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Sample records for high blood drug

  1. Drugs for treatment of very high blood pressure during pregnancy.

    Science.gov (United States)

    Duley, Lelia; Meher, Shireen; Jones, Leanne

    2013-07-31

    Very high blood pressure during pregnancy poses a serious threat to women and their babies. The aim of antihypertensive therapy is to lower blood pressure quickly but safety, to avoid complications. Antihypertensive drugs lower blood pressure but their comparative effectiveness and safety, and impact on other substantive outcomes is uncertain. To compare different antihypertensive drugs for very high blood pressure during pregnancy. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (9 January 2013). Studies were randomised trials. Participants were women with severe hypertension during pregnancy. Interventions were comparisons of one antihypertensive drug with another. Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data and checked them for accuracy. Thirty-five trials (3573 women) with 15 comparisons were included. Women allocated calcium channel blockers were less likely to have persistent high blood pressure compared to those allocated hydralazine (six trials, 313 women; 8% versus 22%; risk ratio (RR) 0.37, 95% confidence interval (CI) 0.21 to 0.66). Ketanserin was associated with more persistent high blood pressure than hydralazine (three trials, 180 women; 27% versus 6%; RR 4.79, 95% CI 1.95 to 11.73), but fewer side-effects (three trials, 120 women; RR 0.32, 95% CI 0.19 to 0.53) and a lower risk of HELLP (haemolysis, elevated liver enzymes and lowered platelets) syndrome (one trial, 44 women; RR 0.20, 95% CI 0.05 to 0.81).Labetalol was associated with a lower risk of hypotension compared to diazoxide (one trial 90 women; RR 0.06, 95% CI 0.00 to 0.99) and a lower risk of caesarean section (RR 0.43, 95% CI 0.18 to 1.02), although both were borderline for statistical significance.Both nimodipine and magnesium sulphate were associated with a high incidence of persistent high blood pressure, but this risk was lower for nimodipine compared to magnesium sulphate (one trial

  2. Hypertension (High Blood Pressure)

    Science.gov (United States)

    ... Surgery? A Week of Healthy Breakfasts Shyness Hypertension (High Blood Pressure) KidsHealth > For Teens > Hypertension (High Blood Pressure) Print ... rest temperature diet emotions posture medicines Why Is High Blood Pressure Bad? High blood pressure means a person's heart ...

  3. High Blood Cholesterol

    Science.gov (United States)

    ... version of this page please turn Javascript on. High Blood Cholesterol What is High Blood Cholesterol? What is Cholesterol? Cholesterol is a ... heart disease. If Your Blood Cholesterol Is Too High Too much cholesterol in your blood is called ...

  4. Insufficient duration of action of antihypertensive drugs mediates high blood pressure in the morning in hypertensive population: the Ohasama study.

    Science.gov (United States)

    Chonan, Kenichi; Hashimoto, Junichiro; Ohkubo, Takayoshi; Tsuji, Ichiro; Nagai, Kenichi; Kikuya, Masahiro; Hozawa, Atsushi; Matsubara, Mitsunobu; Suzuki, Michiko; Fujiwara, Tohru; Araki, Tsutomu; Satoh, Hiroshi; Hisamichi, Shigeru; Imai, Yutaka

    2002-05-01

    Blood pressure (BP) usually peaks in the morning. The circadian variation of the onset of cardiovascular disease mimics this circadian BP variation. To examine the determinants of the BP difference between the self-recorded BP in the morning (home BP) and daytime average ambulatory BP a cross sectional study was done in the general population of Ohasama, Japan. 1207 subjects > or = 20 years measured both home (more than 14 times) and ambulatory BPs (326 treated for hypertension and 881 untreated subjects), The prevalence of subjects with the systolic BP difference (home BP in the morning - daytime ambulatory BP) of > or = 10 mmHg (high morning BP) was 5.6% in untreated normotensives, 2.9% in untreated hypertensives, and 25.8% in treated hypertensives. This trend was also observed for diastolic pressure. Multiple regression analysis demonstrated that age, male sex, and use of antihypertensive drugs were positively associated and day-night difference of BP was negatively associated with the high morning BP, respectively. These results suggest an insufficient duration of antihypertensive action of widely used antihypertensive drugs in Japan from the 1980s to 1990s. The amplitude of the day-night difference of ambulatory BP in subjects with a high morning BP was lower (non-dipping) than that without high morning BP. The high morning BP is not necessarily accompanied by hypertension but might be mediated, at least in part, by an insufficient duration of action of antihypertensive drugs. The high morning BP accompanies so-called non-dipper pattern of circadian BP variation. An insufficient duration of action of drugs may partly mediate non-dipping in subjects with antihypertensive medication.

  5. High Blood Pressure

    Science.gov (United States)

    ... 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 ...

  6. 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 ...

  7. High Blood Cholesterol

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Cholesterol? To understand high blood cholesterol (ko-LES-ter- ... cholesterol from your body. What Is High Blood Cholesterol? High blood cholesterol is a condition in which ...

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

    Science.gov (United States)

    ... workout into three 10-minute sessions of aerobic exercise and get the same benefit as one 30-minute session. Also, if you ... Reports. 2014;13:233. Pal S, et al. Potential benefits of exercise on blood pressure and vascular function. Journal of ...

  9. Hypertension (High Blood Pressure)

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Hypertension (High Blood Pressure) KidsHealth > For Teens > Hypertension (High Blood Pressure) A ... rest temperature diet emotions posture medicines Why Is High Blood Pressure Bad? High blood pressure means a person's heart ...

  10. High Blood Pressure: Medicines to Help You

    Science.gov (United States)

    ... names are given for the drugs in each group.Find your drug. Then read some basic information about your kind of drug. Types of High Blood Pressure Medicines ACE Inhibitors Beta Blockers Calcium Channel Blockers ...

  11. Treating High Blood Pressure

    Science.gov (United States)

    About High Blood Pressure Many people in the United States die from high blood pressure. This condition usually does not cause symptoms. Most ... until it is too late. A person has high blood pressure when the blood pushes against Visit your doctor ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High blood glucose happens when the body has too little insulin or when the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  15. A high aspect ratio SU-8 fabrication technique for hollow microneedles for transdermal drug delivery and blood extraction

    Science.gov (United States)

    Chaudhri, Buddhadev Paul; Ceyssens, Frederik; De Moor, Piet; Van Hoof, Chris; Puers, Robert

    2010-06-01

    Protein drugs, e.g. hormonal drugs, cannot be delivered orally to a patient as they get digested in the gastro-intestinal (GI) tract. Thus, it is imperative that these kinds of drugs are delivered transdermally through the skin. To provide for real-time feedback as well as to test independently for various substances in the blood, we also need a blood sampling system. Microneedles can perform both these functions. Further, microneedles made of silicon or metal have the risk of breaking inside the skin thereby leading to complications. SU-8, being approved of as being biocompatible by the Food and Drug Agency (FDA) of the United States, is an attractive alternative because firstly it is a polymer material, thereby reducing the chances of breakages inside the skin, and secondly it is a negative photoresist, thereby leading to ease of fabrication. Thus, here we present very tall (around 1600 µm) SU-8 polymer-based hollow microneedles fabricated by a simple and repeatable process, which are a very good candidate for transdermal drug delivery as well as blood extraction. The paper elaborates on the details that allow the fabrication of such extreme aspect ratios (>100).

  16. Drug-induced low blood sugar

    Science.gov (United States)

    Drug-induced low blood sugar is low blood glucose that results from taking medicine. ... Low blood sugar (hypoglycemia) is common in people with diabetes who are taking insulin or other medicines to control their diabetes. ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ... Islanders American Indian/Alaska Native Programs Older Adults Family Link Diabetes EXPO Upcoming Diabetes EXPOs EXPO Volunteer ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics Home Symptoms Diagnosis America's Diabetes Challenge Type ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ... Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get Started Safely Get And ...

