2013; (1): .... body fat and displayed it on the screen of the meter. ... inelastible tape measure (Butterfly, China). Blood pressure ...

Detection of the antipsychotic drug quetiapine in the blood, urine and hair samples of the victim of a drug-facilitated sexual assault

DEFF Research Database (Denmark)

Johansen, Sys Stybe

2017-01-01

A drug rape facilitated with the sedative antipsychotic drug quetiapine is presented here. A teenage girl and her girlfriend went to the home of an adult couple they had met at a bar. Here, the teenage girl (victim) felt tired after consuming some alcoholic drinks and fell asleep. While she......-three hours after the suspected drug-facilitated sexual assault (DFSA), blood and urine samples were collected and the initial toxicological screening detected quetiapine. Confirmation and quantification by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) revealed...... a concentration of 0.007mg/kg quetiapine in blood and 0.19mg/l in urine. Six months after the DFSA, a hair sample was collected and segmental hair analysis was performed on four washed segments (0-3cm, 3-5cm, 5-7cm, and 7-9cm). The last segment contained 0.011ng/mg of quetiapine, whereas the other segments were...

Amphiphilic Copolymers Shuttle Drugs Across the Blood-Brain Barrier.

Science.gov (United States)

Clemens-Hemmelmann, Mirjam; Kuffner, Christiane; Metz, Verena; Kircher, Linda; Schmitt, Ulrich; Hiemke, Christoph; Postina, Rolf; Zentel, Rudolf

2016-05-01

Medical treatment of diseases of the central nervous system requires transport of drugs across the blood-brain barrier (BBB). Here, it is extended previously in vitro experiments with a model compound to show that the non-water-soluble and brain-impermeable drug domperidone (DOM) itself can be enriched in the brain by use of an amphiphilic copolymer as a carrier. This carrier consists of poly(N-(2-hydroxypropyl)-methacrylamide), statistically copolymerized with 10 mol% hydrophobic lauryl methacrylate, into whose micellar aggregates DOM is noncovalently absorbed. As tested in a BBB model efficient transport of DOM across, the BBB is achievable over a wide range of formulations, containing 0.8 to 35.5 wt% domperidone per copolymer. In neither case, the polymer itself is translocated across the BBB model. In vivo experiments in mice show that already 10 min after intraperitoneal injection of the polymer/domperidone (PolyDOM) formulation, domperidone can be detected in blood and in the brain. Highest serum and brain levels of domperidone are detected 40 min after injection. At that time point serum domperidone is increased 48-fold. Most importantly, domperidone is exclusively detectable in high amounts in the brain of PolyDOM injected mice and not in mice injected with bare domperidone. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitive screening of abused drugs in dried blood samples using ultra-high-performance liquid chromatography-ion booster-quadrupole time-of-flight mass spectrometry.

Science.gov (United States)

Chepyala, Divyabharathi; Tsai, I-Lin; Liao, Hsiao-Wei; Chen, Guan-Yuan; Chao, Hsi-Chun; Kuo, Ching-Hua

2017-03-31

An increased rate of drug abuse is a major social problem worldwide. The dried blood spot (DBS) sampling technique offers many advantages over using urine or whole blood sampling techniques. This study developed a simple and efficient ultra-high-performance liquid chromatography-ion booster-quadrupole time-of-flight mass spectrometry (UHPLC-IB-QTOF-MS) method for the analysis of abused drugs and their metabolites using DBS. Fifty-seven compounds covering the most commonly abused drugs, including amphetamines, opioids, cocaine, benzodiazepines, barbiturates, and many other new and emerging abused drugs, were selected as the target analytes of this study. An 80% acetonitrile solvent with a 5-min extraction by Geno grinder was used for sample extraction. A Poroshell column was used to provide efficient separation, and under optimal conditions, the analytical times were 15 and 5min in positive and negative ionization modes, respectively. Ionization parameters of both electrospray ionization source and ion booster (IB) source containing an extra heated zone were optimized to achieve the best ionization efficiency of the investigated abused drugs. In spite of their structural diversity, most of the abused drugs showed an enhanced mass response with the high temperature ionization from an extra heated zone of IB source. Compared to electrospray ionization, the ion booster (IB) greatly improved the detection sensitivity for 86% of the analytes by 1.5-14-fold and allowed the developed method to detect trace amounts of compounds on the DBS cards. The validation results showed that the coefficients of variation of intra-day and inter-day precision in terms of the signal intensity were lower than 19.65%. The extraction recovery of all analytes was between 67.21 and 115.14%. The limits of detection of all analytes were between 0.2 and 35.7ngmL -1 . The stability study indicated that 7% of compounds showed poor stability (below 50%) on the DBS cards after 6 months of storage at

Tracking flow of leukocytes in blood for drug analysis

Science.gov (United States)

Basharat, Arslan; Turner, Wesley; Stephens, Gillian; Badillo, Benjamin; Lumpkin, Rick; Andre, Patrick; Perera, Amitha

2011-03-01

Modern microscopy techniques allow imaging of circulating blood components under vascular flow conditions. The resulting video sequences provide unique insights into the behavior of blood cells within the vasculature and can be used as a method to monitor and quantitate the recruitment of inflammatory cells at sites of vascular injury/ inflammation and potentially serve as a pharmacodynamic biomarker, helping screen new therapies and individualize dose and combinations of drugs. However, manual analysis of these video sequences is intractable, requiring hours per 400 second video clip. In this paper, we present an automated technique to analyze the behavior and recruitment of human leukocytes in whole blood under physiological conditions of shear through a simple multi-channel fluorescence microscope in real-time. This technique detects and tracks the recruitment of leukocytes to a bioactive surface coated on a flow chamber. Rolling cells (cells which partially bind to the bioactive matrix) are detected counted, and have their velocity measured and graphed. The challenges here include: high cell density, appearance similarity, and low (1Hz) frame rate. Our approach performs frame differencing based motion segmentation, track initialization and online tracking of individual leukocytes.

Blood Pressure-Lowering Aspects of Lipid-Lowering and Anti-Diabetic Drugs

Directory of Open Access Journals (Sweden)

Peter M. Nilsson

2010-12-01

Full Text Available Several studies have shown that blood pressure can be lowered by the use of drugs that are not traditional antihypertensive drugs. This might be of clinical importance when many risk patients are treated by combination drug therapy in order to prevent cardiovascular disease by way of improving the cardiovascular risk factor profile.

Ambulatory Blood Pressure Monitoring for the Effective Management of Antihypertensive Drug Treatment.

Science.gov (United States)

O'Brien, Eoin; Dolan, Eamon

2016-10-01

This purpose of this article is to review the current recommendations for ambulatory blood pressure measurement (ABPM) and the use of ABPM in assessing treatment. We review current international guidelines and undertake a critical review of evidence supporting the clinical use of ABPM in effectively managing antihypertensive drug treatment. Current guidelines emphasize the diagnostic superiority of ABPM, mainly from the ability of the technique to identify sustained hypertension by allowing for the exclusion of white-coat hypertension and by demonstrating the presence of masked hypertension. ABPM also offers diagnostic insights into nocturnal patterns of blood pressure, such as dipping and nondipping, reverse dipping, and excessive dipping, and the presence of nocturnal hypertension; although less attention is given to the nocturnal behavior of blood pressure in clinical practice, the nocturnal patterns of blood pressure have particular relevance in assessing the response to blood pressure-lowering medication. Surprisingly, although the current guidelines give detailed recommendations on the diagnostic potential and use of ABPM, there are scant recommendations on the benefits and application of the technique for the initiation of blood pressure-lowering therapy in clinical practice and virtually no recommendations on how it might be used to assess the efficacy of drug treatment. In view of a deficiency in the literature on the role of ABPM in assess the efficacy of drug treatment, we put forward proposals to correct this deficiency and guide the prescribing physician on the most appropriate drug administration and dosage over time. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

[Blood components: Are they drugs or special medicines?].

Science.gov (United States)

Garraud, O; Tissot, J-D

2016-09-01

Blood transfusion and plasma derived-drugs significantly differ from other medicines in that their availability strictly depends on blood and plasma collected from healthy donors. Blood collection must comply with a double objective: to maintain donor heath safety, and to avoid any transmitted infections in recipients. This raises several ethical concerns that appear to be different from usual ethical and deontological issues linked to other pharmaceutical and industrial processes. The main concern is the non-commercialization of the human body. Words and concept are of major importance in this context. This short review aims at presenting the main issues relevant to those questions with respect to the various stakeholders. Copyright © 2016. Published by Elsevier SAS.

Therapeutic approach to patients complaining of high blood pressure in a cardiological emergency room

Directory of Open Access Journals (Sweden)

Miguel Gus

1999-03-01

Full Text Available OBJECTIVE: To evaluate the management of patients complaining of high blood pressure (BP in a cardiological emergency room. METHODS: Patients referred to the cardiological emergency room with the main complaint of high blood pressure were consecutively selected. The prescriptions and the choice of antihypertensive drugs were assessed. The classification of these patients as hypertensive emergencies or pseudoemergencies, according to the physician who provided initial care, was recorded. RESULTS: From a total of 858 patients presenting to the emergency room, 80 (9.3% complained of high BP, and 61 (76.3% received antihypertensive drugs. Sublingual nifedipine was the most commonly used drug (59%. One patient received intravenous medication, one patient was hospitalized and 6 patients (7.5% were classified as hypertensive emergencies or pseudoemergencies. CONCLUSION: High BP could seldom be classified as a hypertensive emergency or pseudoemergency, even though it was a frequent complaint (9.3% of visits. Currently, the therapeutic approach is not recommended, even in specialized clinics.

Hyperglycemia (High Blood Glucose)

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Full Text Available ... Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High ... We Are Research Leaders We Support Your Doctor Student Resources Patient Access to Research Research Resources Practice ...

High Blood Pressure Facts

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... Stroke Heart Disease Cholesterol Salt Million Hearts® WISEWOMAN High Blood Pressure Facts Recommend on Facebook Tweet Share Compartir On ... Top of Page CDC Fact Sheets Related to High Blood Pressure High Blood Pressure Pulmonary Hypertension Heart Disease Signs ...

High Blood Pressure (Hypertension)

Science.gov (United States)

... Print Page Text Size: A A A Listen High Blood Pressure (Hypertension) Nearly 1 in 3 American adults has ... weight. How Will I Know if I Have High Blood Pressure? High blood pressure is a silent problem — you ...

NSAID-antihypertensive drug interactions: Which outpatients are at risk for a rise in systolic blood pressure?

NARCIS (Netherlands)

Floor-Schreudering, Annemieke; De Smet, Peter Agm; Buurma, Henk; Kramers, Cornelis; Tromp, P. Chris; Belitser, Svetlana V.; Bouvy, Marcel L.

2015-01-01

Background: Management guidelines for drug-drug interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensives recommend blood pressure monitoring in hypertensive patients. We measured the short-term effect of initiating NSAIDs on systolic blood pressure (SBP) in users of

NSAID-antihypertensive drug interactions: which outpatients are at risk for a rise in systolic blood pressure?

NARCIS (Netherlands)

Floor-Schreudering, A.; Smet, P.A.G.M. de; Buurma, H.; Kramers, C.; Tromp, P.C.; Belitser, S.V.; Bouvy, M.L.

2015-01-01

BACKGROUND: Management guidelines for drug-drug interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensives recommend blood pressure monitoring in hypertensive patients. We measured the short-term effect of initiating NSAIDs on systolic blood pressure (SBP) in users of

Screening for illicit and medicinal drugs in whole blood using fully automated SPE and ultra-high-performance liquid chromatography with TOF-MS with data-independent acquisition.

Science.gov (United States)

Pedersen, Anders Just; Dalsgaard, Petur Weihe; Rode, Andrej Jaroslav; Rasmussen, Brian Schou; Müller, Irene Breum; Johansen, Sys Stybe; Linnet, Kristian

2013-07-01

A broad forensic screening method for 256 analytes in whole blood based on a fully automated SPE robotic extraction and ultra-high-performance liquid chromatography (UHPLC) with TOF-MS with data-independent acquisition has been developed. The limit of identification was evaluated for all 256 compounds and 95 of these compounds were validated with regard to matrix effects, extraction recovery, and process efficiency. The limit of identification ranged from 0.001 to 0.1 mg/kg, and the process efficiency exceeded 50% for 73 of the 95 analytes. As an example of application, 1335 forensic traffic cases were analyzed with the presented screening method. Of these, 992 cases (74%) were positive for one or more traffic-relevant drugs above the Danish legal limits. Commonly abused drugs such as amphetamine, cocaine, and frequent types of benzodiazepines were the major findings. Nineteen less frequently encountered drugs were detected e.g. buprenorphine, butylone, cathine, fentanyl, lysergic acid diethylamide, m-chlorophenylpiperazine, 3,4-methylenedioxypyrovalerone, mephedrone, 4-methylamphetamine, p-fluoroamphetamine, and p-methoxy-N-methylamphetamine. In conclusion, using UHPLC-TOF-MS screening with data-independent acquisition resulted in the detection of common drugs of abuse as well as new designer drugs and more rarely occurring drugs. Thus, TOF-MS screening of blood samples constitutes a practical way for screening traffic cases, with the exception of δ-9-tetrahydrocannabinol, which should be handled in a separate method. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High blood sugar

Science.gov (United States)

... Alternative Names Hyperglycemia - self care; High blood glucose - self care; Diabetes - high blood sugar References American Diabetes Association. Standards of medical care in diabetes - 2017: 4. Lifestyle management and 6. Glycemic targets. Diabetes Care . 2017;40( ...

Red Blood Cell Membrane-Cloaked Nanoparticles For Drug Delivery

Science.gov (United States)

Carpenter, Cody Westcott

Herein we describe the development of the Red Blood Cell coated nanoparticle, RBC-NP. Purified natural erythrocyte membrane is used to coat drug-loaded poly(lacticco-glycolic acid) (PLGA). Synthetic PLGA co-polymer is biocompatible and biodegradable and has already received US FDA approval for drug-delivery and diagnostics. This work looks specifically at the retention of immunosuppressive proteins on RBC-NPs, right-sidedness of natural RBC membranes interfacing with synthetic polymer nanoparticles, sustained and retarded drug release of RBC-NPs as well as further surface modification of RBC-NPs for increased targeting of model cancer cell lines.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ... you should check and what your blood glucose levels should be. Checking your blood and then treating ...

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... Your Carbs Count Glycemic Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get ... the technical term for high blood glucose (blood sugar). High blood glucose happens when the body has ...

Blood pressure reduction, persistence and costs in the evaluation of antihypertensive drug treatment – a review

Directory of Open Access Journals (Sweden)

Hasford Joerg

2009-03-01

Full Text Available Abstract Background Blood pressure lowering drugs are usually evaluated in short term trials determining the absolute blood pressure reduction during trough and the duration of the antihypertensive effect after single or multiple dosing. A lack of persistence with treatment has however been shown to be linked to a worse cardiovascular prognosis. This review explores the blood pressure reduction and persistence with treatment of antihypertensive drugs and the cost consequences of poor persistence with pharmaceutical interventions in arterial hypertension. Methods We have searched the literature for data on blood pressure lowering effects of different antihypertensive drug classes and agents, on persistence with treatment, and on related costs. Persistence was measured as patients' medication possession rate. Results are presented in the form of a systematic review. Results Angiotensin II receptor blocker (ARBs have a competitive blood pressure lowering efficacy compared with ACE-inhibitors (ACEi and calcium channel blockers (CCBs, beta-blockers (BBs and diuretics. 8 studies describing the persistence with treatment were identified. Patients were more persistent on ARBs than on ACEi and CCBs, BBs and diuretics. Thus the product of blood pressure lowering and persistence was higher on ARBs than on any other drug class. Although the price per tablet of more recently developed drugs (ACEi, ARBs is higher than that of older ones (diuretics and BBs, the newer drugs result in a more favourable cost to effect ratio when direct drug costs and indirect costs are also considered. Conclusion To evaluate drugs for the treatment of hypertension several key variables including the blood pressure lowering effect, side effects, compliance/persistence with treatment, as well as drug costs and direct and indirect costs of medical care have to be considered. ARBs, while nominally more expensive when drug costs are considered only, provide substantial cost savings

Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine.

Science.gov (United States)

Wu, Yu-Wen; Goubran, Hadi; Seghatchian, Jerard; Burnouf, Thierry

2016-04-01

Therapeutic and diagnostic applications of nanomedicine are playing increasingly important roles in human health. Various types of synthetic nanoparticles, including liposomes, micelles, and other nanotherapeutic platforms and conjugates, are being engineered to encapsulate or carry drugs for treating diseases such as cancer, cardiovascular disorders, neurodegeneration, and inflammations. Nanocarriers are designed to increase the half-life of drugs, decrease their toxicity and, ideally, target pathological sites. Developing smart carriers with the capacity to deliver drugs specifically to the microenvironment of diseased cells with minimum systemic toxicity is the goal. Blood cells, and potentially also the liposome-like micro- and nano-vesicles they generate, may be regarded as ideally suited to perform such specific targeting with minimum immunogenic risks. Blood cell membranes are "decorated" with complex physiological receptors capable of targeting and communicating with other cells and tissues and delivering their content to the surrounding pathological microenvironment. Blood cells, such as erythrocytes, have been developed as permeable carriers to release drugs to diseased tissues or act as biofactory allowing enzymatic degradation of a pathological substrate. Interestingly, attempts are also being made to improve the targeting capacity of synthetic nanoparticles by "decorating" their surface with blood cell membrane receptor-like biochemical structures. Research is needed to further explore the benefits that blood cell-derived microvesicles, as a Trojan horse delivery systems, can bring to the arsenal of therapeutic micro- and nanotechnologies. This short review focuses on the therapeutic roles that red blood cells and platelets can play as smart drug-delivery systems, and highlights the benefits that blood transfusion expertise can bring to this exciting and novel biomedical engineering field. Copyright © 2016 Elsevier Ltd. All rights reserved.

High Blood Pressure (Hypertension) (For Parents)

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... Safe Videos for Educators Search English Español Hypertension (High Blood Pressure) KidsHealth / For Parents / Hypertension (High Blood Pressure) What's ... High Blood Pressure) Treated? Print What Is Hypertension (High Blood Pressure)? Blood pressure is the pressure of blood against ...

Smuggling Drugs into the Brain : An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood-Brain Barrier

NARCIS (Netherlands)

Zuhorn, Inge; Georgieva, Julia V.; Hoekstra, Dick

2015-01-01

The blood-brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics

Toxicological screening of basic drugs in whole blood using UPLC-TOF-MS

DEFF Research Database (Denmark)

Dalsgaard, Petur Weihe; Rasmussen, Brian Schou; Müller, Irene Breum

2012-01-01

Ultra performance liquid chromatography (UPLC) coupled with time-of-flight (TOF) mass spectrometry (MS) was established for toxicological screening of basic drugs in whole blood and tested on authentic samples. Whole blood samples (0.2 ml) were extracted using a Gilson apparatus equipped with Bond...

Exercise: A Drug-Free Approach to Lowering High Blood Pressure

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... your blood pressure low, you need to keep exercising on a regular basis. It takes about one to three months for regular exercise to have an impact on your blood pressure. The benefits last only as long as you continue to ...

[Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain].

Science.gov (United States)

Domínguez, Alazne; Álvarez, Antonia; Suárez-Merino, Blanca; Goñi-de-Cerio, Felipe

2014-03-01

The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents' entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases.

Association between Selective Beta-adrenergic Drugs and Blood Pressure Elevation: Data Mining of the Japanese Adverse Drug Event Report (JADER) Database.

Science.gov (United States)

Ohyama, Katsuhiro; Inoue, Michiko

2016-01-01

Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events.

Routes for drug translocation across the blood-brain barrier

DEFF Research Database (Denmark)

Kristensen, Mie; Brodin, Birger

2017-01-01

A number of potent drugs for the treatment of brain diseases are available. However, in order for them to reach their target site of action, they must pass the blood-brain barrier (BBB). The capillary endothelium comprises the major barrier of the BBB and allows only passive permeation of some...... small lipophilic molecules. Brain delivery of the larger biopharmaceuticals, which today includes an increasing number of novel drug entities, is therefore restricted; both due to their molecular size and their hydrophilic nature. Thus, the development of novel drug entities intended for the treatment...... of brain diseases such as neurodegenerative diseases or brain cancers, require a delivery strategy for overcoming the BBB before reaching its final target within the brain. Peptide-based delivery vectors is an emerging tool as shuttles for drug delivery across the BBB and one may explore receptor...

Current Trends of Drug Resistance Patterns of Acinetobacter baumannii Infection in Blood Transfusion-dependent Thalassemia Patients.

Science.gov (United States)

Almani, Suhail Ahmed; Naseer, Ali; Maheshwari, Sanjay Kumar; Maroof, Pir; Naseer, Raza; Khoharo, Haji Khan

2017-01-01

The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients. This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016. Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA) was also used for identification. Data were analyzed on Statisti × 8.1 (USA). Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female ( P = 0.0001). Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8%) patients showed growth of A. baumannii . Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin. The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.

Modelling applied to PET-studies ont blood-brain transfer of 11-C-labelled drugs in the dog

International Nuclear Information System (INIS)

Agon, P.; Kaufman, J.M.

1989-01-01

Positron emission tomograph (PET) allows the 'in vivo' monitoring of changes in tissue concentrations of a labelled compounds. In order to validate the technique for the study of the early distribution of drugs into the braiin occuring following intravenous administration. The distribution in anaesthetized dogs of several 11-C-labelled drugs with known physicochemical and pharmacokinetic properties was studied. Twenty five sequential scans of a single slice of the head were performed using a Neuro-ECAT positron camera over 90 minutes following intravenous administration. Arterial blood samples were obtained for monitoring of blood and plasma radioactivity. Blood-brain transfer of the drugs was also studied after blood-brain barrier disruption by intracarotid infusion of a hyperosmolar mannitol solution. A qualitative evaluation of drug distribution can be done by visual inspection of the radioactivity concentration-time curves obtained for blood and tissues; for a quantitative evaluation a mathematical approach was required. A four compartment unit-membrane model can be suggested as a generally applicable model. For all the drugs studied, a model with 2 compartments described the course of the radioactivity quite well. In experiments with blood-brain barrier disruption the conditions for blood-brain exchange are changed and a 4 compartment model was required to describe adequately the course of the radioactivity. The results obtained when applying these models to sets of data for different drugs, were in good agreement with their known properties. (author). 4 refs.; 4 figs

Hyperglycemia (High Blood Glucose)

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[The oral cavity condition in patients with high blood pressure].

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Rosiak, Joanna; Kubić-Filiks, Beata; Szymańska, Jolanta

2015-10-01

The incidence of high blood pressure in adults is estimated at ca. 30-40% of the general population. Both hypertension disease and hypertensive drugs affect the condition of the patients' oral cavity. A review of the current literature shows that disorders most frequently found in the masticatory organ of patients with hypertension include: xerostomia, changes in salivary glands, gum hypertrophy, lichenoid lesions, taste disorders, and paraesthesias. The authors emphasize that patients with high blood pressure, along with the treatment of the underlying disease, should receive prophylactic and therapeutic dental care. This would enable reduction and/or elimination of unpleasant complaints, and also help prevent the emergence of secondary disorders in the patients' oral cavity as a result of hypertension pharmacotherapy. © 2015 MEDPRESS.

Fabric phase sorptive extraction-high performance liquid chromatography-photo diode array detection method for simultaneous monitoring of three inflammatory bowel disease treatment drugs in whole blood, plasma and urine.

Science.gov (United States)

Kabir, Abuzar; Furton, Kenneth G; Tinari, Nicola; Grossi, Laurino; Innosa, Denise; Macerola, Daniela; Tartaglia, Angela; Di Donato, Valentina; D'Ovidio, Cristian; Locatelli, Marcello

2018-05-01

This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-photodiode array detection (FPSE-HPLC-PDA) method for the simultaneous extraction and analysis of three drug residues (ciprofloxacin, sulfasalazine, and cortisone) in human whole blood, plasma, and urine samples, generally administered in human patients to treat inflammatory bowel disease (IBD). The drugs of interest were well resolved using a Luna C 18 column (250 mm × 4.6 mm; 5 μm particle size) in gradient elution mode within 20 min. The analytical method was optimized and validated in the range 0.05-10 μg/mL for whole blood, 0.25-10 μg/mL for human plasma, and 0.10-10 μg/mL for human urine. Blank human whole blood, plasma, and urine were used as the sample matrix for the method development and validation; while methyl-p-hydroxybenzoate was used as the internal standard (IS). Weighted-matrix matched standard calibration curves showed a good linearity up to a concentration of 10 μg/mL. The intra- and inter-day accuracy values (precision and trueness) were found in the range from -10.9% to 12.3%, and the performances of the validated FPSE-HPLC-PDA were further tested on real IBD patient samples. This is the first FPSE procedure applied simultaneously to whole blood, plasma, and urine samples for the determination of residual IBD drugs, which possess a wide range of polarity (logP values ranging from 2.30 for Ciprofloxacin, to 1.66 for Cortisone, and 2.92 for Sulfasalazine). The new approach exhibits high potential for immediate adoptation as a rapid, robust and green analytical tool for future clinical and pharmaceutical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Controlling your high blood pressure

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... medlineplus.gov/ency/patientinstructions/000101.htm Controlling your high blood pressure To use the sharing features on this page, ... JavaScript. Hypertension is another term used to describe high blood pressure. High blood pressure can lead to: Stroke Heart ...

Hyperglycemia (High Blood Glucose)

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Determination of the total drug-related chlorine and bromine contents in human blood plasma using high performance liquid chromatography-tandem ICP-mass spectrometry (HPLC-ICP-MS/MS).

Science.gov (United States)

Klencsár, Balázs; Bolea-Fernandez, Eduardo; Flórez, María R; Balcaen, Lieve; Cuyckens, Filip; Lynen, Frederic; Vanhaecke, Frank

2016-05-30

A fast, accurate and precise method for the separation and determination of the total contents of drug-related Cl and Br in human blood plasma, based on high performance liquid chromatography - inductively coupled plasma - tandem mass spectrometry (HPLC-ICP-MS/MS), has been developed. The novel approach was proved to be a suitable alternative to the presently used standard methodology (i.e. based on a radiolabelled version of the drug molecule and radiodetection), while eliminating the disadvantages of the latter. Interference-free determination of (35)Cl has been accomplished via ICP-MS/MS using H2 as reaction gas and monitoring the (35)ClH2(+) reaction product at mass-to-charge ratio of 37. Br could be measured "on mass" at a mass-to-charge of 79. HPLC was relied on for the separation of the drug-related entities from the substantial amount of inorganic Cl. The method developed was found to be sufficiently precise (repeatability 0.990) from the limit of quantification (0.05 and 0.01 mg/L for Cl and Br in blood plasma, respectively) to at least 5 and 1mg/L for Cl and Br, respectively. Quantification via either external or internal standard calibration provides reliable results for both elements. As a proof-of-concept, human blood plasma samples from a clinical study involving a newly developed Cl- and Br-containing active pharmaceutical ingredient were analysed and the total drug exposure was successfully described. Cross-validation was achieved by comparing the results obtained on Cl- and on Br-basis. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyperglycemia (High Blood Glucose)

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High blood pressure - children

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... this page: //medlineplus.gov/ency/article/007696.htm High blood pressure - children To use the sharing features on this page, please enable JavaScript. High blood pressure (hypertension) is an increase in the force of ...

High blood pressure - infants

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... this page: //medlineplus.gov/ency/article/007329.htm High blood pressure - infants To use the sharing features on this page, please enable JavaScript. High blood pressure (hypertension) is an increase in the force of ...

Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application

Science.gov (United States)

Dancik, Yuri; Anissimov, Yuri G; Jepps, Owen G; Roberts, Michael S

2012-01-01

AIMS To relate the varying dermal, subcutaneous and muscle microdialysate concentrations found in man after topical application to the nature of the drug applied and to the underlying physiology. METHODS We developed a physiologically based pharmacokinetic model in which transport to deeper tissues was determined by tissue diffusion, blood, lymphatic and intersitial flow transport and drug properties. The model was applied to interpret published human microdialysis data, estimated in vitro dermal diffusion and protein binding affinity of drugs that have been previously applied topically in vivo and measured in deep cutaneous tissues over time. RESULTS Deeper tissue microdialysis concentrations for various drugs in vivo vary widely. Here, we show that carriage by the blood to the deeper tissues below topical application sites facilitates the transport of highly plasma protein bound drugs that penetrate the skin, leading to rapid and significant concentrations in those tissues. Hence, the fractional concentration for the highly plasma protein bound diclofenac in deeper tissues is 0.79 times that in a probe 4.5 mm below a superficial probe whereas the corresponding fractional concentration for the poorly protein bound nicotine is 0.02. Their corresponding estimated in vivo lag times for appearance of the drugs in the deeper probes were 1.1 min for diclofenac and 30 min for nicotine. CONCLUSIONS Poorly plasma protein bound drugs are mainly transported to deeper tissues after topical application by tissue diffusion whereas the transport of highly plasma protein bound drugs is additionally facilitated by convective blood, lymphatic and interstitial transport to deep tissues. PMID:21999217

Phytotherapy of High Blood Pressure in Three Phytogeographic Regions of Cameroon.

Science.gov (United States)

Tsabang, Nole; Yedjou, Clement G; Tchounwou, Paul B

2017-01-01

High blood pressure is a public health challenge worldwide. According to World Health Organization, 30% of men and 50% of women 65 to 75 years old are suffering from high blood pressure. The number of hypertensive patients in the world will attain 1.56 billion of people, with 60% increase in prevalence. The incidence of high blood pressure increases with age, but nowadays, is being noticed an increasing incidence in young people. The socio-cultural medicine may provide new solutions in the management of this pathology. Therefore this study was carried out to record and document plants used against high blood pressure in socio-cultural medicine for future drugs discovery worldwide. An ethno botanical survey was realized between 2002 and 2016 to identify manifold plants used to fight against high blood pressure. This survey was carried out in three phytogeographic regions of Cameroon. Amongst people living in those regions, 1131 randomly screened interviewees distributed in 58 socio-cultural groups were involved in this study. This survey reveals that about 70% of interviewees don't know high blood pressure which is a symptomless disease. A total of 28 species of plants were recorded. These plants belong to 25 genera and 24 families. They were used to prepare 28 herbal remedies for the treatment of high blood pressure. In the morphological point of view about 10/28 (36%) plants are herbs; 9/28 (32%) plants are trees and 9/28 (32%) plants are shrubs. Only 3/28 plants (11%) used including Allium sativum, Aloe barteri and Aloe buttneri) are cultivated. This means that the plants used in this study don't usually have some form of protection through cultivation which is encouraging in terms of their conservation. The uncontrolled use of a hypotensive plants can provoke a fatal hypotension in hypertensive patients. Therefore the use of hypotensive plants needs to be controlled by physician or by a patient verification using a blood pressure monitor. Recorded species which

High blood pressure medications

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... this page: //medlineplus.gov/ency/article/007484.htm High blood pressure medicines To use the sharing features on this page, please enable JavaScript. Treating high blood pressure will help prevent problems such as heart disease, ...

Hyperglycemia (High Blood Glucose)

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Hyperglycemia (High Blood Glucose)

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Psoriasis and high blood pressure.

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Salihbegovic, Eldina Malkic; Hadzigrahic, Nermina; Suljagic, Edin; Kurtalic, Nermina; Sadic, Sena; Zejcirovic, Alema; Mujacic, Almina

2015-02-01

Psoriasis is a chronic skin ailment which can be connected with an increased occurrence of other illnesses, including high blood pressure. A prospective study has been conducted which included 70 patients affected by psoriasis, both genders, older than 18 years. Average age being 47,14 (SD= ±15,41) years, from that there were 36 men or 51,43 and 34 women or 48,57%. Average duration of psoriasis was 15,52 (SD=±12,54) years. Frequency of high blood pressure in those affected by psoriasis was 54,28%. Average age of the patients with psoriasis and high blood pressure was 53,79 year (SD=±14,15) and average duration of psoriasis was 17,19 years (SD=±13,51). Average values of PASI score were 16,65. Increase in values of PASI score and high blood pressure were statistically highly related (r=0,36, p=0,0001). Psoriasis was related to high blood pressure and there was a correlation between the severity of psoriasis and high blood pressure.

Hyperglycemia (High Blood Glucose)

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Preventing High Blood Pressure

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... Heart Disease Cholesterol Salt Million Hearts® WISEWOMAN Preventing High Blood Pressure: Healthy Living Habits Recommend on Facebook Tweet Share ... meal and snack options can help you avoid high blood pressure and its complications. Be sure to eat plenty ...

Effects of anesthetic agents on brain blood oxygenation level revealed with ultra-high field MRI

International Nuclear Information System (INIS)

Ciobanu, Luisa; Reynaud, Olivier; Le Bihan, Denis; Uhrig, Lynn; Jarraya, Bechir

2012-01-01

During general anesthesia it is crucial to control systemic hemodynamics and oxygenation levels. However, anesthetic agents can affect cerebral hemodynamics and metabolism in a drug-dependent manner, while systemic hemodynamics is stable. Brain-wide monitoring of this effect remains highly challenging. Because T2'*-weighted imaging at ultra-high magnetic field strengths benefits from a dramatic increase in contrast to noise ratio, we hypothesized that it could monitor anesthesia effects on brain blood oxygenation. We scanned rat brains at 7 T and 17.2 T under general anesthesia using different anesthetics (isoflurane, ketamine-xylazine, medetomidine). We showed that the brain/vessels contrast in T2'*- weighted images at 17.2 T varied directly according to the applied pharmacological anesthetic agent, a phenomenon that was visible, but to a much smaller extent at 7 T. This variation is in agreement with the mechanism of action of these agents. These data demonstrate that preclinical ultra-high field MRI can monitor the effects of a given drug on brain blood oxygenation level in the absence of systemic blood oxygenation changes and of any neural stimulation. (authors)

Hyperglycemia (High Blood Glucose)

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High Blood Pressure (Hypertension)

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... other risk factors, like diabetes, you may need treatment. How does high blood pressure affect pregnant women? A few women will get ... HIV, Birth Control Heart Health for Women Pregnancy Menopause More Women's Health ... High Blood Pressure--Medicines to Help You Women and Diabetes Heart ...

Hyperglycemia (High Blood Glucose)

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Hyperglycemia (High Blood Glucose)

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Distribution of blood derivatives by registered blood establishments that qualify as health care entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; delay of applicability date. Final rule; delay of applicability date.

Science.gov (United States)

2006-11-13

The Food and Drug Administration (FDA) is further delaying, until December 1, 2008, the applicability date of a certain requirement of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720) (the final rule). The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The provisions of the final rule became effective on December 4, 2000, except for certain provisions whose effective or applicability dates were delayed in five subsequent Federal Register notices, until December 1, 2006. The provision with the delayed applicability date would prohibit wholesale distribution of blood derivatives by registered blood establishments that meet the definition of a "health care entity." In the Federal Register of February 1, 2006 (71 FR 5200), FDA published a proposed rule specific to the distribution of blood derivatives by registered blood establishments that qualify as health care entities (the proposed rule). The proposed rule would amend certain limited provisions of the final rule to allow certain registered blood establishments that qualify as health care entities to distribute blood derivatives. In response to the proposed rule, FDA received substantive comments. As explained in the SUPPLEMENTARY INFORMATION section of this document, further delaying the applicability of Sec. 203.3(q) (21 CFR 203.3(q)) to the wholesale distribution of blood derivatives by health care entities is necessary to give the agency additional time to address comments on the proposed rule, consider whether regulatory changes are appropriate, and, if so, to initiate such changes.

Smart surface coating of drug nanoparticles with cross-linkable polyethylene glycol for bio-responsive and highly efficient drug delivery

Science.gov (United States)

Wei, Weijia; Zhang, Xiujuan; Chen, Xianfeng; Zhou, Mengjiao; Xu, Ruirui; Zhang, Xiaohong

2016-04-01

Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability

Targeted liposomes for drug delivery across the blood-brain barrier

NARCIS (Netherlands)

van Rooy, I.

2011-01-01

Our brain is protected by the blood-brain barrier (BBB). This barrier is formed by specialized endothelial cells of the brain vasculature and prevents toxic substances from entering the brain. The downside of this barrier is that many drugs that have been developed to cure brain diseases cannot

Prevalence of alcohol and other drugs and the concentrations in blood of drivers killed in road traffic crashes in Sweden.