  20. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To ... Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & ...

  1. High blood pressure medications

    Science.gov (United States)

    ... 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, ...

  2. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ... Options for the Uninsured Medicare Medicaid & CHIP For Parents & Kids Safe at School Everyday Life Children and ...

  3. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... Clinical Practice Guidelines Patient Education Materials Scientific Sessions Journals for Professionals Professional Books Patient Access to Research ...

  4. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To ... Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get Started Safely Get And ...

  5. High blood cholesterol levels

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000403.htm High blood cholesterol levels To use the sharing features ... stroke, and other problems. The medical term for high blood cholesterol is lipid disorder, hyperlipidemia, or hypercholesterolemia. ...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... an Employer Options for the Uninsured Medicare Medicaid & CHIP For Parents & Kids Safe at School Everyday Life ... blood sugar). High blood glucose happens when the body has too little insulin or when the body ...

  7. Determination of anxiolytic veterinary drugs from biological fertilizer blood meal using liquid chromatography high-resolution mass spectrometry.

    Science.gov (United States)

    Choi, Jeong-Heui; Lamshöft, Marc; Zühlke, Sebastian; Park, Jong-Hyouk; Rahman, Md Musfiqur; Abd El-Aty, A M; Spiteller, Michael; Shim, Jae-Han

    2014-06-01

    A liquid environment-friendly agricultural material originating from animal blood, blood meal, was employed to detect anxiolytic veterinary drugs using a combination of liquid-liquid extraction (LLE) and positive electrospray ionization Orbitrap mass spectrometry. Every positive ion of the analytes was consistent with [M+H](+) , and the accurate mass analysis and mass spectral filtration with a 2-ppm mass tolerance window were applied to identify and quantitate the analytes and metabolites. The developed LLE method was validated with the lowest calibrated level, linearity (r(2) ), recovery, repeatability and the within-laboratory reproducibility, which were in the ranges of 0.3-1 µg/L, 0.9963-0.9995, 48.3-117.5%, 1.1-12.6% and 2.3-15.7%, respectively. The LLE method was compared with a solid-phase extraction (SPE) method; however, its recoveries were liquid blood meal samples, and none of the targeted compounds were observed.

  8. High blood pressure - infants

    Science.gov (United States)

    ... Certain tumors Inherited conditions (problems that run in families) Thyroid problems Blood pressure rises as the baby grows. The average blood ... vomiting constantly Prevention Some causes of high blood pressure run in families. Talk to your provider before you get pregnant ...

  9. High Blood Pressure Facts

    Science.gov (United States)

    ... More black women than men have high blood pressure. 2 Race of Ethnic Group Men (%) Women (%) African Americans 43.0 45.7 Mexican Americans 27.8 28.9 Whites 33.9 31.3 All 34.1 32.7 Top of Page Why Blood Pressure Matters View this graphic snapshot of blood pressure ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics Home Symptoms Diagnosis America's Diabetes Challenge Type 1 Type 2 Facts About Type 2 Enroll in ...

  11. HBV/HCV co-infection is associated with a high level of HCV spontaneous clearance among drug users and blood donors in China.

    Science.gov (United States)

    Xiong, H; Rong, X; Wang, M; Xu, R; Huang, K; Liao, Q; Huang, J; Chen, J; Li, C; Tang, X; Shan, Z; Zhang, M; Nelson, K; Fu, Y

    2016-12-12

    Understanding the biology of spontaneous clearance of hepatitis C virus (HCV) infection could lead to improved strategies to prevent the sequelae associated with chronic HCV infection. Chronic infections with hepatitis virus are very common in China, but the factors associated with spontaneous clearance of HCV have not been adequately studied. We evaluated the spontaneous clearance of HCV among 1918 drug users and 1526 HCV-seropositive blood donors in Guangzhou, China. Among participants who were co-infected with hepatitis B virus (HBV), 41.38% of drug users and 39.47% of blood donors had cleared their HCV infection without antiviral therapy compared to 9.41% of drug users and 16.73% of blood donors who were mono-infected with a single virus (PHCV infection was significantly greater in the co-infected subjects whose serum HBV DNA was greater than 2000IU/mL than those with lower levels. A multiple logistic regression analysis found female gender, IL28B rs8099917 TT genotype, HBV co-infection and blood donors (vs drug users) associated with increased spontaneous clearance of HCV infection. Although acute HCV infections are common in China, the incidence of chronic HCV may be reduced among the high prevalence of chronic HBV and IL28B genotypes associated with spontaneous clearance of HCV in Chinese populations.

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    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 ...

  13. Preventing High Blood Pressure

    Science.gov (United States)

    ... Web Sites Division for Heart Disease and Stroke Prevention Stroke Heart Disease Cholesterol Salt Million Hearts® WISEWOMAN Preventing High Blood Pressure: Healthy Living Habits Recommend on Facebook Tweet Share Compartir By living a healthy lifestyle, you can help keep your blood pressure in ...

  14. High blood pressure - children

    Science.gov (United States)

    ... number is the diastolic pressure. This measures the pressure in the arteries when the heart is at rest. Blood pressure ... Medical Professional Call your child's provider if home monitoring shows that your child's blood pressure is still high. Prevention Your child's provider will ...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... to Give Close Are You at Risk? Home Prevention Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity ...

  16. High Blood Pressure (Hypertension)

    Science.gov (United States)

    ... already been diagnosed with high blood pressure. Try yoga and meditation. Yoga and meditation not only can strengthen your body ... Accessed Sept. 21, 2015. Hu B, et al. Effects of psychological stress on hypertension in middle-aged ...

  17. Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots.

    NARCIS (Netherlands)

    Meesters, R.J.; Kampen, J.J. van; Reedijk, M.L.; Scheuer, R.D.; Dekker, L.J.; Burger, D.M.; Hartwig, N.G.; Osterhaus, A.D.; Luider, T.M.; Gruters, R.A.

    2010-01-01

    Kaletra (Abott Laboratories) is a co-formulated medication used in the treatment of HIV-1-infected children, and it contains the two antiretroviral protease inhibitor drugs lopinavir and ritonavir. We validated two new ultrafast and high-throughput mass spectrometric assays to be used for therapeuti

  18. Prevention of High Blood Pressure

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Prevention of High Blood Pressure Healthy lifestyle habits, proper use of medicines, and ... prevent high blood pressure or its complications. Preventing High Blood Pressure Onset Healthy lifestyle habits can help prevent high ...

  19. High Blood Pressure Fact Sheet

    Science.gov (United States)

    ... High Blood Pressure Salt Cholesterol Million Hearts® WISEWOMAN High Blood Pressure Fact Sheet Language: English Español (Spanish) Recommend on ... time. High blood pressure is also called hypertension. High Blood Pressure in the United States Having high blood pressure ...

  20. Hyperglycemia (High Blood Glucose)

    Medline Plus

    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 ...

  1. Blood pressure response to out-patient drug treatment of ...

    African Journals Online (AJOL)

    Blood pressure response to out-patient drug treatment of hypertension in 1973 ... as the increased number of drugs did not decrease blood pressure significantly. Keywords: Hypertension, Antihypertensive drugs, Blood pressure treatment, ...

  2. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... the NHLBI on Twitter. Diagnosis of High Blood Pressure For most patients, health care providers diagnose high ... 140/90 mmHg or above. Confirming High Blood Pressure A blood pressure test is easy and painless ...

  3. 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 ...

  4. Hypertension (High Blood Pressure)

    Science.gov (United States)

    ... over the years led to verification of the important role of high blood pressure—especially in concert with ... is specific for that person will be an important key to improving prevention, ... an international team of investigators, funded in part by the NIH, ...

  5. What Causes High Blood Pressure?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Causes of High Blood Pressure Changes, either from genes or the environment, in ... and blood vessel structure and function. Biology and High Blood Pressure Researchers continue to study how various changes in ...

  6. High Red Blood Cell Count

    Science.gov (United States)

    Symptoms High red blood cell count By Mayo Clinic Staff A high red blood cell count is an increase in oxygen-carrying cells in your bloodstream. Red blood cells transport oxygen from your lungs to tissues throughout ...

  7. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Blood Pressure » Diagnosis of High Blood Pressure Explore High Blood Pressure What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical ...

  8. Living with High Blood Pressure

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Living With High Blood Pressure If you have high blood pressure, the best thing to do is to talk ... help you track your blood pressure. Pregnancy Planning High blood pressure can cause problems for mother and baby. High ...

  9. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... High Blood Pressure Explore High Blood Pressure What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living ... Confirming High Blood Pressure A blood pressure test is easy and painless and can be done in ...

  10. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... providers diagnose high blood pressure when blood pressure readings are consistently 140/90 mmHg or above. Confirming ... minutes before the test. To track blood pressure readings over a period of time, the health care ...

  11. Therapeutic drug monitoring for sirolimus in whole blood of organ transplants by high-performance liquid chromatography with ultraviolet detection.

    Science.gov (United States)

    Campanero, Miguel Angel; Cardenas, Ernesto; Sádaba, Belén; García-Quetglas, Emilio; Muñoz-Juarez, Maria Jose; Gil-Aldea, Isabel; Pazo, David; Azanza, Jose Ramón; Honorato, Jesús

    2004-03-26

    We developed and validated an accurate, sensitive, precise and rapid HPLC method with UV detection for the determination of sirolimus in blood samples from renal, cardiac and hepatic transplants. This method overcomes most of the problems related to previously published assays using a narrow-bore column with base deactivated C18 reversed phase. Whole blood samples were purified by a combination of a precipitating blood matrix with zinc sulphate and a single step liquid-liquid extraction with acetone and 1-chlorobutane. Calibration curves (range 2.5-150 ng/ml), were linear with coefficients of correlation better than 0.996. The relative standard deviation was determined to be less than 8%. The present method has also been validated by a reference laboratory (St. George's Hospital Medical School, London, UK). More of 300 clinical samples have been analysed with this method.

  12. Phenotyping drug polypharmacology via eicosanoid profiling of blood[S

    Science.gov (United States)

    Song, Jiao; Liu, Xuejun; Rao, Tadimeti S.; Chang, Leon; Meehan, Michael J.; Blevitt, Jonathan M.; Wu, Jiejun; Dorrestein, Pieter C.; Milla, Marcos E.

    2015-01-01

    It is widely accepted that small-molecule drugs, despite their selectivity at primary targets, exert pharmacological effects (and safety liabilities) through a multiplicity of pathways. As such, it has proved extremely difficult to experimentally assess polypharmacology in an agnostic fashion. Profiling of metabolites produced as part of physiological responses to pharmacological stimuli provides a unique opportunity to explore drug pharmacology. A total of 122 eicosanoid lipids in human whole blood were monitored from 10 different donors upon stimulation with several inducers of immunological responses and treatment with modulators of prostaglandin (PG) and leukotriene biosynthesis, including clinical and investigational molecules. Such analysis revealed differentiation between drugs nominally targeting different eicosanoid biosynthetic enzymes, or even those designed to target the same enzyme. Profiled agents, some of them marketed products, affect eicosanoid biosynthesis in ways that cannot be predicted from information on their intended targets. As an example, we used this platform to discriminate drugs based on their ability to silence PG biosynthesis in response to bacterial lipopolysaccharide, resulting in differential pharmacological activity in an in vivo model of endotoxemia. Some of the observed effects are subject to variability among individuals, indicating a potential application of this methodology to the patient stratification, based on their responses to benchmark drugs and experimental compounds read on the eicosanome via a simple blood test. PMID:26022804

  13. A Nutritional Strategy for the Treatment of High Blood Pressure.

    Science.gov (United States)

    Podell, Richard N.

    1984-01-01

    Some physicians wonder if high blood pressure can be controlled without the use of drugs and their potential side effects. Current findings concerning nutrition and high blood pressure are presented. (RM)

  14. Stroke and High Blood Pressure

    Science.gov (United States)

    ... More How High Blood Pressure Can Lead to Stroke Updated:Dec 2,2016 Stroke and high blood ... Changes That Matter • Find Tools & Resources Show Your Stroke Support! Show your stroke support with our new ...

  15. High Blood Pressure Increasing Worldwide

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162977.html High Blood Pressure Increasing Worldwide And health risks may appear even ... of people around the world with elevated or high blood pressure increases, so do the number of deaths linked ...

  16. Medications for High Blood Pressure

    Science.gov (United States)

    ... 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 ...

  17. Influence of smoking cessation drugs on blood pressure and heart rate in patients with cardiovascular disease or high risk score: real life setting.

    Science.gov (United States)

    Silva, André Pacheco; Scholz, Jaqueline; Abe, Tania Ogawa; Pinheiro, Gabriela Gouveia; Gaya, Patricia Viviane; Pereira, Alexandre Costa; Santos, Paulo Caleb Junior Lima

    2016-01-05

    Smoking is the most important reversible cardiovascular risk factor. It is well established that quitting smoking reduces coronary events. However, on several occasions, the cardiovascular safety of smoking cessation drugs has been questioned. Our goal is to evaluate the effects of smoking cessation drugs on blood pressure and heart rate in patients from a smoking cessation service in a cardiology hospital. We examined the PAF database (Smoking Cessation Assistance Program database) between January 2008 and March 2014. We analyzed data from 900 patients who were compliant with the treatment (50.5% male, average age 53 ± 17 years). The most frequent clinical diagnoses were coronary artery disease (25.2%), hypertension (57.2%), and diabetes (13.4%). Blood pressure, heart rate, and carbon monoxide (CO) concentration in exhaled air were analyzed at consecutive visits during the first 45 days of treatment (mean visits - 3). Analysis of repeated measures was used for the statistical analysis (p blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). Significant reductions in CO concentrations occurred in all smoking cessation drug groups. Smoking cessation drugs used in monotherapy or in combined regimens did not influence systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) in this group of patients during the observation period.

  18. High Blood Pressure

    Science.gov (United States)

    ... mmHg People read "118 over 76" millimeters of mercury. Normal Blood Pressure Normal blood pressure for adults ... health. Share your story with other women on Facebook . The Heart Truth campaign offers a variety of ...

  19. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... page from the NHLBI on Twitter. Diagnosis of High Blood Pressure For most patients, health care providers diagnose high ... are consistently 140/90 mmHg or above. Confirming High Blood Pressure A blood pressure test is easy and painless ...

  20. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... page from the NHLBI on Twitter. Diagnosis of High Blood Pressure For most patients, health care providers diagnose high ... are consistently 140/90 mmHg or above. Confirming High Blood Pressure A blood pressure test is easy and painless ...

  1. Controlling your high blood pressure

    Science.gov (United States)

    ... 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 ...

  2. Diagnosis of High Blood Pressure

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Diagnosis of High Blood Pressure For most patients, health care providers diagnose high ... are consistently 140/90 mmHg or above. Confirming High Blood Pressure A blood pressure test is easy and painless ...

  3. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... and Obesity Smoking and Your Heart Stroke Send a link to NHLBI to someone by E-MAIL | ... 90 mmHg or above. Confirming High Blood Pressure A blood pressure test is easy and painless and ...

  4. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... of Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & ... blood pressure is due to other conditions or medicines or if you have primary high blood pressure. ...