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Ahlner, Johan; Holmgren, Anita; Jones, Alan Wayne

2014-03-01

Drunk or drug-impaired drivers represent a major public health and societal problem worldwide. Because over 95% of drivers killed on the roads in Sweden are autopsied, reliable information is available about the use of alcohol and/or other drug before the crash. This retrospective 4-year study (2008-2011) used a forensic toxicology database (TOXBASE) to evaluate the concentrations of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes. The mean age of all victims (N = 895) was 48 ± 20 years, and the majority were male (86%). In 504 drivers (56%), the results of toxicological analysis were negative and these victims were older; mean age (± SD) 47 ± 20 years, than alcohol positive cases (35 ± 14 years) and illicit drug users (34 ± 15 years). In 21% of fatalities, blood-alcohol concentration (BAC) was above the statutory limit for driving (0.2 g/L), although the median BAC was appreciably higher (1.72 g/L). Illicit drugs (mainly amphetamine and cannabis) were identified in ~7% of victims, either alone (2.5%), together with alcohol (1.8%) or a prescription drug (2%). The psychoactive prescription drugs identified were mainly benzodiazepines, z-hypnotics and tramadol, which were found in the blood of 7.6% of crash victims. The high median BAC in fatally-injured drivers speaks strongly towards alcohol-induced impairment as being responsible for the crash. Compared with alcohol, the prevalence of illicit and psychoactive prescription drugs was fairly low despite a dramatic increase in the number of drug-impaired drivers arrested by the police after a zero-tolerance law was introduced in 1999.

African Americans and High Blood Pressure

Science.gov (United States)

ANSWERS by heart Lifestyle + Risk Reduction High Blood Pressure What About African Americans and High Blood Pressure? African Americans in the U.S. have a higher prevalence of high blood pressure (HBP) than ...

When Blood Sugar Is Too High

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... Videos for Educators Search English Español When Blood Sugar Is Too High KidsHealth / For Teens / When Blood ... often can be unhealthy. What Is High Blood Sugar? The blood glucose level is the amount of ...

An in vivo approach for globally estimating the drug flow between blood and tissue for nafamostat mesilate: the main hydrolysis site determination in human.

Science.gov (United States)

Cao, Yan-Guang; Chen, Yuan-Cheng; Hao, Kun; Zhang, Ming; Liu, Xiao-Quan

2008-11-01

Nafamostat mesilate, an ester drug with extensive hydrolysis in vivo, exhibits species difference in the relative contribution for its hydrolysis in blood and tissues. For the rat, the main hydrolysis site may be blood and human may be tissue (mainly by liver). The paper gave in vivo evidence that human tissue may give more contribution for its hydrolysis. In the initial phase of drug administration, the drug accumulating level in tissue was low; the efflux fraction from tissue into blood can be ignorable comparing with the drug influx into tissue. Based on urine and plasma metabolite analysis, we concluded that in the initial phase almost all the drug hydrolysis in blood was excreted into urine. Then according to the initial urine metabolite analysis, we can estimate the drug hydrolysis rate in blood. The rate of drug diffusion from blood into tissues can be deduced based on the mass balance analysis of the initial blood drug. With the estimated rate constants, the drug efflux from tissues into blood was calculated according to equation: OFT-B (efflux from tissues) = OFB-U (blood hydrolysis fraction)+OFB-T (influx into tissues)-DB (hydrolysis in blood). The net flow (influent flux minus effluent flux) represented the drug hydrolysis fraction in tissue. As the result indicated, in human about 20% drug administrated was hydrolyzed in blood and nearly 80% in tissues. The relative hydrolysis fraction indicated that the main hydrolysis site in human body may locate in tissue, which was different to rats.

Influence of antiplatelet-anticoagulant drugs on the need of blood components transfusion after vesical transurethral resection

Directory of Open Access Journals (Sweden)

Alvaro Julio Virseda-Rodríguez

2015-07-01

Full Text Available Aims: The effect of the antithrombotic preventive therapy on haemorrhage keeps uncertain. We investigate the influence of the antiplatelet and anticoagulant drugs (AP/AC drugs on the transfusion requirement after vesical transurethral resection (VTUR. We also describe the epidemiology of the blood components transfusion in our department. Materials and Methods: Retrospective observational study of a series of patients needing blood transfusion at the Urology Department between June 2010 and June 2013. Selection of 100 consecutive patients who were transfused after VTUR due to bladder transitional cell carcinoma (BTCC (group A = GA. Control group: 100 consecutive patients who underwent VTUR due to BTCC and were not transfused (group B = GB. Transfusion criteria: Haemoglobin < 8 g/dl + anaemia symptoms. Age, gender, associated AP/AC treatment, secondary diagnoses, toxics, tumour stage and grade were analysed. Results: 212 patients required transfusion of a blood component. 169 were men (79% and 43 women (21%. Median age 77.59 years (SD 9.42, range 50-92. Secondary diagnoses: Diabetes Mellitus 64%, high blood pressure 77%, dyslipidemia 52%. 60% of patients were previously treated with AP/AC drugs. Average Haemoglobin pre-transfusion values: 7.4 g/dl (DE ± 0.7. Average Haemoglobin post-transfusion values: 8.9 g/Dl (DE ± 0.72. Most frequent transfusion indications were bladder cancer (37%, kidney cancer (11%, prostate cancer (8%, benign prostatic hyperplasia (BHP (8%, other urological diagnoses (36%. Intraoperative transfusions indicated by the anaesthesiologist: kidney cancer (33%, BPH (28%. Patients who underwent VTUR due to BTCC were older in GA (77.59 years SD 9.42 than in GB (68.98 years SD 11.78 (p = 0.0001. Similar gender distribution (15 women in GA and 24 in GB. Less patients were asked to keep their treatment with ASA 100mg (AcetylSalicylicAcid in GA (25.64% than in GB (50% (p = 0.0330. More aggressive tumour grade in GA (p = 0.0003 and

Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier

DEFF Research Database (Denmark)

Tornabene, Erica; Brodin, Birger

2016-01-01

of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain......Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food...... and Drug Administration-approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding...

Effects of anesthetic agents on brain blood oxygenation level revealed with ultra-high field MRI.

Directory of Open Access Journals (Sweden)

Luisa Ciobanu

Full Text Available During general anesthesia it is crucial to control systemic hemodynamics and oxygenation levels. However, anesthetic agents can affect cerebral hemodynamics and metabolism in a drug-dependent manner, while systemic hemodynamics is stable. Brain-wide monitoring of this effect remains highly challenging. Because T(2*-weighted imaging at ultra-high magnetic field strengths benefits from a dramatic increase in contrast to noise ratio, we hypothesized that it could monitor anesthesia effects on brain blood oxygenation. We scanned rat brains at 7T and 17.2T under general anesthesia using different anesthetics (isoflurane, ketamine-xylazine, medetomidine. We showed that the brain/vessels contrast in T(2*-weighted images at 17.2T varied directly according to the applied pharmacological anesthetic agent, a phenomenon that was visible, but to a much smaller extent at 7T. This variation is in agreement with the mechanism of action of these agents. These data demonstrate that preclinical ultra-high field MRI can monitor the effects of a given drug on brain blood oxygenation level in the absence of systemic blood oxygenation changes and of any neural stimulation.

What Is High Blood Pressure?

Science.gov (United States)

... Disease Venous Thromboembolism Aortic Aneurysm More What is High Blood Pressure? Updated:Feb 27,2018 First, let’s define high ... resources . This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

Drug and xenobiotic biotransformation in the blood-brain barrier: A neglected issue.

Directory of Open Access Journals (Sweden)

José A.G. Agúndez

2014-10-01

Full Text Available Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to BBB as a drug-metabolizing barrier. The presence of drug metabolizing enzymes in the BBB is likely to have functional implications because local metabolism may inactivate drugs or may modify the drug's ability to cross the BBB, thus modifying the drug response and the risk of developing adverse drug reactions. In this perspective paper, we discuss the expression of relevant xenobiotic metabolizing enzymes in the brain and in the BBB, and we cover current advances and future directions on the potential role of these BBB drug-metabolizing enzymes as modifiers of drug response.

Cerebral blood flow autoregulation in hypertension and effects of antihypertensive drugs

DEFF Research Database (Denmark)

Barry, David; Lassen, N A

1984-01-01

If antihypertensive treatment, especially emergency blood pressure lowering, is always to be safe, more thought should be given to autoregulation of cerebral blood in the hypertensive patient. This topic is reviewed in the present article, in the hypertensive patient. This topic is reviewed...... in the present article, particular emphasis being placed on the resetting of the lower limit of autoregulation to higher pressure in hypertension and the effects of acute administration of anti-hypertensive drugs on CBF and CBF-autoregulation....

High blood pressure: prevalence and adherence to guidelines in a population-based cohort.

Science.gov (United States)

Walther, Diana; Curjuric, Ivan; Dratva, Julia; Schaffner, Emmanuel; Quinto, Carlos; Rochat, Thierry; Gaspoz, Jean-Michel; Burdet, Luc; Bridevaux, Pierre-Olivier; Pons, Marco; Gerbase, Margaret W; Schindler, Christian; Probst-Hensch, Nicole

2016-01-01

High blood pressure, the single leading health risk factor worldwide, contributes greatly to morbidity and mortality. This study aimed to add to the understanding of diagnosed and undiagnosed high blood pressure in Switzerland and to evaluate adherence to hypertension guidelines. Included were 3962 participants from the first (2001-2003) and second (2010-2011) follow-ups of the population-based Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults. High blood pressure was defined as blood pressure ≥140/90 mm Hg and the prevalence of doctor-diagnosed hypertension was based on questionnaire information. High blood pressure was found in 34.9% of subjects, 49.1% of whom were unaware of this condition; 30.0% had doctor-diagnosed hypertension and, although 82.1% of these received drug treatments, in only 40.8% was blood pressure controlled (<140/90 mm Hg). Substantial first-line beta-blocker use and nonadherence to comorbidity-specific prescription guidelines were observed and remained mostly unexplained. Age-adjusted rates of unawareness and uncontrolled hypertension were more than 20% higher than in the USA. There is room for improvement in managing hypertension in Switzerland. Population-based observational studies are essential for identifying and evaluating unmet needs in healthcare; however, to pinpoint the underlying causes it is imperative to facilitate linkage of cohort data to medical records.

Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair.

Science.gov (United States)

Sharma, Aruna; Menon, Preeti; Muresanu, Dafin F; Ozkizilcik, Asya; Tian, Z Ryan; Lafuente, José V; Sharma, Hari S

2016-01-01

The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.

Experimental methods and transport models for drug delivery across the blood-brain barrier.

Science.gov (United States)

Fu, Bingmei M

2012-06-01

The blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the micro-environment of the brain. Although the special anatomical features of the BBB determine its protective role for the central nervous system (CNS) from blood-born neurotoxins, however, the BBB extremely limits the therapeutic efficacy of drugs into the CNS, which greatly hinders the treatment of major brain diseases. This review summarized the unique structures of the BBB, described a variety of in vivo and in vitro experimental methods for determining the transport properties of the BBB, e.g., the permeability of the BBB to water, ions, and solutes including nutrients, therapeutic agents and drug carriers, and presented newly developed mathematical models which quantitatively correlate the anatomical structures of the BBB with its barrier functions. Finally, on the basis of the experimental observations and the quantitative models, several strategies for drug delivery through the BBB were proposed.

Hyperglycemia (High Blood Glucose)

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Full Text Available ... breast cancer and AIDS combined. Your gift today will help us get closer to curing diabetes and ... blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. How ...

Hyperglycemia (High Blood Glucose)

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Full Text Available ... your blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. ... to detect hyperglycemia so you can treat it early — before it gets worse. If you're new ...

Drug accumulation by means of noninvasive magnetic drug delivery system

International Nuclear Information System (INIS)

Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.

2011-01-01

The medication is one of the most general treatment methods, but drugs diffuse in the normal tissues other than the target part by the blood circulation. Therefore, side effect in the medication, particularly for a drug with strong effect such as anti-cancer drug, are a serious issue. Drug Delivery System (DDS) which accumulates the drug locally in the human body is one of the techniques to solve the side-effects. Magnetic Drug Delivery System (MDDS) is one of the active DDSs, which uses the magnetic force. The objective of this study is to accumulate the ferromagnetic drugs noninvasively in the deep part of the body by using MDDS. It is necessary to generate high magnetic field and magnetic gradient at the target part to reduce the side-effects to the tissues with no diseases. The biomimetic model was composed, which consists of multiple model organs connected with diverged blood vessel model. The arrangement of magnetic field was examined to accumulate ferromagnetic drug particles in the target model organ by using a superconducting bulk magnet which can generate high magnetic fields. The arrangement of magnet was designed to generate high and stable magnetic field at the target model organ. The accumulation experiment of ferromagnetic particles has been conducted. In this study, rotating HTS bulk magnet around the axis of blood vessels by centering on the target part was suggested, and the model experiment for magnet rotation was conducted. As a result, the accumulation of the ferromagnetic particles to the target model organ in the deep part was confirmed.

High blood pressure and eye disease

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... this page: //medlineplus.gov/ency/article/000999.htm High blood pressure and eye disease To use the sharing features on this page, please enable JavaScript. High blood pressure can damage blood vessels in the retina . The ...

Common High Blood Pressure Myths

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... Disease Venous Thromboembolism Aortic Aneurysm More Common High Blood Pressure Myths Updated:May 4,2018 Knowing the facts ... This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

Medications for High Blood Pressure

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... Consumers Home For Consumers Consumer Updates Medications for High Blood Pressure Share Tweet Linkedin Pin it More sharing options ... age and you cannot tell if you have high blood pressure by the way you feel, so have your ...

High blood pressure and diet

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... this page: //medlineplus.gov/ency/article/007483.htm High blood pressure and diet To use the sharing features on ... diet is a proven way to help control high blood pressure . These changes can also help you lose weight ...

75 FR 73107 - Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability

Science.gov (United States)

2010-11-29

...] Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability AGENCY... announcing the availability of the guidance entitled ``Guidance for Industry and Food and Drug Administration... single copies of the guidance document entitled ``Guidance for Industry and Food and Drug Administration...

Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier

International Nuclear Information System (INIS)

Friden, P.M.; Walus, L.R.; Musso, G.F.; Taylor, M.A.; Malfroy, B.; Starzyk, R.M.

1991-01-01

Delivery of nonlipophilic drugs to the brain is hindered by the tightly apposed capillary endothelial cells that make up the blood-brain barrier. The authors have examined the ability of a monoclonal antibody (OX-26), which recognizes the rat transferrin receptor, to function as a carrier for the delivery of drugs across the blood-brain barrier. This antibody, which was previously shown to bind preferentially to capillary endothelial cells in the brain after intravenous administration, labels the entire cerebrovascular bed in a dose-dependent manner. The initially uniform labeling of brain capillaries becomes extremely punctate ∼ 4 hr after injection, suggesting a time-dependent sequestering of the antibody. Capillary-depletion experiments, in which the brain is separated into capillary and parenchymal fractions, show a time-dependent migration of radiolabeled antibody from the capillaries into the brain parenchyma, which is consistent with the transcytosis of compounds across the blood-brain barrier. Antibody-methotrexate conjugates were tested in vivo to assess the carrier ability of this antibody. Immunohistochemical staining for either component of an OX-26-methotrexate conjugate revealed patterns of cerebrovascular labeling identical to those observed with the unaltered antibody. Accumulation of radiolabeled methotrexate in the brain parenchyma is greatly enhanced when the drug is conjugated to OX-26

Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

Science.gov (United States)

van der Elst, Kim C. M.; Span, Lambert F. R.; van Hateren, Kai; Vermeulen, Karin M.; van der Werf, Tjip S.; Greijdanus, Ben; Kosterink, Jos G. W.; Uges, Donald R. A.

2013-01-01

Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P = 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling. PMID:23896473

Anxiety: A Cause of High Blood Pressure?

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... of high blood pressure? Can anxiety cause high blood pressure? Answers from Sheldon G. Sheps, M.D. Anxiety doesn't cause long-term high blood pressure (hypertension). But episodes of anxiety can cause dramatic, ...

High Blood Pressure - Multiple Languages

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... Being 8 - High Blood Pressure - Amarɨñña / አማርኛ (Amharic) MP3 Siloam Family Health Center Arabic (العربية) Expand Section ... Being 8 - High Blood Pressure - myanma bhasa (Burmese) MP3 Siloam Family Health Center Chinese, Simplified (Mandarin dialect) ( ...

Alcohol consumption and its impact on the risk of high blood pressure in Russia.

Science.gov (United States)

Akhmedjonov, Alisher; Suvankulov, Farrukh

2013-05-01

This study aims to examine the causal effect of alcohol consumption on the risk of high blood pressure in Russia. Using data from the Russian Longitudinal Monitoring Survey, we estimated the influence of alcohol consumption on high blood pressure, controlling for social and other factors related to alcohol use. To address the issue of causality, we instrumented alcohol consumption by the number of frequent alcohol drinkers in the household. We found that frequent consumption of vodka and beer has an adverse impact on health. In particular, frequent vodka consumption increases the likelihood of high blood pressure by 2.88% while frequent beer consumption increases it by 2.06%. Controlling for the endogeneity of frequent alcohol consumption using the instrumental variable method produces an even larger effect for frequent vodka consumption, with a marginal effect of 7.23%. Prevention policies as well as government programs aimed at treating alcohol-related health outcomes should take into consideration the significant adverse effect of alcohol consumption on high blood pressure. It is also recommended that policy interventions aimed to address alcohol addiction issues in Russia explicitly differentiate between vodka and beer drinkers. © 2012 Australasian Professional Society on Alcohol and other Drugs.

High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery.

Science.gov (United States)

Phenix, Christopher Peter; Togtema, Melissa; Pichardo, Samuel; Zehbe, Ingeborg; Curiel, Laura

2014-01-01

Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality. Indeed, HIFU has been used for the thermal ablation of pathological lesions; localized, minimally invasive ultrasound-mediated drug delivery through the transient formation of pores on cell membranes; the temporary disruption of skin and the blood brain barrier; the ultrasound induced break-down of blood clots; and the targeted release of drugs using ultrasound and temperature sensitive drug carriers. This review seeks to engage the pharmaceutical research community by providing an overview on the biological effects of ultrasound as well as highlighting important therapeutic applications, current deficiencies and future directions.

High Blood Pressure: Medicines to Help You

Science.gov (United States)

... For Consumers Consumer Information by Audience For Women High Blood Pressure--Medicines to Help You Share Tweet Linkedin Pin ... Click here for the Color Version (PDF 533KB) High blood pressure is a serious illness. High blood pressure is ...

Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs.

Science.gov (United States)

Skrzypecki, Janusz; Gawlak, Maciej; Huc, Tomasz; Szulczyk, Paweł; Ufnal, Marcin

2017-01-01

The effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.

Postmortem detection of hepatitis B, C, and human immunodeficiency virus genomes in blood samples from drug-related deaths in Denmark*

DEFF Research Database (Denmark)

Eriksen, Mette Brandt; Jakobsen, Marianne Antonius; Kringsholm, Birgitte

2009-01-01

Blood-borne viral infections are widespread among injecting drug users; however, it is difficult to include these patients in serological surveys. Therefore, we developed a national surveillance program based on postmortem testing of persons whose deaths were drug related. Blood collected...

Selective drug-induced reduction of blood flow in tumor transplants

International Nuclear Information System (INIS)

Knapp, W.H.; Debatin, J.; Layer, K.; Helus, F.; Altmann, A.; Sinn, H.J.; Ostertag, H.

1985-01-01

The effect of a calcium antagonist and a physiological amine on tumor and muscle perfusion was investigated with the aim of improving the preconditions for external hyperthermia treatment of cancer. Nisoldipine and 5-hydroxy tryptamine (5-HT) were administered ip in Sprague-Dawley rats bearing Walker 256 carcinoma, Yoshida sarcoma, or a homologous tumor transplant derived from a spontaneous leiomyosarcoma of the uterus. At the maximum dosage used, nisoldipine injection caused a decrease of the regional washout rate of Xenon-133 in the Walker carcinoma and an increase in the muscle of the hind leg. 5-HT caused a drop in the Walker carcinoma and only a slight fall of the washout rate in muscle. Tumor-to-muscle uptake ratios of 11 C-butanol fell. Both drugs representing two different rationales of vasomotor action were able to reduce blood flow specifically in transplanted tumors; nisoldipine increased muscle blood flow and decreased arterial blood pressure, whereas 5-HT acted without substantial systemic effects

78 FR 38994 - Implanted Blood Access Devices for Hemodialysis; Draft Guidance for Industry and Food and Drug...

Science.gov (United States)

2013-06-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0749] Implanted Blood Access Devices for Hemodialysis; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food...

Delivery of peptide and protein drugs over the blood-brain barrier.

Science.gov (United States)

Brasnjevic, Ivona; Steinbusch, Harry W M; Schmitz, Christoph; Martinez-Martinez, Pilar

2009-04-01

Peptide and protein (P/P) drugs have been identified as showing great promises for the treatment of various neurodegenerative diseases. A major challenge in this regard, however, is the delivery of P/P drugs over the blood-brain barrier (BBB). Intense research over the last 25 years has enabled a better understanding of the cellular and molecular transport mechanisms at the BBB, and several strategies for enhanced P/P drug delivery over the BBB have been developed and tested in preclinical and clinical-experimental research. Among them, technology-based approaches (comprising functionalized nanocarriers and liposomes) and pharmacological strategies (such as the use of carrier systems and chimeric peptide technology) appear to be the most promising ones. This review combines a comprehensive overview on the current understanding of the transport mechanisms at the BBB with promising selected strategies published so far that can be applied to facilitate enhanced P/P drug delivery over the BBB.

Sodium blood test

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... medicines that may affect the test. These include: Antibiotics Antidepressants Some high blood pressure medicines Lithium Nonsteroidal anti-inflammatory drugs (NSAIDs) Water pills (diuretics) DO NOT stop ...

High Blood Pressure

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... factors Diabetes High blood pressure Family history Obesity Race/ethnicity Full list of causes and risk factors ... give Give monthly Memorials and tributes Donate a car Donate gently used items Stock donation Workplace giving ...

High Blood Pressure

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... kidney disease, diabetes, or metabolic syndrome Read less Unhealthy lifestyle habits Unhealthy lifestyle habits can increase the risk of high blood pressure. These habits include: Unhealthy eating patterns, such as eating too much sodium ...

High Blood Pressure in Pregnancy

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... of the baby. Controlling your blood pressure during pregnancy and getting regular prenatal care are important for ... your baby. Treatments for high blood pressure in pregnancy may include close monitoring of the baby, lifestyle ...

What Is High Blood Pressure Medicine?

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... a medicine calendar. • Set a reminder on your smartphone. What types of medicine may be prescribed? One ... High Blood Pressure Medicine? What are their side effects? For many people, high blood pressure medicine can ...

In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma.

Directory of Open Access Journals (Sweden)

Susanna J E Veringa

Full Text Available Pediatric high-grade gliomas (pHGG, including diffuse intrinsic pontine gliomas (DIPG, are the leading cause of cancer-related death in children. While it is clear that surgery (if possible, and radiotherapy are beneficial for treatment, the role of chemotherapy for these tumors is still unclear. Therefore, we performed an in vitro drug screen on primary glioma cells, including three DIPG cultures, to determine drug sensitivity of these tumours, without the possible confounding effect of insufficient drug delivery. This screen revealed a high in vitro cytotoxicity for melphalan, doxorubicine, mitoxantrone, and BCNU, and for the novel, targeted agents vandetanib and bortezomib in pHGG and DIPG cells. We subsequently determined the expression of the drug efflux transporters P-gp, BCRP1, and MRP1 in glioma cultures and their corresponding tumor tissues. Results indicate the presence of P-gp, MRP1 and BCRP1 in the tumor vasculature, and expression of MRP1 in the glioma cells themselves. Our results show that pediatric glioma and DIPG tumors per se are not resistant to chemotherapy. Treatment failure observed in clinical trials, may rather be contributed to the presence of drug efflux transporters that constitute a first line of drug resistance located at the blood-brain barrier or other resistance mechanism. As such, we suggest that alternative ways of drug delivery may offer new possibilities for the treatment of pediatric high-grade glioma patients, and DIPG in particular.

DASH diet to lower high blood pressure

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... patientinstructions/000770.htm DASH diet to lower high blood pressure To use the sharing features on this page, ... Hypertension. The DASH diet can help lower high blood pressure and cholesterol and other fats in your blood. ...

Experimental Methods and Transport Models for Drug Delivery across the Blood-Brain Barrier

OpenAIRE

Fu, Bingmei M

2012-01-01

The blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the micro-environment of the brain. Although the special anatomical features of the BBB determine its protective role for the central nervous system (CNS) from blood-born neurotoxins, however, the BBB extremely limits the therapeutic efficacy of drugs into the CNS, which greatly hinders the treatment of major brain diseases. This review summarized the unique structures of the BBB, described a variety of in vivo and i...

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... Know Your Rights Employment Discrimination Health Care Professionals Law Enforcement Driver's License For Lawyers Food & Fitness Home ... symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ...

Hyperglycemia (High Blood Glucose)

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Full Text Available ... 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High ... What Can I Drink? Fruit Dairy Food Tips Eating Out Quick Meal Ideas Snacks Nutrient Content Claims ...

Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides as Delivery Vectors.

Science.gov (United States)

Kristensen, Mie; Brodin, Birger

2017-09-01

A number of potent drugs for the treatment of brain diseases are available. However, in order for them to reach their target site of action, they must pass the blood-brain barrier (BBB). The capillary endothelium comprises the major barrier of the BBB and allows only passive permeation of some small lipophilic molecules. Brain delivery of the larger biopharmaceuticals, which today includes an increasing number of novel drug entities, is therefore restricted, both due to their molecular size and their hydrophilic nature. Thus, the development of novel drug entities intended for the treatment of brain diseases such as neurodegenerative diseases or brain cancers require a delivery strategy for overcoming the BBB before reaching its final target within the brain. Peptide-based delivery vector is an emerging tool as shuttles for drug delivery across the BBB and one may explore receptor-mediated transcytosis, adsorptive-mediated transcytosis, and the paracellular route. The latter, however, being controversial due to the risk of co-delivery of blood-borne potential harmful substances. On the other hand, a number of studies report on drug delivery across the BBB exploiting receptor-mediated transcytosis and adsorptive-mediated transcytosis, indicating that peptides and peptide vectors may be of use in a central nervous system delivery context. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Prescriptive Oriented Drug Analysis of Multiple Sclerosis Disease by LC-UV in Whole Human Blood.

Science.gov (United States)

Suneetha, A; Rajeswari, Raja K

2016-02-01

As a polytherapy treatment, multiple sclerosis disease demands prescriptions with more than one drug. Polytherapy is sometimes rational for drug combinations chosen to minimize adverse effects. Estimation of drugs that are concomitantly administered in polytherapy is acceptable as it shortens the analytical timepoints and also the usage of biological matrices. In clinical phase trials, the withdrawal of biofluids is a critical issue for each analysis. Estimating all the coadminsitered drugs in a single shot will be more effective and economical for pharmaceuticals. A single, simple, rapid and sensitive high-performance liquid chromatography assay method has been developed with UV detection and fully validated for the quantification of 14 drugs (at random combinations) used in the treatment of multiple sclerosis disease. The set of combinations was based on prescriptions to patients. Separations were achieved on an X-Terra MS C18 (100 × 3.9 mm, 5 µm) column. The analytes were extracted from 50 µL aliquots of whole human blood with protein precipitation using acetonitrile. All the drugs were sufficiently stable during storage for 24 h at room temperature and for 23 days at 2-8°C. The percentage recoveries of all drugs were between 90 and 115%, with RSD values <10.6%. This method has been shown to be reproducible and sensitive and can be applied to clinical samples from pharmacokinetic studies and also a useful tool in studying the drug interaction studies. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Silica Coated Paper Substrate for Paper-Spray Analysis of Therapeutic Drugs in Dried Blood Spots

Science.gov (United States)

Zhang, Zhiping; Xu, Wei; Manicke, Nicholas E.; Cooks, R. Graham; Ouyang, Zheng

2011-01-01

Paper spray is a newly developed ambient ionization method that has been applied for direct qualitative and quantitative analysis of biological samples. The properties of the paper substrate and spray solution have a significant impact on the release of chemical compounds from complex sample matrices, the diffusion of the analytes through the substrate, and the formation of ions for mass spectrometry analysis. In this study, a commercially available silica-coated paper was explored in an attempt to improve the analysis of therapeutic drugs in dried blood spots (DBS). The dichloromethane/isopropanol solvent has been identified as an optimal spray solvent for the analysis. The comparison was made with paper spray using chromatography paper as substrate with methanol/water as solvent for the analysis of verapamil, citalopram, amitriptyline, lidocaine and sunitinib in dried blood spots. It has been demonstrated the efficiency of recovery of the analytes was notably improved with the silica coated paper and the limit of quantitation (LOQ) for the drug analysis was 0.1 ng mL−1 using a commercial triple quadrupole mass spectrometer. The use of silica paper substrate also resulted in a sensitivity improvement of 5-50 fold in comparison with chromatography papers, including the Whatmann ET31 paper used for blood card. Analysis using a handheld miniature mass spectrometer Mini 11 gave LOQs of 10~20 ng mL−1 for the tested drugs, which is sufficient to cover the therapeutic ranges of these drugs. PMID:22145627

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... around 4:00 a.m. to 5:00 a.m.). What are the Symptoms of Hyperglycemia? The signs and symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ...

Gastrointestinal blood loss induced by three different non-steroidal anti-inflammatory drugs.

Science.gov (United States)

Bidlingmaier, A; Hammermaier, A; Nagyiványi, P; Pabst, G; Waitzinger, J

1995-04-01

A clinical study was performed on 18 healthy volunteers to compare the gastrointestinal daily blood loss induced by oral intake of three different non-steroidal anti-inflammatory drugs, lysine clonixinate (CAS 55837-30-4), ibuprofen (CAS 15687-27-1) and acetylsalicylic acid (CAS 50-78-2 ASA). For quantitative determination of gastrointestinal blood loss, autologous erythrocytes were radiolabelled in vitro with 51Cr and reinfused at study start. The amount of radioactivity excreted in faeces was measured during a placebo baseline phase of three days, a treatment phase of five days with thrice daily dosing of ASA, ibuprofen or lysine clonixinate and a subsequent wash-out phase of five days. The highest increase of mean daily blood loss over baseline was observed after treatment with ASA (+ 1.66 ml/d versus baseline). Treatment with ibuprofen led to an increase of mean daily blood loss by + 0.52 ml/d. During treatment with lysine clonixinate the mean increase of daily blood loss was +0.32 ml/d versus baseline. In the ibuprofen and lysine clonixinate treatment groups the values of mean daily blood loss decreased during the wash-out phase with respect to the verum phase, whereas the mean daily blood loss during the wash-out phase after treatment with ASA even increased in comparison to the verum phase (mean daily blood loss: +2.07 ml/d versus baseline.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high ... function (data) { $('#survey-errors').remove(); $('.survey-form .form-group .survey-alert-wrap').remove(); if (data.submitSurveyResponse.success == ' ...

Nutrition label experience, obesity, high blood pressure, and high blood lipids in a cohort of 42,750 Thai adults.

Science.gov (United States)

Rimpeekool, Wimalin; Yiengprugsawan, Vasoontara; Kirk, Martyn; Banwell, Cathy; Seubsman, Sam-Ang; Sleigh, Adrian

2017-01-01

Nutrition labels have been promoted for nearly two decades in Thailand to educate people about healthy eating and to combat nutrient-related non-communicable diseases (NCDs). But little is known about how nutrition labels are experienced and whether they are linked with better health. Our objective was to investigate the associations between nutrition label experience, obesity and nutrient-related NCDs in Thai consumers. A cross-sectional study was undertaken with a nationwide cohort of 42,750 distance learning Thai adult students enrolled in an Open University in 2013. We measured exposure as nutrition label experience (read, understand, use). Health outcomes were high blood pressure, high blood lipids, and high Body Mass Index (overweight at risk and obesity). Multivariate logistic regression was used to determine the association between nutrition label experience and health outcome adjusting for sociodemographic attributes, physical activity, smoking, and alcohol intake. Frequent nutrition label use varied by cohort attributes and health outcomes and was least for those with low physical activity and high blood pressure. Being male, older, an urban resident or with low physical activity was associated with increasing high blood pressure and high blood lipids. Compared to those who read, understand and use nutrition labels, participants who did not (read, understand, and use), were more likely to report high blood pressure (Adjusted Odds Ratio 1.33; 1.17-1.51), high blood lipids (AOR 1.26; 1.14-1.39), and obesity (AOR 1.23; 1.13-1.33), but were not more likely to be overweight at risk (AOR 1.06; 0.97-1.16). We found cross-sectional associations between low nutrition label experience and increased likelihood of high blood pressure, high blood lipids, and obesity among Thai adults. Nutrition label education should be promoted as part of a public health approach to appropriate food choices and better lifestyles to reduce obesity and nutrient-related NCDs.

Nutrition label experience, obesity, high blood pressure, and high blood lipids in a cohort of 42,750 Thai adults.

Directory of Open Access Journals (Sweden)

Wimalin Rimpeekool

Full Text Available Nutrition labels have been promoted for nearly two decades in Thailand to educate people about healthy eating and to combat nutrient-related non-communicable diseases (NCDs. But little is known about how nutrition labels are experienced and whether they are linked with better health. Our objective was to investigate the associations between nutrition label experience, obesity and nutrient-related NCDs in Thai consumers.A cross-sectional study was undertaken with a nationwide cohort of 42,750 distance learning Thai adult students enrolled in an Open University in 2013. We measured exposure as nutrition label experience (read, understand, use. Health outcomes were high blood pressure, high blood lipids, and high Body Mass Index (overweight at risk and obesity. Multivariate logistic regression was used to determine the association between nutrition label experience and health outcome adjusting for sociodemographic attributes, physical activity, smoking, and alcohol intake.Frequent nutrition label use varied by cohort attributes and health outcomes and was least for those with low physical activity and high blood pressure. Being male, older, an urban resident or with low physical activity was associated with increasing high blood pressure and high blood lipids. Compared to those who read, understand and use nutrition labels, participants who did not (read, understand, and use, were more likely to report high blood pressure (Adjusted Odds Ratio 1.33; 1.17-1.51, high blood lipids (AOR 1.26; 1.14-1.39, and obesity (AOR 1.23; 1.13-1.33, but were not more likely to be overweight at risk (AOR 1.06; 0.97-1.16.We found cross-sectional associations between low nutrition label experience and increased likelihood of high blood pressure, high blood lipids, and obesity among Thai adults. Nutrition label education should be promoted as part of a public health approach to appropriate food choices and better lifestyles to reduce obesity and nutrient-related NCDs.

Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.

Science.gov (United States)

Kralberg, B E; Tolagen, K

1976-05-31

The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin

Hyperglycemia (High Blood Glucose)

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Full Text Available ... Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High ... Holiday Meal Planning What Can I Eat? Making Healthy Food Choices Diabetes ... Tips Eating Out Quick Meal Ideas Snacks Nutrient Content Claims ...

Access to and use of high blood pressure medications in Brazil.