  5. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... to keep a written log of all your results. Whenever you have an appointment with the health ... appointments to diagnose high blood pressure. Using the results of your blood pressure test, your health care ...

  6. High Blood Pressure in Pregnancy

    Science.gov (United States)

    ... 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 ...

  7. What Causes High Blood Cholesterol?

    Science.gov (United States)

    ... the NHLBI on Twitter. What Causes High Blood Cholesterol? Many factors can affect the cholesterol levels in your blood. You can control some ... but not others. Factors You Can Control Diet Cholesterol is found in foods that come from animal ...

  8. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... ask for your readings. Blood Pressure Severity and Type Your health care provider usually takes 2–3 ... any other location. Health care providers diagnose this type of high blood pressure by reviewing readings in ...

  9. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... ask for your readings. Blood Pressure Severity and Type Your health care provider usually takes 2–3 ... any other location. Health care providers diagnose this type of high blood pressure by reviewing readings in ...

  10. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... above. Confirming High Blood Pressure A blood pressure test is easy and painless and can be done ... provider’s office or clinic. To prepare for the test: Don’t drink coffee or smoke cigarettes for ...

  11. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... readings. Blood Pressure Severity and Type Your health care provider usually takes 2–3 readings at several medical appointments to diagnose high blood pressure. Using the ...

  12. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... and Obesity Smoking and Your Heart Stroke Send a link to NHLBI to someone by E-MAIL | ... 90 mmHg or above. Confirming High Blood Pressure A blood pressure test is easy and painless and ...

  13. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... above. Confirming High Blood Pressure A blood pressure test is easy and painless and can be done ... provider’s office or clinic. To prepare for the test: Don’t drink coffee or smoke cigarettes for ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... events, such as eating breakfast, take on exaggerated importance. It's a world where a person needs a ... Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood Glucose A1C and eAG Hypoglycemia ( ...

  15. High Blood Cholesterol: What You Need to Know

    Science.gov (United States)

    ... Audiences Contact The Health Information Center High Blood Cholesterol: What You Need To Know Table of Contents ... Lifestyle Changes (TLC) Drug Treatment Resources Why Is Cholesterol Important? Your blood cholesterol level has a lot ...

  16. High Blood Pressure

    Science.gov (United States)

    ... giving Gift and estate planning Circle of Champions Corporate sponsorship Join us at an event The Hope ... blood pressure is the #2 cause of kidney failure. It accounts for about one-fourth of all ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... how to handle this condition. Medical IDs Many people with diabetes, particularly those who use insulin, should ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... Type 2 Diabetes Program Food & Fitness Food Recipes Planning Meals What Can I Eat Weight Loss Fitness ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... also help. Work with your dietitian to make changes in your meal plan. If exercise and changes ...

  20. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... Sleeve Custom jerseys for your Tour de Cure team benefits the cause. Ask the Experts: Learn to ...

  1. 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 ... Diabetes Pro: Professional Resources Online We Support Your Doctor Clinical Practice Guidelines Patient Education Materials Scientific Sessions ...

  2. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy ...

  3. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  4. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  5. High Blood Pressure (Hypertension)

    Science.gov (United States)

    ... possible. Practice healthy coping techniques, such as muscle relaxation, deep breathing or meditation. Getting regular physical activity ... you monitor your blood pressure at home. Practice relaxation or slow, deep breathing. Practice taking deep, slow ...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C ... your doctor may change the amount of your medication or insulin or possibly the timing of when ...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... How Grant Money is Divided Funding the Next Generation of Brilliant Researchers Our Research Foundation Diabetes Pro: ... they build up in your blood, which can lead to ketoacidosis. Ketoacidosis is life-threatening and needs ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... blood glucose early will help you avoid problems associated with hyperglycemia. How Do I Treat Hyperglycemia? You ... Advocacy Take Action Advocacy Priorities News & Events The Cost of Diabetes Advocate Toolkit Call to Congress Research & ...

  9. Concentrations of alprazolam in blood from impaired drivers and forensic autopsies were not much different but showed a high prevalence of co-ingested illicit drugs.

    Science.gov (United States)

    Jones, Alan Wayne; Holmgren, Anita

    2013-03-01

    Alprazolam is a benzodiazepine anxiolytic widely prescribed for treatment of panic-disorder and social phobias, although this medication is also subject to abuse. In this paper, the concentrations of alprazolam in venous blood samples from impaired drivers were compared with femoral blood samples from forensic autopsies classified as intoxication or other causes of death (e.g. natural, trauma). After liquid-liquid extraction (n-butyl acetate) alprazolam was determined in blood by capillary gas chromatography with a nitrogen-phosphorous detector. The mean (median) and range of alprazolam concentrations in blood from impaired drivers (n = 773) were 0.08 mg/L (0.05 mg/L) and 0.02-3.9 mg/L, respectively. Many traffic offenders had co-ingested ethanol (13%), amphetamine (46%), cannabis (32%), or heroin (14%), as well as other drugs. In deaths attributed to drug intoxication, the mean (median) and range of alprazolam concentrations in blood (n = 438) were 0.10 mg/L (0.06 mg/L) and 0.02-1.6 mg/L, respectively, which were not much different from other causes of death (n = 278); 0.08 mg/L (0.05 mg/L) and 0.02-0.9 mg/L. Median concentrations of alprazolam in blood from living and deceased persons did not seem to depend on the number of co-ingested substances. The result of this pharmacoepidemiological study suggests that alprazolam is a fairly innocent drug when used as monotherapy, but toxicity problems arise when co-ingested with illicit drugs and/or psychoactive medication.

  10. High Blood Pressure and Women

    Science.gov (United States)

    ... blood pressure during a previous pregnancy, have a family history of high blood pressure or mild kidney disease. The combination of birth ... Print (PDF) | Online How to Measure Your Blood Pressure (PDF) Questions To Ask ... FREE digital-only, quarterly magazine for patients, families, and caregivers, which focuses on the prevention and ...

  11. High throughput drug profiling

    OpenAIRE

    Entzeroth, Michael; Chapelain, Béatrice; Guilbert, Jacques; Hamon, Valérie

    2000-01-01

    High throughput screening has significantly contributed to advances in drug discovery. The great increase in the number of samples screened has been accompanied by increases in costs and in the data required for the investigated compounds. High throughput profiling addresses the issues of compound selectivity and specificity. It combines conventional screening with data mining technologies to give a full set of data, enabling development candidates to be more fully compared.

  12. What Is High Blood Pressure?

    Science.gov (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More What is High Blood Pressure? Updated:Oct 31,2016 First, let’s define high ... resources . This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

  13. High Blood Calcium (Hypercalcemia)

    Science.gov (United States)

    ... as well as kidney function and levels of calcium in your urine. Your provider may do other tests to further assess your condition, such as checking your blood levels of phosphorus (a mineral). Imaging studies also may be helpful, such as bone ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... work with your doctor to find the safest way for you to lower your blood glucose level. Cutting down on the amount of food you eat might also help. Work with your dietitian to make changes in your meal plan. If exercise and changes ...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers Health Insurance Health Insurance ...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Care > Blood Glucose Testing Share: Print Page Text Size: A A A Listen En Español Hyperglycemia ( ... Advocacy Take Action Advocacy Priorities News & Events The Cost of Diabetes Advocate ... Resources Shop Diabetes » Close nonprofit software

  17. 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.

  18. Common High Blood Pressure Myths

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Common High Blood Pressure Myths Updated:Dec 9,2016 Knowing the facts ... health. This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

  19. High Blood Cholesterol Prevention

    Science.gov (United States)

    ... Million Hearts® WISEWOMAN Program Prevention and Management of High LDL Cholesterol: What You Can Do Recommend on ... like eating a healthy diet, can help prevent high cholesterol. High low-density lipoprotein (LDL) cholesterol increases ...