Science.gov (United States)

Mengue, Sotero Serrate; Bertoldi, Andréa Dâmaso; Ramos, Luiz Roberto; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Tavares, Noemia Urruth Leão; Arrais, Paulo Sergio Dourado; Luiza, Vera Lucia; Pizzol, Tatiane da Silva Dal

2016-12-01

To analyze the access to and use of medicines for high blood pressure among the Brazilian population according to social and demographic conditions. Analysis of data from Pesquisa Nacional Sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), a nationwide cross-sectional, population-based study, with probability sampling, carried out between September 2013 and February 2014 in urban households in the five Brazilian regions. The study evaluated the access and use of medicines to treat people with high blood pressure. The independent variables were gender, age, socioeconomic status and Brazilian region. The study also described the most commonly used drugs and the percentage of people treated with one, two, three or more drugs. Point estimations and confidence intervals were calculated considering the sample weights and sample complex plan. Prevalence of high blood pressure was 23.7% (95%CI 22.8-24.6). Regarding people with this condition, 93.8% (95%CI 92.8-94.8) had indication for drug therapy and, of those, 94.6% (95%CI 93.5-95.5) were using the medication at the time of interview. Full access to medicines was 97.9% (95%CI 97.3-98.4); partial access, 1.9% (95%CI 1.4-2.4); and no access, 0.2% (95%CI 0.1-0.4). The medication used to treat high blood pressure, 56.0% (95%CI 52.6-59.2) were obtained from SUS (Brazilian Unified Health System), 16.0% (95%CI 14.3-17.9) from Popular Pharmacy Program, 25.7% (95%CI 23.4-28.2) were paid for by the patients themselves and 2.3% (95%CI 1.8-2.9) were obtained from other locations. The five most commonly used drugs were, in descending order, hydrochlorothiazide, losartan, captopril, enalapril and atenolol. Of the total number of patients on treatment, 36.1% (95%CI 34.1-37.1) were using two medicines and 13.5% (95%CI 12.3-14.9) used three or more. Access to medicines for the treatment of high blood pressure may be considered high

Clonidine versus captopril for treatment of postpartum very high blood pressure: study protocol for a randomized controlled trial (CLONCAP).

Science.gov (United States)

Noronha-Neto, Carlos; Katz, Leila; Coutinho, Isabela C; Maia, Sabina B; Souza, Alex Sandro Rolland; Amorim, Melania Maria Ramos

2013-07-30

The behavior of arterial blood pressure in postpartum of women with hypertension and pregnancy and the best treatment for very high blood pressure in this period still need evidence. The Cochrane systematic review assessing prevention and treatment of postpartum hypertension found only two trials (120 patients) comparing hydralazine with nifedipine and labetalol for the treatment of severe hypertension and did not find enough evidence to know how best to treat women with hypertension after birth. Although studies have demonstrated the effectiveness of treatment with captopril, side effects were reported. Because of these findings, new classes of antihypertensive drugs began to be administered as an alternative therapy. Data on the role of clonidine in this particular group of patients, its effects in the short and long term are still scarce in the literature. To determine the effectiveness of clonidine, compared to captopril, for the treatment of postpartum very high blood pressure in women with hypertension in pregnancy. The study is a triple blind randomized controlled trial including postpartum women with diagnosis of hypertension in pregnancy presenting very high blood pressure, and exclusion criteria will be presence of heart disease, smoking, use of illicit drugs, any contraindication to the use of captopril or clonidine and inability to receive oral medications.Eligible patients will be invited to participate and those who agree will be included in the study and receive captopril or clonidine according to a random list of numbers. The subjects will receive the study medication every 20 minutes until blood pressure is over 170 mmHg of systolic blood pressure and 110 mmHg diastolic blood pressure. A maximum of six pills a day for very high blood pressure will be administered. In case of persistent high blood pressure levels, other antihypertensive agents will be used.During the study the women will be subject to strict control of blood pressure and urine

HIGH BLOOD PRESSURE: DOES THIS CONCERN ME?

CERN Multimedia

2007-01-01

To find out, the Medical Service's nurses are organising A HIGH BLOOD PRESSURE SCREENING AND PREVENTION CAMPAIGN from Monday, 26th to Thursday, 29th March 2007 at the Infirmary - Building 57 - ground floor A blood pressure test, advice, information and, if necessary, referral for specialist medical treatment will be offered to any person working on the CERN site. High blood pressure is a silent threat to health. So come and get your blood pressure checked.

HIGH BLOOD PRESSURE: DOES THIS CONCERN ME?

CERN Multimedia

2007-01-01

To find out, the Medical Service's nurses are organising A HIGH BLOOD PRESSURE SCREENING AND PREVENTION CAMPAIGN from Monday, 26th to Thursday, 29th March 2007 at the Infirmary - Building 57 - ground floor A blood pressure test, advice, information and, if necessary, referral for specialist medical treatment will be offered to any person working on the CERN site. High blood pressure is a stealth threat to health. So come and get your blood pressure checked.

Changes in the regional cerebral blood flow after drug-induced blood-pressure reduction in patients with hypertensive intracerebral hemorrhages

International Nuclear Information System (INIS)

Kuwata, Noriyuki; Kuroda, Kiyoshi; Sato, Naoya; Konno, Hiromu; Iwabuchi, Takashi; Ogawa, Akira; Kanaya, Haruyuki.

1993-01-01

In patients with hypertensive intracerebral hemorrhages, changes in the regional cerebral blood flow (rCBF) after drug-induced blood-pressure reduction were examined by means of subtraction SPECT. The subjects were 38 patients with hypertensive intracerebral hemorrhages; 22 were putaminal hemorrhages (mean age, 56.8 years; mean hematoma volume, 18.4 cc), while 16 were thalamic hemorrhages (mean age, 61.9 years; mean hematoma volume, 7.8 cc). The rCBF was measured by means of SPECT (Tomomatic 64) with 133 Xe inhalation. Trimethaphan (an autonomic ganglion blocker) and diltiazem hydrochloride (a calcium antagonist) were used for the reduction of the blood pressure. The results were as follows: In the acute stage, the mean CBF was reduced when the blood pressure fell by more than 20% in both the putaminal hemorrhages and the thalamic hemorrhages. A similar tendency was observed in the subacute stage, except that a greater reduction in the blood pressure was needed to induce mean CBF reduction. The subtraction of rCBF maps before and after hypotension treatment shows a reduction of the rCBF in the lateral region of hematoma and the contralateral hemisphere. (author)

Continuing versus discontinuing antiplatelet drugs, vasodilators, and/or cerebral ameliorators on perioperative total blood loss in total knee arthroplasty without pneumatic tourniquet

Directory of Open Access Journals (Sweden)

Sachiyuki Tsukada, MD

2018-03-01

Full Text Available Background: Although studies have supported the utility of perioperative continuation of antiplatelet drugs, vasodilators, and cerebral ameliorators in most procedures, no study compared total volume of blood loss after total knee arthroplasty (TKA in patients continuing and discontinuing these drugs. Methods: We retrospectively reviewed 266 consecutive patients undergoing TKA, and included 67 patients (25.2% taking antiplatelet drugs, vasodilators, or cerebral ameliorators in this study. All TKAs were performed without a pneumatic tourniquet. The primary outcome was perioperative total blood loss calculated from blood volume and change in hemoglobin. As subgroup analysis, we compared perioperative total blood loss in patients taking antiplatelet drugs. Results: There was no significant difference between the continuing group (n = 38 and discontinuing group (n = 29 in terms of the perioperative total blood loss (1025 ± 364 vs 1151 ± 327 mL, respectively; mean difference 126 mL; 95% confidence interval −45 to 298 mL; P = .15. No major bleeding or thrombotic events occurred in either group until postoperative 3-month follow-up. In patients taking antiplatelet drugs (n = 51, no significant difference was observed in the total blood loss between the continuing group (n = 30 and discontinuing group (n = 21 (1056 ± 287 vs 1151 ± 305 mL, respectively; mean difference 95 mL; 95% confidence interval −75 to 264 mL; P = .27. Conclusions: No significant differences in terms of perioperative total blood loss were observed between patients continuing and discontinuing study drugs. Continuing these drugs may be preferable in the perioperative period of TKA. Keywords: Knee, Primary arthroplasty, Bleeding events, Thrombotic events, Noncardiac surgery

Effects of blood-activating and stasis-removing drugs combined with VEGF gene transfer on angiogenesis in ischemic necrosis of the femoral head.

Science.gov (United States)

Li, Jun-Hui; Wu, Ya-Ling; Ye, Jian-Hong; Ning, Ya-Gong; Yu, Hai-Ying; Peng, Zhong-Jie; Luan, Xiao-Wen

2009-09-01

To observe the promoting effects of blood-activating and stasis-removing Chinese drugs combined with vascular endothelial growth factor (VEGF) gene transfer on angiogenesis in ischemic necrosis of the femoral head. Forty Japanese giant-ear rabbits were randomly divided into a control group, a model group, a Chinese drug group, a gene group, and a combined group. After 8 weeks of treatment, the rate of VEGF positive cell expression in the synovium of the femoral head was measured using the immunohistochemical method, and the number of blood vessels in the femoral head was measured by digital subtraction angiography. The rate of VEGF positive cell expression in the model group was significantly lower than that in the Chinese drug group (P 0.05). Either the blood-activating and stasis-removing Chinese drugs or VEGF gene transfer can promote the angiogenesis and building of collateral circulation for femoral head ischemic necrosis, and the combined therapy with Chinese drugs or VEGF gene transfer may show a better therapeutic effect. The present study provides an experimental basis for clinical application of the combined therapy with the blood-activating and stasis-removing Chinese drugs and VEGF gene transfer.

Non-Steroidal Anti-Inflammatory Drug Use and Genomic DNA Methylation in Blood.

Directory of Open Access Journals (Sweden)

Lauren E Wilson

Full Text Available Non-steroidal anti-inflammatory drug (NSAID use is associated with decreased risk of some cancers. NSAID use modulates the epigenetic profile of normal colonic epithelium and may reduce risk of colon cancer through this pathway; however, the effect of NSAID use on the DNA methylation profile of other tissues including whole blood has not yet been examined.Using the Sister Study cohort, we examined the association between NSAID usage and whole genome methylation patterns in blood DNA. Blood DNA methylation status across 27,589 CpG sites was evaluated for 871 women using the Illumina Infinium HumanMethylation27 Beadchip, and in a non-overlapping replication sample of 187 women at 485,512 CpG sites using the Infinium HumanMethylation450 Beadchip. We identified a number of CpG sites that were differentially methylated in regular, long-term users of NSAIDs in the discovery group, but none of these sites were statistically significant in our replication group.We found no replicable methylation differences in blood related to NSAID usage. If NSAID use does effect blood DNA methylation patterns, differences are likely small.

Drug Reactions

Science.gov (United States)

... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

Stress and High Blood Pressure: What's the Connection?

Science.gov (United States)

Stress and high blood pressure: What's the connection? Stress and long-term high blood pressure may not be linked, but taking steps to reduce your stress can improve your general health, including your blood ...

Blood alcohol analysis alone versus comprehensive toxicological analysis - Systematic investigation of missed co-ingested other drugs in suspected alcohol-impaired drivers.

Science.gov (United States)

Steuer, Andrea E; Eisenbeiss, Lisa; Kraemer, Thomas

2016-10-01

Driving under the influence of alcohol and/or drugs (DUID) is a safety issue of increasing public concern. When a police officer has reasonable grounds to classify a driver as impaired, he may arrange for a blood sample to be taken. In many countries, alcohol analysis only is ordered if impairment is suspected to be exclusively due to alcohol while comprehensive toxicological screening will be performed if additional suspicion for other illegal drugs of abuse (DoA) or medicinal drugs is on hand. The aim of the present study was firstly to evaluate whether signs of impairment can be differentiated to be caused by alcohol alone or a combination of alcohol and other driving-impairing drugs and secondly to which extent additional drugs are missed in suspected alcohol-impaired drivers. A total of 293 DUID cases (negative n=41; alcohol positive only, n=131; alcohol+active drug positive, n=121) analyzed in 2015 in the Canton of Zurich were evaluated for their documented impairment symptoms by translating these into a severity score and comparing them applying principle component analysis (PCA). Additional 500 cases suspected for alcohol-impaired driving only were reanalyzed using comprehensive LC-MS/MS screening methods covering about 1500 compounds. Drugs detected were classified for severity of driving impairment using the classification system established in the DRUID study of the European Commission. As partly expected from the pharmacological and toxicological point of view, PCA analysis revealed no differences between signs of impairment caused by alcohol alone and those caused by alcohol plus at least one active drug. Breaking it down to different blood alcohol concentration ranges, only between 0.3 and 0.5g/kg trends could be observed in terms of more severe impairment for combined alcohol and drug intake. In the 500 blood samples retrospectively analyzed in this study, a total of 330 additional drugs could be detected; in some cases up to 9 co-ingested ones. In

"DRUG RESISTANCE PATTERN IN ISOLATED BACTERIA FROM BLOOD CULTURES"

Directory of Open Access Journals (Sweden)

A. Sobhani

2004-05-01

Full Text Available Bacteremia is an important infectious disease which may lead to death. Common bacteria and pattern of antibiotic resistance in different communities are different and understanding these differences is important. In the present study, relative frequency and pattern of drug resistance have been examined in bacteria isolated from blood cultures in Razi Hospital laboratory. The method of the study was descriptive. Data collection was carried out retrospectively. Total sample consisted of 311 positive blood cultures from 1999 to 2001. Variables under study were bacterial strains, antibiotics examined in antibiogram, microbial resistance, and patients' age and sex. The most common isolated bacteria were Salmonella typhi (22.2% and the least common ones were Citrobacter (1.6%. The highest antibiotic resistance was seen against amoxicillin (88.4%. The proportion of males to females was1: 1/1 and the most common age group was 15-44 (47.3%. Common bacteria and pattern of antibiotic resistance were different in some areas and this subject requires further studies in the future.

Dose critical in-vivo detection of anti-cancer drug levels in blood

Science.gov (United States)

Miller, Holly H.; Hirschfeld, deceased, Tomas B.

1991-01-01

A method and apparatus are disclosed for the in vivo and in vitro detection and measurement of dose critical levels of DNA-binding anti-cancer drug levels in biological fluids. The apparatus comprises a laser based fiber optic sensor (optrode) which utilizes the secondary interactions between the drug and an intercalating fluorochrome bound to a probe DNA, which in turn is attached to the fiber tip at one end thereof. The other end of the optical fiber is attached to an illumination source, detector and recorder. The fluorescence intensity is measured as a function of the drug concentration and its binding constant to the probe DNA. Anticancer drugs which lend themselves to analysis by the use of the method and the optrode of the present invention include doxorubicin, daunorubicin, carminomycin, aclacinomycin, chlorambucil, cyclophosphamide, methotrexate, 5-uracil, arabinosyl cytosine, mitomycin, cis-platinum 11 diamine dichloride procarbazine, vinblastine vincristine and the like. The present method and device are suitable for the continuous monitoring of the levels of these and other anticancer drugs in biological fluids such as blood, serum, urine and the like. The optrode of the instant invention also enables the measurement of the levels of these drugs from a remote location and from multiple samples.

Field study of dried blood spot specimens for HIV-1 drug resistance genotyping.

Science.gov (United States)

Parry, C M; Parkin, N; Diallo, K; Mwebaza, S; Batamwita, R; DeVos, J; Bbosa, N; Lyagoba, F; Magambo, B; Jordan, M R; Downing, R; Zhang, G; Kaleebu, P; Yang, C; Bertagnolio, S

2014-08-01

Dried blood spots (DBS) are an alternative specimen type for HIV drug resistance genotyping in resource-limited settings. Data relating to the impact of DBS storage and shipment conditions on genotyping efficiency under field conditions are limited. We compared the genotyping efficiencies and resistance profiles of DBS stored and shipped at different temperatures to those of plasma specimens collected in parallel from patients receiving antiretroviral therapy in Uganda. Plasma and four DBS cards from anti-coagulated venous blood and a fifth card from finger-prick blood were prepared from 103 HIV patients with a median viral load (VL) of 57,062 copies/ml (range, 1,081 to 2,964,191). DBS were stored at ambient temperature for 2 or 4 weeks or frozen at -80 °C and shipped from Uganda to the United States at ambient temperature or frozen on dry ice for genotyping using a broadly sensitive in-house method. Plasma (97.1%) and DBS (98.1%) stored and shipped frozen had similar genotyping efficiencies. DBS stored frozen (97.1%) or at ambient temperature for 2 weeks (93.2%) and shipped at ambient temperature also had similar genotyping efficiencies. Genotyping efficiency was reduced for DBS stored at ambient temperature for 4 weeks (89.3%, P = 0.03) or prepared from finger-prick blood and stored at ambient temperature for 2 weeks (77.7%, P blood and handled similarly. Resistance profiles were similar between plasma and DBS specimens. This report delineates the optimal DBS collection, storage, and shipping conditions and opens a new avenue for cost-saving ambient-temperature DBS specimen shipments for HIV drug resistance (HIVDR) surveillances in resource-limited settings. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

High Blood Pressure: Unique to Older Adults

Science.gov (United States)

... our e-newsletter! Aging & Health A to Z High Blood Pressure Hypertension Unique to Older Adults This section provides ... Pressure Targets are Different for Very Old Adults High blood pressure (also called hypertension) increases your chance of having ...

Managing Stress to Control High Blood Pressure

Science.gov (United States)

... Aortic Aneurysm More Managing Stress to Control High Blood Pressure Updated:Jan 29,2018 The importance of stress ... This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline.

Science.gov (United States)

Ferraris, Victor A; Ferraris, Suellen P; Saha, Sibu P; Hessel, Eugene A; Haan, Constance K; Royston, B David; Bridges, Charles R; Higgins, Robert S D; Despotis, George; Brown, Jeremiah R; Spiess, Bruce D; Shore-Lesserson, Linda; Stafford-Smith, Mark; Mazer, C David; Bennett-Guerrero, Elliott; Hill, Steven E; Body, Simon

2007-05-01

A minority of patients having cardiac procedures (15% to 20%) consume more than 80% of the blood products transfused at operation. Blood must be viewed as a scarce resource that carries risks and benefits. A careful review of available evidence can provide guidelines to allocate this valuable resource and improve patient outcomes. We reviewed all available published evidence related to blood conservation during cardiac operations, including randomized controlled trials, published observational information, and case reports. Conventional methods identified the level of evidence available for each of the blood conservation interventions. After considering the level of evidence, recommendations were made regarding each intervention using the American Heart Association/American College of Cardiology classification scheme. Review of published reports identified a high-risk profile associated with increased postoperative blood transfusion. Six variables stand out as important indicators of risk: (1) advanced age, (2) low preoperative red blood cell volume (preoperative anemia or small body size), (3) preoperative antiplatelet or antithrombotic drugs, (4) reoperative or complex procedures, (5) emergency operations, and (6) noncardiac patient comorbidities. Careful review revealed preoperative and perioperative interventions that are likely to reduce bleeding and postoperative blood transfusion. Preoperative interventions that are likely to reduce blood transfusion include identification of high-risk patients who should receive all available preoperative and perioperative blood conservation interventions and limitation of antithrombotic drugs. Perioperative blood conservation interventions include use of antifibrinolytic drugs, selective use of off-pump coronary artery bypass graft surgery, routine use of a cell-saving device, and implementation of appropriate transfusion indications. An important intervention is application of a multimodality blood conservation program

High blood pressure - adults

Science.gov (United States)

... pressure is found. This is called essential hypertension. High blood pressure that is caused by another medical condition or medicine you are taking is called secondary hypertension. Secondary hypertension may be due to: Chronic ...

Laser microbeams for DNA damage induction, optical tweezers for the search on blood pressure relaxing drugs: contributions to ageing research

Science.gov (United States)

Grigaravicius, P.; Monajembashi, S.; Hoffmann, M.; Altenberg, B.; Greulich, K. O.

2009-08-01

One essential cause of human ageing is the accumulation of DNA damages during lifetime. Experimental studies require quantitative induction of damages and techniques to visualize the subsequent DNA repair. A new technique, the "immuno fluorescent comet assay", is used to directly visualize DNA damages in the microscope. Using DNA repair proteins fluorescently labeled with green fluorescent protein, it could be shown that the repair of the most dangerous DNA double strand breaks starts with the inaccurate "non homologous end joining" pathway and only after 1 - 1 ½ minutes may switch to the more accurate "homologous recombination repair". One might suggest investigating whether centenarians use "homologous recombination repair" differently from those ageing at earlier years and speculate whether it is possible, for example by nutrition, to shift DNA repair to a better use of the error free pathway and thus promote healthy ageing. As a complementary technique optical tweezers, and particularly its variant "erythrocyte mediated force application", is used to simulate the effects of blood pressure on HUVEC cells representing the inner lining of human blood vessels. Stimulating one cell induces in the whole neighbourhood waves of calcium and nitric oxide, known to relax blood vessels. NIFEDIPINE and AMLODIPINE, both used as drugs in the therapy of high blood pressure, primarily a disease of the elderly, prolong the availability of nitric oxide. This partially explains their mode of action. In contrast, VERAPAMILE, also a blood pressure reducing drug, does not show this effect, indicating that obviously an alternative mechanism must be responsible for vessel relaxation.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... blood glucose High levels of sugar in the urine Frequent urination Increased thirst Part of managing your ... glucose is above 240 mg/dl, check your urine for ketones. If you have ketones, do not ...

Fully automated drug screening of dried blood spots using online LC-MS/MS analysis

Directory of Open Access Journals (Sweden)

Stefan Gaugler

2018-01-01

Full Text Available A new and fully automated workflow for the cost effective drug screening of large populations based on the dried blood spot (DBS technology was introduced in this study. DBS were prepared by spotting 15 μL of whole blood, previously spiked with alprazolam, amphetamine, cocaine, codeine, diazepam, fentanyl, lysergic acid diethylamide (LSD, 3,4-methylenedioxymethamphet-amine (MDMA, methadone, methamphetamine, morphine and oxycodone onto filter paper cards. The dried spots were scanned, spiked with deuterated standards and directly extracted. The extract was transferred online to an analytical LC column and then to the electrospray ionization tandem mass spectrometry system. All drugs were quantified at their cut-off level and good precision and correlation within the calibration range was obtained. The method was finally applied to DBS samples from two patients with back pain and codeine and oxycodone could be identified and quantified accurately below the level of misuse of 89.6 ng/mL and 39.6 ng/mL respectively.

Teaming Up Against High Blood Pressure PSA (:60)

Centers for Disease Control (CDC) Podcasts

Nearly one-third of American adults have high blood pressure, and more than half of them don’t have it under control. Simply seeing a doctor and taking medications isn’t enough for many people who have high blood pressure. A team-based approach by patients, health care systems, and health care providers is one of the best ways to treat uncontrolled high blood pressure.

Blood pressure in childhood : epidemiological probes into the aetiology of high blood pressure

NARCIS (Netherlands)

A. Hofman (Albert)

1983-01-01

textabstractHigh arterial blood pressure takes a heavy toll in western populations (1 ). Its causes are still largely unknown, but its sequelae, a variety of cardiovascular and renal diseases, have been referred to as "a modern scourge" (2). High blood pressure of unknown cause, or

Management of high blood pressure in Blacks: an update of the International Society on Hypertension in Blacks consensus statement.

Science.gov (United States)

Flack, John M; Sica, Domenic A; Bakris, George; Brown, Angela L; Ferdinand, Keith C; Grimm, Richard H; Hall, W Dallas; Jones, Wendell E; Kountz, David S; Lea, Janice P; Nasser, Samar; Nesbitt, Shawna D; Saunders, Elijah; Scisney-Matlock, Margaret; Jamerson, Kenneth A

2010-11-01

Since the first International Society on Hypertension in Blacks consensus statement on the "Management of High Blood Pressure in African American" in 2003, data from additional clinical trials have become available. We reviewed hypertension and cardiovascular disease prevention and treatment guidelines, pharmacological hypertension clinical end point trials, and blood pressure-lowering trials in blacks. Selected trials without significant black representation were considered. In this update, blacks with hypertension are divided into 2 risk strata, primary prevention, where elevated blood pressure without target organ damage, preclinical cardiovascular disease, or overt cardiovascular disease for whom blood pressure consistently secondary prevention, where elevated blood pressure with target organ damage, preclinical cardiovascular disease, and/or a history of cardiovascular disease, for whom blood pressure consistently blood pressure is ≤10 mm Hg above target levels, monotherapy with a diuretic or calcium channel blocker is preferred. When blood pressure is >15/10 mm Hg above target, 2-drug therapy is recommended, with either a calcium channel blocker plus a renin-angiotensin system blocker or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a renin-angiotensin system blocker. Effective multidrug therapeutic combinations through 4 drugs are described. Comprehensive lifestyle modifications should be initiated in blacks when blood pressure is ≥115/75 mm Hg. The updated International Society on Hypertension in Blacks consensus statement on hypertension management in blacks lowers the minimum target blood pressure level for the lowest-risk blacks, emphasizes effective multidrug regimens, and de-emphasizes monotherapy.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term ... body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If ...

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... Care > Blood Glucose Testing Share: Print Page Text Size: A A A Listen En Español Hyperglycemia (High ...

Are patients reliable when self-reporting medication use? Validation of structured drug interviews and home visits by drug analysis and prescription data in acutely hospitalized patients

DEFF Research Database (Denmark)

Glintborg, Bente; Hillestrøm, Peter René; Olsen, Lenette Holm

2007-01-01

inspected, and patients were interviewed about their drug use. Additional blood samples were drawn for drug analysis. The median age of included patients was 72 years, and 298 patients (60%) were women. Patients reported use of 3 (median) prescription-only medications (range, 0-14) during the structured...... interview. The congruence between self-report and drug analysis was high for all 5 drugs measured (all kappa >0.8). However, 9 patients (2%) reported use of drugs that were not detected in their blood samples. In 29 patients (6%), the blood samples contained drugs not reported during the structured...... to an acute medical department at a Danish university hospital were interviewed on the day of admission about their recent medication use. Blood samples drawn immediately after admission were screened for contents of 5 drugs (digoxin, bendroflumethiazide, amlodipine, simvastatin, glimepiride), and the results...

[A model list of high risk drugs].

Science.gov (United States)

Cotrina Luque, J; Guerrero Aznar, M D; Alvarez del Vayo Benito, C; Jimenez Mesa, E; Guzman Laura, K P; Fernández Fernández, L

2013-12-01

«High-risk drugs» are those that have a very high «risk» of causing death or serious injury if an error occurs during its use. The Institute for Safe Medication Practices (ISMP) has prepared a high-risk drugs list applicable to the general population (with no differences between the pediatric and adult population). Thus, there is a lack of information for the pediatric population. The main objective of this work is to develop a high-risk drug list adapted to the neonatal or pediatric population as a reference model for the pediatric hospital health workforce. We made a literature search in May 2012 to identify any published lists or references in relation to pediatric and/or neonatal high-risk drugs. A total of 15 studies were found, from which 9 were selected. A model list was developed mainly based on the ISMP one, adding strongly perceived pediatric risk drugs and removing those where the pediatric use was anecdotal. There is no published list that suits pediatric risk management. The list of pediatric and neonatal high-risk drugs presented here could be a «reference list of high-risk drugs » for pediatric hospitals. Using this list and training will help to prevent medication errors in each drug supply chain (prescribing, transcribing, dispensing and administration). Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

21 CFR 864.9195 - Blood mixing devices and blood weighing devices.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood mixing devices and blood weighing devices. 864.9195 Section 864.9195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That...

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... In Memory In Honor Become a Member En Español Type 1 Type 2 About Us Online Community ... Page Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical ...

Drug detection in breath: non-invasive assessment of illicit or pharmaceutical drugs.

Science.gov (United States)

Trefz, Phillip; Kamysek, Svend; Fuchs, Patricia; Sukul, Pritam; Schubert, Jochen K; Miekisch, Wolfram

2017-03-20

Breath analysis not only holds great potential for the development of new non-invasive diagnostic methods, but also for the identification and follow up of drug levels in breath. This is of interest for both, forensic and medical science. On the one hand, the detection of drugs of abuse in exhaled breath-similar to the well-known breath alcohol tests-would be highly desirable as an alternative to blood or urine analysis in situations such as police controls for drugged driving. The non-invasive detection of drugs and their metabolites is thus of great interest in forensic science, especially since marijuana is becoming legalized in certain parts of the US and the EU. The detection and monitoring of medical drugs in exhaled breath without the need of drawing blood samples on the other hand, is of high relevance in the clinical environment. This could facilitate a more precise medication and enable therapy control without any burden to the patient. Furthermore, it could be a step towards personalized medicine. This review gives an overview of the current state of drug detection in breath, including both volatile and non-volatile substances. The review is divided into two sections. The first section deals with qualitative detection of drugs (drugs of abuse), while the second is related to quantitative drug detection (medical drugs). Chances and limitations are discussed for both aspects. The detection of the intravenous anesthetic propofol is presented as a detailed example that demonstrates the potential, requirements, pitfalls and limitations of therapeutic drug monitoring by means of breath analysis.

Delivery of Biologics Across the Blood-Brain Barrier Through Nanoencapsulation

DEFF Research Database (Denmark)

Bruun, Jonas

is a polymeric micelle made from an anionic triblock copolymer and was intended for delivery of drugs to the central nervous system (CNS), which is protected by the largely impermeable blood-brain barrier (BBB). In order to target the nanocarrier to the brain endothelial cells and obtain receptor...... of the reporter protein. One of the great challenges for drug delivery by nanocarriers is the dilemma of designing a particle that is highly stable whit no cellular interaction while in the blood stream but has a high uptake and efficient drug release in the diseased cells. As a solution to this dilemma...

Five-year update on the occurrence of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes in Sweden.

Science.gov (United States)

Jones, Alan Wayne; Kugelberg, Fredrik C; Holmgren, Anita; Ahlner, Johan

2009-04-15

According to statistics provided by the Swedish National Road Administration (Vägverket), a total of 1403 drivers were killed in road-traffic crashes in Sweden between 2003 and 2007. Forensic autopsies were performed in approximately 97% of all deaths and specimens of blood and urine were sent for toxicological analysis. In 60% of cases (N=835) the toxicology results were negative and 83% of these victims were men. The blood-alcohol concentration (BAC) was above the legal limit for driving (>0.2g/L) in 22% of cases (N=315) at mean, median and highest concentrations of 1.7 g/L, 1.7 g/L and 4.9 g/L, respectively. The proportions of male to female drivers with BAC>0.2g/L were 93% vs 7% compared with 83% vs 17% for those with drugs other than alcohol in blood. Drivers with a punishable BAC were over-represented in single vehicle crashes compared with multiple vehicle crashes (67% vs 33%). The opposite held for drivers who had taken a prescription drug (39% vs 61%) and also for drug-negative cases (31% vs 69%). Drugs other than alcohol were identified in 253 cases (18%); illicit drugs only in 39 cases (2.8%), both licit and illicit in 28 cases (2.0%) and in 186 cases (13.3%) one or more therapeutic drugs were present. Amphetamine was the most common illicit drug identified at mean, median and highest concentrations of 1.5mg/L, 1.1mg/L and 5.0mg/L, respectively (N=39). Blood specimens contained a wide spectrum of pharmaceutical products (mean 2.4 drugs/person), comprising sedative-hypnotics (N=93), opiates/opioids (N=69) as well non-scheduled substances, such as paracetamol (N=78) and antidepressants (N=93). The concentrations of these substances in blood were mostly in the therapeutic range. Despite an appreciable increase (12-fold) in number of arrests made by the police for drug-impaired driving after a zero-tolerance law was introduced (July 1999), alcohol still remains the psychoactive substance most frequently identified in the blood of drivers killed in road

Particle size, magnetic field, and blood velocity effects on particle retention in magnetic drug targeting.

Science.gov (United States)

Cherry, Erica M; Maxim, Peter G; Eaton, John K

2010-01-01

A physics-based model of a general magnetic drug targeting (MDT) system was developed with the goal of realizing the practical limitations of MDT when electromagnets are the source of the magnetic field. The simulation tracks magnetic particles subject to gravity, drag force, magnetic force, and hydrodynamic lift in specified flow fields and external magnetic field distributions. A model problem was analyzed to determine the effect of drug particle size, blood flow velocity, and magnetic field gradient strength on efficiency in holding particles stationary in a laminar Poiseuille flow modeling blood flow in a medium-sized artery. It was found that particle retention rate increased with increasing particle diameter and magnetic field gradient strength and decreased with increasing bulk flow velocity. The results suggest that MDT systems with electromagnets are unsuitable for use in small arteries because it is difficult to control particles smaller than about 20 microm in diameter.

Donating Blood

Science.gov (United States)

... The medical history includes questions that help blood bank staff decide if a person is healthy enough to donate blood. They'll ... Food and Drug Administration (FDA) regulates U.S. blood banks. All blood ... operating. Sometimes people who donate blood notice a few minor side ...

High blood pressure - what to ask your doctor

Science.gov (United States)

What to ask your doctor about high blood pressure; Hypertension - what to ask your doctor ... problems? What medicines am I taking to treat high blood pressure? Do they have any side effects? What should ...

Occupational status moderates the association between current perceived stress and high blood pressure: evidence from the IPC cohort study

Science.gov (United States)

Wiernik, Emmanuel; Pannier, Bruno; Czernichow, Sébastien; Nabi, Hermann; Hanon, Olivier; Simon, Tabassome; Simon, Jean-Marc; Thomas, Frédérique; Bean, Kathy; Consoli, Silla; Danchin, Nicolas; Lemogne, Cédric

2013-01-01

Although lay beliefs commonly relate high blood pressure to psychological stress exposure, research findings are conflicting. This study examined the association between current perceived stress and high blood pressure and explored the potential impact of occupational status on this association. Resting blood pressure was measured in 122,816 adults (84,994 men), aged ≥30 years (mean age ± standard deviation: 46.8±9.9 years), without history of cardiovascular and renal disease and not on either psychotropic or antihypertensive drugs. High blood pressure was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg. Perceived stress in the past month was measured with the 4-item perceived stress scale. A total of 33,154 participants (27.0%) had high blood pressure (151±14/90±9 mmHg). After adjustment for all variables except occupational status, perceived stress was associated with high blood pressure (odds ratio for a 5-point increase: 1.06, 95% confidence interval: [1.03–1.09]). This association was no longer significant after additional adjustment for occupational status (odds ratio: 1.01 [0.99–1.04]). There was a significant interaction (phigh blood pressure among individuals of high occupational status (odds ratio: 0.91, [0.87–0.96]) but positively associated among those of low status (odds ratio: 1.10, [1.03–1.17]) or unemployed (odds ratio: 1.13, [1.03–1.24]). Sensitivity analyses yielded similar results. The association between current perceived stress and blood pressure depends upon occupational status. This interaction may account for previous conflicting results and warrants further studies to explore its underlying mechanisms. PMID:23319539

How to Prevent High Blood Pressure: MedlinePlus Health Topic

Science.gov (United States)

... Spanish Understanding Blood Pressure Readings (American Heart Association) Weightlifting: Bad for Your Blood Pressure? (Mayo Foundation for ... High Blood Pressure High Blood Pressure in Pregnancy Nutrition Quitting Smoking Stress National Institutes of Health The ...

Hair Testing for Drugs of Abuse and New Psychoactive Substances in a High-Risk Population.

Science.gov (United States)

Salomone, Alberto; Palamar, Joseph J; Gerace, Enrico; Di Corcia, Daniele; Vincenti, Marco

2017-06-01

Hundreds of new psychoactive substances (NPS) have emerged in the drug market over the last decade. Few drug surveys in the USA, however, ask about use of NPS, so prevalence and correlates of use are largely unknown. A large portion of NPS use is unintentional or unknown as NPS are common adulterants in drugs like ecstasy/Molly, and most NPS are rapidly eliminated from the body, limiting efficacy of urine, blood and saliva testing. We utilized a novel method of examining prevalence of NPS use in a high-risk population utilizing hair-testing. Hair samples from high-risk nightclub and dance music attendees were tested for 82 drugs and metabolites (including NPS) using ultra-high performance liquid chromatography-tandem mass spectrometry. Eighty samples collected from different parts of the body were analyzed, 57 of which detected positive for at least one substance-either a traditional or new drug. Among these, 26 samples tested positive for at least one NPS-the most common being butylone (25 samples). Other new drugs detected include methylone, methoxetamine, 5/6-APB, α-PVP and 4-FA. Hair analysis proved a powerful tool to gain objective biological drug-prevalence information, free from possible biases of unintentional or unknown intake and untruthful reporting of use. Such testing can be used actively or retrospectively to validate survey responses and inform research on consumption patterns, including intentional and unknown use, polydrug-use, occasional NPS intake and frequent or heavy use. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

ADME evaluation in drug discovery. 1. Applications of genetic algorithms to the prediction of blood-brain partitioning of a large set of drugs.