  20. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High ... excused. 86 million Americans have prediabetes. Take the test. Know where you stand. sticky en -- Chef Ronaldo's ...

  1. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High ... You at Risk? Diagnosis Lower Your Risk Risk Test Alert Day Prediabetes My Health Advisor Tools to ...

  2. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Planning, & Legislative Advisory Committees Jobs Contact Us FAQs Home » Health Information for the Public » Health Topics » High ... also may ask you to check readings at home or at other locations that have blood pressure ...

  3. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Explore High Blood Pressure What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Atherosclerosis DASH Eating Plan Overweight and Obesity Smoking and Your Heart ...

  4. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Health care providers diagnose this type of high blood pressure by reviewing readings in the office and readings taken anywhere else. ... The Heart Truth ® —a national heart disease awareness campaign for ...

  5. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... to check readings at home or at other locations that have blood pressure equipment and to keep ... office compared with readings taken in any other location. Health care providers diagnose this type of high ...

  6. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... provider usually takes 2–3 readings at several medical appointments to diagnose high blood pressure. Using the ... Researchers believe stress, which can occur during the medical appointment, causes white coat hypertension. Rate This Content: ...

  7. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs Contact Us FAQs Home » Health Information for the Public » Health Topics » High Blood Pressure » ...

  8. High Blood Pressure and Kidney Disease

    Science.gov (United States)

    ... Disease Mineral & Bone Disorder View All Content High Blood Pressure & Kidney Disease What is high blood pressure? Blood pressure is the force of blood ... million filtering units called nephrons. How does high blood pressure affect the kidneys? High blood pressure can ...

  9. Drug Beats Steroids for Controlling Blood Vessel Inflammation in Study

    Science.gov (United States)

    ... html Drug Beats Steroids for Controlling Blood Vessel Inflammation in Study With tocilizumab's approval, there's an alternative ... treating the most common form of blood vessel inflammation known as giant cell arteritis, a new study ...

  10. High Blood Pressure Prevention

    Science.gov (United States)

    ... or "no added salt." Look for the sodium content in milligrams and the Percent Daily Value. Aim for foods that are less than 5 percent of the Daily Value of sodium. Foods with 20 percent or more Daily Value of sodium are considered high. To learn more about reading nutrition labels, see ...

  11. When Blood Sugar Is Too High

    Science.gov (United States)

    ... Help Someone Who's Being Bullied? Volunteering 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 ...

  12. CHRONOBIOLOGY OF HIGH BLOOD PRESSURE

    Science.gov (United States)

    Cornélissen, G.; Halberg, F.; Bakken, E. E.; Wang, Z.; Tarquini, R.; Perfetto, F.; Laffi, G.; Maggioni, C.; Kumagai, Y.; Homolka, P.; Havelková, A.; Dušek, J.; Svačinová, H.; Siegelová, J.; Fišer, B.

    2008-01-01

    BIOCOS, the project aimed at studying BIOlogical systems in their COSmos, has obtained a great deal of expertise in the fields of blood pressure (BP) and heart rate (HR) monitoring and of marker rhythmometry for the purposes of screening, diagnosis, treatment, and prognosis. Prolonging the monitoring reduces the uncertainty in the estimation of circadian parameters; the current recommendation of BIOCOS requires monitoring for at least 7 days. The BIOCOS approach consists of a parametric and a non-parametric analysis of the data, in which the results from the individual subject are being compared with gender- and age-specified reference values in health. Chronobiological designs can offer important new information regarding the optimization of treatment by timing its administration as a function of circadian and other rhythms. New technological developments are needed to close the loop between the monitoring of blood pressure and the administration of antihypertensive drugs. PMID:19122770

  13. High blood sugar - self-care

    Science.gov (United States)

    ... High blood glucose - self care; Diabetes - high blood sugar ... Symptoms of high blood sugar can include: Being very thirsty or having a dry mouth Having blurry vision Having dry skin Feeling weak or tired ...

  14. Anxiety: A Cause of High Blood Pressure?

    Science.gov (United States)

    ... Conditions High blood pressure (hypertension) 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, ...

  15. High Blood Pressure Often Undiagnosed, Untreated

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162996.html High Blood Pressure Often Undiagnosed, Untreated Half of mobile clinic patients ... that's often referred to as a "silent killer" -- high blood pressure, a new Canadian study reveals. High blood pressure, ...

  16. 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.

  17. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... any other location. Health care providers diagnose this type of high blood pressure by reviewing readings in the office and readings taken anywhere else. Researchers believe stress, which can occur during the medical appointment, causes white coat hypertension. Rate This Content: NEXT >> Updated: ...

  18. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Explore High Blood Pressure What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Atherosclerosis DASH Eating Plan Overweight and Obesity Smoking and Your Heart Stroke Send a link ...

  19. High blood pressure and eye disease

    Science.gov (United States)

    ... 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 ...

  20. Phenotyping drug polypharmacology via eicosanoid profiling of blood[S

    OpenAIRE

    Song, Jiao; liu,xuejun; Rao, Tadimeti S; Chang, Leon; Meehan, Michael J; Blevitt, Jonathan M.; Wu, Jiejun; Dorrestein, Pieter C.; Milla, Marcos E.

    2015-01-01

    It is widely accepted that small-molecule drugs, despite their selectivity at primary targets, exert pharmacological effects (and safety liabilities) through a multiplicity of pathways. As such, it has proved extremely difficult to experimentally assess polypharmacology in an agnostic fashion. Profiling of metabolites produced as part of physiological responses to pharmacological stimuli provides a unique opportunity to explore drug pharmacology. A total of 122 eicosanoid lipids in human whol...

  1. Questions and Answers about High Blood Pressure

    Science.gov (United States)

    ... checked out by a doctor. Am I at risk for high blood pressure? Anyone can develop high blood pressure. But there are several factors that increase your risk: Being overweight or obese Not ... if I have high blood pressure? High blood pressure is often called "the silent ...

  2. High Blood Pressure (Hypertension) (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old High Blood Pressure (Hypertension) KidsHealth > For Parents > High Blood Pressure (Hypertension) A ... posture, and medications. continue Long-Term Effects of High Blood Pressure When someone has high blood pressure, the heart ...

  3. High Blood Pressure (Hypertension) (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old High Blood Pressure (Hypertension) KidsHealth > For Parents > High Blood Pressure (Hypertension) ... posture, and medications. continue Long-Term Effects of High Blood Pressure When someone has high blood pressure, the heart ...

  4. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... blood pressure test is easy and painless and can be done in a health care provider’s office ... severity of your blood pressure, he or she can order additional tests to determine if your blood ...

  5. 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...

  6. 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.

  7. Dragon's Blood incense: misbranded as a drug of abuse?

    Science.gov (United States)

    Ford, S L; Steiner, R R; Thiericke, R; Young, R; Soine, W H

    2001-01-01

    An unknown red substance was being sold and used with other drugs of abuse in Virginia (often being used in conjunction with marihuana). The red substance was identified as Dragon's Blood incense from Daemonorops draco. In bioassays, Dragon's Blood incense exhibited a low, but measurable cytotoxicity in in vitro cell lines. Dragon's Blood incense or Volatilized Dragon's Blood had no adverse effect on mouse motor performance based on the inclined screen and rotorod tests. delta(9)-Tetrahydrocannibinol (THC) produced a dose-related decline in mouse performance on the rotorod test. The combination of Dragon's Blood incense or Volatilized Dragon's Blood with delta(9)-THC did not contribute further to the impairment of the mice on the rotorod. This data suggests that the abuse potential for Dragon's Blood incense alone or in combination with marihuana is minimal.