Science.gov (United States)

Hou, Tingjun; Xu, Xiaojie

2002-12-01

In this study, the relationships between the brain-blood concentration ratio of 96 structurally diverse compounds with a large number of structurally derived descriptors were investigated. The linear models were based on molecular descriptors that can be calculated for any compound simply from a knowledge of its molecular structure. The linear correlation coefficients of the models were optimized by genetic algorithms (GAs), and the descriptors used in the linear models were automatically selected from 27 structurally derived descriptors. The GA optimizations resulted in a group of linear models with three or four molecular descriptors with good statistical significance. The change of descriptor use as the evolution proceeds demonstrates that the octane/water partition coefficient and the partial negative solvent-accessible surface area multiplied by the negative charge are crucial to brain-blood barrier permeability. Moreover, we found that the predictions using multiple QSPR models from GA optimization gave quite good results in spite of the diversity of structures, which was better than the predictions using the best single model. The predictions for the two external sets with 37 diverse compounds using multiple QSPR models indicate that the best linear models with four descriptors are sufficiently effective for predictive use. Considering the ease of computation of the descriptors, the linear models may be used as general utilities to screen the blood-brain barrier partitioning of drugs in a high-throughput fashion.

Teaming Up Against High Blood Pressure PSA (:60)

Centers for Disease Control (CDC) Podcasts

2012-09-04

Nearly one-third of American adults have high blood pressure, and more than half of them don’t have it under control. Simply seeing a doctor and taking medications isn’t enough for many people who have high blood pressure. A team-based approach by patients, health care systems, and health care providers is one of the best ways to treat uncontrolled high blood pressure.  Created: 9/4/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 9/4/2012.

How Potassium Can Help Control High Blood Pressure

Science.gov (United States)

... Aneurysm More How Potassium Can Help Control High Blood Pressure Updated:Jan 29,2018 Understanding the heart-healthy ... This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

How High Blood Pressure Can Lead to Stroke

Science.gov (United States)

... Disease Venous Thromboembolism Aortic Aneurysm More How High Blood Pressure Can Lead to Stroke Updated:Jan 29,2018 ... This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

Energy Technology Data Exchange (ETDEWEB)

Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François, E-mail: francois.marceau@crchul.ulaval.ca

2013-07-15

Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K{sub M} 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V{sub max}. PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion

High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

International Nuclear Information System (INIS)

Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François

2013-01-01

Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K M 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V max . PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion trapping

Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles.

Science.gov (United States)

Meairs, Stephen

2015-08-31

Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood-brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer's disease is presented.

Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system

Science.gov (United States)

Aryal, Muna; Arvanitis, Costas D.; Alexander, Phillip M.; McDannold, Nathan

2014-01-01

The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB. PMID:24462453

High-dose antibiotic therapy is superior to a 3-drug combination of prostanoids and lipid A derivative in protecting irradiated canines

International Nuclear Information System (INIS)

Kumar, K.S.; Srinivasan, V.; Toles, R.E.; Miner, V.L.; Jackson, W.E.; Seed, T.M.

2002-01-01

There is an urgent need to develop non-toxic radioprotectors. We tested the efficacy of a 3-drug combination (3-DC) of iloprost, misoprostol, and 3D-MPL (3-deacylated monophosphoryl lipid A) and the effects of postirradiation clinical support with high doses of antibiotics and blood transfusion. Canines were given 3-DC or the vehicle and exposed to 3.4 Gy or 4.1 Gy of 60 Co radiation. Canines irradiated at 4.1 Gy were also given clinical support, which consisted of blood transfusion and antibiotics (gentamicin, and cefoxitin or cephalexin). Peripheral blood cell profile and 60-day survival were used as indices of protection. At 3.4 Gy, 3-DC- or vehicle-treated canines without postirradiation clinical support survived only for 10 to 12 days. Fifty percent of the canines treated with 3-DC or vehicle and provided postirradiation clinical support survived 4.1-Gy irradiation. Survival of canines treated with vehicle before irradiation significantly correlated with postirradiation antibiotic treatments, but not with blood transfusion. The recovery profile of peripheral blood cells in 4.1 Gy-irradiated canines treated with vehicle and antibiotics was better than drug-treated canines. These results indicate that therapy with high doses of intramuscular aminoglycoside antibiotic (gentamicin) and an oral cephalosporin (cephalexin) enhanced survival of irradiated canines. Although blood transfusion correlated with survival of 3-DC treated canines, there were no additional survivors with 3-DC treated canines than the controls. (author)

Syringe access for the prevention of blood borne infections among injection drug users

Directory of Open Access Journals (Sweden)

Rich Josiah D

2003-11-01

Full Text Available Abstract Background Approximately one-third of acquired immunodeficiency syndrome cases in the United States are associated with the practice of sharing of injection equipment and are preventable through the once-only use of syringes, needles and other injection equipment. Discussion Sterile syringes may be obtained legally by 4 methods depending on the state. They may be purchased over the counter, prescribed, obtained at syringe exchange programs or furnished by authorized agencies. Each of these avenues has advantages and disadvantages; therefore, legal access through all means is the most likely way to promote the use of sterile syringes. Summary By assisting illicit drug injectors to obtain sterile syringes the primary care provider is able to reduce the incidence of blood borne infections, and educate patients about safe syringe disposal. The provider is also able to initiate discussion about drug use in a nonjudgmental manner and to offer care to patients who are not yet ready to consider drug treatment.

High risk behavior for HIV transmission among former injecting drug users:a survey from Indonesia

Directory of Open Access Journals (Sweden)

Iskandar Shelly

2010-08-01

Full Text Available Abstract Background Injecting drug use is an increasingly important cause of HIV transmission in most countries worldwide, especially in eastern Europe, South America, and east and southeast Asia. Among people actively injecting drugs, provision of clean needles and opioid substitution reduce HIV-transmission. However, former injecting drug users (fIDUs are often overlooked as a high risk group for HIV transmission. We compared HIV risk behavior among current and former injecting drug users (IDUs in Indonesia, which has a rapidly growing HIV-epidemic largely driven by injecting drug use. Methods Current and former IDUs were recruited by respondent driven sampling in an urban setting in Java, and interviewed regarding drug use and HIV risk behavior using the European Addiction Severity Index and the Blood Borne Virus Transmission Questionnaire. Drug use and HIV transmission risk behavior were compared between current IDUs and former IDUs, using the Mann-Whitney and Pearson Chi-square test. Results Ninety-two out of 210 participants (44% were self reported former IDUs. Risk behavior related to sex, tattooing or piercing was common among current as well as former IDUs, 13% of former IDUs were still exposed to contaminated injecting equipment. HIV-infection was high among former (66% and current (60% IDUs. Conclusion Former IDUs may contribute significantly to the HIV-epidemic in Indonesia, and HIV-prevention should therefore also target this group, addressing sexual and other risk behavior.

High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors.

Directory of Open Access Journals (Sweden)

Rodrigo Pessôa

Full Text Available An improved understanding of the prevalence of low-abundance transmitted drug-resistance mutations (TDRM in therapy-naïve HIV-1-infected patients may help determine which patients are the best candidates for therapy. In this study, we aimed to obtain a comprehensive picture of the evolving HIV-1 TDRM across the massive parallel sequences (MPS of the viral entire proviral genome in a well-characterized Brazilian blood donor naïve to antiretroviral drugs.The MPS data from 128 samples used in the analysis were sourced from Brazilian blood donors and were previously classified by less-sensitive (LS or "detuned" enzyme immunoassay as non-recent or longstanding HIV-1 infections. The Stanford HIV Resistance Database (HIVDBv 6.2 and IAS-USA mutation lists were used to interpret the pattern of drug resistance. The minority variants with TDRM were identified using a threshold of ≥ 1.0% and ≤ 20% of the reads sequenced. The rate of TDRM in the MPS data of the proviral genome were compared with the corresponding published consensus sequences of their plasma viruses.No TDRM were detected in the integrase or envelope regions. The overall prevalence of TDRM in the protease (PR and reverse transcriptase (RT regions of the HIV-1 pol gene was 44.5% (57/128, including any mutations to the nucleoside analogue reverse transcriptase inhibitors (NRTI and non-nucleoside analogue reverse transcriptase inhibitors (NNRTI. Of the 57 subjects, 43 (75.4% harbored a minority variant containing at least one clinically relevant TDRM. Among the 43 subjects, 33 (76.7% had detectable minority resistant variants to NRTIs, 6 (13.9% to NNRTIs, and 16 (37.2% to PR inhibitors. The comparison of viral sequences in both sources, plasma and cells, would have detected 48 DNA provirus disclosed TDRM by MPS previously missed by plasma bulk analysis.Our findings revealed a high prevalence of TDRM found in this group, as the use of MPS drastically increased the detection of these

Announcement: National High Blood Pressure Education Month - May 2016.

Science.gov (United States)

2016-05-27

May is National High Blood Pressure Education Month. High blood pressure (hypertension) is a major contributor to heart disease and stroke, two leading causes of death in the United States.* High blood pressure affects one third of U.S. adults, or approximately 75 million persons, yet approximately 11 million of these persons are not aware they have hypertension, and approximately 18 million are not being treated (unpublished data) (1,2).

The association between neighborhood socioeconomic disadvantage and high-risk injection behavior among people who inject drugs.

Science.gov (United States)

DeCuir, Jennifer; Lovasi, Gina S; El-Sayed, Abdulrahman; Lewis, Crystal Fuller

2018-02-01

Although much research has been conducted on the determinants of HIV risk behavior among people who inject drugs (PWID), the influence of the neighborhood context on high-risk injection behavior remains understudied. To address this gap in the literature, we measured associations between neighborhood socioeconomic disadvantage and high-risk injection behavior, and determined whether these associations were modified by drug-related police activity and syringe exchange program (SEP) accessibility. Our sample was comprised of 484 pharmacy-recruited PWID in New York City. Measures of neighborhood socioeconomic disadvantage were created using data from the 2006-2010 American Community Survey. Associations with high-risk injection behavior were estimated using multivariable Poisson regression. Effect modification by drug-related police activity and SEP accessibility was assessed by entering cross-product terms into adjusted models of high-risk injection behavior. Neighborhood socioeconomic disadvantage was associated with decreased receptive syringe sharing and unsterile syringe use. In neighborhoods with high drug-related police activity, associations between neighborhood disadvantage and unsterile syringe use were attenuated to the null. In neighborhoods with high SEP accessibility, neighborhood disadvantage was associated with decreased acquisition of syringes from an unsafe source. PWID in disadvantaged neighborhoods reported safer injection behaviors than their counterparts in neighborhoods that were relatively better off. The contrasting patterns of effect modification by SEP accessibility and drug-related police activity support the use of harm reduction approaches over law enforcement-based strategies for the control of blood borne virus transmission among PWID in disadvantaged urban areas. Copyright © 2017 Elsevier B.V. All rights reserved.

High blood pressure in acute ischemic stroke and clinical outcome.

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Manabe, Yasuhiro; Kono, Syoichiro; Tanaka, Tomotaka; Narai, Hisashi; Omori, Nobuhiko

2009-11-16

This study aimed to evaluate the prognostic value of acute phase blood pressure in patients with acute ischemic stroke by determining whether or not it contributes to clinical outcome. We studied 515 consecutive patients admitted within the first 48 hours after the onset of ischemic strokes, employing systolic and diastolic blood pressure measurements recorded within 36 hours after admission. High blood pressure was defined when the mean of at least 2 blood pressure measurements was ≥200 mmHg systolic and/or ≥110 mmHg diastolic at 6 to 24 hours after admission or ≥180 mmHg systolic and/or ≥105 mmHg diastolic at 24 to 36 hours after admission. The high blood pressure group was found to include 16% of the patients. Age, sex, diabetes mellitus, hypercholesterolemia, atrial fibrillation, ischemic heart disease, stroke history, carotid artery stenosis, leukoaraiosis, NIH Stroke Scale (NIHSS) on admission and mortality were not significantly correlated with either the high blood pressure or non-high blood pressure group. High blood pressure on admission was significantly associated with a past history of hypertension, kidney disease, the modified Rankin Scale (mRS) on discharge and the length of stay. On logistic regression analysis, with no previous history of hypertension, diabetes mellitus, atrial fibrillation, and kidney disease were independent risk factors associated with the presence of high blood pressure [odds ratio (OR), 1.85 (95% confidence interval (CI): 1.06-3.22), 1.89 (95% CI: 1.11-3.22), and 3.31 (95% CI: 1.36-8.04), respectively]. Multi-organ injury may be presented in acute stroke patients with high blood pressure. Patients with high blood pressure had a poor functional outcome after acute ischemic stroke.

Prevalence of pre-high blood pressure and high blood pressure among non-overweight children and adolescents using international blood pressure references in developed regions in China.

Science.gov (United States)

Tian, Changwei; Xu, Shuang; Wang, Hua; Wang, Wenming; Shen, Hui

2017-09-01

There is a lack of data on the prevalence of pre-high blood pressure (PreHBP) and high blood pressure (HBP), based on recent international blood pressure references, in non-overweight children and adolescents. To describe the prevalence of PreHBP and HBP in non-overweight children and adolescents in developed regions of China. In total, 588 097 non-overweight children and adolescents aged 6-17 years from the National Surveys on Chinese Students' Constitution and Health in 2015 were included. The prevalence of PreHBP was 13.41% and subjects in urban areas had a higher prevalence of PreHBP (14.14%) than those in rural areas (12.92%). Subjects in regions with a high (13.56%) or moderate (13.61%) socioeconomic status showed a higher prevalence of PreHBP than those in regions with a relatively low socioeconomic status (12.76%). A similar pattern was found for the prevalence of HBP, and the prevalence of HBP was 18.25% for all participants, 20.55% for subjects in urban areas, 16.71% in rural areas, 18.76% in high socioeconomic areas, 18.62% in moderate socioeconomic areas and 16.70% in relatively low socioeconomic areas. A large proportion of non-overweight children and adolescents had elevated blood pressure and there were urban-rural and socioeconomic disparities in the prevalence of elevated blood pressure.

Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial.

Science.gov (United States)

Burke, Valerie; Beilin, Lawrie J; Cutt, Hayley E; Mansour, Jacqueline; Wilson, Amy; Mori, Trevor A

2005-06-01

To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals. Randomized controlled trial. Research studies unit. Overweight hypertensive patients, receiving one or two antihypertensive drugs, were recruited by advertising, and allocated randomly to a usual care group (controls; n = 118) or a lifestyle modification group (programme group; n = 123). A 4-month programme of weight loss, a low-sodium 'Dietary Approaches to Stop Hypertension'-type diet with added fish, physical activity and moderation of alcohol intake. After 4 months, if mean 24-h ambulatory blood pressure (ABP) was less than 135/85 mmHg, antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun. Antihypertensive drug requirements, ABP, weight, waist girth at 4 months and 1-year follow-up. Ninety control group and 102 programme group participants completed the study. Mean 24-h ABP changed after 4 months by -1.0/-0.3 +/- 0.5/0.4 mmHg in controls and -4.1/-2.1 +/- 0.7/0.5 mmHg with the lifestyle programme (P lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.

High Blood Pressure and Women

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... is known as gestational hypertension, a form of secondary hypertension caused by the pregnancy that usually disappears after delivery. If the mother is not treated, high blood pressure can be dangerous to both the mother ...

21 CFR 864.9050 - Blood bank supplies.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood bank supplies. 864.9050 Section 864.9050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... and Blood Products § 864.9050 Blood bank supplies. (a) Identification. Blood bank supplies are general...

High fat diet and GLP-1 drugs induce pancreatic injury in mice

Energy Technology Data Exchange (ETDEWEB)

Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron; Zhang, Jun

2014-04-15

Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.

High fat diet and GLP-1 drugs induce pancreatic injury in mice

International Nuclear Information System (INIS)

Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun

2014-01-01

Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment

Drug metabolism and ageing.

Science.gov (United States)

Wynne, Hilary

2005-06-01

Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

Science.gov (United States)

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

Transport of drugs across the blood-brain barrier by nanoparticles.

Science.gov (United States)

Wohlfart, Stefanie; Gelperina, Svetlana; Kreuter, Jörg

2012-07-20

The central nervous system is well protected by the blood-brain barrier (BBB) which maintains its homeostasis. Due to this barrier many potential drugs for the treatment of diseases of the central nervous system (CNS) cannot reach the brain in sufficient concentrations. One possibility to deliver drugs to the CNS is the employment of polymeric nanoparticles. The ability of these carriers to overcome the BBB and to produce biologic effects on the CNS was shown in a number of studies. Over the past few years, progress in understanding of the mechanism of the nanoparticle uptake into the brain was made. This mechanism appears to be receptor-mediated endocytosis in brain capillary endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants enabling the adsorption of specific plasma proteins are necessary for this receptor-mediated uptake. The delivery of drugs, which usually are not able to cross the BBB, into the brain was confirmed by the biodistribution studies and pharmacological assays in rodents. Furthermore, the presence of nanoparticles in the brain parenchyma was visualized by electron microscopy. The intravenously administered biodegradable polymeric nanoparticles loaded with doxorubicin were successfully used for the treatment of experimental glioblastoma. These data, together with the possibility to employ nanoparticles for delivery of proteins and other macromolecules across the BBB, suggest that this technology holds great promise for non-invasive therapy of the CNS diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

Antibody-linked drug destroys tumor cells and tumor blood vessels in many types of cancer | Center for Cancer Research

Science.gov (United States)

A team led by Brad St. Croix, Ph.D., Senior Associate Scientist, Mouse Cancer Genetics Program, has developed an antibody-drug conjugate (ADC) that destroys both tumor cells and the blood vessels that nourish them. The drug significantly shrank breast tumors, colon tumors and several other types of cancer and prolonged survival. Learn more...  

High-speed imaging of blood splatter patterns

Energy Technology Data Exchange (ETDEWEB)

McDonald, T.E.; Albright, K.A.; King, N.S.P.; Yates, G.J. (Los Alamos National Lab., NM (United States)); Levine, G.F. (California Dept. of Justice, Sacramento, CA (United States). Bureau of Forensic Services)

1993-01-01

The interpretation of blood splatter patterns is an important element in reconstructing the events and circumstances of an accident or crime scene. Unfortunately, the interpretation of patterns and stains formed by blood droplets is not necessarily intuitive and study and analysis are required to arrive at a correct conclusion. A very useful tool in the study of blood splatter patterns is high-speed photography. Scientists at the Los Alamos National Laboratory, Department of Energy (DOE), and Bureau of Forensic Services, State of California, have assembled a high-speed imaging system designed to image blood splatter patterns. The camera employs technology developed by Los Alamos for the underground nuclear testing program and has also been used in a military mine detection program. The camera uses a solid-state CCD sensor operating at approximately 650 frames per second (75 MPixels per second) with a microchannel plate image intensifier that can provide shuttering as short as 5 ns. The images are captured with a laboratory high-speed digitizer and transferred to an IBM compatible PC for display and hard copy output for analysis. The imaging system is described in this paper.

High-speed imaging of blood splatter patterns

Energy Technology Data Exchange (ETDEWEB)

McDonald, T.E.; Albright, K.A.; King, N.S.P.; Yates, G.J. [Los Alamos National Lab., NM (United States); Levine, G.F. [California Dept. of Justice, Sacramento, CA (United States). Bureau of Forensic Services

1993-05-01

The interpretation of blood splatter patterns is an important element in reconstructing the events and circumstances of an accident or crime scene. Unfortunately, the interpretation of patterns and stains formed by blood droplets is not necessarily intuitive and study and analysis are required to arrive at a correct conclusion. A very useful tool in the study of blood splatter patterns is high-speed photography. Scientists at the Los Alamos National Laboratory, Department of Energy (DOE), and Bureau of Forensic Services, State of California, have assembled a high-speed imaging system designed to image blood splatter patterns. The camera employs technology developed by Los Alamos for the underground nuclear testing program and has also been used in a military mine detection program. The camera uses a solid-state CCD sensor operating at approximately 650 frames per second (75 MPixels per second) with a microchannel plate image intensifier that can provide shuttering as short as 5 ns. The images are captured with a laboratory high-speed digitizer and transferred to an IBM compatible PC for display and hard copy output for analysis. The imaging system is described in this paper.

An analysis of respondent-driven sampling with injecting drug users in a high HIV prevalent state of India.

Science.gov (United States)

Phukan, Sanjib Kumar; Medhi, Gajendra Kumar; Mahanta, Jagadish; Adhikary, Rajatashuvra; Thongamba, Gay; Paranjape, Ramesh S; Akoijam, Brogen S

2017-07-03

Personal networks are significant social spaces to spread of HIV or other blood-borne infections among hard-to-reach population, viz., injecting drug users, female sex workers, etc. Sharing of infected needles or syringes among drug users is one of the major routes of HIV transmission in Manipur, a high HIV prevalence state in India. This study was carried out to describe the network characteristics and recruitment patterns of injecting drug users and to assess the association of personal network with injecting risky behaviors in Manipur. A total of 821 injecting drug users were recruited into the study using respondent-driven sampling (RDS) from Bishnupur and Churachandpur districts of Manipur; data on demographic characteristics, HIV risk behaviors, and network size were collected from them. Transition probability matrices and homophily indices were used to describe the network characteristics, and recruitment patterns of injecting drug users. Univariate and multivariate binary logistic regression models were performed to analyze the association between the personal networks and sharing of needles or syringes. The average network size was similar in both the districts. Recruitment analysis indicates injecting drug users were mostly engaged in mixed age group setting for injecting practice. Ever married and new injectors showed lack of in-group ties. Younger injecting drug users had mainly recruited older injecting drug users from their personal network. In logistic regression analysis, higher personal network was found to be significantly associated with increased likelihood of injecting risky behaviors. Because of mixed personal network of new injectors and higher network density associated with HIV exposure, older injecting drug users may act as a link for HIV transmission or other blood-borne infections to new injectors and also to their sexual partners. The information from this study may be useful to understanding the network pattern of injecting drug users

Renal function evaluation in the aged with normal blood pressure and high blood pressure

International Nuclear Information System (INIS)

Jacob Filho, W.; Carvalho Filho, E.T. de; Papaleo Netto, M.; Baptista, M.C.

1986-01-01

Thirty-four patients older than 65 years were divided into two groups according to their ages: I - 66 to 74 years (17 patients), II - 75 and over (17 patients). These elderly patients were also divided according to their arterial blood pressure level (BP): A - normal BP (14 patients), B high BP (20 patients). None of these patients presented any other disease that could affect kidney function, nor have used drugs that could interfere on the BP or on the kidney function. Glomerular filtration rate (GFR) and effective renal plasmatic flow (ERPF) were analysed by radioisotopic techniques. Furthermore the filtration fraction (FF) was evaluated by the GFR/ERPF ratio. The observed GFR, ERPF and FF variations in the age groups or in normotensive and hypertensive patients were not significant, but we could assume that the physiopathological mechanisms that cause a decreased GFR in consequence of age or of systemic hypertension could be of different origins. Thus in the old hypertensive patients, alterations in the autoregulated hemodynamic mechanism could occur. (author) [pt

Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain.

Science.gov (United States)

Patel, Mayur M; Patel, Bhoomika M

2017-02-01

CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting. Several approaches have been investigated to allow therapeutics to cross the BBB. As the molecular structure of the BBB is better elucidated, several key approaches for brain targeting include physiological transport mechanisms such as adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, cell-mediated endocytosis, and the use of peptide vectors. Drug-delivery approaches comprise delivery from microspheres, biodegradable wafers, and colloidal drug-carrier systems (e.g., liposomes, nanoparticles, nanogels, dendrimers, micelles, nanoemulsions, polymersomes, exosomes, and quantum dots). The current review discusses the latest advancements in these approaches, with a major focus on articles published in 2015 and 2016. In addition, we also cover the alternative delivery routes, such as intranasal and convection-enhanced diffusion methods, and disruption of the BBB for brain targeting.

Rat muscle blood flows during high-speed locomotion

International Nuclear Information System (INIS)

Armstrong, R.B.; Laughlin, M.H.

1985-01-01

We previously studied blood flow distribution within and among rat muscles as a function of speed from walking (15 m/min) through galloping (75 m/min) on a motor-driven treadmill. The results showed that muscle blood flows continued to increase as a function of speed through 75 m/min. The purpose of the present study was to have rats run up to maximal treadmill speeds to determine if blood flows in the muscles reach a plateau as a function of running speed over the animals normal range of locomotory speeds. Muscle blood flows were measured with radiolabeled microspheres at 1 min of running at 75, 90, and 105 m/min in male Sprague-Dawley rats. The data indicate that even at these relatively high treadmill speeds there was still no clear evidence of a plateau in blood flow in most of the hindlimb muscles. Flows in most muscles continued to increase as a function of speed. These observed patterns of blood flow vs. running speed may have resulted from the rigorous selection of rats that were capable of performing the high-intensity exercise and thus only be representative of a highly specific population of animals. On the other hand, the data could be interpreted to indicate that the cardiovascular potential during exercise is considerably higher in laboratory rats than has normally been assumed and that inadequate blood flow delivery to the muscles does not serve as a major limitation to their locomotory performance

Nasal Delivery of High Molecular Weight Drugs

Directory of Open Access Journals (Sweden)

Erdal Cevher

2009-09-01

Full Text Available Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nanoand micro-particulate carrier systems will be summarised.

[Effect of Chinese drugs for activating blood circulation and removing blood stasis on carotid atherosclerosis and ischemic cerebrovascular events].

Science.gov (United States)

Lu, Yan; Li, Tao

2014-03-01

To explore the effect of Chinese drugs for activating blood circulation and removing blood stasis (CDABCRBS) on carotid atherosclerotic plaque and long-term ischemic cerebrovascular events. By using open and control method, effect of 4 groups of platelet antagonists, platelet antagonists + CDABCRBS, platelet antagonists +atorvastatin, platelet antagonists +atorvastatin +CDABCRBS on carotid atherosclerotic plaque and long-term ischemic cerebrovascular events of 90 cerebral infarction patients were analyzed. Through survival analysis, there was no statistical difference in the effect of the 4 interventions on the variation of carotid stenosis rates or ischemic cerebrovascular events (P > 0.05). The occurrence of ischemic cerebrovascular events could be postponed by about 4 months in those treated with platelet antagonists + CDABCRBS and platelet antagonists + atorvastatin +CDABCRBS. By multivariate Logistic analysis, age, hypertension, and clopidogrel were associated with stenosis of extracranial carotid arteries (P cerebrovascular accidents (P cerebrovascular events. CDABCRBS could effectively prolong the occurrence time of ischemic cerebrovascular events.

Prediction of Central Nervous System Side Effects Through Drug Permeability to Blood-Brain Barrier and Recommendation Algorithm.

Science.gov (United States)

Fan, Jun; Yang, Jing; Jiang, Zhenran

2018-04-01

Drug side effects are one of the public health concerns. Using powerful machine-learning methods to predict potential side effects before the drugs reach the clinical stages is of great importance to reduce time consumption and protect the security of patients. Recently, researchers have proved that the central nervous system (CNS) side effects of a drug are closely related to its permeability to the blood-brain barrier (BBB). Inspired by this, we proposed an extended neighborhood-based recommendation method to predict CNS side effects using drug permeability to the BBB and other known features of drug. To the best of our knowledge, this is the first attempt to predict CNS side effects considering drug permeability to the BBB. Computational experiments demonstrated that drug permeability to the BBB is an important factor in CNS side effects prediction. Moreover, we built an ensemble recommendation model and obtained higher AUC score (area under the receiver operating characteristic curve) and AUPR score (area under the precision-recall curve) on the data set of CNS side effects by integrating various features of drug.

High Blood Pressure and Cold Remedies: Which Are Safe?

Science.gov (United States)

... counter cold remedies safe for people who have high blood pressure? Answers from Sheldon G. Sheps, M.D. Over- ... remedies aren't off-limits if you have high blood pressure, but it's important to make careful choices. Among ...

Ex vivo investigation of magnetically targeted drug delivery system

International Nuclear Information System (INIS)

Yoshida, Y.; Fukui, S.; Fujimoto, S.; Mishima, F.; Takeda, S.; Izumi, Y.; Ohtani, S.; Fujitani, Y.; Nishijima, S.

2007-01-01

In conventional systemic drug delivery the drug is administered by intravenous injection; it then travels to the heart from where it is pumped to all regions of the body. When the drug is aimed at a small target region, this method is extremely inefficient and leads to require much larger doses than those being necessary. In order to overcome this problem a number of targeted drug delivery methods are developed. One of these, magnetically targeted drug delivery system (MT-DDS) will be a promising way, which involves binding a drug to small biocompatible magnetic particles, injecting these into the blood stream and using a high gradient magnetic field to pull them out of suspension in the target region. In the present paper, we describe an ex vivo experimental work. It is also reported that navigation and accumulation test of the magnetic particles in the Y-shaped glass tube was performed in order to examine the threshold of the magnetic force for accumulation. It is found that accumulation of the magnetic particles was succeeded in the blood vessel when a permanent magnet was placed at the vicinity of the blood vessel. This result indicates the feasibility of the magnetically drug targeting in the blood vessel

High Blood Pressure, Afib and Your Risk of Stroke

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... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More High Blood Pressure, AFib and Your Risk of Stroke Updated:Aug ... have a stroke for the first time have high blood pressure . And an irregular atrial heart rhythm — a condition ...

Glucosylceramide and Lysophosphatidylcholines as Potential Blood Biomarkers for Drug-Induced Hepatic Phospholipidosis

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Saito, Kosuke; Maekawa, Keiko; Ishikawa, Masaki; Senoo, Yuya; Urata, Masayo; Murayama, Mayumi; Nakatsu, Noriyuki; Yamada, Hiroshi; Saito, Yoshiro

2014-01-01

Drug-induced phospholipidosis is one of the major concerns in drug development and clinical treatment. The present study involved the use of a nontargeting lipidomic analysis with liquid chromatography-mass spectrometry to explore noninvasive blood biomarkers for hepatic phospholipidosis from rat plasma. We used three tricyclic antidepressants (clomipramine [CPM], imipramine [IMI], and amitriptyline [AMT]) for the model of phospholipidosis in hepatocytes and ketoconazole (KC) for the model of phospholipidosis in cholangiocytes and administered treatment for 3 and 28 days each. Total plasma lipids were extracted and measured. Lipid molecules contributing to the separation of control and drug-treated rat plasma in a multivariate orthogonal partial least squares discriminant analysis were identified. Four lysophosphatidylcholines (LPCs) (16:1, 18:1, 18:2, and 20:4) and 42:1 hexosylceramide (HexCer) were identified as molecules separating control and drug-treated rats in all models of phospholipidosis in hepatocytes. In addition, 16:1, 18:2, and 20:4 LPCs and 42:1 HexCer were identified in a model of hepatic phospholipidosis in cholangiocytes, although LPCs were identified only in the case of 3-day treatment with KC. The levels of LPCs were decreased by drug-induced phospholipidosis, whereas those of 42:1 HexCer were increased. The increase in 42:1 HexCer was much higher in the case of IMI and AMT than in the case of CPM; moreover, the increase induced by IMI was dose-dependent. Structural characterization determining long-chain base and hexose delineated that 42:1 HexCer was d18:1/24:0 glucosylceramide (GluCer). In summary, our study demonstrated that d18:1/24:0 GluCer and LPCs are potential novel biomarkers for drug-induced hepatic phospholipidosis. PMID:24980264

Perceived neighborhood illicit drug selling, peer illicit drug disapproval and illicit drug use among U.S. high school seniors

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2014-01-01

Background This study examined associations between perceived neighborhood illicit drug selling, peer illicit drug disapproval and illicit drug use among a large nationally representative sample of U.S. high school seniors. Methods Data come from Monitoring the Future (2007–2011), an annual cross-sectional survey of U.S. high school seniors. Students reported neighborhood illicit drug selling, friend drug disapproval towards marijuana and cocaine use, and past 12-month and past 30-day illicit drug use (N = 10,050). Multinomial logistic regression models were fit to explain use of 1) just marijuana, 2) one illicit drug other than marijuana, and 3) more than one illicit drug other than marijuana, compared to “no use”. Results Report of neighborhood illicit drug selling was associated with lower friend disapproval of marijuana and cocaine; e.g., those who reported seeing neighborhood sales “almost every day” were less likely to report their friends strongly disapproved of marijuana (adjusted odds ratio [AOR] = 0.38, 95% CI: 0.29, 0.49) compared to those who reported never seeing neighborhood drug selling and reported no disapproval. Perception of neighborhood illicit drug selling was also associated with past-year drug use and past-month drug use; e.g., those who reported seeing neighborhood sales “almost every day” were more likely to report 30-day use of more than one illicit drug (AOR = 11.11, 95% CI: 7.47, 16.52) compared to those who reported never seeing neighborhood drug selling and reported no 30-day use of illicit drugs. Conclusions Perceived neighborhood drug selling was associated with lower peer disapproval and more illicit drug use among a population-based nationally representative sample of U.S. high school seniors. Policy interventions to reduce “open” (visible) neighborhood drug selling (e.g., problem-oriented policing and modifications to the physical environment such as installing and monitoring surveillance cameras) may

Association between parity and breastfeeding with maternal high blood pressure.

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Lupton, Samantha J; Chiu, Christine L; Lujic, Sanja; Hennessy, Annemarie; Lind, Joanne M

2013-06-01

The objective of this study was to determine how parity and breastfeeding were associated with maternal high blood pressure, and how age modifies this association. Baseline data for 74,785 women were sourced from the 45 and Up Study, Australia. These women were 45 years of age or older, had an intact uterus, and had not been diagnosed with high blood pressure before pregnancy. Odds ratios (ORs) and 99% confidence intervals (CIs) for the association between giving birth, breastfeeding, lifetime breastfeeding duration, and average breastfeeding per child with high blood pressure were estimated using logistic regression. The combination of parity and breastfeeding was associated with lower odds of having high blood pressure (adjusted OR, 0.89; 99% CI, 0.82-0.97; P high blood pressure when compared with parous women who never breastfed. The odds were lower with longer breastfeeding durations and were no longer significant in the majority of women over the age of 64 years. Women should be encouraged to breastfeed for as long as possible and a woman's breastfeeding history should be taken into account when assessing her likelihood of high blood pressure in later life. Copyright © 2013 Mosby, Inc. All rights reserved.

Interactions between the adducin 2 gene and antihypertensive drug therapies in determining blood pressure in people with hypertension

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Barkley Ruth

2007-09-01

Full Text Available Abstract Background As part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy (GENOA recruited 575 sibships (n = 1583 individuals from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms (SNPs typed in 7 positional candidate genes, including adducin 2 (ADD2. Method To investigate whether blood pressure (BP levels in these hypertensives (n = 1133 were influenced by gene-by-drug interactions, we used cross-validation statistical methods (i.e., estimating a model for predicting BP levels in one subgroup and testing it in a different subgroup. These methods greatly reduced the chance of false positive findings. Results Eight SNPs in ADD2 were significantly associated with systolic BP in untreated hypertensives (p-value Conclusion Our findings suggest that hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients who will benefit most from particular antihypertensive drug therapies.

High blood pressure in older subjects with cognitive impairment.

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Mossello, Enrico; Simoni, David

2016-06-22

High blood pressure and cognitive impairment often coexist in old age, but their pathophysiological association is complex. Several longitudinal studies have shown that high blood pressure at midlife is a risk factor for cognitive impairment and dementia, although this association is much less clear in old age. The effect of blood pressure lowering in reducing the risk of dementia is only borderline significant in clinical trials of older subjects, partly due to the insufficient follow-up time. Conversely, dementia onset is associated with a decrease of blood pressure values, probably secondary to neurodegeneration. Prognostic effect of blood pressure values in cognitively impaired older subjects is still unclear, with aggressive blood pressure lowering being potentially harmful in this patients category. Brief cognitive screening, coupled with simple motor assessment, are warranted to identify frail older subjects who need a more cautious approach to antihypertensive treatment. Values obtained with ambulatory blood pressure monitoring seem more useful than clinical ones to predict the outcome of cognitively impaired older subjects. Future studies should identify the most appropriate blood pressure targets in older subjects with cognitive impairment.

High Blood Pressure in Adolescents of Curitiba: Prevalence and Associated Factors.

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Bozza, Rodrigo; Campos, Wagner de; Barbosa Filho, Valter Cordeiro; Stabelini Neto, Antonio; Silva, Michael Pereira da; Maziero, Renato Silva Barbosa

2016-05-01

Arterial hypertension is a major public health problem and has increased considerably in young individuals in past years. Thus, identifying factors associated with this condition is important to guide intervention strategies in this population. To determine high blood pressure prevalence and its associated factors in adolescents. A random sample of 1,242 students enrolled in public schools of the city of Curitiba (PR) was selected. Self-administered questionnaires provided family history of hypertension, daily energy expenditure, smoking habit, daily fat intake, and socioeconomic status. Waist circumference was measured following standardized procedures, and blood pressure was measured with appropriate cuffs in 2 consecutive days to confirm high blood pressure. Relative frequency and confidence interval (95%CI) indicated high blood pressure prevalence. Bivariate and multivariate analyses assessed the association of risk factors with high blood pressure. The high blood pressure prevalence was 18.2% (95%CI 15.2-21.6). Individuals whose both parents had hypertension [odds ratio (OR), 2.22; 95%CI 1.28-3.85] and those with high waist circumference (OR, 2.1; 95%CI 1.34-3.28) had higher chances to develop high blood pressure. Positive family history of hypertension and high waist circumference were associated with high blood pressure in adolescents. These factors are important to guide future interventions in this population.

High Blood Pressure in Adolescents of Curitiba: Prevalence and Associated Factors

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Rodrigo Bozza

2016-01-01

Full Text Available Abstract Background: Arterial hypertension is a major public health problem and has increased considerably in young individuals in past years. Thus, identifying factors associated with this condition is important to guide intervention strategies in this population. Objective: To determine high blood pressure prevalence and its associated factors in adolescents. Methods: A random sample of 1,242 students enrolled in public schools of the city of Curitiba (PR was selected. Self-administered questionnaires provided family history of hypertension, daily energy expenditure, smoking habit, daily fat intake, and socioeconomic status. Waist circumference was measured following standardized procedures, and blood pressure was measured with appropriate cuffs in 2 consecutive days to confirm high blood pressure. Relative frequency and confidence interval (95%CI indicated high blood pressure prevalence. Bivariate and multivariate analyses assessed the association of risk factors with high blood pressure. Results: The high blood pressure prevalence was 18.2% (95%CI 15.2-21.6. Individuals whose both parents had hypertension [odds ratio (OR, 2.22; 95%CI 1.28-3.85] and those with high waist circumference (OR, 2.1; 95%CI 1.34-3.28 had higher chances to develop high blood pressure. Conclusion: Positive family history of hypertension and high waist circumference were associated with high blood pressure in adolescents. These factors are important to guide future interventions in this population.

Effect of antifibrinolytic drugs on transfusion requirement and blood loss during orthotopic liver transplantation: Results from a single center

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Devi A

2008-01-01

Full Text Available Background: During orthotopic liver transplantation (OLT, activation of the fibrinolytic system can contribute significantly to perioperative bleeding. Prophylactic administration of antifibrinolytic agents has been shown to reduce blood loss and the need for allogenic transfusion. Objective: To study the effect of antifibrinolytics on requirement of blood components, blood loss and operative time during OLT in patients with end stage liver disease, reporting to a single centre. Materials and Methods: Consecutive patients who underwent OLT at this centre during the period February 2003-October 2007 were the subjects of this study. Based on the individual anesthesiologist′s preference, patients were assigned to receive either two million units of aprotinin (AP as a bolus followed by 5,00,000 units/hour or 10 mg/kg tranexamic acid (TAas a bolus followed by 10 mg/kg every six to eight hours, administered from the induction till the end of the surgery. Transfusion policy was standardized in all patients. Intraoperative red cell salvage was done wherever possible. The effect of these two antifibrinolytic drugs on transfusion requirement was evaluated as a whole and in a sub group of patients from each treatment group and compared with a concurrent control group that did not receive antifibrinolytic drugs. Results: Fifty patients (40 M / 10 F, 44 adults, 6 pediatric patients underwent OLT in the study period. Fourteen patients were given AP, 25 patients were given TA and 11 patients did not receive any of the agents(control group. The median volume of total blood components transfused in antifibrinolytic group (n=39 was 4540 ml(0-19,200ml, blood loss 5 l(0.7-35l and operative time 9h (4.5-17h and that of control group(n=11 was 5700 ml(0-15,500ml, 10 l(0.6-25 l and 9h (6.4-15.8h respectively. The median volume of blood transfusions, blood loss and operative time was lesser in AP group(n=14 than that of TA group(n=25. Conclusion: There is definite

Blood group genotyping: from patient to high-throughput donor screening.

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Veldhuisen, B; van der Schoot, C E; de Haas, M

2009-10-01

Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human platelet antigens is known. In many laboratories, blood group genotyping assays are routinely used for diagnostics in cases where patient red cells cannot be used for serological typing due to the presence of auto-antibodies or after recent transfusions. In addition, DNA genotyping is used to support (un)-expected serological findings. Fetal genotyping is routinely performed when there is a risk of alloimmune-mediated red cell or platelet destruction. In case of patient blood group antigen typing, it is important that a genotyping result is quickly available to support the selection of donor blood, and high-throughput of the genotyping method is not a prerequisite. In addition, genotyping of blood donors will be extremely useful to obtain donor blood with rare phenotypes, for example lacking a high-frequency antigen, and to obtain a fully typed donor database to be used for a better matching between recipient and donor to prevent adverse transfusion reactions. Serological typing of large cohorts of donors is a labour-intensive and expensive exercise and hampered by the lack of sufficient amounts of approved typing reagents for all blood group systems of interest. Currently, high-throughput genotyping based on DNA micro-arrays is a very feasible method to obtain a large pool of well-typed blood donors. Several systems for high-throughput blood group genotyping are developed and will be discussed in this review.

Nursing Education in High Blood Pressure Control. Report of the Task Force on the Role of Nursing in High Blood Pressure Control.

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National Institutes of Health (DHEW), Bethesda, MD. High Blood Pressure Information Center.

This curriculum guide on high blood pressure (hypertension) for nursing educators has five sections: (1) Introduction and Objectives provides information regarding the establishment and objectives of the National Task Force on the Role of Nursing in High Blood Pressure Control and briefly discusses nursing's role in hypertension control; (2) Goals…

Hyperglycemia (High Blood Glucose)

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Full Text Available ... how often you should check and what your blood glucose levels should be. Checking your blood and then treating ... I Treat Hyperglycemia? You can often lower your blood glucose level by exercising. However, if your blood glucose is ...

Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

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Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

2014-10-06

The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of PEGylation on ligand-based targeting of drug carriers to the vascular wall in blood flow.

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Onyskiw, Peter J; Eniola-Adefeso, Omolola

2013-09-03

The blood vessel wall plays a prominent role in the development of many life-threatening diseases and as such is an attractive target for treatment. To target diseased tissue, particulate drug carriers often have their surfaces modified with antibodies or epitopes specific to vascular wall-expressed molecules, along with poly(ethylene glycol) (PEG) to improve carrier blood circulation time. However, little is known about the effect of poly(ethylene glycol) on carrier adhesion dynamics-specifically in blood flow. Here we examine the influence of different molecular weight PEG spacers on particle adhesion in blood flow. Anti-ICAM-1 or Sialyl Lewis(a) were grafted onto polystyrene 2 μm and 500 nm spheres via PEG spacers and perfused in blood over activated endothelial cells at physiological shear conditions. PEG spacers were shown to improve, reduce, or have no effect on the binding density of targeted-carriers depending on the PEG surface conformation, shear rate, and targeting moiety.

Permeabilization of the blood-brain barrier via mucosal engrafting: implications for drug delivery to the brain.

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Bleier, Benjamin S; Kohman, Richie E; Feldman, Rachel E; Ramanlal, Shreshtha; Han, Xue

2013-01-01

Utilization of neuropharmaceuticals for central nervous system(CNS) disease is highly limited due to the blood-brain barrier(BBB) which restricts molecules larger than 500Da from reaching the CNS. The development of a reliable method to bypass the BBB would represent an enormous advance in neuropharmacology enabling the use of many potential disease modifying therapies. Previous attempts such as transcranial catheter implantation have proven to be temporary and associated with multiple complications. Here we describe a novel method of creating a semipermeable window in the BBB using purely autologous tissues to allow for high molecular weight(HMW) drug delivery to the CNS. This approach is inspired by recent advances in human endoscopic transnasal skull base surgical techniques and involves engrafting semipermeable nasal mucosa within a surgical defect in the BBB. The mucosal graft thereby creates a permanent transmucosal conduit for drugs to access the CNS. The main objective of this study was to develop a murine model of this technique and use it to evaluate transmucosal permeability for the purpose of direct drug delivery to the brain. Using this model we demonstrate that mucosal grafts allow for the transport of molecules up to 500 kDa directly to the brain in both a time and molecular weight dependent fashion. Markers up to 40 kDa were found within the striatum suggesting a potential role for this technique in the treatment of Parkinson's disease. This proof of principle study demonstrates that mucosal engrafting represents the first permanent and stable method of bypassing the BBB thereby providing a pathway for HMW therapeutics directly into the CNS.

Sleep Deprivation: A Cause of High Blood Pressure?

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... it true that sleep deprivation can cause high blood pressure? Answers from Sheldon G. Sheps, M.D. Possibly. It's thought that ... hours a night could be linked to increased blood pressure. People who sleep five hours or less a ...

Postmortem Blood Concentrations of R- and S-Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein Genotype

DEFF Research Database (Denmark)

Buchard, Anders; Linnet, Kristian; Johansen, Sys Stybe

2010-01-01

We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S-enantiome......We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S...

[Targeting high-risk drugs to optimize clinical pharmacists' intervention].

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Mouterde, Anne-Laure; Bourdelin, Magali; Maison, Ophélie; Coursier, Sandra; Bontemps, Hervé

2016-12-01

By the Order of 6 April 2011, the pharmacist must validate all the prescriptions containing "high-risk drugs" or those of "patients at risk". To optimize this clinical pharmacy activity, we identified high-risk drugs. A list of high-risk drugs has been established using literature, pharmacists' interventions (PI) performed in our hospital and a survey sent to hospital pharmacists. In a prospective study (analysis of 100 prescriptions for each high-risk drug selected), we have identified the most relevant to target. We obtained a statistically significant PI rate (P<0.05) for digoxin, oral anticoagulants direct, oral methotrexate and colchicine. This method of targeted pharmaceutical validation based on high-risk drugs is relevant to detect patients with high risk of medicine-related illness. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Drug Delivery to the Brain in Alzheimer’s Disease: Consideration of the Blood-brain Barrier

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Banks, William A.

2012-01-01

The successful treatment of Alzheimer’s disease (AD) will require drugs that can negotiate the blood-brain barrier (BBB). However, the BBB is not simply a physical barrier, but a complex interface that is in intimate communication with the rest of the central nervous system (CNS) and influenced by peripheral tissues. This review examines three aspects of the BBB in AD. First, it considers how the BBB may be contributing to the onset and progression of AD. In this regard, the BBB itself is a therapeutic target in the treatment of AD. Second, it examines how the BBB restricts drugs that might otherwise be useful in the treatment of AD and examines strategies being developed to deliver drugs to the CNS for the treatment of AD. Third, it considers how drug penetration across the AD BBB may differ from the BBB of normal aging. In this case, those differences can complicate the treatment of CNS diseases such as depression, delirium, psychoses, and pain control in the AD population. PMID:22202501

The Use of Limited Fluid Resuscitation and Blood Pressure-Controlling Drugs in the Treatment of Acute Upper Gastrointestinal Hemorrhage Concomitant with Hemorrhagic Shock.

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Lu, Bo; Li, Mao-Qin; Li, Jia-Qiong

2015-06-01

The aim of this study was to evaluate the usefulness of the limited fluid resuscitation regimen combined with blood pressure-controlling drugs in treating acute upper gastrointestinal hemorrhage concomitant with hemorrhagic shock. A total of 51 patients were enrolled and divided into a group that received traditional fluid resuscitation group (conventional group, 24 patients) and a limited fluid resuscitation group (study group, 27 patients). Before and after resuscitation, the blood lactate, base excess, and hemoglobin values, as well as the volume of fluid resuscitation and resuscitation time were examined. Compared with conventional group, study group had significantly better values of blood lactate, base excess, and hemoglobin (all p controlling drugs effectivelyxxx maintains blood perfusion of vital organs, improves whole body perfusion indicators, reduces the volume of fluid resuscitation, and achieves better bleeding control and resuscitation effectiveness.

21 CFR 864.9100 - Empty container for the collection and processing of blood and blood components.

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2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Empty container for the collection and processing of blood and blood components. 864.9100 Section 864.9100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products...

Rapid screening for drugs of abuse in biological fluids by ultra high performance liquid chromatography/Orbitrap mass spectrometry.

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Jagerdeo, Eshwar; Schaff, Jason E

2016-08-01

We present a UPLC(®)-High Resolution Mass Spectrometric method to simultaneously screen for nineteen benzodiazepines, twelve opiates, cocaine and three metabolites, and three "Z-drug" hypnotic sedatives in both blood and urine specimens. Sample processing consists of a high-speed, high-temperature enzymatic hydrolysis for urine samples followed by a rapid supported liquid extraction (SLE). The combination of ultra-high resolution chromatography with high resolution mass spectrometry allows all 38 analytes to be uniquely detected with a ten minute analytical run. Limits of detection for all target analytes are 3ng/mL or better, with only 0.3mL of specimen used for analysis. The combination of low sample volume with fast processing and analysis makes this method a suitable replacement for immunoassay screening of the targeted drug classes, while providing far superior specificity and better limits of detection than can routinely be obtained by immunoassay. Published by Elsevier B.V.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs

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Luisa Gilardini

2016-07-01

Full Text Available Objective: To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP levels in hypertensive (controlled or not obese patients. Methods: In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP Results: 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average -4.9 ± 2.7% was independent of the antihypertensive drugs employed. Systolic BP (SBP decreased by 23 mm Hg and diastolic BP (DBP by 9 mm Hg, in patients with UH most of whom (89% normalized BP levels (in 49% after a weight loss Conclusion: Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs.

Promising cardiovascular and blood pressure effects of the SGLT2 inhibitors: a new class of antidiabetic drugs.

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Chrysant, S G

2017-03-01

Patients with type 2 diabetes mellitus (T2DM) exhibit an increased risk of cardiovascular (CV) events. Treatment of these patients with traditional as well as newer glucose-lowering drugs has not demonstrated superiority in CV outcomes compared to placebo, despite effective control of diabetes. However, the recently FDA-approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of T2DM have demonstrated promising CV-protecting and blood pressure-lowering effects in addition to their effectiveness in glucose lowering, making them a novel class of drugs for the treatment of T2DM. So far, there are three SGLT2 inhibitors approved by the FDA and EMA for the treatment of T2DM: canagliflozin, dapagliflozin and empagliflozin. They exert their antihyperglycemic effect through inhibition of SGLT2 in the kidney and significantly reduce glucose reabsorption from the proximal renal tubule. By blocking glucose reabsorption, they lead to loss of calories, weight, abdominal and total body fat, blood pressure and CV complications. One CV outcomes randomized trial and several short-term studies have shown reductions in CV events and blood pressure in patients with T2DM. It is the hope that large ongoing long-term outcome studies will provide further much-needed information, when they are completed. Copyright 2017 Clarivate Analytics.

Managing Hyperglycemia (High Blood Sugar) in the Hospital: a Patient's Guide

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Managing Hyperglycemia (High Blood Sugar) in the Hospital A Patient’s Guide Hyperglycemia is the medical term for blood glucose (sugar) ... org/guidelines/index.cfm). www.hormone.org Managing Hyperglycemia (High Blood Sugar) in the Hospital Patient Guide ...

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging

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Estrada Giovani

2010-03-01

Full Text Available Abstract Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB, a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical

Increased Risk of Drug-Induced Hyponatremia during High Temperatures

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Anna K Jönsson

2017-07-01

Full Text Available Purpose: To investigate the relationship between outdoor temperature in Sweden and the reporting of drug-induced hyponatremia to the Medical Products Agency (MPA. Methods: All individual adverse drug reactions (ADR reported to MPA from 1 January 2010 to 31 October 2013 of suspected drug-induced hyponatremia and random controls were identified. Reports where the ADR had been assessed as having at least a possible relation to the suspected drug were included. Information on administered drugs, onset date, causality assessment, sodium levels, and the geographical origin of the reports was extracted. A case-crossover design was used to ascertain the association between heat exposure and drug-induced hyponatremia at the individual level, while linear regression was used to study its relationship to sodium concentration in blood. Temperature exposure data were obtained from the nearest observation station to the reported cases. Results: During the study period, 280 reports of hyponatremia were identified. More cases of drug-induced hyponatremia were reported in the warmer season, with a peak in June, while other ADRs showed an opposite annual pattern. The distributed lag non-linear model indicated an increasing odds ratio (OR with increasing temperature in the warm season with a highest odds ratio, with delays of 1–5 days after heat exposure. A cumulative OR for a lag time of 1 to 3 days was estimated at 2.21 at an average daily temperature of 20 °C. The change in sodium per 1 °C increase in temperature was estimated to be −0.37 mmol/L (95% CI: −0.02, −0.72. Conclusions: Warm weather appears to increase the risk of drug-induced hyponatremia

Patents associated with high-cost drugs in Australia.

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Andrew F Christie

Full Text Available Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by "evergreening" blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug's originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators.

Patents associated with high-cost drugs in Australia.

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Christie, Andrew F; Dent, Chris; McIntyre, Peter; Wilson, Lachlan; Studdert, David M

2013-01-01

Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by "evergreening" blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug's originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators.

Supercritical fluid chromatography coupled with tandem mass spectrometry: A high-efficiency detection technique to quantify Taxane drugs in whole-blood samples.

Science.gov (United States)

Jin, Chan; Guan, Jibin; Zhang, Dong; Li, Bing; Liu, Hongzhuo; He, Zhonggui

2017-10-01

We present a technique to rapid determine taxane in blood samples by supercritical fluid chromatography together with mass spectrometry. The aim of this study was to develop a supercritical fluid chromatography with mass spectrometry method for the analysis of paclitaxel, cabazitaxel, and docetaxel in whole-blood samples of rats. Liquid-dry matrix spot extraction was selected in sample preparation procedure. Supercritical fluid chromatography separation of paclitaxel, cabazitaxel, docetaxel, and glyburide (internal standard) was accomplished within 3 min by using the gradient mobile phase consisted of methanol as the compensation solvent and carbon dioxide at a flow rate of 1.0 mL/min. The method was validated regarding specificity, the lower limit of quantification, repeatability, and reproducibility of quantification, extraction recovery, and matrix effects. The lower limit of quantification was found to be 10 ng/mL since it exhibited acceptable precision and accuracy at the corresponding level. All interday accuracies and precisions were within the accepted criteria of ±15% of the nominal value and within ±20% at the lower limit of quantification, implying that the method was reliable and reproducible. In conclusion, this method is a promising tool to support and improve preclinical or clinical pharmacokinetic studies with the taxanes anticancer drugs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Teaming Up Against High Blood Pressure

Centers for Disease Control (CDC) Podcasts

This podcast is based on the September 2012 CDC Vital Signs report. A team-based approach by patients, health care systems, and health care providers is one of the best ways to treat uncontrolled high blood pressure.

[Applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis].

Science.gov (United States)

Wang, Feng-Qin; Chen, Cen; Xia, Zhi-Ning; Yang, Feng-Qing

2014-08-01

Thrombotic diseases in different forms become a great threat to human health. Such anti-platelet aggregation drugs as aspirin and clopidogrel are common drugs in clinic. However, along with the appearance of resistance and side effects of western anti-platelet aggregation drugs, anti-platelet aggregation traditional Chinese medicines promoting blood circulation to remove blood stasis have gradually become an important study orientation. Platelet is one of major participant in thrombosis, and plays an important role as a bioactive material in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, mainly involving two aspects--the evaluation for the anti-platelet aggregation activity of traditional Chinese medicines and the screening of their active components. This paper summarized the applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, so as to provide basis for further studies.

Vital Signs - High Blood Pressure

Centers for Disease Control (CDC) Podcasts

2012-10-02

In the U.S., nearly one third of the adult population have high blood pressure, the leading risk factor for heart disease and stroke - two of the nation's leading causes of death.  Created: 10/2/2012 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/17/2012.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... can often lower your blood glucose level by exercising. However, if your blood glucose is above 240 ... ketones. If you have ketones, do not exercise. Exercising when ketones are present may make your blood ...

Blood-brain barrier in vitro models as tools in drug discovery: assessment of the transport ranking of antihistaminic drugs.

Science.gov (United States)

Neuhaus, W; Mandikova, J; Pawlowitsch, R; Linz, B; Bennani-Baiti, B; Lauer, R; Lachmann, B; Noe, C R

2012-05-01

In the course of our validation program testing blood-brain barrier (BBB) in vitro models for their usability as tools in drug discovery it was evaluated whether an established Transwell model based on porcine cell line PBMEC/C1-2 was able to differentiate between the transport properties of first and second generation antihistaminic drugs. First generation antihistamines can permeate the BBB and act in the central nervous system (CNS), whereas entry to the CNS of second generation antihistamines is restricted by efflux pumps such as P-glycoprotein (P-gP) located in brain endothelial cells. P-gP functionality of PBMEC/C1-2 cells grown on Transwell filter inserts was proven by transport studies with P-gP substrate rhodamine 123 and P-gP blocker verapamil. Subsequent drug transport studies with the first generation antihistamines promethazine, diphenhydramine and pheniramine and the second generation antihistamines astemizole, ceterizine, fexofenadine and loratadine were accomplished in single substance as well as in group studies. Results were normalised to diazepam, an internal standard for the transcellular transport route. Moreover, effects after addition of P-gP inhibitor verapamil were investigated. First generation antihistamine pheniramine permeated as fastest followed by diphenhydramine, diazepam, promethazine and second generation antihistaminic drugs ceterizine, fexofenadine, astemizole and loratadine reflecting the BBB in vivo permeability ranking well. Verapamil increased the transport rates of all second generation antihistamines, which suggested involvement of P-gP during their permeation across the BBB model. The ranking after addition of verapamil was significantly changed, only fexofenadine and ceterizine penetrated slower than internal standard diazepam in the presence of verapamil. In summary, permeability data showed that the BBB model based on porcine cell line PBMEC/C1-2 was able to reflect the BBB in vivo situation for the transport of

Transferrin-conjugated magnetic dextran-spermine nanoparticles for targeted drug transport across blood-brain barrier.

Science.gov (United States)

Ghadiri, Maryam; Vasheghani-Farahani, Ebrahim; Atyabi, Fatemeh; Kobarfard, Farzad; Mohamadyar-Toupkanlou, Farzaneh; Hosseinkhani, Hossein

2017-10-01

Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested. The superparamagnetic characteristic of TDS-NPs was verified by vibration simple magnetometer. Capecitabine loaded TDS-NPs exhibited pH-sensitive release behavior with enhanced cytotoxicity against U87MG cells, compared to DS-NPs and free capecitabine. Prussian-blue staining and TEM-imaging showed the significant cellular uptake of TDS-NPs. Furthermore, a remarkable increase of Fe concentrations in brain was observed following their biodistribution and histological studies in vivo, after 1 and 7 days of post-injection. Enhanced drug transport across BBB and pH-triggered cellular uptake of TDS-NPs indicated that these theranostic nanocarriers are promising candidate for the brain malignance treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2851-2864, 2017. © 2017 Wiley Periodicals, Inc.

Xenon-133 determination of muscle blood flow: Use in evaluating cardioactive drugs

International Nuclear Information System (INIS)

Wexler, J.P.; Davis, L.; Mancini, D.; Chadwick, B.; Le Jemtel, T.

1985-01-01

Cardioactive drugs may effect both the central and peripheral circulatory systems. The effects on the central and peripheral circulatory systems of chronic Captorpril therapy in 7 pts with severe congestive heart failure (CHF) were evaluated simultaneously. Skeletal muscle blood flow (SMBF) determined using 133-Xe washout and a Cd/Te detector, oxygen consumption (VO/sub 2/), and radial artery and femoral vein O/sub 2/ concentration difference (A-V) were determined at rest and peak upright bicycle exercise before (BT) and after (AT) 6-12 weeks of Captopril therapy. In CI pts there was a significant increase in VO/sub 2/ and SMBF AT vs BT. In contrast, in CNC pts there was no change in VO/sub 2/ and a significant decrease in SMBF AT vs BT. In pts with severe CHF who are CI, there is an apparent fall in peripheral vascular resistance (PVR). In contrast, in CNC pts there is an increase in PVR. This study demonstrates that SMBF determines using 133-Xe is an important method for determining the effects of cardioactive drugs

Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model.

Science.gov (United States)

Serpe, Loredana; Canaparo, Roberto; Daperno, Marco; Sostegni, Raffaello; Martinasso, Germana; Muntoni, Elisabetta; Ippolito, Laura; Vivenza, Nicoletta; Pera, Angelo; Eandi, Mario; Gasco, Maria Rosa; Zara, Gian Paolo

2010-03-18

Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants. There was a significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion, whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 microM), at 24h exposure. There was a significant decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested. The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model. Copyright 2010 Elsevier B.V. All rights reserved.

Chagas disease, a risk factor for high blood pressure.

Science.gov (United States)

Vicco, Miguel Hernán; Rodeles, Luz; Yódice, Agustina; Marcipar, Iván

2014-12-01

Chagas disease is a parasite infection caused by the protozoan Trypanosoma cruzi. Its most common complications is chronic Chagas heart disease but impairments of the systemic vasculature also has been observed. Although the different mechanisms that regulate blood pressure are disrupted, to our knowledge data on the association of hypertension and chronic Chagas disease are scarce. In this regard we evaluate whether Chagas disease constitutes a high blood pressure risk factor. We recruited 200 individuals, half of them with positive serology for T. cruzi. They were subjected to a complete clinical examination. The mean age of sampled individuals was 46.7 ± 12.3, and the mean of systolic and diastolic blood pressure were 124 ± 12 mmHg and 82 ± 10 mmHg, respectively. There were no between-group differences regarding age, sex distribution or body mass index. Chagas disease contributed significantly to high blood pressure (OR = 4, 95% CI 1.8323-7.0864, p = 0.0002). Our results reveal an important association between Chagas disease and high blood pressure, which should be contemplated by physicians in order to promote preventive cardiovascular actions in patients with Chagas disease.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... by Mail Close www.diabetes.org > Living With Diabetes > Treatment and Care > Blood Glucose Testing Share: Print Page ... and-how-tos, . In this section Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood ...

Red blood cell aggregation changes are depended on its initial value: Effect of long-term drug treatment and short-term cell incubation with drug.

Science.gov (United States)

Muravyov, A V; Tikhomirova, I A; Maimistova, A A; Bulaeva, S V; Mikhailov, P V; Kislov, N V

2011-01-01

This study was designed to investigate whether the red cell aggregation depends on its initial level under drug therapy or cell incubation with bioactive chemical compounds. Sixty six subjects were enrolled onto this study, and sub-divided into two groups: the first group of patients (n = 36) with cerebral atherosclerosis received pentoxifylline therapy (400 mg, thrice daily) for 4 weeks. The patients of the second group were initially treated with Epoetin beta 10,000 units subcutaneously thrice a week, for 4 weeks. The second group - adult anemic patients (n = 30) with the confirmed diagnosis of solid cancer (Hb treatment the red cell aggregation increased (p treatment with pentoxifylline reduced it markedly (p treatment 75% the anemic patients with initially high RBCA had an aggregation lowering. The drop of aggregation was about 34% (p treatment. The initially low red cell aggregation after incubation with epoetin-beta was markedly increased by 122% (p drugs depend markedly on the initial, pre-treatment aggregation status of the patients. These results demonstrate that the different red blood cell aggregation responses to the biological stimuli depend strongly on the initial, pre-treatment status of the subject and the most probably it is connected with the crosstalk between the adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism.

Determination of telmisartan in human blood plasma: Part I: Immunoassay development

NARCIS (Netherlands)

Hempen, C.M.; Gläsle-Schwarz, Liane; Kunz, Ulrich; Karst, U.

2006-01-01

Telmisartan is an angiotensin II receptor antagonist and a known drug against high blood pressure. In this report, the development of a new and rapid analytical technique, an enzyme-linked immunosorbent assay (ELISA) for the determination of telmisartan in human blood plasma is described. The

High Blood Pressure and Chronic Kidney Disease in Children: A Guide for Parents

Science.gov (United States)

... Events Advocacy Donate A to Z Health Guide High Blood Pressure and Kidney Disease in Children Print Email High ... such as the heart and brain. What is high blood pressure? Blood pressure is the force of your blood ...

Symptoms of Blood Disorders

Science.gov (United States)

... or immune system proteins can cause increased blood viscosity (thickening of the blood). Increased platelets or blood ... by anemia Pica (eating of ice, dirt, or clay) suggests iron deficiency anemia Drugs Mentioned In This ...

Flow cytometric assay for analysis of cytotoxic effects of potential drugs on human peripheral blood leukocytes

Science.gov (United States)

Nieschke, Kathleen; Mittag, Anja; Golab, Karolina; Bocsi, Jozsef; Pierzchalski, Arkadiusz; Kamysz, Wojciech; Tarnok, Attila

2014-03-01

Toxicity test of new chemicals belongs to the first steps in the drug screening, using different cultured cell lines. However, primary human cells represent the human organism better than cultured tumor derived cell lines. We developed a very gentle toxicity assay for isolation and incubation of human peripheral blood leukocytes (PBL) and tested it using different bioactive oligopeptides (OP). Effects of different PBL isolation methods (red blood cell lysis; Histopaque isolation among others), different incubation tubes (e.g. FACS tubes), anticoagulants and blood sources on PBL viability were tested using propidium iodide-exclusion as viability measure (incubation time: 60 min, 36°C) and flow cytometry. Toxicity concentration and time-depended effects (10-60 min, 36 °C, 0-100 μg /ml of OP) on human PBL were analyzed. Erythrocyte lysis by hypotonic shock (dH2O) was the fastest PBL isolation method with highest viability (>85%) compared to NH4Cl-Lysis (49%). Density gradient centrifugation led to neutrophil granulocyte cell loss. Heparin anticoagulation resulted in higher viability than EDTA. Conical 1.5 mL and 2 mL micro-reaction tubes (both polypropylene (PP)) had the highest viability (99% and 97%) compared to other tubes, i.e. three types of 5.0 mL round-bottom tubes PP (opaque-60%), PP (blue-62%), Polystyrene (PS-64%). Viability of PBL did not differ between venous and capillary blood. A gentle reproducible preparation and analytical toxicity-assay for human PBL was developed and evaluated. Using our assay toxicity, time-course, dose-dependence and aggregate formation by OP could be clearly differentiated and quantified. This novel assay enables for rapid and cost effective multiparametric toxicological screening and pharmacological testing on primary human PBL and can be adapted to high-throughput-screening.°z

What You Should Know About High Blood Pressure and Medications

Science.gov (United States)

... Aortic Aneurysm More What You Should Know About High Blood Pressure and Medications Updated:Jan 18,2017 Is medication ... resources . This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

The first Iranian recommendations on prevention, evaluation and management of high blood pressure

Directory of Open Access Journals (Sweden)

Feridoun Noohi

2012-10-01

Full Text Available This paper presents the complete report of the first Iranian Recommendations on Prevention, Evaluation and Management of High Blood Pressure. The purpose is to provide an evidence-based approach to the prevention, management and control of hypertension (HTN by adapting the most internationally known and used guidelines to the local health care status with consideration of the currently available data and based on the locally conducted researches on HTN as well as social and health care requirements. A working group of national and international experts participated in discussions and collaborated in decision-making, writing and reviewing the whole report. Multiple subcommittees worked together to review the recent national and international literature on HTN in different areas. We used the evaluation tool that is called “AGREE” and considered a score of > 60% as a high score. We adapted the Canadian Hypertension Education Program (CHEP, the United Kingdom’s National Institute for Health and Clinical Excellence (NICE and the US-based joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7. The key topics that are highlighted in this report include: The importance of ambulatory and self-measurement of blood pressure, evaluation of cardiovascular risk in HTN patients, the role of lifestyle modification in the prevention of HTN and its control with more emphasis on salt intake reduction and weight control, introducing pharmacotherapy suitable for uncomplicated HTN or specific situations and the available drugs in Iran, highlighting the importance of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers and calcium channel blockers as the first line therapy in many situations, the non-use of beta blockers as the first time treatment except in specific conditions, treating HTN in women, children, obese and elderly patients, the patient compliance to improve HTN control, practical

Rapid detection of cancer related DNA nanoparticulate biomarkers and nanoparticles in whole blood

Science.gov (United States)

Heller, Michael J.; Krishnan, Raj; Sonnenberg, Avery

2010-08-01

The ability to rapidly detect cell free circulating (cfc) DNA, cfc-RNA, exosomes and other nanoparticulate disease biomarkers as well as drug delivery nanoparticles directly in blood is a major challenge for nanomedicine. We now show that microarray and new high voltage dielectrophoretic (DEP) devices can be used to rapidly isolate and detect cfc-DNA nanoparticulates and nanoparticles directly from whole blood and other high conductance samples (plasma, serum, urine, etc.). At DEP frequencies of 5kHz-10kHz both fluorescent-stained high molecular weight (hmw) DNA, cfc-DNA and fluorescent nanoparticles separate from the blood and become highly concentrated at specific DEP highfield regions over the microelectrodes, while blood cells move to the DEP low field-regions. The blood cells can then be removed by a simple fluidic wash while the DNA and nanoparticles remain highly concentrated. The hmw-DNA could be detected at a level of <260ng/ml and the nanoparticles at <9.5 x 109 particles/ml, detection levels that are well within the range for viable clinical diagnostics and drug nanoparticle monitoring. Disease specific cfc-DNA materials could also be detected directly in blood from patients with Chronic Lymphocytic Leukemia (CLL) and confirmed by PCR genotyping analysis.

Longitudinal assessment of high blood pressure in children with nonalcoholic fatty liver disease.

Science.gov (United States)

Schwimmer, Jeffrey B; Zepeda, Anne; Newton, Kimberly P; Xanthakos, Stavra A; Behling, Cynthia; Hallinan, Erin K; Donithan, Michele; Tonascia, James

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD. Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks. Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003). Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m2, 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively). Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05). In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD.

Longitudinal assessment of high blood pressure in children with nonalcoholic fatty liver disease.

Directory of Open Access Journals (Sweden)

Jeffrey B Schwimmer

Full Text Available Nonalcoholic fatty liver disease (NAFLD affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD.Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks.Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003. Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m2, 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively. Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05.In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD.

The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication

Directory of Open Access Journals (Sweden)

Mohamed eOuzzine

2014-10-01

Full Text Available UDP-glucuronosyltransferases (UGTs form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-Dglucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds by the linkage of glucuronic acid from the high energy donor, UDP-αD-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier. They are also associated to brain interfaces devoid of blood-brain barrier, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed.

High discordance in blood and genital tract HIV-1 drug resistance in Indian women failing first-line therapy.

Science.gov (United States)

Saravanan, Shanmugam; Gomathi, Selvamurthi; Delong, Allison; Kausalya, Bagavathi; Sivamalar, Sathasivam; Poongulali, Selvamuthu; Brooks, Katherine; Kumarasamy, Nagalingeswaran; Balakrishnan, Pachamuthu; Solomon, Sunil S; Cu-Uvin, Susan; Kantor, Rami

2018-05-24

Examine HIV-1 plasma viral load (PVL) and genital tract (GT) viral load (GVL) and drug resistance in India. At the YRG Centre for AIDS Research and Education, Chennai, we tested: PVL in women on first-line ART for ≥6 months; GVL when PVL >2000 copies/mL; and plasma, genital and proviral reverse transcriptase drug resistance when GVL >2000 copies/mL. Wilcoxon rank-sum and Fisher's exact tests were used to identify failure and resistance associations. Pearson correlations were calculated to evaluate PVL-GVL associations. Inter-compartmental resistance discordance was evaluated using generalized estimating equations. Of 200 women, 37% had detectable (>400 copies/mL) PVL and 31% had PVL >1000 copies/mL. Of women with detectable PVL, 74% had PVL >2000 copies/mL, of which 74% had detectable GVL. Higher PVL was associated with higher GVL. Paired plasma and genital sequences were available for 21 women; mean age of 34 years, median ART duration of 33 months, median CD4 count of 217 cells/mm3, median PVL of 5.4 log10 copies/mL and median GVL of 4.6 log10 copies/mL. Drug resistance was detected in 81%-91% of samples and 67%-76% of samples had dual-class resistance. Complete three-compartment concordance was seen in only 10% of women. GT-proviral discordance was significantly larger than plasma-proviral discordance. GT or proviral mutations discordant from plasma led to clinically relevant resistance in 24% and 30%, respectively. We identified high resistance and high inter-compartmental resistance discordance in Indian women, which might lead to unrecognized resistance transmission and re-emergence compromising treatment outcomes, particularly relevant to countries like India, where sexual HIV transmission is predominant.