  8. Managing Stress to Control High Blood Pressure

    Science.gov (United States)

    ... Aneurysm More Managing Stress to Control High Blood Pressure Updated:Jan 10,2017 The importance of stress ... content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

  9. Avoid the Consequences of High Blood Pressure

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More Avoid the Consequences of High Blood Pressure Infographic Updated:Oct 31,2016 View a downloadable version of this infographic High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

  10. 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 ...

  11. High Blood Pressure: Keep the Beat Recipes

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: High Blood Pressure Keep the Beat Recipes Past Issues / Fall 2011 ... 65 million American adults—one in three—with high blood pressure, you have probably heard the advice, "watch your ...

  12. High-performance liquid chromatographic determination of anti- hypertensive drugs on dried blood spots using a fluorescence detector--method development and validation.

    Science.gov (United States)

    Rao, R Nageswara; Bompelli, Sravan; Maurya, Pawan K

    2011-11-01

    A selective and sensitive high-performance liquid chromatography method with fluorescence detection for simultaneous determination of irbesartan, losartan and valsartan on dried blood spots (DBS) has been developed and validated. It involves solvent extraction of a punch of DBS followed by reversed-phase liquid chromatography on a Lichrospher(®) 100 RP-18e column. Fluorescence detection was performed at 259 and 385 nm as excitation and emission wavelengths, respectively. The detection limits of irbesartan, losartan and valsartan were 1.8, 3.6 and 1.8 ng/mL respectively. The mean recoveries of irbesartan, losartan and valsartan were 98.68, 98.42 and 97.81%, respectively. The mean inter-day and intra-day precisions of irbesartan, losartan and valsartan were 2.07 and 1.34%, 1.42 and 1.48%, and 3.20 and 2.15% respectively. The proposed method was simple and rapid. Design of experiments was used to evaluate the robustness of the method.

  13. Risk Factors for High Blood Pressure

    Science.gov (United States)

    ... Share this page from the NHLBI on Twitter. Risk Factors for High Blood Pressure Anyone can develop high blood pressure; however, age, ... Lifestyle Habits Unhealthy lifestyle habits can raise your risk for high blood pressure, and they include: Eating too much sodium or ...

  14. How Is High Blood Pressure Treated?

    Science.gov (United States)

    ... or focusing on something calm or peaceful Performing yoga or tai chi Meditating Medicines Blood pressure medicines work in different ways to stop or slow some of the body’s functions that cause high blood pressure. Medicines to lower ...

  15. [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.

  16. 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.

  17. 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.

  18. Ultra high performance liquid chromatographic-tandem mass spectrometric multi-analyte procedure for target screening and quantification in human blood plasma: validation and application for 31 neuroleptics, 28 benzodiazepines, and Z-drugs.

    Science.gov (United States)

    Remane, Daniela; Meyer, Markus R; Wissenbach, Dirk K; Maurer, Hans H

    2011-09-01

    For fast and reliable screening, identification, and quantification of as many analytes as possible, multi-analyte approaches are very useful in clinical and forensic toxicology. Using ultra high performance liquid chromatography-tandem mass spectrometry, such an approach has been developed for blood plasma analysis after simple liquid-liquid extraction. In the present paper, validation and application is described for 31 neuroleptics, 28 benzodiazepines, and Z-drugs (zaleplone, zolpidem, and zopiclone). The validation parameters included recovery, matrix effects, process efficiency, ion suppression/enhancement of co-eluting analytes, selectivity, crosstalk, accuracy and precision, stabilities, and limits of quantification and detection. The results showed that the approach was selective, sensitive, accurate, and precise for 24 neuroleptics and 21 benzodiazepines and Z-drugs. The remaining analytes were unstable and/or too low dosed. Cost- and time-saving one-point calibration was applicable only for half of the analytes. The applicability was successfully shown for most of the drugs by analyzing authentic plasma samples and external quality control samples.

  19. High blood pressure in women.

    Science.gov (United States)

    Calhoun, D A; Oparil, S

    1997-01-01

    There is a sexual dimorphism in blood pressure of humans and experimental animals: males tend to have higher blood pressure than females with functional ovaries, while ovariectomy or menopause tends to abolish the sexual dimorphism and cause females to develop a "male" pattern of blood pressure. Hypertensive male laboratory animals tend to have NaCl-sensitive blood pressure, while females are NaCl resistant unless their ovaries are removed, in which case NaCl sensitivity appears. The hormonal basis of NaCl sensitivity of blood pressure and of the sexual dimorphism of hypertension remains to be defined. Synthetic estrogens and progestins, as found in oral contraceptives, tend to elevate blood pressure, while naturally occurring estrogens lower it, or have no effect. Hypertension increases cardiovascular risk in women, as well as men, although the benefits of antihypertensive treatment have been more difficult to demonstrate in women. In the population of the United States, women are more aware of their hypertension, more likely to be treated medically, and more likely to have their blood pressure controlled.

  20. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs ... track blood pressure readings over a period of time, the health care provider may ask you to ...

  1. High Speed Blood and Transfusion Equipment

    Science.gov (United States)

    2013-10-14

    used to calculate percent hemolysis of red blood cells. Plasma Free Hemoglobin Assay - pRBCs samples were assayed for plasma free hemoglobin (PFH...resulting in high temperatures gradients that preludes blood hemolysis if fluid flow stops. • The solenoid valve has been replaced with a valve of a more...pRBCs to test efficacy. Both pre and post cartridge blood samples were evaluated to determine if any damage may have occurred to blood cells. The

  2. Nano carriers for drug transport across the blood-brain barrier.

    Science.gov (United States)

    Li, Xinming; Tsibouklis, John; Weng, Tingting; Zhang, Buning; Yin, Guoqiang; Feng, Guangzhu; Cui, Yingde; Savina, Irina N; Mikhalovska, Lyuba I; Sandeman, Susan R; Howel, Carol A; Mikhalovsky, Sergey V

    2017-01-01

    Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully

  3. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Technology Transfer Clinical Trials What Are Clinical Trials? Children & Clinical Studies NHLBI Trials Clinical Trial Websites News & ... are consistently higher than 120/80 mmHg. Your child’s blood pressure numbers are outside average numbers for ...

  4. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... Related Topics Atherosclerosis DASH Eating Plan Overweight and Obesity Smoking and Your Heart Stroke Send a link ... are consistently higher than 120/80 mmHg. Your child’s blood pressure numbers are outside average numbers for ...

  5. Phenotyping drug polypharmacology via eicosanoid profiling of blood.

    Science.gov (United States)

    Song, Jiao; Liu, Xuejun; Rao, Tadimeti S; Chang, Leon; Meehan, Michael J; Blevitt, Jonathan M; Wu, Jiejun; Dorrestein, Pieter C; Milla, Marcos E

    2015-08-01

    It is widely accepted that small-molecule drugs, despite their selectivity at primary targets, exert pharmacological effects (and safety liabilities) through a multiplicity of pathways. As such, it has proved extremely difficult to experimentally assess polypharmacology in an agnostic fashion. Profiling of metabolites produced as part of physiological responses to pharmacological stimuli provides a unique opportunity to explore drug pharmacology. A total of 122 eicosanoid lipids in human whole blood were monitored from 10 different donors upon stimulation with several inducers of immunological responses and treatment with modulators of prostaglandin (PG) and leukotriene biosynthesis, including clinical and investigational molecules. Such analysis revealed differentiation between drugs nominally targeting different eicosanoid biosynthetic enzymes, or even those designed to target the same enzyme. Profiled agents, some of them marketed products, affect eicosanoid biosynthesis in ways that cannot be predicted from information on their intended targets. As an example, we used this platform to discriminate drugs based on their ability to silence PG biosynthesis in response to bacterial lipopolysaccharide, resulting in differential pharmacological activity in an in vivo model of endotoxemia. Some of the observed effects are subject to variability among individuals, indicating a potential application of this methodology to the patient stratification, based on their responses to benchmark drugs and experimental compounds read on the eicosanome via a simple blood test.