Moessbauer studies of blood diseases: thalassemia and malaria

International Nuclear Information System (INIS)

Bauminger, E.R.

1988-01-01

In 57 F Moessbauer studies of blood samples obtained from patients with thalassemia large amounts of iron, yielding a well defined spectrum, different from that obtained in oxy - or deoxy-hemoglobin, were found. The additional iron component was identified as due to ferritin - the iron storage protein. The amounts of ferritin-like iron were comparable to those of hemoglobin iron and were especially large in reticulocytes. Desferral was found to remove ferritin-like iron from serum, but not from red blood cells. In malaria, a parasite induced blood disease, the iron containing compound in the malarial pigment in rats infected by Plasmodium berghei was found to be trivalent high spin, different from any known iron porphyrin, yet was found to be similar to hemin in human blood cells infected by P. falciparum. The difference in the spectra obtained in RBC infected with drug sensitive and drug resistance strains and the effect of medication on the spectra is discussed. (author)

An invertebrate model for CNS drug discovery

DEFF Research Database (Denmark)

Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré

2015-01-01

BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery....

High blood pressure and visual sensitivity

Science.gov (United States)

Eisner, Alvin; Samples, John R.

2003-09-01

The study had two main purposes: (1) to determine whether the foveal visual sensitivities of people treated for high blood pressure (vascular hypertension) differ from the sensitivities of people who have not been diagnosed with high blood pressure and (2) to understand how visual adaptation is related to standard measures of systemic cardiovascular function. Two groups of middle-aged subjects-hypertensive and normotensive-were examined with a series of test/background stimulus combinations. All subjects met rigorous inclusion criteria for excellent ocular health. Although the visual sensitivities of the two subject groups overlapped extensively, the age-related rate of sensitivity loss was, for some measures, greater for the hypertensive subjects, possibly because of adaptation differences between the two groups. Overall, the degree of steady-state sensitivity loss resulting from an increase of background illuminance (for 580-nm backgrounds) was slightly less for the hypertensive subjects. Among normotensive subjects, the ability of a bright (3.8-log-td), long-wavelength (640-nm) adapting background to selectively suppress the flicker response of long-wavelength-sensitive (LWS) cones was related inversely to the ratio of mean arterial blood pressure to heart rate. The degree of selective suppression was also related to heart rate alone, and there was evidence that short-term changes of cardiovascular response were important. The results suggest that (1) vascular hypertension, or possibly its treatment, subtly affects visual function even in the absence of eye disease and (2) changes in blood flow affect retinal light-adaptation processes involved in the selective suppression of the flicker response from LWS cones caused by bright, long-wavelength backgrounds.

HIGH ALTITUDES EFFECTS ON HEMATOLOGIC BLOOD PARAMETERS

Directory of Open Access Journals (Sweden)

Hasim Rushiti

2015-05-01

Full Text Available The approach and the objective of this experiment are consistent with the determination of changes of blood parameters after the stay of the students at an altitude of 1800-2300 meters, for a ten-day long ski course. In this paper are included a total of 64 students of the Faculty of Sport Sciences in Prishtina, of the age group of 19-25 (the average age is 21. All students previously have undergone a medical check for TA, arterial pulse and respiratory rate. In particular, the health situation is of subjects was examined, then, all students, at the same time, gave blood for analysis. In this experiment, three main hematologic parameters were taken in consideration: such as hemoglobin, hematocrit and red blood cells. The same analyses were carried out after the 10-day stay at a high altitude. The results of the experiment have shown significant changes after the ten-day stay at high altitude, despite the previous results that show changes only after the twenty-day stay in such elevations.

21 CFR 864.8200 - Blood cell diluent.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood cell diluent. 864.8200 Section 864.8200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8200 Blood cell diluent. (a...

Interaction of mianserin and some hypotensive drugs in Wistar rats.

Science.gov (United States)

Górska, Dorota; Andrzejczak, Dariusz

2004-01-01

Mianserin is thought to exert little effect on the cardiovascular system. In fact its safety in comparison with tricyclic drugs is high. Various experiments gave varying results as for the influence of the drug on arterial blood pressure in people and animals. Therefore, a study was undertaken in Wistar rats to evaluate interactions of mianserin administered intraperitoneally as a single dose, and for 21 days with 3 hypotensive drugs showing different mechanism of action (propranolol, enalapril, prazosine). The systolic, diastolic and mean blood pressure was measured with a LETICA apparatus. The results of the study revealed that administration of mianserin in normotensive rats leads to a short-term decrease in blood pressure and significantly enhanced the hypotensive effect of prazosine. Repeated doses of mianserin lead to a temporary increase in blood pressure after 2 weeks of administration. Single and repeated administration of mianserin did not change the hypotensive effect of propranolol and enalapril. Three-week therapy with mianserin significantly enhanced the hypotensive effect of prazosine.

High sugar consumption and poor nutrient intake among drug addicts in Oslo, Norway.

Science.gov (United States)

Saeland, M; Haugen, M; Eriksen, F-L; Wandel, M; Smehaugen, A; Böhmer, T; Oshaug, A

2011-02-01

Poor dietary habits among drug addicts represent health hazards. However, very few studies have focused on dietary intake as an independent health risk factor in relation to this group. The objective of the present study was to examine the dietary habits of drug addicts living on the fringes of an affluent society. The study focused on food access, food preferences, intake of energy and nutrients, and related nutrient blood concentrations. The respondent group consisted of 123 male and seventy-two female drug addicts, who participated in a cross-sectional study that included a 24 h dietary recall, blood samples, anthropometrical measurements and a semi-structured interview concerning food access and preferences. Daily energy intake varied from 0 to 37 MJ. Food received from charitable sources and friends/family had a higher nutrient density than food bought by the respondents. Added sugar accounted for 30 % of the energy intake, which was mirrored in biomarkers. Sugar and sugar-sweetened food items were preferred by 61 % of the respondents. Of the respondents, 32 % had a TAG concentration above the reference values, while 35 % had a cholesterol concentration beneath the reference values. An elevated serum Cu concentration indicated inflammation among the respondents. Further research on problems related to the diets of drug addicts should focus on dietary habits and aim to uncover connections that may reinforce inebriation and addiction.

BOOGIE: Predicting Blood Groups from High Throughput Sequencing Data.

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Giollo, Manuel; Minervini, Giovanni; Scalzotto, Marta; Leonardi, Emanuela; Ferrari, Carlo; Tosatto, Silvio C E

2015-01-01

Over the last decade, we have witnessed an incredible growth in the amount of available genotype data due to high throughput sequencing (HTS) techniques. This information may be used to predict phenotypes of medical relevance, and pave the way towards personalized medicine. Blood phenotypes (e.g. ABO and Rh) are a purely genetic trait that has been extensively studied for decades, with currently over thirty known blood groups. Given the public availability of blood group data, it is of interest to predict these phenotypes from HTS data which may translate into more accurate blood typing in clinical practice. Here we propose BOOGIE, a fast predictor for the inference of blood groups from single nucleotide variant (SNV) databases. We focus on the prediction of thirty blood groups ranging from the well known ABO and Rh, to the less studied Junior or Diego. BOOGIE correctly predicted the blood group with 94% accuracy for the Personal Genome Project whole genome profiles where good quality SNV annotation was available. Additionally, our tool produces a high quality haplotype phase, which is of interest in the context of ethnicity-specific polymorphisms or traits. The versatility and simplicity of the analysis make it easily interpretable and allow easy extension of the protocol towards other phenotypes. BOOGIE can be downloaded from URL http://protein.bio.unipd.it/download/.

Role of therapeutic drug monitoring in pulmonary infections : use and potential for expanded use of dried blood spot samples

NARCIS (Netherlands)

Hofman, Susan; Bolhuis, Mathieu S.; Koster, Remco A.; Akkerman, Onno W.; van Assen, Sander; Stove, Christophe; Alffenaar, Jan-Willem C.

Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample

Blood-brain barrier transport of drugs for the treatment of brain diseases.

Science.gov (United States)

Gabathuler, Reinhard

2009-06-01

The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively manage disease.

21 CFR 870.1110 - Blood pressure computer.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood pressure computer. 870.1110 Section 870.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... computer. (a) Identification. A blood pressure computer is a device that accepts the electrical signal from...

21 CFR 864.6550 - Occult blood test.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Occult blood test. 864.6550 Section 864.6550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a...

[Social network analysis and high risk behavior characteristics of recreational drug users: a qualitative study].

Science.gov (United States)

Wu, Di; Wang, Zhenhong; Jiang, Zhenxia; Fu, Xiaojing; Li, Hui; Zhang, Dapeng; Liu, Hui; Hu, Yifei

2014-11-01

To understand the characteristics of recreational drug users' behaviors and social network, as well as their potential impact to the transmission of sexual transmitted infections (STI). Qualitative interview was used to collect information on rough estimation of population size and behavior change before and after recreational drug use. A total of 120 participants were recruited by convenient sampling from April to October, 2013 in a community of Qingdao city. Blood specimens were taken for HIV/syphilis serological testing and social network analysis was performed to understand the characteristics of their behavior and social network. All participants used methamphetamine and 103 of them showed social connection. The prevalence of syphilis and HIV were 24.2% (29/120) and 2.5% (3/120) respectively. The estimated size of recreational drug users was big with a wide diversity of occupations and age range, and males were more frequent than females. Drug use may affect condom use and frequent drug users showed symptom of psychosis and neuro-toxicities. The size of social network was 2.45 ± 1.63 in the past 6 months, which indicated an increasing trend of the sexual partner number and risky behaviors. Recreational drug use could increase the size of social network among sex partners, the frequency of risky sexual behaviors and syphilis prevalence, which indicate a high risk of HIV/STI among this population as well as a huge burden of disease prevention and control in the future.

Accuracy of Handheld Blood Glucose Meters at High Altitude

NARCIS (Netherlands)

de Mol, Pieter; Krabbe, Hans G.; de Vries, Suzanna T.; Fokkert, Marion J.; Dikkeschei, Bert D.; Rienks, Rienk; Bilo, Karin M.; Bilo, Henk J. G.

2010-01-01

Background: Due to increasing numbers of people with diabetes taking part in extreme sports (e. g., high-altitude trekking), reliable handheld blood glucose meters (BGMs) are necessary. Accurate blood glucose measurement under extreme conditions is paramount for safe recreation at altitude. Prior

A newly validated high-performance liquid chromatography method with diode array ultraviolet detection for analysis of the antimalarial drug primaquine in the blood plasma.

Science.gov (United States)

Carmo, Ana Paula Barbosa do; Borborema, Manoella; Ribeiro, Stephan; De-Oliveira, Ana Cecilia Xavier; Paumgartten, Francisco Jose Roma; Moreira, Davyson de Lima

2017-01-01

Primaquine (PQ) diphosphate is an 8-aminoquinoline antimalarial drug with unique therapeutic properties. It is the only drug that prevents relapses of Plasmodium vivax or Plasmodium ovale infections. In this study, a fast, sensitive, cost-effective, and robust method for the extraction and high-performance liquid chromatography with diode array ultraviolet detection (HPLC-DAD-UV ) analysis of PQ in the blood plasma was developed and validated. After plasma protein precipitation, PQ was obtained by liquid-liquid extraction and analyzed by HPLC-DAD-UV with a modified-silica cyanopropyl column (250mm × 4.6mm i.d. × 5μm) as the stationary phase and a mixture of acetonitrile and 10mM ammonium acetate buffer (pH = 3.80) (45:55) as the mobile phase. The flow rate was 1.0mL·min-1, the oven temperature was 50OC, and absorbance was measured at 264nm. The method was validated for linearity, intra-day and inter-day precision, accuracy, recovery, and robustness. The detection (LOD) and quantification (LOQ) limits were 1.0 and 3.5ng·mL-1, respectively. The method was used to analyze the plasma of female DBA-2 mice treated with 20mg.kg-1 (oral) PQ diphosphate. By combining a simple, low-cost extraction procedure with a sensitive, precise, accurate, and robust method, it was possible to analyze PQ in small volumes of plasma. The new method presents lower LOD and LOQ limits and requires a shorter analysis time and smaller plasma volumes than those of previously reported HPLC methods with DAD-UV detection. The new validated method is suitable for kinetic studies of PQ in small rodents, including mouse models for the study of malaria.

A newly validated high-performance liquid chromatography method with diode array ultraviolet detection for analysis of the antimalarial drug primaquine in the blood plasma

Directory of Open Access Journals (Sweden)

Ana Paula Barbosa do Carmo

Full Text Available Abstract INTRODUCTION: Primaquine (PQ diphosphate is an 8-aminoquinoline antimalarial drug with unique therapeutic properties. It is the only drug that prevents relapses of Plasmodium vivax or Plasmodium ovale infections. In this study, a fast, sensitive, cost-effective, and robust method for the extraction and high-performance liquid chromatography with diode array ultraviolet detection (HPLC-DAD-UV analysis of PQ in the blood plasma was developed and validated. METHODS: After plasma protein precipitation, PQ was obtained by liquid-liquid extraction and analyzed by HPLC-DAD-UV with a modified-silica cyanopropyl column (250mm × 4.6mm i.d. × 5μm as the stationary phase and a mixture of acetonitrile and 10mM ammonium acetate buffer (pH = 3.80 (45:55 as the mobile phase. The flow rate was 1.0mL·min-1, the oven temperature was 50OC, and absorbance was measured at 264nm. The method was validated for linearity, intra-day and inter-day precision, accuracy, recovery, and robustness. The detection (LOD and quantification (LOQ limits were 1.0 and 3.5ng·mL-1, respectively. The method was used to analyze the plasma of female DBA-2 mice treated with 20mg.kg-1 (oral PQ diphosphate. RESULTS: By combining a simple, low-cost extraction procedure with a sensitive, precise, accurate, and robust method, it was possible to analyze PQ in small volumes of plasma. The new method presents lower LOD and LOQ limits and requires a shorter analysis time and smaller plasma volumes than those of previously reported HPLC methods with DAD-UV detection. CONCLUSIONS: The new validated method is suitable for kinetic studies of PQ in small rodents, including mouse models for the study of malaria.

P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments

DEFF Research Database (Denmark)

Ejsing, Thomas B.; Pedersen, Anne D.; Linnet, Kristian

2005-01-01

P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice......P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice...

Relationship between initial therapy and blood pressure control for high-risk hypertension patients in the UK: a retrospective cohort study from the THIN general practice database.

Science.gov (United States)

Weir, Sharada; Juhasz, Attila; Puelles, Jorge; Tierney, Travis S

2017-07-28

To examine the UK practice patterns in treating newly diagnosed hypertension and to determine whether subgroups of high-risk patients are more or less likely to follow particular therapeutic protocols and to reach blood pressure goals. Retrospective cohort study. This study examined adults in The Health Improvement Network (THIN) UK general practice medical records database who were initiated on medication for hypertension. 48 131 patients with essential hypertension diagnosed between 2008 and 2010 who were registered with a participating practice for a minimum of 13 months prior to, and 6 months following, initiation of therapy. We excluded patients with gestational hypertension or secondary hypertension. Patients were classified into risk groups based on blood pressure readings and comorbid conditions. Odds of receiving single versus fixed or free-drug combination therapy and odds of achieving blood pressure control were assessed using multivariable logistic regression. The vast majority of patients (95.8%) were initiated on single drug therapy. Patients with high cardiovascular risk (patients with grade 2-3 hypertension or those with high normal/grade 1 hypertension plus at least one cardiovascular condition pretreatment) had a statistically significant benefit of starting immediately on combination therapy when blood pressure control was the desired goal (OR: 1.23; 95% CI: 1.06 to 1.42) but, surprisingly, were less likely than patients with no risk factors to receive combination therapy (OR: 0.53; 95% CI: 0.47 to 0.59). Our results suggest that combination therapy may be indicated for patients with high cardiovascular risk, who accounted for 60.6% of our study population. The National Institute for Health and Care Excellence guideline CG34 of 2006 (in effect during the study period) recommended starting with single drug class therapy for most patients, and this advice does seem to have been followed even in cases where a more aggressive approach might

A high content screening assay to predict human drug-induced liver injury during drug discovery.

Science.gov (United States)

Persson, Mikael; Løye, Anni F; Mow, Tomas; Hornberg, Jorrit J

2013-01-01

Adverse drug reactions are a major cause for failures of drug development programs, drug withdrawals and use restrictions. Early hazard identification and diligent risk avoidance strategies are therefore essential. For drug-induced liver injury (DILI), this is difficult using conventional safety testing. To reduce the risk for DILI, drug candidates with a high risk need to be identified and deselected. And, to produce drug candidates without that risk associated, risk factors need to be assessed early during drug discovery, such that lead series can be optimized on safety parameters. This requires methods that allow for medium-to-high throughput compound profiling and that generate quantitative results suitable to establish structure-activity-relationships during lead optimization programs. We present the validation of such a method, a novel high content screening assay based on six parameters (nuclei counts, nuclear area, plasma membrane integrity, lysosomal activity, mitochondrial membrane potential (MMP), and mitochondrial area) using ~100 drugs of which the clinical hepatotoxicity profile is known. We find that a 100-fold TI between the lowest toxic concentration and the therapeutic Cmax is optimal to classify compounds as hepatotoxic or non-hepatotoxic, based on the individual parameters. Most parameters have ~50% sensitivity and ~90% specificity. Drugs hitting ≥2 parameters at a concentration below 100-fold their Cmax are typically hepatotoxic, whereas non-hepatotoxic drugs typically hit based on nuclei count, MMP and human Cmax, we identified an area without a single false positive, while maintaining 45% sensitivity. Hierarchical clustering using the multi-parametric dataset roughly separates toxic from non-toxic compounds. We employ the assay in discovery projects to prioritize novel compound series during hit-to-lead, to steer away from a DILI risk during lead optimization, for risk assessment towards candidate selection and to provide guidance of safe

Determination of Efavirenz in Human Dried Blood Spots by Reversed-Phase High Performance Liquid Chromatography with UV Detection

Science.gov (United States)

Hoffman, Justin T; Rossi, Steven S; Espina-Quinto, Rowena; Letendre, Scott; Capparelli, Edmund V

2013-01-01

Background Previously published methods for determination of efavirenz (EFV) in human dried blood spots (DBS) employ costly and complex liquid chromatography/mass spectrometry. We describe the validation and evaluation of a simple and inexpensive high-performance liquid chromatography (HPLC) method for EFV quantification in human DBS and dried plasma spots (DPS), using ultraviolet (UV) detection appropriate for resource-limited settings. Methods 100μl of heparinized whole blood or plasma were spotted onto blood collection cards, dried, punched, and eluted. Eluates are injected onto a C-18 reversed phase HPLC column. EFV is separated isocratically using a potassium phosphate and ACN mobile phase. UV detection is at 245nm. Quantitation is by use of external calibration standards. Following validation, the method was evaluated using whole blood and plasma from HIV-positive patients undergoing EFV therapy. Results Mean recovery of drug from dried blood spots is 91.5%. The method is linear over the validated concentration range of 0.3125 – 20.0μg/mL. A good correlation (Spearman r=0.96) between paired plasma and DBS EFV concentrations from the clinical samples was observed, and hematocrit level was not found to be a significant determinant of the EFV DBS level. The mean observed CDBS/Cplasma ratio was 0.68. A good correlation (Spearman r=0.96) between paired plasma and DPS EFV concentrations from the clinical samples was observed. The mean percent deviation of DPS samples from plasma samples is 1.68%. Conclusions Dried whole blood spot or dried plasma spot sampling is well suited for monitoring EFV therapy in resource limited settings, particularly when high sensitivity is not essential. PMID:23503446

A Physiologically Based Pharmacokinetic Model to Predict the Pharmacokinetics of Highly Protein-Bound Drugs and Impact of Errors in Plasma Protein Binding

Science.gov (United States)

Ye, Min; Nagar, Swati; Korzekwa, Ken

2015-01-01

Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data was often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding, and blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for terminal elimination half-life (t1/2, 100% of drugs), peak plasma concentration (Cmax, 100%), area under the plasma concentration-time curve (AUC0–t, 95.4%), clearance (CLh, 95.4%), mean retention time (MRT, 95.4%), and steady state volume (Vss, 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. PMID:26531057

Family Adaptability and Cohesion and High Blood Pressure among Urban African American women

Science.gov (United States)

Brittain, Kelly; Taylor, Jacquelyn Y.; Wu, Chun Yi

2010-01-01

African American women are at greater risk for complications related to high blood pressure. This study examined relationships between high blood pressure, pulse pressure, body mass index, family adaptability, family cohesion and social support among 146 Urban African American women. Significant relationships were found between family adaptability and systolic blood pressure (p = .03) and between adaptability and pulse pressure (p ≤ .01). Based on study results, practitioners should routinely assess family functioning, specifically family adaptability, in African American women who are at risk for high blood pressure or diagnosed with high blood pressure to minimize complications associated with hypertension. PMID:21076625

A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility.

Directory of Open Access Journals (Sweden)

Michael J Smout

Full Text Available BACKGROUND: Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective high-throughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a novel application for a real-time cell monitoring device (xCELLigence that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC(50 values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and -resistant isolates of H. contortus. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing.

High-Throughput Cytochrome P450 Cocktail Inhibition Assay for Assessing Drug-Drug and Drug-Botanical Interactions.

Science.gov (United States)

Li, Guannan; Huang, Ke; Nikolic, Dejan; van Breemen, Richard B

2015-11-01

Detection of drug-drug interactions is essential during the early stages of drug discovery and development, and the understanding of drug-botanical interactions is important for the safe use of botanical dietary supplements. Among the different forms of drug interactions that are known, inhibition of cytochrome P450 (P450) enzymes is the most common cause of drug-drug or drug-botanical interactions. Therefore, a rapid and comprehensive mass spectrometry-based in vitro high-throughput P450 cocktail inhibition assay was developed that uses 10 substrates simultaneously against nine CYP isoforms. Including probe substrates for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and two probes targeting different binding sites of CYP3A4/5, this cocktail simultaneously assesses at least as many P450 enzymes as previous assays while remaining among the fastest due to short incubation times and rapid analysis using ultrahigh pressure liquid chromatography-tandem mass spectrometry. The method was validated using known inhibitors of each P450 enzyme and then shown to be useful not only for single-compound testing but also for the evaluation of potential drug-botanical interactions using the botanical dietary supplement licorice (Glycyrrhiza glabra) as an example. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Synopsis of the 2017 American College of Cardiology/American Heart Association Hypertension Guideline.

Science.gov (United States)

Carey, Robert M; Whelton, Paul K

2018-03-06

In November 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) released a clinical practice guideline for the prevention, detection, evaluation, and treatment of high blood pressure (BP) in adults. This article summarizes the major recommendations. In 2014, the ACC and the AHA appointed a multidisciplinary committee to update previous reports of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The committee reviewed literature and commissioned systematic reviews and meta-analyses on out-of-office BP monitoring, the optimal target for BP lowering, the comparative benefits and harms of different classes of antihypertensive agents, and the comparative benefits and harms of initiating therapy with a single antihypertensive agent or a combination of 2 agents. This article summarizes key recommendations in the following areas: BP classification, BP measurement, screening for secondary hypertension, nonpharmacologic therapy, BP thresholds and cardiac risk estimation to guide drug treatment, treatment goals (general and for patients with diabetes mellitus, chronic kidney disease, and advanced age), choice of initial drug therapy, resistant hypertension, and strategies to improve hypertension control.

Pathogens causing blood stream infections and their drug susceptibility profile in immunocompromised patients.

Science.gov (United States)

Fayyaz, Muhammad; Mirza, Irfan Ali; Ikram, Aamer; Hussain, Aamir; Ghafoor, Tahir; Shujat, Umer

2013-12-01

To determine the types of pathogens causing blood stream infections and their drug susceptibility profile in immunocompromised patients. Cross-sectional, observational study. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from January to September 2012. Blood culture bottles received from immunocompromised patients were dealt by two methods, brain heart infusion (BHI) broth based manual method and automated BACTEC system. The samples yielding positive growth from either of two methods were further analyzed. The identification of isolates was done with the help of biochemical reactions and rapid tests. Antimicrobial susceptibility of the isolates was carried out as per recommendations of Clinical and Laboratory Standards Institute (CLSI). Out of the 938 blood culture specimens received from immunocompromised patients, 188 (20%) yielded positive growth. Out of these, 89 (47.3%) isolates were Gram positive and Gram negative each, while 10 (5.3%) isolates were fungi (Candida spp.). In case of Gram positive isolates, 75 (84.3%) were Staphylococcus spp. and 51 (67%) were Methicillin resistant. Amongst Gram negative group 49 (55.1%) isolates were of enterobacteriaceae family, while 40 (44.9%) were non-lactose fermenters (NLF). In vitro antimicrobial susceptibility of Staphylococci revealed 100% susceptibility to vancomycin and linezolid. The enterobacteriaceae isolates had better susceptibility against amikacin 85.7% compared to tigecycline 61.2% and imipenem 59.2%. For NLF, the in vitro efficacy of aminoglycosides was 72.5%. The frequency of Gram positive and Gram negative organisms causing blood stream infections in immunocompromised patients was equal. Vancomycin in case of Gram positive and amikacin for Gram negative organisms revealed better in vitro efficacy as compared to other antibiotics.

Pathogens Causing Blood Stream Infections and their Drug Susceptibility Profile in Immunocompromised Patients

International Nuclear Information System (INIS)

Fayyaz, M.; Mirza, I.A.; Ikram, A.; Hussain, A.; Ghafoor, T.; Shujat, U.

2013-01-01

Objective: To determine the types of pathogens causing blood stream infections and their drug susceptibility profile in immunocompromised patients. Study Design: Cross-sectional, observational study. Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from January to September 2012. Methodology: Blood culture bottles received from immunocompromised patients were dealt by two methods, brain heart infusion (BHI) broth based manual method and automated BACTEC system. The samples yielding positive growth from either of two methods were further analyzed. The identification of isolates was done with the help of biochemical reactions and rapid tests. Antimicrobial susceptibility of the isolates was carried out as per recommendations of Clinical and Laboratory Standards Institute (CLSI). Results: Out of the 938 blood culture specimens received from immunocompromised patients, 188 (20%) yielded positive growth. Out of these, 89 (47.3%) isolates were Gram positive and Gram negative each, while 10 (5.3%) isolates were fungi (Candida spp.). In case of Gram positive isolates, 75 (84.3%) were Staphylococcus spp. and 51 (67%) were Methicillin resistant. Amongst Gram negative group 49 (55.1%) isolates were of enterobacteriaceae family, while 40 (44.9%) were non-lactose fermenters (NLF). In vitro antimicrobial susceptibility of Staphylococci revealed 100% susceptibility to vancomycin and linezolid. The enterobacteriaceae isolates had better susceptibility against amikacin 85.7% compared to tigecycline 61.2% and imipenem 59.2%. For NLF, the in vitro efficacy of aminoglycosides was 72.5%. Conclusion: The frequency of Gram positive and Gram negative organisms causing blood stream infections in immunocompromised patients was equal. Vancomycin in case of Gram positive and amikacin for Gram negative organisms revealed better in vitro efficacy as compared to other antibiotics. (author)

Influence of some drugs, used in coronary artery disease on in vitro labelling red blood cells with technetium 99mTc

International Nuclear Information System (INIS)

Poniatowicz-Frasunek, E.

1997-01-01

In some patients investigated by radionuclide ventriculography poor labeling efficiency of red blood cells with technetium 99m Tc is observed. Among possible mechanisms responsible for this phenomenon, the pharmacological treatment applied to the patients should be taken into consideration. The aim of the study was to define the effect of selected drugs used in CAD on technetium binding efficiency by erythrocytes in vitro. Blood samples were obtained from 40 normal individuals receiving no medication. The effect of the following drugs were examined: Aerosonit, Isoptin, Bemecor, Dopegyt, Enarenal, Binazin, Furosemid, Aspirin, Vitamin E and Propranolol. Only Enarenal and Vitamin E proved to have no effect on technetium binding efficiency. The most expressed reduction was observed in experiments with Aerosonit, Furosemid and Propranolol and the smallest changes were found in blood samples with Bemecor, Binazin and Aspirin. The results of the study suggest that pharmacological treatment may influence the quality of scintigraphic images obtained with radioisotope ventriculography. For that reason the medicines applied to the patients should be as much as possible reduced or withdrawn for at least several days before examination. (author)

What Are High Blood Cholesterol and Triglycerides?

Science.gov (United States)

... Reduction Cholesterol What Are High Blood Cholesterol and Triglycerides? Cholesterol travels to the body’s cells through the ... doctor about medicines that can help. What are triglycerides? Triglycerides are the most common type of fat ...

Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

Science.gov (United States)

Cone, Edward J; Bigelow, George E; Herrmann, Evan S; Mitchell, John M; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

2015-09-01

The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Design, development, and validation of a high-throughput drug-screening assay for targeting of human leukemia

Science.gov (United States)

Karjalainen, Katja; Pasqualini, Renata; Cortes, Jorge E.; Kornblau, Steven M.; Lichtiger, Benjamin; O'Brien, Susan; Kantarjian, Hagop M.; Sidman, Richard L.; Arap, Wadih; Koivunen, Erkki

2015-01-01

Background We introduce an ex vivo methodology to perform drug library screening against human leukemia. Method Our strategy relies on human blood or bone marrow cultures under hypoxia; under these conditions, leukemia cells deplete oxygen faster than normal cells, causing a hemoglobin oxygenation shift. We demonstrate several advantages: (I) partial recapitulation of the leukemia microenvironment, (ii) use of native hemoglobin oxygenation as real-time sensor/reporter, (iii) cost-effectiveness, (iv) species-specificity, and (v) format that enables high-throughput screening. Results As a proof-of-concept, we screened a chemical library (size ∼20,000) against human leukemia cells. We identified 70 compounds (“hit” rate=0.35%; Z-factor=0.71) with activity; we examined 20 to find 18 true-positives (90%). Finally, we show that carbonohydraxonic diamide group-containing compounds are potent anti-leukemia agents that induce cell death in leukemia cells and patient-derived samples. Conclusions This unique functional assay can identify novel drug candidates as well as find future applications in personalized drug selection for leukemia patients. PMID:24496871

Occupational Noise Exposure, Bilateral High-Frequency Hearing Loss, and Blood Pressure.

Science.gov (United States)

Gan, Wen Qi; Mannino, David M

2017-11-13

The aim of this study was to investigate the relationships between occupational noise exposure and blood pressure using self-reported occupational exposure and bilateral high-frequency hearing loss. This study included 4548 participants aged 20 to 69 years from the National Health and Nutrition Examination Survey 1999 to 2004. On the basis of self-reported exposure status, participants were divided into the current, former, or never exposed groups. Bilateral high-frequency hearing loss was defined as the average high-frequency hearing threshold at least 25 dB in both ears. The currently exposed participants had slightly increased diastolic blood pressure compared with those never exposed. Among previously exposed participants, those with bilateral high-frequency hearing loss had increased systolic blood pressure, heart rate, and the prevalence of hypertension compared with those with normal high-frequency hearing. Although there were some significant results, the evidence was not consistent to support the associations between occupational noise exposure and blood pressure.

High-risk sexual behavior among drug-using men.

Science.gov (United States)

Seidman, S N; Sterk-Elifson, C; Aral, S O

1994-01-01

Drug-using men are at high risk for acquisition and transmission of STD, presumably due to the risky behaviors practiced in environments of drug use. To study behaviors associated with STD transmission among drug-using men. Drug outreach workers distributed vouchers to self-identified drug-using men in urban Atlanta. Vouchers could be redeemed for cash at a storefront clinic where subjects provided urine for a urethritis screening test (leukocyte esterase test) and a drug screen, and were interviewed. Of 382 voucher recipients, 252 (66%) came to the clinic. Subjects were predominantly black (92%), homeless (70%), and aged 20 to 40 (88%). All used illicit drugs; none were currently receiving drug abuse treatment. Urine drug screen confirmed recent cocaine use in 63%, and recent opiate use in 4%. Three-fourths reported a history of STD, mostly gonorrhea. In the preceding 3 months, 14% had not had sex, 80% had sex exclusively with women, 4% had sex with both men and women, and 2% had sex exclusively with men. Of the heterosexually active men, 29% had 5 or more recent partners. Compared to other heterosexually active men, these men were more likely to always use alcohol or crack before having sex (prevalence ratio [PR] = 2.0, 95% CI = 1.3-2.5) and to drink alcohol every day (PR = 2.0, 95% CI = 1.2-3.3). Daily crack use was associated with choosing partners at elevated STD risk; daily alcohol use with having more partners. Positive drug screen for cocaine was associated with self-reported crack use. Urethritis, detected in 16%, was not correlated with behavior. A substantial number of drug-using men practice high-risk sexual behavior and should be targeted for intervention. Monetary and other incentives should be considered for recruitment. Further study is needed to clarify the relationship between sexual behavior, cocaine use, and STD.

Past oral contraceptive use and self-reported high blood pressure in postmenopausal women.

Science.gov (United States)

Chiu, Christine L; Lind, Joanne M

2015-01-31

Studies have reported current hormonal contraceptive use is associated with adverse cardiovascular outcomes, including high blood pressure. The aim of this study was to determine the association between past hormonal contraception use and high blood pressure in Australian postmenopausal women. Women were recruited from the 45 and Up Study, an observational cross-sectional study, conducted from February 2006 to December 2009, NSW Australia. All of the variables used in this study were derived from self-reported data. These women reported being postmenopausal, having an intact uterus, and had given birth to one or more children. Odds ratios and 99% confidence intervals for the association between past hormonal contraceptive use and current treatment for high blood pressure, stratified by current age (high blood pressure, menopausal hormone therapy use, number of children, whether they breastfed, and age of menopause. A total of 34,289 women were included in the study. No association between past hormonal contraception use and odds of having high blood pressure were seen in any of the age groups (high blood pressure was observed. Past hormonal contraception use and duration of use is not associated with high blood pressure in postmenopausal women.

High-resolution ultrasound imaging and noninvasive optoacoustic monitoring of blood variables in peripheral blood vessels

Science.gov (United States)

Petrov, Irene Y.; Petrov, Yuriy; Prough, Donald S.; Esenaliev, Rinat O.

2011-03-01

Ultrasound imaging is being widely used in clinics to obtain diagnostic information non-invasively and in real time. A high-resolution ultrasound imaging platform, Vevo (VisualSonics, Inc.) provides in vivo, real-time images with exceptional resolution (up to 30 microns) using high-frequency transducers (up to 80 MHz). Recently, we built optoacoustic systems for probing radial artery and peripheral veins that can be used for noninvasive monitoring of total hemoglobin concentration, oxyhemoglobin saturation, and concentration of important endogenous and exogenous chromophores (such as ICG). In this work we used the high-resolution ultrasound imaging system Vevo 770 for visualization of the radial artery and peripheral veins and acquired corresponding optoacoustic signals from them using the optoacoustic systems. Analysis of the optoacoustic data with a specially developed algorithm allowed for measurement of blood oxygenation in the blood vessels as well as for continuous, real-time monitoring of arterial and venous blood oxygenation. Our results indicate that: 1) the optoacoustic technique (unlike pure optical approaches and other noninvasive techniques) is capable of accurate peripheral venous oxygenation measurement; and 2) peripheral venous oxygenation is dependent on skin temperature and local hemodynamics. Moreover, we performed for the first time (to the best of our knowledge) a comparative study of optoacoustic arterial oximetry and a standard pulse oximeter in humans and demonstrated superior performance of the optoacoustic arterial oximeter, in particular at low blood flow.

Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis.