  6. Nanoscale drug delivery systems and the blood-brain barrier.

    Science.gov (United States)

    Alyautdin, Renad; Khalin, Igor; Nafeeza, Mohd Ismail; Haron, Muhammad Huzaimi; Kuznetsov, Dmitry

    2014-01-01

    The protective properties of the blood-brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain's vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual's age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.

  7. "DRUG RESISTANCE PATTERN IN ISOLATED BACTERIA FROM BLOOD CULTURES"

    OpenAIRE

    A Sobhani; H. Shodjai S. Javanbakht

    2004-01-01

    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 pos...

  8. Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgrim, Oliver;

    2016-01-01

    a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles....... In vivo data validate that albumin endows the conjugate with a blood residence time similar to that of the protein and well exceeding that of the polymer. Therapeutic activity of the conjugates is validated using prodrugs of panobinostat, an HIV latency reversal agent, in which case the conjugates matched......Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...

  9. Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgram, Oliver

    2016-01-01

    Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...... a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles....... In vivo data validate that albumin endows the conjugate with a blood residence time similar to that of the protein and well exceeding that of the polymer. Therapeutic activity of the conjugates is validated using prodrugs of panobinostat, an HIV latency reversal agent, in which case the conjugates matched...

  10. Quantitative Analysis of Therapeutic Drugs in Dried Blood Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring

    Science.gov (United States)

    Manicke, Nicholas Edward; Abu-Rabie, Paul; Spooner, Neil; Ouyang, Zheng; Cooks, R. Graham

    2011-09-01

    A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry. The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation (RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample. We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique may be a viable option for therapeutic drug monitoring.

  11. High Blood Pressure May Hike Dementia Risk

    Science.gov (United States)

    ... fullstory_161398.html High Blood Pressure May Hike Dementia Risk New statement from American Heart Association warns ... in middle age, might open the door to dementia, the American Heart Association warns in a new ...

  12. Quantitative dynamic nuclear polarization-NMR on blood plasma for assays of drug metabolism.

    Science.gov (United States)

    Lerche, Mathilde H; Meier, Sebastian; Jensen, Pernille R; Hustvedt, Svein-Olaf; Karlsson, Magnus; Duus, Jens Ø; Ardenkjaer-Larsen, Jan H

    2011-01-01

    Analytical platforms for the fast detection, identification and quantification of circulating drugs with a narrow therapeutic range are vital in clinical pharmacology. As a result of low drug concentrations, analytical tools need to provide high sensitivity and specificity. Dynamic nuclear polarization-NMR (DNP-NMR) in the form of the hyperpolarization-dissolution method should afford the sensitivity and spectral resolution for the direct detection and quantification of numerous isotopically labeled circulating drugs and their metabolites in single liquid-state NMR transients. This study explores the capability of quantitative in vitro DNP-NMR to assay drug metabolites in blood plasma. The lower limit of detection for the anti-epileptic drug (13)C-carbamazepine and its pharmacologically active metabolite (13)C-carbamazepine-10,11-epoxide is 0.08 µg/mL in rabbit blood plasma analyzed by single-scan (13)C DNP-NMR. An internal standard is used for the accurate quantification of drug and metabolite. Comparison of quantitative DNP-NMR data with an established analytical method (liquid chromatography-mass spectrometry) yields a Pearson correlation coefficient r of 0.99. Notably, all DNP-NMR determinations were performed without analyte derivatization or sample purification other than plasma protein precipitation. Quantitative DNP-NMR is an emerging methodology which requires little sample preparation and yields quantitative data with high sensitivity for therapeutic drug monitoring.

  13. 75 FR 73107 - Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability

    Science.gov (United States)

    2010-11-29

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff... ``Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling.'' FDA is issuing this....regulations.gov . To receive ``Guidance for Industry and Food and Drug Administration Staff; Blood...

  14. 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

  15. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    Directory of Open Access Journals (Sweden)

    Ravi Kant Upadhyay

    2014-01-01

    Full Text Available Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

  16. Nasal Delivery of High Molecular Weight Drugs

    OpenAIRE

    Erdal Cevher; Yıldız Ozsoy; Sevgi Gungor

    2009-01-01

    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 particula...

  17. Delivery of antihuman African trypanosomiasis drugs across the blood-brain and blood-CSF barriers.

    Science.gov (United States)

    Sekhar, Gayathri N; Watson, Christopher P; Fidanboylu, Mehmet; Sanderson, Lisa; Thomas, Sarah A

    2014-01-01

    Human African trypanosomiasis (HAT or sleeping sickness) is a potentially fatal disease caused by the parasite, Trypanosoma brucei sp. The parasites are transmitted by the bite of insect vectors belonging to the genus Glossina (tsetse flies) and display a life cycle strategy that is equally spread between human and insect hosts. T.b. gambiense is found in western and central Africa whereas, T.b. rhodesiense is found in eastern and southern Africa. The disease has two clinical stages: a blood stage after the bite of an infected tsetse fly, followed by a central nervous system (CNS) stage where the parasite penetrates the brain; causing death if left untreated. The blood-brain barrier (BBB) makes the CNS stage difficult to treat because it prevents 98% of all known compounds from entering the brain, including some anti-HAT drugs. Those that do enter the brain are toxic compounds in their own right and have serious side effects. There are only a few drugs available to treat HAT and those that do are stage specific. This review summarizes the incidence, diagnosis, and treatment of HAT and provides a close examination of the BBB transport of anti-HAT drugs and an overview of the latest drugs in development.

  18. Lamotrigine in pregnancy - therapeutic drug monitoring in maternal blood, amniotic fluid, and cord blood.

    Science.gov (United States)

    Paulzen, Michael; Lammertz, Sarah E; Veselinovic, Tanja; Goecke, Tamme W; Hiemke, Christoph; Gründer, Gerhard

    2015-09-01

    This study is the first to measure and correlate lamotrigine concentrations in maternal blood, amniotic fluid, and umbilical cord blood and account for distribution of the drug between these three compartments. Concentrations of lamotrigine were measured in six mother-infant pairs at the time of delivery. Daily doses of lamotrigine ranged between 200 and 650 mg. Daily doses were correlated with maternal serum and umbilical cord blood concentrations, and serum levels were correlated with levels in amniotic fluid. Lamotrigine levels in serum correlated strongly with the lamotrigine levels in amniotic fluid (r=+0.986, Pamniotic fluid was in a range between 0.31 and 0.75 (mean 0.58, SD 0.17); the penetration ratio into the fetal circulation, calculated on the basis of umbilical cord blood levels, was found to be in a range between 0.48 and 1.27 (mean 0.81, SD 0.28). Lamotrigine concentrations in amniotic fluid provided evidence that maternally administered lamotrigine is accessible to the fetus in a manner not previously appreciated. Furthermore, the penetration ratio into umbilical cord blood calculated here is in line with the largest study carried out so far to explore transplacental transfer.