Science.gov (United States)

Wang, Caixia; Ye, Yuqiu; Liu, Chunyong; Zhou, Yongming; Lv, Linsheng; Cheng, Cailian; Li, Shaomin; Lou, Tanqi; Liu, Xun

2017-08-01

Evening dosing regimen drug therapy on blood pressure (BP) control is used widely, but its clinical benefits and preservation or re-establishment of the normal 24-h BP dipping pattern in chronic kidney disease (CKD) patients is not known. To investigate the effect of an evening dosing regimen of antihypertensive drugs on BP patterns of CKD patients with hypertension. A systematic review was conducted by searching PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference lists of relevant articles of published papers. All trials designed to evaluate the effects of evening versus morning dosing regimen drug therapy for CKD patients with hypertension were included. Meta-analysis was performed using random or fixed effects models. Five randomised controlled trials and one comparative study, including 3732 patients, met the inclusion criteria. Compared with morning dosing regimen drug therapy, evening administration of antihypertensive medication was associated with a significant reduction of 40% in non-dipper BP patterns (risk ratio (RR), 95% CI, (0.43, 0.84)). We noted a significant decrease in nocturnal systolic blood pressure (SBP) (MD -3.17 mmHg, 95% CI (-5.41, -0.94)), a significant reduction in nocturnal diastolic blood pressure (DBP) (MD -1.37 mmHg, 95% CI (-2.05, -0.69)) and a significant increase in awake SBP (MD 1.15 mmHg, 95% CI (0.10, 2.19)) in patients assigned to the evening dosing regimen drug therapy group. Patients showed no significant differences for all-cause mortality and cardiovascular mortality. This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients. © 2017 Royal Australasian College of Physicians.

Blood Pressure Out of the Office: Its Time Has Finally Come.

Science.gov (United States)

Krakoff, Lawrence R

2016-03-01

The diagnosis of hypertension includes measurement of blood pressure out of the office by either 24-hour ambulatory monitoring or home blood pressure monitoring. These methods have led to recognition of "white coat hypertension" (WCH) and "masked hypertension" (MH). Research in the 1930s first demonstrated that blood pressures in the office were often far different from those out of the office, at a time when there was no effective treatment. International attention was focused on another imminent world war and a highly controversial election in the United States. Hypertension was not a priority for concern. From the 1950s onward: (i) epidemiology linked hypertension to risk of cardiovascular disease, (ii) effective and safe drugs for treatment of hypertension appeared, (iii) randomized clinical trials demonstrated that drug treatment of hypertension is highly effective for prevention of cardiovascular disease, and (iv) advances in technology led to development of small, portable devices for recording blood pressure noninvasively at home or during usual activities. Accurate measurement of blood pressure in "real life" is now necessary and feasible for appropriate diagnosis and assessment of treatment. Out-of-office blood pressure measurement is emerging as the standard of care for hypertension. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Formulation and Optimization of Multiparticulate Drug Delivery System Approach for High Drug Loading.

Science.gov (United States)

Shah, Neha; Mehta, Tejal; Gohel, Mukesh

2017-08-01

The aim of the present work was to develop and optimize multiparticulate formulation viz. pellets of naproxen by employing QbD and risk assessment approach. Mixture design with extreme vertices was applied to the formulation with high loading of drug (about 90%) and extrusion-spheronization as a process for manufacturing pellets. Independent variables chosen were level of microcrystalline cellulose (MCC)-X 1 , polyvinylpyrrolidone K-90 (PVP K-90)-X 2 , croscarmellose sodium (CCS)-X 3 , and polacrilin potassium (PP)-X 4 . Dependent variables considered were disintegration time (DT)-Y 1 , sphericity-Y 2 , and percent drug release-Y 3 . The formulation was optimized based on the batches generated by MiniTab 17 software. The batch with maximum composite desirability (0.98) proved to be optimum. From the evaluation of design batches, it was observed that, even in low variation, the excipients affect the pelletization property of the blend and also the final drug release. In conclusion, pellets with high drug loading can be effectively manufactured and optimized systematically using QbD approach.

Generic Drugs: Questions and Answers

Science.gov (United States)

... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

[Users sceptical about generic drugs: an anthropological approach].

Science.gov (United States)

Sarradon-Eck, A; Blanc, M-A; Faure, M

2007-06-01

Since the enactment of the 2002 legislative measures favoring the prescription of generic drugs, various quantitative studies have shown that approval by prescribers and users has risen in France. Nevertheless, scepticism remains as well as distrust towards these drugs focusing on their effectiveness compared with brand-name drugs, on potential dangers, and on the interruption they cause in prescription and consumption habits. Using a comprehensive approach, this article analyzes the social and cultural logic behind the negative image of generic drugs. The materials issued from an ethnographic study on the prescription of drugs for high blood pressure. Sixty-eight interviews were undertaken between April 2002 and October 2004 with people (39 women and 29 men, between the age of 40 and 95, 52 over the age of 60) treated for over a year for high blood pressure in rural areas in the Southeast of France. Thirteen people provided unsolicited opinions about generic drugs. Analysis of the information collected shows that users have various representations of generic drugs, including the idea of counterfeited and foreign drugs. These representations interfere with the adjustment process and the development of consumer loyalty. They are part of a set of social representations about drugs which form and express the user's reality. In these representations, the drug is an ambivalent object, carrier of both biological effectiveness and toxicity; it is also the metonymical extension of the prescriber, bestowing upon the prescription a symbolic value. By placing the generic drug in its network of symbolic and social meaning, this study highlights the coherence of the scepticism towards generic drugs by consumers (and prescribers) with a system of common opinion in which drugs are everyday things, personalized and compatible with users, symbolic exchange carriers in the physician-patient relationship, and in which confidence in the drug is also that given to the health care

21 CFR 864.9185 - Blood grouping view box.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood grouping view box. 864.9185 Section 864.9185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture Blood...

Specific Antibody Production by Blood B Cells is Retained in Late Stage Drug-naïve HIV-infected Africans

Directory of Open Access Journals (Sweden)

Lydie Béniguel

2004-01-01

Full Text Available Unseparated peripheral blood mononuclear cells (PBMCs obtained from drug-naïve African individuals living in a context of multi-infections and presenting with high viral load (VL, were cultured in vitro and tested for their ability to produce antibodies (Abs reacting with HIV-1 antigens. Within these PBMCs, circulating B cells were differentiated in vitro and produced IgG Abs against not only ENV, but also GAG and POL proteins. Under similar experimental conditions, HAART treated patients produced Abs to ENV proteins only. The in vitro antibody production by drug-naïve individuals' PBMCs depended on exogenous cytokines (IL-2 and IL-10 but neither on the re-stimulation of reactive cells in cultures by purified HIV-1-gp 160 antigen nor on the re-engagement of CD40 surface molecules. Further, it was not abrogated by the addition of various monoclonal Abs (mAbs to co-stimulatory molecules. This suggests that the in vitro antibody production by drug-naïve individuals' PBMCs resulted from the maturation of already envelope and core antigen-primed, differentiated B cells, presumably pre-plasma cells, which are not known to circulate at homeostasy. As in vitro produced Abs retained the capacity of binding antigen and forming complexes, this study provides pre-clinical support for functional humoral responses despite major HIV- and other tropical pathogen-induced B cell perturbations.

High activity enables life on a high-sugar diet : blood glucose regulation in nectar-feeding bats

NARCIS (Netherlands)

Kelm, Detlev H; Simon, Ralph; Kuhlow, Doreen; Voigt, Christian C; Ristow, Michael

2011-01-01

High blood glucose levels caused by excessive sugar consumption are detrimental to mammalian health and life expectancy. Despite consuming vast quantities of sugar-rich floral nectar, nectar-feeding bats are long-lived, provoking the question of how they regulate blood glucose. We investigated blood

Effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome after radical gastrectomy.

Science.gov (United States)

Sun, Li; Zhou, Pingping; Hua, Qingli; Jin, Changming; Guo, Chunling; Song, Bing

2018-06-01

This study aimed to investigate the effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome (MS) after radical gastrectomy. A total of 150 patients with gastric cancer, who were treated in Daqing Longnan Hospital from November, 2015 to May, 2017, were enrolled in this study. The patients were divided into the MS group (80 cases) and non-MS group (70 cases). Patients in the MS group were given corresponding drugs to control blood pressure, blood lipids and blood glucose, while patients in the non-MS group were not treated with those drugs. Patients in the MS group were divided into the normal and abnormal groups according to the levels of blood glucose, blood lipids and blood pressure. Moreover, occurrences of complications were compared between the normal and abnormal groups. Before surgery, blood glucose, blood lipids and blood pressure in the MS group were significantly higher than those in the non-MS group (pblood glucose, blood lipids and blood pressure of the MS group decreased significantly compared to those before operation (pblood glucose, 2 h postprandial blood glucose, glycosylated hemoglobin, total triglycerides (TGs), LDL, mean blood pressure and BMI (pblood glucose, blood lipids and blood pressure in patients with gastric cancer complicated with MS after radical gastrectomy can reduce the incidence of postoperative complications and promote postoperative recovery.

Teaming Up Against High Blood Pressure

Centers for Disease Control (CDC) Podcasts

2012-09-04

This podcast is based on the September 2012 CDC Vital Signs report. A team-based approach by patients, health care systems, and health care providers is one of the best ways to treat uncontrolled high blood pressure.  Created: 9/4/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 9/4/2012.

Waist circumference as an indicator of high blood pressure in preschool obese children.

Science.gov (United States)

Chen, Bin; Li, Hai-fei

2011-01-01

To investigate the relationship between waist circumference and blood pressure (BP) to determine if waist circumference was an indicator of BP in preschool children. Body weight, height, waist circumference (WC), hip circumference, and blood pressure of 939 3-6-year-old preschool children were collected. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) in obese children were significantly higher than that in normal weight children in both sexes (phigh blood pressure in children of both sexes. Multiple linear stepwise regression analysis using SBP as the dependent variable showed that BMI and WC were significant independent factors that influence high blood pressure adjusted for age, WtHr and waist-to-hip circumference ratio (WHr) in boys. When using DBP as the dependent variable, BMI was the only significant independent factor that influenced high blood pressure adjusted for age, WtHr and WHr, in both sex-es. Waist circumference was independently associated with high blood pressure in boys aged 3-6 years. In addition to BMI, increased waist circumference was found to be an indicator of high blood pressure in the preschool children, especially in boys.

Drug poisoning deaths in Sweden show a predominance of ethanol in mono-intoxications, adverse drug-alcohol interactions and poly-drug use.

Science.gov (United States)

Jones, A W; Kugelberg, F C; Holmgren, A; Ahlner, J

2011-03-20

Over a 10-year period (1998-2007) all deaths in Sweden classified by forensic pathologists as fatal drug poisonings (N = 6894) were retrieved from a toxicology database (TOXBASE) belonging to the National Board of Forensic Medicine. The deaths were further classified as suicides N = 2288 (33%), undetermined N = 2260 (33%) and accidental N = 2346 (34%). The average age (± SD) of all victims was 49.1 ± 15.9 years and men 47.4 ± 15.6 years were 5-year younger than women 52.2 ± 15.8 years (p intoxications) was found in 22% of all poisoning deaths (p intoxication deaths were mostly ethanol-related (N = 976) and the mean and median blood-alcohol concentration (BAC) was 3.06 g/L and 3.10 g/L, respectively. The BAC decreased as the number of additional drugs in blood increased from 2.15 g/L with one drug to 1.25 g/L with 6 or more drugs. The mean (median) concentrations of non-alcohol drugs in mono-intoxication deaths were morphine (N = 93) 0.5mg/L (0.2mg/L), amphetamine (N = 39) 2.0mg/L (1.2mg/L), dextropropoxyphene (N = 33) 3.9 mg/L (2.9 mg/L), dihydro-propiomazine (N = 32) 1.6 mg/L (1.0mg/L) and 7-amino-flunitrazepam (N = 28), 0.4 mg/L (0.3mg/L). Elevated blood morphine in these poisoning deaths mostly reflected abuse of heroin as verified by finding 6-monoacetyl morphine (6-MAM) in the blood samples. When investigating drug poisoning deaths a comprehensive toxicological analysis is essential although the results do not reveal the extent of prior exposure to drugs or the development of pharmacological tolerance. The concentrations of drugs determined in post-mortem blood are one element in the case. The autopsy report, the police investigation, the findings at the scene and eye-witness statements should all be carefully considered when the cause and manner of death are determined. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The first Iranian recommendations on prevention, evaluation and management of high blood pressure.

Science.gov (United States)

Noohi, Feridoun; Sarrafzadegan, Nizal; Khosravi, Alireza; Andalib, Elham

2012-01-01

This paper presents the complete report of the first Iranian Recommendations on Prevention, Evaluation and Management of High Blood Pressure. The purpose is to provide an evidence-based approach to the prevention, management and control of hypertension (HTN) by adapting the most internationally known and used guidelines to the local health care status with consideration of the currently available data and based on the locally conducted researches on HTN as well as social and health care requirements. A working group of national and international experts participated in discussions and collaborated in decision-making, writing and reviewing the whole report. Multiple subcommittees worked together to review the recent national and international literature on HTN in different areas. We used the evaluation tool that is called "AGREE" and considered a score of > 60% as a high score. We adapted the Canadian Hypertension Education Program (CHEP), the United Kingdom's National Institute for Health and Clinical Excellence (NICE) and the US-based joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7). The key topics that are highlighted in this report include: The importance of ambulatory and self-measurement of blood pressure, evaluation of cardiovascular risk in HTN patients, the role of lifestyle modification in the prevention of HTN and its control with more emphasis on salt intake reduction and weight control, introducing pharmacotherapy suitable for uncomplicated HTN or specific situations and the available drugs in Iran, highlighting the importance of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers and calcium channel blockers as the first line therapy in many situations, the non-use of beta blockers as the first time treatment except in specific conditions, treating HTN in women, children, obese and elderly patients, the patient compliance to improve HTN control, practical guidelines to improve

Income inequality and high blood pressure in Colombia: a multilevel analysis.

Science.gov (United States)

Lucumi, Diego I; Schulz, Amy J; Roux, Ana V Diez; Grogan-Kaylor, Andrew

2017-11-21

The objective of this research was to examine the association between income inequality and high blood pressure in Colombia. Using a nationally representative Colombian sample of adults, and data from departments and municipalities, we fit sex-stratified linear and logistic multilevel models with blood pressure as a continuous and binary variable, respectively. In adjusted models, women living in departments with the highest quintile of income inequality in 1997 had higher systolic blood pressure than their counterparts living in the lowest quintile of income inequality (mean difference 4.42mmHg; 95%CI: 1.46, 7.39). Women living in departments that were at the fourth and fifth quintile of income inequality in 1994 were more likely to have hypertension than those living in departments at the first quintile in the same year (OR: 1.56 and 1.48, respectively). For men, no associations of income inequality with either systolic blood pressure or hypertension were observed. Our findings are consistent with the hypothesis that income inequality is associated with increased risk of high blood pressure for women. Future studies to analyze pathways linking income inequality to high blood pressure in Colombia are needed.

Preeclampsia and High Blood Pressure During Pregnancy

Science.gov (United States)

... Gynecologists f AQ FREQUENTLY ASKED QUESTIONS FAQ034 PREGNANCY Preeclampsia and High Blood Pressure During Pregnancy • What is ... is chronic hypertension during pregnancy managed? • What is preeclampsia? • When does preeclampsia occur? • What causes preeclampsia? • What ...

High blood pressure at old age : The Leiden 85 plus study

NARCIS (Netherlands)

Bemmel, Thomas van

2010-01-01

The last decades have shown an increasing interest in treatment of high blood pressure. Copious amounts of data have been published on the mortality and morbidity risks of high blood pressure. Overall these data have resulted in an increasing awareness of the deleterious effects of only modest

Ultra high performance liquid chromatography of seized drugs

NARCIS (Netherlands)

Lurie, I.S.

2010-01-01

The primary goal of this thesis is to investigate the use of ultra high performance liquid chromatography (UHPLC) for the analysis of seized drugs. This goal was largely achieved and significant progress was made in achieving improved separation and detection of drugs of forensic interest.

Patents Associated with High-Cost Drugs in Australia

OpenAIRE

Christie, Andrew F.; Dent, Chris; McIntyre, Peter; Wilson, Lachlan; Studdert, David M.

2013-01-01

Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by "evergreening" blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent...

Legal and ethical issues in safe blood transfusion

Directory of Open Access Journals (Sweden)

Shivaram Chandrashekar

2014-01-01

Full Text Available Legal issues play a vital role in providing a framework for the Indian blood transfusion service (BTS, while ethical issues pave the way for quality. Despite licensing of all blood banks, failure to revamp the Drugs and Cosmetic Act (D and C Act is impeding quality. Newer techniques like chemiluminescence or nucleic acid testing (NAT find no mention in the D and C Act. Specialised products like pooled platelet concentrates or modified whole blood, therapeutic procedures like erythropheresis, plasma exchange, stem cell collection and processing technologies like leukoreduction and irradiation are not a part of the D and C Act. A highly fragmented BTS comprising of over 2500 blood banks, coupled with a slow and tedious process of dual licensing (state and centre is a hindrance to smooth functioning of blood banks. Small size of blood banks compromises blood safety. New blood banks are opened in India by hospitals to meet requirements of insurance providers or by medical colleges as this a Medical Council of India (MCI requirement. Hospital based blood banks opt for replacement donation as they are barred by law from holding camps. Demand for fresh blood, lack of components, and lack of guidelines for safe transfusion leads to continued abuse of blood. Differential pricing of blood components is difficult to explain scientifically or ethically. Accreditation of blood banks along with establishment of regional testing centres could pave the way to blood safety. National Aids Control Organisation (NACO and National Blood Transfusion Council (NBTC deserve a more proactive role in the licensing process. The Food and Drug Administration (FDA needs to clarify that procedures or tests meant for enhancement of blood safety are not illegal.

Study on Blood Cortisol in Patients treated with Oral Corticosteroid Drugs

International Nuclear Information System (INIS)

Park, J. H.; Kim, K. W.; Yoo, H. S.; Lee, J. T.; Park, C. Y.; Ryu, K. J.

1980-01-01

This is an analysis of 32 patients who received long continuous corticosteroid drug due to some diseases. Patients were collected from June 1976 to March 1980. Blood cortisol level, variation of diurnal rhythm and side effects were studied. The Result as follows: 1) Side effects were observed in 24 patients (75%) and most common complaint was obesity. 2) Diurnal rhythm analysed by Doe's method shows abnormal diurnal rhythm is 21 out 32 (66%) 3) Mean durations of therapy of abnormal diurnal rhythm were 55.7±4.4 months and 43.9±7.0 months respectively which shows statistically significant difference. 4) Mean cortisol value of steroid treated patients were lower than normal. 5) Reverse diurnal rhythm was 4 out of 21 patients. 6) 8 A.M. cortisol value is lower than 2 times of 8 P.M. in all patients who showed abnormal diurnal rhythm except one.

Alleged drug facilitated sexual assault (DFSA) in Northern Ireland from 1999 to 2005. A study of blood alcohol levels.

Science.gov (United States)

Hall, Janet; Goodall, Edward A; Moore, Tara

2008-11-01

Alleged sexual assault cases, identified from the forensic science Northern Ireland (FSNI) database, which had toxicology assays carried out on either blood or urine samples, were examined for the years 1999 up to and including 2005. In 1999 there were 30 toxicology requests while in 2005 there were 51, representing a 70% increase. The percentage of cases containing alcohol, drugs or both increased from 66% in 1999 to 78% in 2005. The estimated average blood alcohol concentration remained broadly similar throughout the spread of years. It was found to be 218mg% (milligrams per 100 millilitres) in 1999 and 217mg% in 2005. The actual number of cases studied within the 12h cut-off time rose from 9 in 1999 to 22 in 2005. The relationship between negative toxicology results and time delay between the alleged assault and forensic sampling was examined. This showed that between 44% and 74% of cases were found to have a time delay of >12h. Some of these cases may therefore represent false negative results. The presence of drugs, either alone or in combination with other drugs, doubled between 1999 and 2005. Increased identification was found with antidepressants, recreational drugs, benzodiazepines and analgesics, some of which were also associated with alcohol consumption. The findings are sufficient to cause alarm for the health and safety of certain individuals and their increased vulnerability to sexual assault in some social settings. Additionally, the legal implications of what constitutes valid consent needs to be considered further in the light of these findings, if attrition rates are to improve.

Quantification of 31 illicit and medicinal drugs and metabolites in whole blood by fully automated solid-phase extraction and ultra-performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Bjørk, Marie Kjærgaard; Simonsen, Kirsten Wiese; Andersen, David Wederkinck; Dalsgaard, Petur Weihe; Sigurðardóttir, Stella Rögn; Linnet, Kristian; Rasmussen, Brian Schou

2013-03-01

An efficient method for analyzing illegal and medicinal drugs in whole blood using fully automated sample preparation and short ultra-high-performance liquid chromatography-tandem mass spectrometry (MS/MS) run time is presented. A selection of 31 drugs, including amphetamines, cocaine, opioids, and benzodiazepines, was used. In order to increase the efficiency of routine analysis, a robotic system based on automated liquid handling and capable of handling all unit operation for sample preparation was built on a Freedom Evo 200 platform with several add-ons from Tecan and third-party vendors. Solid-phase extraction was performed using Strata X-C plates. Extraction time for 96 samples was less than 3 h. Chromatography was performed using an ACQUITY UPLC system (Waters Corporation, Milford, USA). Analytes were separated on a 100 mm × 2.1 mm, 1.7 μm Acquity UPLC CSH C(18) column using a 6.5 min 0.1 % ammonia (25 %) in water/0.1 % ammonia (25 %) in methanol gradient and quantified by MS/MS (Waters Quattro Premier XE) in multiple-reaction monitoring mode. Full validation, including linearity, precision and trueness, matrix effect, ion suppression/enhancement of co-eluting analytes, recovery, and specificity, was performed. The method was employed successfully in the laboratory and used for routine analysis of forensic material. In combination with tetrahydrocannabinol analysis, the method covered 96 % of cases involving driving under the influence of drugs. The manual labor involved in preparing blood samples, solvents, etc., was reduced to a half an hour per batch. The automated sample preparation setup also minimized human exposure to hazardous materials, provided highly improved ergonomics, and eliminated manual pipetting.

21 CFR 862.1120 - Blood gases (PCO2, PO2) and blood pH test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood gases (PCO2, PO2) and blood pH test system... Test Systems § 862.1120 Blood gases (PCO2, PO2) and blood pH test system. (a) Identification. A blood gases (PCO2, PO2) and blood pH test system is a device intended to measure certain gases in blood, serum...

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for ... is checking your blood glucose often. Ask your doctor how often you should ... associated with hyperglycemia. How Do I Treat Hyperglycemia? ...

21 CFR 864.9275 - Blood bank centrifuge for in vitro diagnostic use.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood bank centrifuge for in vitro diagnostic use. 864.9275 Section 864.9275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Manufacture Blood and Blood Products § 864.9275 Blood bank centrifuge for in vitro diagnostic use. (a...

Paper Spray and Extraction Spray Mass Spectrometry for the Direct and Simultaneous Quantification of Eight Drugs of Abuse in Whole Blood

NARCIS (Netherlands)

Espy, R.D.; Teunissen, S.F.; Manicke, N.E.; Ren, Y.; Ouyang, Z.; van Asten, A.; Cooks, R.G.

2014-01-01

Determination of eight drugs of abuse in blood has been performed using paper spray or extraction spray mass spectrometry in under 2 min with minimal sample preparation. A method has been optimized for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA),

42 CFR 409.87 - Blood deductible.

Science.gov (United States)

2010-10-01

..., from an individual or a blood bank, a replacement offer that meets the criteria specified in paragraph... replacement of blood. A blood replacement offer made by a beneficiary, or an individual or a blood bank on... red cells if the replacement blood meets the applicable criteria specified in Food and Drug...

Validation of an LC-MS/MS method for analysis of anti-diabetic drugs in botanical dietary supplements labeled for blood sugar management.

Science.gov (United States)

Ma, Jun; Pawar, Rahul S; Grundel, Erich

2018-03-01

We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect and quantitate 14 anti-diabetic, 2 anti-obesity, and 3 cholesterol-lowering drugs in botanical dietary supplements marketed for blood sugar management. Many botanical dietary supplements which carry label statements related to blood sugar management are available over the Internet. Potential adulteration of such dietary supplements with anti-diabetic and other prescription drugs, some of which have been removed from the market due to adverse events, is of concern. No significant matrix effects were observed and mean recoveries of all 19 analytes from a single product matrix were 88 to 113% at spiking concentrations from 500 to 2000 μg/g. Mean recoveries of metformin, phenformin, and sibutramine from matrices prepared from multiple product composites ranged from 93 to 115% at a spiking concentration of 100 μg/g. The relative standard deviations (RSD) (%) of intra-day analyses ranged from 0.2 to 13 for all recovery studies. Eighty dietary supplements obtained in the USA and carrying label statements related to blood sugar management were analyzed using this method and none were found to be adulterated with the above 19 drugs. Two products obtained outside of the USA and known to be adulterated were also analyzed by this method and found to contain phenformin, glibenclamide, and sibutramine. This method provided satisfactory selectivity, linearity, accuracy, precision, and sensitivity for rapid determination of 19 drugs and has broad applicability for the analysis of dietary supplements for possible adulteration with these compounds. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Severe obesity and high blood pressure among children, Philadelphia health centers, 2010.

Science.gov (United States)

Nguyen, John V; Robbins, Jessica M; Houck, Kevin L; Nobis, Elizabeth A; Inman, Katelyn A; Khan, Khudsiya S; Robbins, Susan W

2014-04-01

Child obesity is a major health problem particularly affecting disadvantaged population groups. Severe obesity carries additional health risks for children. In the context of the childhood obesity epidemic, high blood pressure among children is of increasing concern. Chart reviews were carried out to examine the prevalence of severe obesity and its association with high blood pressure measurements among randomly selected patients aged 3 to 17 years who had well-child care visits at 8 public community health centers during 2010. A majority of the 691 patients reviewed were African American (58%); an additional 16% were Hispanic. The prevalence of severe obesity was 7.7% (95% confidence interval = 5.8% to 9.9%) and the prevalence of high blood pressure measurements was 17.5% (95% confidence interval = 14.8% to 20.6%). Patients who were severely obese were more than twice as likely as other children to have high blood pressure values. Severe obesity is associated with substantially increased frequency of high blood pressure measurements in children, and should be investigated further as a potential marker for hypertension in children. Primary care providers should be prepared to diagnose and treat hypertension in severely obese children.

Weight Status and High Blood Pressure Among Low-Income African American Men

Science.gov (United States)

Bruce, Marino A.; Beech, Bettina M.; Edwards, Christopher L.; Sims, Mario; Scarinci, Isabel; Whitfield, Keith E.; Gilbert, Keon; Crook, Errol D.

2016-01-01

Obesity is a biological risk factor or comorbidity that has not received much attention from scientists studying hypertension among African American men. The purpose of this study was to examine the relationship between weight status and high blood pressure among African American men with few economic resources. The authors used surveillance data collected from low-income adults attending community- and faith-based primary care clinics in West Tennessee to estimate pooled and group-specific regression models of high blood pressure. The results from group-specific logistic regression models indicate that the factors associated with hypertension varied considerably by weight status. This study provides a glimpse into the complex relationship between weight status and high blood pressure status among African American men. Additional research is needed to identify mechanisms through which excess weight affects the development and progression of high blood pressure. PMID:20937738

Remote Blood Pressure Waveform Sensing Method and Apparatus

Science.gov (United States)

2008-06-02

test the effects of drugs, exercise, or other stimuli, whereby an increase or decrease in the ratio may indicate an improvement or worsening of systolic...even though high blood pressure in animals can be symptomatic of a variety of diseases including chronic renal failure, hyperthyroidism , Cushing’s

A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery.

Science.gov (United States)

Yang, Conglian; Wu, Tingting; Qin, Yuting; Qi, Yan; Sun, Yu; Kong, Miao; Jiang, Xue; Qin, Xianya; Shen, Yaqi; Zhang, Zhiping

2018-01-01

Doxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns. An amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor. Doxorubicin-dichloroacetate conjugate can self-assemble into nanoparticles with small amount of DSPE-PEG 2000 , leading to high drug loading (71.8%, w/w) and diminished excipient associated concerns. The nanoparticles exhibited invisible systemic toxicity and high maximum tolerated dose of 75 mg DOX equiv./kg, which was 15-fold higher than that of free DOX. It also showed good tumor targeting capability and enhanced antitumor efficacy in murine melanoma model. This work provides a promising strategy to simplify the drug preparation process, increase drug loading content, reduce systemic toxicity as well as enhance antitumor efficiency.

A physiologically based pharmacokinetic model to predict the pharmacokinetics of highly protein-bound drugs and the impact of errors in plasma protein binding.

Science.gov (United States)

Ye, Min; Nagar, Swati; Korzekwa, Ken

2016-04-01

Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data were often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding and the blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate the model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for the terminal elimination half-life (t1/2 , 100% of drugs), peak plasma concentration (Cmax , 100%), area under the plasma concentration-time curve (AUC0-t , 95.4%), clearance (CLh , 95.4%), mean residence time (MRT, 95.4%) and steady state volume (Vss , 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Swedish high-school pupils’ attitudes towards drugs in relation to drug usage, impulsiveness and other risk factors

Directory of Open Access Journals (Sweden)

Fariba Mousavi

2014-06-01

Full Text Available Background. Illicit drug use influences people’s lives and elicits unwanted behaviour. Current research shows that there is an increase in young people’s drug use in Sweden. The aim was to investigate Swedish high-school pupils’ attitudes, impulsiveness and gender differences linked to drug use. Risk and protective factors relative to drug use were also a focus of interest.Method. High school pupils (n = 146 aged 17–21 years, responded to the Adolescent Health and Development Inventory, Barratt Impulsiveness Scale and Knowledge, and the Attitudes and Beliefs. Direct logistic, multiple regression analyses, and Multivariate Analysis of Variance were used to analyze the data.Results. Positive Attitudes towards drugs were predicted by risk factors (odds ratio = 37.31 and gender (odds ratio = .32. Risk factors (odds ratio = 46.89, positive attitudes towards drugs (odds ratio = 4.63, and impulsiveness (odds ratio = 1.11 predicted drug usage. Risk factors dimensions Family, Friends and Individual Characteristic were positively related to impulsiveness among drug users. Moreover, although boys reported using drugs to a greater extent, girls expressed more positive attitude towards drugs and even reported more impulsiveness than boys.Conclusion. This study reinforces the notion that research ought to focus on gender differences relative to pro-drug attitudes along with testing for differences in the predictors of girls’ and boys’ delinquency and impulsiveness. Positive attitudes towards drugs among adolescents seem to be part of a vicious circle including risk factors, such as friendly drug environments (e.g., friends who use drugs and unsupportive family environments, individual characteristics, and impulsiveness.

Blood vessel growth blocker may treat AIDS-related Kaposi’s sarcoma

Science.gov (United States)

Patients with an AIDS-associated cancer, Kaposi's sarcoma (KS), showed improvement after receiving the combination of bevacizumab, a cancer drug that blocks the growth of new blood vessels, and highly active antiretroviral therapy (HAART).

Red blood cells and polyelectrolyte multilayer capsules: natural carriers versus polymer-based drug delivery vehicles.

Science.gov (United States)

Kolesnikova, Tatiana A; Skirtach, Andre G; Möhwald, Helmuth

2013-01-01

Red blood cells (RBCs) and lipid-based carriers on the one hand and polymeric capsules on the other hand represent two of the most widely used carriers in drug delivery. Each class of these carriers has its own set of properties, specificity and advantages. Thorough comparative studies of such systems are reported here for the first time. In this review, RBCs are described in comparison with synthetic polymeric drug delivery vehicles using polyelectrolyte multilayer capsules as an example. Lipid-based composition of the shell in the former case is particularly attractive due to their inherent biocompatibility and flexibility of the carriers. On the other hand, synthetic approaches to fabrication of polyelectrolyte multilayer capsules permit manipulation of the permeability of their shell as well as tuning their composition, mechanical properties, release methods and targeting. In conclusion, properties of RBCs and polyelectrolyte multilayer capsules are reported here highlighting similarities and differences in their preparation and applications. In addition, their advantages and disadvantages are discussed.

Simplifying sample pretreatment: application of dried blood spot (DBS) method to blood samples, including postmortem, for UHPLC-MS/MS analysis of drugs of abuse.

Science.gov (United States)

Odoardi, Sara; Anzillotti, Luca; Strano-Rossi, Sabina

2014-10-01

The complexity of biological matrices, such as blood, requires the development of suitably selective and reliable sample pretreatment procedures prior to their instrumental analysis. A method has been developed for the analysis of drugs of abuse and their metabolites from different chemical classes (opiates, methadone, fentanyl and analogues, cocaine, amphetamines and amphetamine-like substances, ketamine, LSD) in human blood using dried blood spot (DBS) and subsequent UHPLC-MS/MS analysis. DBS extraction required only 100μL of sample, added with the internal standards and then three droplets (30μL each) of this solution were spotted on the card, let dry for 1h, punched and extracted with methanol with 0.1% of formic acid. The supernatant was evaporated and the residue was then reconstituted in 100μL of water with 0.1% of formic acid and injected in the UHPLC-MS/MS system. The method was validated considering the following parameters: LOD and LOQ, linearity, precision, accuracy, matrix effect and dilution integrity. LODs were 0.05-1ng/mL and LOQs were 0.2-2ng/mL. The method showed satisfactory linearity for all substances, with determination coefficients always higher than 0.99. Intra and inter day precision, accuracy, matrix effect and dilution integrity were acceptable for all the studied substances. The addition of internal standards before DBS extraction and the deposition of a fixed volume of blood on the filter cards ensured the accurate quantification of the analytes. The validated method was then applied to authentic postmortem blood samples. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Advances towards reliable identification and concentration determination of rare cells in peripheral blood

Science.gov (United States)

Alemany Server, R.; Martens, D.; Jans, K.; Bienstman, P.; Hill, D.

2016-03-01

Through further development, integration and validation of micro-nano-bio and biophotonics systems FP7 CanDo is developing an instrument that will permit highly reproducible and reliable identification and concentration determination of rare cells in peripheral blood for two key societal challenges, early and low cost anti-cancer drug efficacy determination and cancer diagnosis/monitoring. A cellular link between the primary malignant tumour and the peripheral metastases, responsible for 90% of cancerrelated deaths, has been established in the form of circulating tumour cells (CTCs) in peripheral blood. Furthermore, the relatively short survival time of CTCs in peripheral blood means that their detection is indicative of tumour progression thereby providing in addition to a prognostic value an evaluation of therapeutic efficacy and early recognition of tumour progression in theranostics. In cancer patients however blood concentrations are very low (=1 CTC/1E9 cells) and current detection strategies are too insensitive, limiting use to prognosis of only those with advanced metastatic cancer. Similarly, problems occur in therapeutics with anti-cancer drug development leading to lengthy and costly trials often preventing access to market. The novel cell separation/Raman analysis technologies plus nucleic acid based molecular characterization of the CanDo platform will provide an accurate CTC count with high throughput and high yield meeting both key societal challenges. Being beyond the state of art it will lead to substantial share gains not just in the high end markets of drug discovery and cancer diagnostics but due to modular technologies also in others. Here we present preliminary DNA hybridization sensing results.

76 FR 44613 - Designation of Eight Counties as High Intensity Drug Trafficking Areas

Science.gov (United States)

2011-07-26

... OFFICE OF NATIONAL DRUG CONTROL POLICY Designation of Eight Counties as High Intensity Drug Trafficking Areas AGENCY: Office of National Drug Control Policy. ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy has designated eight additional counties as High Intensity Drug...

Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

Directory of Open Access Journals (Sweden)

Giovanni Sotgiu

2015-03-01

Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

21 CFR 864.7100 - Red blood cell enzyme assay.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Red blood cell enzyme assay. 864.7100 Section 864.7100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7100 Red blood cell...

Flushable reagent stool blood test

Science.gov (United States)

Stool occult blood test - flushable home test; Fecal occult blood test - flushable home test ... This test is performed at home with disposable pads. You can buy the pads at the drug store without ...

21 CFR 640.10 - Red Blood Cells.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Red Blood Cells. 640.10 Section 640.10 Food and... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Red Blood Cells § 640.10 Red Blood Cells. The proper name of this product shall be Red Blood Cells. The product is defined as red blood cells remaining...

Association between general and abdominal obesity with high blood pressure: difference between genders.

Science.gov (United States)

Silva, Alison O; Silva, Micaelly V; Pereira, Lisley K N; Feitosa, Wallacy M N; Ritti-Dias, Raphael M; Diniz, Paula R B; Oliveira, Luciano M F T

2016-01-01

To assess the association between general and abdominal obesity with high blood pressure in adolescents of both genders from the public school system. This was an epidemiological, descriptive, exploratory study, with a quantitative approach and local scope whose sample consisted of 481 high school students (aged 14-19), selected by using a random cluster sampling strategy. Blood pressure was measured through the use of automated monitor and was considered high when the pressure values were at or above the 95th percentile. The analyses were performed using the chi-squared test and binary logistic regression. The prevalence of high blood pressure was 6.4%, and it was higher among boys (9.0% vs. 4.7%, phigh blood pressure was associated with general (OR=6.4; phigh blood pressure only in boys, regardless of age. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain

Directory of Open Access Journals (Sweden)

Shanshan Liu

2018-01-01

Full Text Available Epilepsy is considered as a common and diverse set of chronic neurological disorders and its symptoms can be controlled by antiepileptic drugs (AEDs. The presence of p-glycoprotein and multi-drug resistance transporters in the blood-brain barrier could prevent the entry of AEDs into the brain, causing drug resistant epilepsy. To overcome this problem, we propose using carboxymethyl chitosan nanoparticles as a carrier to deliver carbamazepine (CBZ intra-nasally with the purpose to bypass the blood-brain barrier thus to enhance the brain drug concentration and the treatment efficacy. Results so far indicate that the developed CBZ-NPs have small particle size (218.76 ± 2.41 nm with high drug loading (around 35% and high entrapment efficiency (around 80%. The in vitro release profiles of CBZ from the NPs are in accordance with the Korsmeyer-peppas model. The in vivo results show that both encapsulation of CBZ in nanoparticles and the nasal route determined the enhancement of the drug bioavailability and brain targeting characteristics.

REACTIVITY OF BLOOD LYMPHOCYTES IN PULMONARY TUBERCULOSIS

Directory of Open Access Journals (Sweden)

R. R. Khasanova

2009-01-01

Full Text Available Evaluation of proliferative and IL-2-producing activity of peripheral blood lymphocytes wasperformed, using cultural methods, in patients with drug-sensitive and drug-resistant infiltrative pulmonary tuberculosis. The cell testing was performed at basal level and following in vitro stimulation with recombinant IL-2 and M. tuberculosis antigens. It was established that clinical course of infiltrative pulmonary tuberculosis, independently on drug sensitivity/resistance of the infectious pathogen, is accompanied by suppression of spontaneous lymphoproliferation. The levels of induced IL-2 production in drug-sensitive tuberculosis proved to be increased, whereas a reserve of IL-2-secreting reactivity of blood lymphocytes was lower than in drugresistant infection. Also, it was revealed that the level of lymphoproliferative response induced by IL-2, does not depend on clinical variant of tuberculosis, whereas stimulation of IL-2 production in blood lymphocytes is attained only in cases of drug-resistant tuberculosis variant.

Morpho-functional Blood Changes Under the Influence of Hydrazine and Correction with “Salsokollin” Drug

Directory of Open Access Journals (Sweden)

Marat R. Khanturin

2012-09-01

Full Text Available Hydrazine derivatives are used in different areas: airspace industry, healthcare, laboratory-diagnostic activity, that’s why the environment is subjected to contamination by hydrazines. For Kazakhstan, which houses the "Baikonur" Cosmodrome, the problem of environmental pollution by rocket fuel and its components is a burning issue nowadays. This article deals with the impacts by industrial hydrazines on biochemical data of the blood and its correction with the “Salsokollin” Drug. The samples of bilirubin, the whole protein, urea, creatinine, cholesterol, glucose, aminotransferase a-amylases, α-amylase were taken. The thymol test was carried out.

Addictive drugs and their duration affecting on trace elements levels in men

International Nuclear Information System (INIS)

Nadeem, A.; Iqbal, K.; Shafiq, T.; Rehman, S.

2008-01-01

During the drug addiction the blood biochemistry particularly level of trace elements in blood is widely affected. Eighty male addicts of various age groups along with seventeen normal subjects were studied. The plasma Zinc and manganese concentration was high in addict person as compared to normal subjects. Where as a significant decrease in iron concentration was observed in addicts. The plasma copper concentration was also low in addicts as compared to normal subjects. In conclusion drug addiction leads to many biochemical changes that may have detritus effects on health status of addicts. (author)

Optimization of the Ultrasound-Induced Blood-Brain Barrier Opening

OpenAIRE

Konofagou, Elisa E.

2012-01-01

Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly non-invasive, transient, and regionally selective brain drug delivery method. The brain is particularly difficult to deliver drugs to because of the blood-brain barrier (BBB). The impermeability of the BBB is due to the tight junctions connecting adjacent endothelial cells and highly regulatory transport systems of the endothelial cell membranes. The main function of the BBB is ion and vol...

Impact of drug permeability of blood-brain barrier after whole brain conventional fractionation irradiation

International Nuclear Information System (INIS)

Zhang Longzhen; Cao Yuandong; Chen Yong; Yu Changzhou; Zhuang Ming

2006-01-01

Objective: To explore the effect of drug permeability in rat blood-brain barrier(BBB) after different doses of whole brain conventional fractionation irradiation in rats and provide the experimental basis for the optimum time of clinical chemotherapy. Methods: According to different irradiation doses, 100 adult Sprague-Dowley rats were divided randomly into 5 groups: the normal control group(0 Gy); 10 Gy; 20 Gy; 30 Gy; and 40 Gy group. All rats were exposed to conventional fractionation(2 Gy/d, 5 d/w) with 60 Co γ-ray. MTX(25 mg/kg) was injected through the tail mainline 16 hours after whole brain irradiation. Cerebrospinal fluid(CSF) and blood were collected 2 hours later. Those samples were used to assay MTX concentration using RP-HPLC. Results: MTX mean concentrations in CSF was 0.07, 0.08, 0.12, 0.24, 0.23 mg/L in the control, 10 Gy, 20 Gy, 30 Gy, 40 Gy groups, respectively. All the data was analyzed with rank test of transform. MTX concentration of CSF was significantly different except the control and 10 Gy, 30 Gy and 40 Gy group. MTX concentration of blood was not significantly different in all groups (P>0.05). Conclusions: Irradiation can directly damage the function of BBB. BBB would be opened gradually following the increase of irradiation dose. It could be considered as the optimum time of chemotherapy when the whole brain irradiation ranges from 20 Gy to 30 Gy. (authors)

High plasma corticosterone levels persist during frequent automatic blood sampling in rats

DEFF Research Database (Denmark)

Abelson, Klas S P; Adem, Bashir; Royo, Felix

2005-01-01

Corticosterone levels in blood may be used as a marker of stress in rodents, provided that the blood sampling procedure itself is non-stressful. Automated blood sampling equipment (Accusampler) allows blood sampling without any interference with the animal and might be useful as a tool for an on......-line measurement of stress markers in blood. However, the impact of the blood sampling itself on the corticosterone levels in blood is unknown. The present study was designed to evaluate whether the frequency of blood sampling influences the plasma corticosterone levels in male and female rats. During anaesthesia...... the importance of considering the frequency of blood withdrawal during automated blood sampling. This parameter may have an impact on the experimental results when using blood corticosterone levels as a stress marker, but also during any in vivo study where blood is collected, since high corticosterone levels...

Impact of valproates on haemostasis and blood cell count in children

Directory of Open Access Journals (Sweden)

Igrutinović Zoran

2008-01-01

Full Text Available INTRODUCTION Epilepsy is a highly prevalent disease affecting 0.5-1.5% of the world's population. One of the most frequently used antiepileptics are valproates. These medicines show a negative impact on haemostasis and peripheral blood count. OBJECTIVE The objective of the study was to examine the negative impact of valproates on haemostasis and peripheral blood count in children and to analyse whether these disturbances were dependent on the dosage of valproates and drug level in blood. METHOD A two-year research was conducted. The research included: 35 children using valproates, 12 children using the therapy of both valproates and carbamazepine and 30 healthy children. Complete peripheral blood count, screening tests of haemostasis (bleeding time, prothrombin time, prothrombin ratio, activated partial thromboplastin time, fibrinogen and capacity of thrombocyte aggregation research were done in all the children. RESULTS We found significantly more common frequency of leukopenia and neutropenia in children using valproates in comparison with the healthy children group. We also found the more common frequency of eosinophilia in comparison with healthy children. The children with the valproate therapy have lower approximate values of the number of platelets, fibrinogen and platelet aggregation in comparison with healthy children, but they have a higher approximate value of bleeding time and prothrombin time. These disturbances are in correlation with the dosage and the level of the medicine in blood. CONCLUSION Valproates have a negative effect on certain blood count parameters and haemostasis in children. Drug dosage and blood drug level are correlated with their negative impact on haemostasis parameters.

Factors associated with high probability of target blood pressure non-achievement in hypertensive patients

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S. P. Zhemanyuk

2017-12-01

Full Text Available One of the topic issue of modern cardiology is factors of target blood pressure level non-achievement clarifying due to a better understanding how we can reduce cardiovascular complications. The aim of the study is to determine the factors of poor blood pressure control using the ambulatory blood pressure monitoring parameters and adenosine 5'-diphosphate-induced platelet aggregation parameters in patients with arterial hypertension. Material and methods. The study involved 153 patients with essential hypertension (EH stage II, II degree. The ambulatory blood pressure monitoring (ABPM was performed in patients during at least two of first-line antihypertensive drugs in optimal daily doses usage by the ABPM bifunctional device (Incart, S.-P., R.F.. Platelet aggregation was carried out using light transmittance aggregation by optical analyzer (Solar, R.B. with adenosine 5'-diphosphate (Sigma-Aldrich at final concentration of 10.0 × 10-6 mol / L. The first group were inadequately controlled essential hypertensive individuals with high systolic or/and diastolic BP level according to the ABPM results, and the second one were patients with adequately controlled EH. Groups of patients were comparable in age (60.39 ± 10.74 years vs. 62.80 ± 9.63; p = 0.181, respectively. In the group of EH patients who reached the target level of blood pressure, women predominated (60% vs. 39.81%; p = 0.021, respectively. We used the binary logistic regression analysis to determine the predictors of target blood pressure level poor reaching using ABPM and platelet aggregation parameters. Results According to the univariate logistic regression analysis, the dependent factors influencing the target blood pressure level poor reaching are the average diurnal diastolic blood pressure (DBP (OR = 44.8; diurnal variability of systolic blood pressure (SBP (OR = 4.4; square index of hypertension for diurnal periods SBP (OR = 318.9; square index of hypertension for diurnal

Awareness of high blood pressure status, treatment and control in a ...

African Journals Online (AJOL)

west LGA of Edo State to assess the level of awareness of high blood pressure status, treatment and control. Cluster sampling method was used to select participants and data collection was by researcher administered questionnaire. Blood ...

The transport of nifurtimox, an anti-trypanosomal drug, in an in vitro model of the human blood-brain barrier: evidence for involvement of breast cancer resistance protein.

Science.gov (United States)

Watson, Christopher P; Dogruel, Murat; Mihoreanu, Larisa; Begley, David J; Weksler, Babette B; Couraud, Pierre O; Romero, Ignacio A; Thomas, Sarah A

2012-02-03

Human African trypanosomiasis (HAT) is a parasitic disease affecting sub-Saharan Africa. The parasites are able to traverse the blood-brain barrier (BBB), which marks stage 2 (S2) of the disease. Delivery of anti-parasitic drugs across the BBB is key to treating S2 effectively and the difficulty in achieving this goal is likely to be a reason why some drugs require highly intensive treatment regimes to be effective. This study aimed to investigate not only the drug transport mechanisms utilised by nifurtimox at the BBB, but also the impact of nifurtimox-eflornithine combination therapy (NECT) and other anti-HAT drug combination therapies (CTs) on radiolabelled-nifurtimox delivery in an in vitro model of drug accumulation and the human BBB, the hCMEC/D3 cell line. We found that nifurtimox appeared to use several membrane transporters, in particular breast-cancer resistance protein (BCRP), to exit the BBB cells. The addition of eflornithine caused no change in the accumulation of nifurtimox, nor did the addition of clinically relevant doses of the other anti-HAT drugs suramin, nifurtimox or melarsoprol, but a significant increase was observed with the addition of pentamidine. The results provide evidence that anti-HAT drugs are interacting with membrane transporters at the human BBB and suggest that combination with known transport inhibitors could potentially improve their efficacy. Copyright © 2011 Elsevier B.V. All rights reserved.

Statin Drugs Markedly Inhibit Testosterone Production by Rat Leydig Cells In Vitro: Implications for Men

Science.gov (United States)

Statin drugs lower blood cholesterol by inhibiting hepatic 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase. During drug development it was shown that statins inhibit production of cholesterol in the testis. We evaluated testosterone production in vitro, using highly purified rat ...

High blood oxygen affinity in the air-breathing swamp eel Monopterus albus.

Science.gov (United States)

Damsgaard, Christian; Findorf, Inge; Helbo, Signe; Kocagoz, Yigit; Buchanan, Rasmus; Huong, Do Thi Thanh; Weber, Roy E; Fago, Angela; Bayley, Mark; Wang, Tobias

2014-12-01

The Asian swamp eel (Monopterus albus, Zuiew 1793) is a facultative air-breathing fish with reduced gills. Previous studies have shown that gas exchange seems to occur across the epithelium of the buccopharyngeal cavity, the esophagus and the integument, resulting in substantial diffusion limitations that must be compensated by adaptations in others steps of the O₂ transport system to secure adequate O₂ delivery to the respiring tissues. We therefore investigated O₂ binding properties of whole blood, stripped hemoglobin (Hb), two major isoHb components and the myoglobin (Mb) from M. albus. Whole blood was sampled using indwelling catheters for blood gas analysis and determination of O₂ equilibrium curves. Hb was purified to assess the effects of endogenous allosteric effectors, and Mb was isolated from heart and skeletal muscle to determine its O₂ binding properties. The blood of M. albus has a high O₂ carrying capacity [hematocrit (Hct) of 42.4±4.5%] and binds O₂ with an unusually high affinity (P₅₀=2.8±0.4mmHg at 27°C and pH7.7), correlating with insensitivity of the Hb to the anionic allosteric effectors that normally decrease Hb-O₂ affinity. In addition, Mb is present at high concentrations in both heart and muscle (5.16±0.99 and 1.08±0.19mg ∙ g wet tissue⁻¹, respectively). We suggest that the high Hct and high blood O₂ affinity serve to overcome the low diffusion capacity in the relatively inefficient respiratory surfaces, while high Hct and Mb concentration aid in increasing the O₂ flux from the blood to the muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

Rapid and sensitive detection of ketamine in blood using novel fluorescence genosensor.

Science.gov (United States)

Ding, Yanjun; Li, Xingmei; Guo, Yadong; Yan, Jie; Ling, Jiang; Li, Weichen; Lan, Lingmei; Chang, Yunfeng; Cai, Jifeng; Zha, Lagabaiyla

2017-12-01

In recent years, drug abuse has been considered as a most challenging social problem that aroused public attention. Ketamine has increased in unregulated use as a 'recreational drug' in teenagers. However, there is no suitable and maneuverable detection method for ketamine in situ at the moment. Fluorescence sensor technique, with predominant recognition and simple operation, is a good potential application in drug detection. Here, we first reported a highly sensitive and selective fluorescence genosensor for rapid detection of ketamine based on DNA-templated silver nanoclusters (DNA-AgNCs) probes, in which the DNA sequence could specially recognize ketamine with high affinity. Parameters affecting detection efficiency were investigated and optimized. Under optimum conditions, the as-prepared genosensor can allow for the determination of ketamine in the concentration range of 0.0001-20 μg/mL with two linear equations: one is y = 2.84x-7.139 (R 2 = 0.987) for 0.0001-0.1 μg/mL, and the other is y = 1.87x-0.091 (R 2 = 0.962) for 0.1-20 μg/mL, and the estimated detection limit of ketamine is 0.06 ng/mL. Moreover, the feasibility of this proposed method was also demonstrated by analyzing forensic blood samples. Compared with official gas chromatography/mass spectrometry (GC/MS), this fluorescence genosensor is simple, rapid, and accurate for quantitative determination of ketamine in blood for pharmaceutical and forensic analysis. Overall, it is the first report on a fluorescence genosensor for detecting ketamine directly in blood. This research may provide a new insight for the analyst to band fluorescence genosensor technology together with drug monitoring in the battle against drug abuse and forensic examination. Graphical abstract High selectively detection of ketamine using a novel fluorescence genosensor based on DNA-AgNCs probe.

Biodegradable polymeric nanocarriers for pulmonary drug delivery.

Science.gov (United States)

Rytting, Erik; Nguyen, Juliane; Wang, Xiaoying; Kissel, Thomas

2008-06-01

Pulmonary drug delivery is attractive for both local and systemic drug delivery as a non-invasive route that provides a large surface area, thin epithelial barrier, high blood flow and the avoidance of first-pass metabolism. Nanoparticles can be designed to have several advantages for controlled and targeted drug delivery, including controlled deposition, sustained release, reduced dosing frequency, as well as an appropriate size for avoiding alveolar macrophage clearance or promoting transepithelial transport. This review focuses on the development and application of biodegradable polymers to nanocarrier-based strategies for the delivery of drugs, peptides, proteins, genes, siRNA and vaccines by the pulmonary route. The selection of natural or synthetic materials is important in designing particles or nanoparticle clusters with the desired characteristics, such as biocompatibility, size, charge, drug release and polymer degradation rate.

Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior

Directory of Open Access Journals (Sweden)

Samantha J. Hindle

2017-10-01

Full Text Available Summary: Central nervous system (CNS chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB. Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice. Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. : Hindle et al. shed light on the curious finding that some drugs cause behavioral side-effects despite negligible access into the brain. These authors propose a unifying hypothesis that links blood-brain barrier drug transporter function and brain access of circulating steroids to common CNS adverse drug responses. Keywords: drug side effect mechanisms, central nervous system, blood brain barrier, behavior, toxicology, drug transporters, endobiotics, steroid hormones

Drugs and drug delivery systems targeting amyloid-β in Alzheimer's disease

Directory of Open Access Journals (Sweden)

Morgan Robinson

2015-07-01

Full Text Available Alzheimer's disease (AD is a devastating neurodegenerative disorder with no cure and limited treatment solutions that are unable to target any of the suspected causes. Increasing evidence suggests that one of the causes of neurodegeneration is the overproduction of amyloid beta (Aβ and the inability of Aβ peptides to be cleared from the brain, resulting in self-aggregation to form toxic oligomers, fibrils and plaques. One of the potential treatment options is to target Aβ and prevent self-aggregation to allow for a natural clearing of the brain. In this paper, we review the drugs and drug delivery systems that target Aβ in relation to Alzheimer's disease. Many attempts have been made to use anti-Aβ targeting molecules capable of targeting Aβ (with much success in vitro and in vivo animal models, but the major obstacle to this technique is the challenge posed by the blood brain barrier (BBB. This highly selective barrier protects the brain from toxic molecules and pathogens and prevents the delivery of most drugs. Therefore novel Aβ aggregation inhibitor drugs will require well thought-out drug delivery systems to deliver sufficient concentrations to the brain.

75 FR 52780 - Designation of Nine Counties as High Intensity Drug Trafficking Areas

Science.gov (United States)

2010-08-27

... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Nine Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated nine additional counties as High Drug Trafficking Areas pursuant to...

75 FR 21368 - Designation of Five Counties as High Intensity Drug Trafficking Areas

Science.gov (United States)

2010-04-23

... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Five Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated five additional counties as High Drug Trafficking Areas pursuant to...

Evaluation of an Immunomodulator Drug as a Radioprotectant on Human Peripheral Blood Lymphocytes In Vitro

Directory of Open Access Journals (Sweden)

Zahra Sattarpour

2018-01-01

Full Text Available Background: IMOD™, a selenium enriched extract of the plants Tanacetum vulgare, Urtica dioica, and Rosa canina, has an excellent effect on oxidative stress. In this study, we investigated the radioprotective effects of this immunomodulatory drug on human peripheral blood lymphocytes. Methods: Peripheral blood samples obtained from venipuncture of the brachial vein were treated with IMOD™ (5, 10, 15, 20 μl for 30 min and Cobalt 60 γ-rays (0.25, 0.5, 1, 2 Gy as the test groups and cultured with the control. We used the micronuclei assay, cell death detection, and cell toxicity assay to analyze the treatment effects. Results: The frequency of micronuclei were 1.66 (0 Gy, 5.33 (0.25 Gy, 9.67 (0.5 Gy, 17.67 (1 Gy, and 23.67 (2 Gy in the irradiated lymphocytes (P<0.001. The percentage of micronuclei frequency reduced to 20%, 26.83%, 37.68%, 16%, and 20.47% with IMOD™. Apoptosis and necrosis decreased significantly in the IMOD™ treated groups (P<0.05. Conclusion: IMOD™ may protect these cells against ionizing radiation.

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers.

Science.gov (United States)

Nair, Madhavan; Guduru, Rakesh; Liang, Ping; Hong, Jeongmin; Sagar, Vidya; Khizroev, Sakhrat

2013-01-01

Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacy-targeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5'-triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe2O4@BaTiO3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs.

Science.gov (United States)

Savino, Maria; Seripa, Davide; Gallo, Antonietta P; Garrubba, Maria; D'Onofrio, Grazia; Bizzarro, Alessandra; Paroni, Giulia; Paris, Francesco; Mecocci, Patrizia; Masullo, Carlo; Pilotto, Alberto; Santini, Stefano A

2011-01-01

Recent studies investigating the single cytochrome P450 (CYP) 2D6 allele *2A reported an association with the response to drug treatments. More genetic data can be obtained, however, by high-throughput based-technologies. Aim of this study is the high-throughput analysis of the CYP2D6 polymorphisms to evaluate its effectiveness in the identification of patient responders/non-responders to CYP2D6-metabolized drugs. An attempt to compare our results with those previously obtained with the standard analysis of CYP2D6 allele *2A was also made. Sixty blood samples from patients treated with CYP2D6-metabolized drugs previously genotyped for the allele CYP2D6*2A, were analyzed for the CYP2D6 polymorphisms with the AutoGenomics INFINITI CYP4502D6-I assay on the AutoGenomics INFINITI analyzer. A higher frequency of mutated alleles in responder than in non-responder patients (75.38 % vs 43.48 %; p = 0.015) was observed. Thus, the presence of a mutated allele of CYP2D6 was associated with a response to CYP2D6-metabolized drugs (OR = 4.044 (1.348 - 12.154). No difference was observed in the distribution of allele *2A (p = 0.320). The high-throughput genetic analysis of the CYP2D6 polymorphisms better discriminate responders/non-responders with respect to the standard analysis of the CYP2D6 allele *2A. A high-throughput genetic assay of the CYP2D6 may be useful to identify patients with different clinical responses to CYP2D6-metabolized drugs.

21 CFR 640.23 - Testing the blood.

Science.gov (United States)

2010-04-01

... this chapter and § 640.5 (a), (b), and (c). (b) The tests shall be performed on a sample of blood... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Testing the blood. 640.23 Section 640.23 Food and... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Platelets § 640.23 Testing the blood. (a) Blood from...

Baseline Blood Pressure, the 2017 ACC/AHA High Blood Pressure Guidelines, and Long-Term Cardiovascular Risk in SPRINT.

Science.gov (United States)

Vaduganathan, Muthiah; Pareek, Manan; Qamar, Arman; Pandey, Ambarish; Olsen, Michael H; Bhatt, Deepak L

2018-02-05

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines include lower thresholds to define hypertension than previous guidelines. Little is known about the impact of these guideline changes in patients with or at high risk for cardiovascular disease. In this exploratory analysis using baseline blood pressure assessments in Systolic Blood Pressure Intervention Trial (SPRINT), we evaluated the prevalence and associated cardiovascular prognosis of patients newly reclassified with hypertension based on the 2017 ACC/AHA (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg) compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) guidelines (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg). The primary endpoint was the composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or cardiovascular death. In 4683 patients assigned to the standard treatment arm of SPRINT, 2328 (49.7%) met hypertension thresholds by JNC 7 guidelines, and another 1424 (30.4%) were newly reclassified as having hypertension based on the 2017 ACC/AHA guidelines. Over 3.3-year median follow-up, 319 patients experienced the primary endpoint (87 of whom were newly reclassified with hypertension based on the revised guidelines). Patients with hypertension based on prior guidelines compared with those newly identified with hypertension based on the new guidelines had similar risk of the primary endpoint (2.3 [95% confidence interval {CI}, 2.0-2.7] vs 2.0 [95% CI, 1.6-2.4] events per 100 patient-years; adjusted HR, 1.10 [95% CI, 0.84-1.44]; P = .48). The 2017 ACC/AHA high blood pressure guidelines are expected to significantly increase the prevalence of patients with hypertension (perhaps to a greater extent in higher-risk patient cohorts compared with the general population) and

[Health and exercise: effects of exercise on high blood pressure].

Science.gov (United States)

Ikeda, M; Nanri, H; Himeno, E

1993-09-01

Many factors, such as genetic, psychological, environmental, and socioeconomical factors, influence the health of individuals. Recently behavioral risks which cause preventable chronic diseases or premature death have been increasing. These risk factors are mainly due to living habits, such as over-eating, less exercise and psychological stress. Physical activity or fitness is reported to be inversely associated with morbidity and mortality from chronic diseases, such as cardiovascular diseases diabetes mellitus, cancer and so on. Hypertension has also been reported to be associated with low physical fitness in cross-sectional studies. We have so far reported a significant blood pressure reduction in mild hypertensive patients who completed mild intensity exercise training in well controlled studies. Exercise seemed to modify the multiple factors that might participate in raising and maintaining high blood pressure. The mechanisms of lowering blood pressure by exercise training are mainly due to a depletion of blood volume or the reduction of both cardiac output and the sympathetic tone. They were supported by the evidence of increased levels of prostaglandin E, dopamine, taurine, and decreased levels of plasma norepinephrine and endogenous ouavain-like substance. In this article, we have reviewed the physiological and biochemical roles of exercise, the effects of exercise on high blood pressure, and the hypotensive mechanism of mild aerobic exercise hypertensive patients.

Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude

DEFF Research Database (Denmark)

Møller, Kirsten; Paulson, Olaf B; Hornbein, Thomas F.

2002-01-01

The authors investigated the effect of acclimatization to high altitude on cerebral blood flow and oxidative metabolism at rest and during exercise. Nine healthy, native sea-level residents were studied 3 weeks after arrival at Chacaltaya, Bolivia (5,260 m) and after reacclimatization to sea level....... At high altitude at rest, arterial carbon dioxide tension, oxygen saturation, and oxygen tension were significantly reduced, and arterial oxygen content was increased because of an increase in hemoglobin concentration. Global cerebral blood flow was similar in the four conditions. Cerebral oxygen delivery...... and cerebral metabolic rates of oxygen and glucose also remained unchanged, whereas cerebral metabolic rates of lactate increased slightly but nonsignificantly at high altitude during exercise compared with high altitude at rest. Reaction time was unchanged. The data indicate that cerebral blood flow...

A lab-on-CD prototype for high-speed blood separation

International Nuclear Information System (INIS)

Zhang Jinlong; Liu Mei; Yang Jun; Guo Qiuquan

2008-01-01

Blood separation is the first step for subsequent blood tests in clinical diagnosis. Lab-on-a-chip technology provides an automatic, cost-effective and fast solution for a wide variety of blood analyses. The objective of this work is to design a new lab-on-CD microstructure capable of separating blood cells from the whole blood into different reservoirs directly. A CD platform including a microchannel network consisting of a straight main microchannel, a curved microchannel and a branching microchannel has been proposed. The merits of this design are its simple structure, less operating time and high separation efficiency because it utilizes multiple separation mechanisms, for instance, two centrifugal forces and Coriolis force. One centrifugal force is due to the system rotation; the other centrifugal force is due to the curvature of the specifically designed curved channel. In this work, systematical evaluation on the functionality and performance of such a design has been done. Ninety-nine per cent separation efficiency is achieved for diluted blood of 6% hematocrit

A lab-on-CD prototype for high-speed blood separation

Science.gov (United States)

Zhang, Jinlong; Guo, Qiuquan; Liu, Mei; Yang, Jun

2008-12-01

Blood separation is the first step for subsequent blood tests in clinical diagnosis. Lab-on-a-chip technology provides an automatic, cost-effective and fast solution for a wide variety of blood analyses. The objective of this work is to design a new lab-on-CD microstructure capable of separating blood cells from the whole blood into different reservoirs directly. A CD platform including a microchannel network consisting of a straight main microchannel, a curved microchannel and a branching microchannel has been proposed. The merits of this design are its simple structure, less operating time and high separation efficiency because it utilizes multiple separation mechanisms, for instance, two centrifugal forces and Coriolis force. One centrifugal force is due to the system rotation; the other centrifugal force is due to the curvature of the specifically designed curved channel. In this work, systematical evaluation on the functionality and performance of such a design has been done. Ninety-nine per cent separation efficiency is achieved for diluted blood of 6% hematocrit.

High dead-space syringe use among people who inject drugs in Tijuana, Mexico.

Science.gov (United States)

Rafful, Claudia; Zule, William; González-Zúñiga, Patricia E; Werb, Dan; Medina-Mora, María Elena; Magis-Rodriguez, Carlos; Strathdee, Steffanie A

2015-05-01

High dead-space syringes (HDSS) are believed to confer an elevated risk of acquiring HIV and other blood-borne infections. We identified prevalence and correlates of HDSS use among injection drug users (IDU) in Tijuana, Mexico, where syringe purchase and possession is legal without a prescription. Beginning in 2011, IDU who reported being 18 years or older and injected drugs within the last month were recruited into a prospective study. At baseline and semi-annually, 557 IDU underwent HIV-testing and interviewer-administered surveys. Logistic regression was used to identify correlates of using HDSS. Of 557 IDU, 40% had ever used HDSS, mostly because no other syringe type was available (72%), or because they were easier to get (20%). Controlling for sex and age at first injection, use of HDSS was associated with cocaine as the first drug injected (Adjusted Odds Ratio [AOR]: 2.68; Confidence Interval 95% [CI]: 1.15-6.22), having been stopped or arrested by police (AOR: 1.84; 95% CI: 1.11-3.07), being deported from the US (AOR: 1.64; 95% CI:1.06-2.53), and believing it is illegal to carry syringes (AOR:1.78; 95% CI: 1.01-3.15). Use of HDSS is surprisingly common among IDU in Tijuana. Efforts are needed to expand coverage of low-dead space syringes through existing syringe exchange programs. Education is required to increase awareness of the harms associated with HDSS, and to inform IDU that syringe possession is legal across Mexico.

Blood and Blood Components: From Similarities to Differences

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Olivier Garraud

2018-04-01

Full Text Available Blood transfusion is made possible because, in most countries and organizations, altruistic individuals voluntarily, anonymously, and generously donate (without compensation either whole blood or separated components that are then processed and distributed by professionals, prior to being allocated to recipients in need. Being part of modern medicine, blood transfusion uses so-called standard blood components when relative to cellular fractions and fresh plasma. However, as will be discussed in this paper, strictly speaking, such so-called labile blood components are not completely standard. Furthermore, the prevalent system based on voluntary, non-remunerated blood donation is not yet universal and, despite claims by the World Health Organization that 100% of blood collection will be derived from altruistic donations by 2020 (postponed to 2025, many obstacles may hinder this ambition, especially when relative to the collection of the enormous amount of plasma destined for fractionation into plasma derivative or drugs. Finally, country organizations also vary due to the economy, sociology, politics, and epidemiology. This paper then, discusses the particulars (of which ethical considerations of blood transfusion diversity and the consequences for donors, patients, and society.

Blood and Blood Components: From Similarities to Differences

Science.gov (United States)

Garraud, Olivier; Tissot, Jean-Daniel

2018-01-01

Blood transfusion is made possible because, in most countries and organizations, altruistic individuals voluntarily, anonymously, and generously donate (without compensation) either whole blood or separated components that are then processed and distributed by professionals, prior to being allocated to recipients in need. Being part of modern medicine, blood transfusion uses so-called standard blood components when relative to cellular fractions and fresh plasma. However, as will be discussed in this paper, strictly speaking, such so-called labile blood components are not completely standard. Furthermore, the prevalent system based on voluntary, non-remunerated blood donation is not yet universal and, despite claims by the World Health Organization that 100% of blood collection will be derived from altruistic donations by 2020 (postponed to 2025), many obstacles may hinder this ambition, especially when relative to the collection of the enormous amount of plasma destined for fractionation into plasma derivative or drugs. Finally, country organizations also vary due to the economy, sociology, politics, and epidemiology. This paper then, discusses the particulars (of which ethical considerations) of blood transfusion diversity and the consequences for donors, patients, and society. PMID:29686986

Guidelines of the French Society of Otorhinolaryngology (SFORL). Epistaxis and high blood pressure.

Science.gov (United States)

Michel, J; Prulière Escabasse, V; Bequignon, E; Vérillaud, B; Robard, L; Crampette, L; Malard, O

2017-02-01

The authors present the guidelines of the French Oto-Rhino-Laryngology - Head and Neck Surgery Society (Société Française d'Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou: SFORL) on epistaxis in high blood pressure. A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. It is recommended to measure the blood pressure of patients in acute-phase epistaxis (Grade A); to control high blood pressure medically in the acute phase of bleeding, to reduce its duration; to monitor blood pressure at the waning of nosebleed; and to control high blood pressure medically in the waning phase to reduce the risk of recurrence. In case of persistent high blood pressure on waning of severe epistaxis, it is recommended to prescribe cardiovascular evaluation to screen for underlying hypertensive disease (Grade B). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?

Science.gov (United States)

Abdullahi, Wazir; Davis, Thomas P; Ronaldson, Patrick T

2017-07-01

Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. Therefore, our laboratory has proposed that optimization of CNS drug delivery, particularly for treatment of diseases with an H/R component, can be achieved by targeting Oatp isoforms at the BBB. As the major drug transporting Oatp isoform, Oatp1a4 has demonstrated blood-to-brain transport of substrate drugs with neuroprotective properties. Furthermore, our laboratory has shown that targeting Oatp1a4 regulation (i.e., TGF-β signaling mediated via the ALK-1 and ALK-5 transmembrane receptors) represents an opportunity to control Oatp1a4 functional expression for the purpose of delivering therapeutics to the CNS. In this review, we will discuss limitations of targeting P-gp-mediated transport activity and the advantages of targeting Oatp-mediated transport. Through this discussion, we will also provide critical information on novel approaches to improve CNS drug delivery by targeting endogenous uptake transporters expressed at the BBB.

Characterising the extent of misreporting of high blood pressure, high cholesterol, and diabetes using the Australian Health Survey.

Science.gov (United States)

Peterson, Karen Louise; Jacobs, Jane Philippa; Allender, Steven; Alston, Laura Veronica; Nichols, Melanie

2016-08-02

Measuring and monitoring the true prevalence of risk factors for chronic conditions is essential for evidence-based policy and health service planning. Understanding the prevalence of risk factors for cardiovascular disease (CVD) in Australia relies heavily on self-report measures from surveys, such as the triennial National Health Survey. However, international evidence suggests that self-reported data may substantially underestimate actual risk factor prevalence. This study sought to characterise the extent of misreporting in a large, nationally-representative health survey that included objective measures of clinical risk factors for CVD. This study employed a cross-sectional analysis of 7269 adults aged 18 years and over who provided fasting blood samples as part of the 2011-12 Australian Health Survey. Self-reported prevalence of high blood pressure, high cholesterol and diabetes was compared to measured prevalence, and univariate and multivariate logistic regression analyses identified socio-demographic characteristics associated with underreporting for each risk factor. Approximately 16 % of the total sample underreported high blood pressure (measured to be at high risk but didn't report a diagnosis), 33 % underreported high cholesterol, and 1.3 % underreported diabetes. Among those measured to be at high risk, 68 % did not report a diagnosis for high blood pressure, nor did 89 % of people with high cholesterol and 29 % of people with high fasting plasma glucose. Younger age was associated with underreporting high blood pressure and high cholesterol, while lower area-level disadvantage and higher income were associated with underreporting diabetes. Underreporting has important implications for CVD risk factor surveillance, policy planning and decisions, and clinical best-practice guidelines. This analysis highlights concerns about the reach of primary prevention efforts in certain groups and implications for patients who may be unaware of their