  19. Using improved serial blood sampling method of mice to study pharmacokinetics and drug-drug interaction.

    Science.gov (United States)

    Watanabe, Ayahisa; Watari, Ryosuke; Ogawa, Keiko; Shimizu, Ryosuke; Tanaka, Yukari; Takai, Nozomi; Nezasa, Ken-ichi; Yamaguchi, Yoshitaka

    2015-03-01

    In pharmacokinetic evaluation of mice, using serial sampling methods rather than a terminal blood sampling method could reduce the number of animals needed and lead to more reliable data by excluding individual differences. In addition, using serial sampling methods can be valuable for evaluation of the drug-drug interaction (DDI) potential of drug candidates. In this study, we established an improved method for serially sampling the blood from one mouse by only one incision of the lateral tail vein, and investigated whether our method could be adapted to pharmacokinetic and DDI studies. After intravenous and oral administration of ibuprofen and fexofenadine (BCS class II and III), the plasma concentration and pharmacokinetic parameters were evaluated by our method and a terminal blood sampling method, with the result that both methods gave comparable results (ibuprofen: 63.8 ± 4.0% and 64.4%, fexofenadine: 6.5 ± 0.7% and 7.9%, respectively, in bioavailability). In addition, our method could be adapted to DDI study for cytochrome P450 and organic anion transporting polypeptide inhibition. These results demonstrate that our method can be useful for pharmacokinetic evaluation from the perspective of reliable data acquisition as well as easy handling and low stress to mice and improve the quality of pharmacokinetic and DDI studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Too Many Americans Have High Blood Pressure, Doctors Warn

    Science.gov (United States)

    ... news/fullstory_163468.html Too Many Americans Have High Blood Pressure, Doctors Warn With February designated National Heart Month, ... physicians warns that too many Americans struggle with high blood pressure. High blood pressure is a major risk factor ...

  1. High Blood Pressure and Children: What Parents Need to Know

    Science.gov (United States)

    ... Lung, and Blood Institute Alternate Language URL Español High Blood Pressure and Children: What Parents Need to Know Page Content Children can have high blood pressure. Did you know that children could have high ...

  2. 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 drug interaction studies.

  3. Automated High Throughput Drug Target Crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Rupp, B

    2005-02-18

    The molecular structures of drug target proteins and receptors form the basis for 'rational' or structure guided drug design. The majority of target structures are experimentally determined by protein X-ray crystallography, which as evolved into a highly automated, high throughput drug discovery and screening tool. Process automation has accelerated tasks from parallel protein expression, fully automated crystallization, and rapid data collection to highly efficient structure determination methods. A thoroughly designed automation technology platform supported by a powerful informatics infrastructure forms the basis for optimal workflow implementation and the data mining and analysis tools to generate new leads from experimental protein drug target structures.

  4. "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.

  5. 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.

  6. Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis

    Science.gov (United States)

    Yu, Caitong; Zhou, Mengjiao; Zhang, Xiujuan; Wei, Weijia; Chen, Xianfeng; Zhang, Xiaohong

    2015-03-01

    Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in previous reports. These PEG stabilized DOX NPs exhibit good biocompatibility and stability, long blood circulation time, fast release in an acidic environment and high accumulation in tumors. Compared with free DOX, DOX NPs display a dramatically enhanced anticancer therapeutic efficacy in the inhibition of cell and tumor growth. Moreover, they can also be readily incorporated with other anticancer drugs for synergistic chemotherapy to overcome the drug resistance of cancers. The fluorescence properties of DOX also endow these NPs with imaging capabilities, thus making it a multifunctional system for diagnosis and treatment. This work demonstrates great potential of DOX NPs for cancer diagnosis, therapy and overcoming drug tolerance.Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in

  7. High Drug Prices Hurt Everyone

    OpenAIRE

    Halpenny, Genevieve M.

    2016-01-01

    Turing Pharmaceuticals raised the price of Daraprim 5,500%, illustrating how the absence of competition in the sale of low-volume, low-price drugs can lead to price gouging. For patented medicines, society allows supracompetitive pricing to incentivize innovation. However, Gilead���s decision to sell Sovaldi for $84,000 per course of treatment raised the question whether society must accept any price set by the patent holder. Unfortunately, these incidents illustrate a br...

  8. Yoga Called Good Medicine for High Blood Pressure

    Science.gov (United States)

    ... fullstory_162446.html Yoga Called Good Medicine for High Blood Pressure People who added this practice to a healthy ... elevated blood pressure] are likely to develop hypertension [high blood pressure] unless they improve their lifestyle," said study author ...

  9. Aging, High Altitude, and Blood Pressure: A Complex Relationship.

    Science.gov (United States)

    Parati, Gianfranco; Ochoa, Juan Eugenio; Torlasco, Camilla; Salvi, Paolo; Lombardi, Carolina; Bilo, Grzegorz

    2015-06-01

    Parati, Gianfranco, Juan Eugenio Ochoa, Camilla Torlasco, Paolo Salvi, Carolina Lombardi, and Grzegorz Bilo. Aging, high altitude, and blood pressure: A complex relationship. High Alt Biol Med 16:97-109, 2015.--Both aging and high altitude exposure may induce important changes in BP regulation, leading to significant increases in BP levels. By inducing atherosclerotic changes, stiffening of large arteries, renal dysfunction, and arterial baroreflex impairment, advancing age may induce progressive increases in systolic BP levels, promoting development and progression of arterial hypertension. It is also known, although mainly from studies in young or middle-aged subjects, that exposure to high altitude may influence different mechanisms involved in BP regulation (i.e., neural central and reflex control of sympathetic activity), leading to important increases in BP levels. The evidence is less clear, however, on whether and to what extent advancing age may influence the BP response to acute or chronic high altitude exposure. This is a question not only of scientific interest but also of practical relevance given the consistent number of elderly individuals who are exposed for short time periods (either for leisure or work) or live permanently at high altitude, in whom arterial hypertension is frequently observed. This article will review the evidence available on the relationship between aging and blood pressure levels at high altitude, the pathophysiological mechanisms behind this complex association, as well as some questions of practical interest regarding antihypertensive treatment in elderly subjects, and the effects of antihypertensive drugs on blood pressure response during high altitude exposure.

  10. Menopause and High Blood Pressure: What's the Connection?

    Science.gov (United States)

    ... blood pressure (hypertension) Is there a connection between menopause and high blood pressure? Answers from Shannon K. ... Tommaso, M.D. Blood pressure generally increases after menopause. Some doctors think this increase suggests that hormonal ...

  11. Transporter protein and drug-conjugated gold nanoparticles capable of bypassing the blood-brain barrier

    Science.gov (United States)

    Zhang, Yanhua; Walker, Janelle Buttry; Minic, Zeljka; Liu, Fangchao; Goshgarian, Harry; Mao, Guangzhao

    2016-05-01

    Drug delivery to the central nervous system (CNS) is challenging due to the inability of many drugs to cross the blood-brain barrier (BBB). Here, we show that wheat germ agglutinin horse radish peroxidase (WGA-HRP) chemically conjugated to gold nanoparticles (AuNPs) can be transported to the spinal cord and brainstem following intramuscular injection into the diaphragm of rats. We synthesized and determined the size and chemical composition of a three-part nanoconjugate consisting of WGA-HRP, AuNPs, and drugs for the treatment of diaphragm paralysis associated with high cervical spinal cord injury (SCI). Upon injection into the diaphragm muscle of rats, we show that the nanoconjugate is capable of delivering the drug at a much lower dose than the unconjugated drug injected systemically to effectively induce respiratory recovery in rats following SCI. This study not only demonstrates a promising strategy to deliver drugs to the CNS bypassing the BBB but also contributes a potential nanotherapy for the treatment of respiratory muscle paralysis resulted from cervical SCI.

  12. Impacts of Blood-Brain Barrier in Drug Delivery and Targeting of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi

    2012-02-01

    Full Text Available Introduction: Entry of blood circulating agents into the brain is highly selectively controlled by specific transport machineries at the blood brain barrier (BBB, whose excellent barrier restrictiveness make brain drug delivery and targeting very challenging. Methods: Essential information on BBB cellular microenvironment were reviewed and discussed towards impacts of BBB on brain drug delivery and targeting. Results: Brain capillary endothelial cells (BCECs form unique biological structure and architecture in association with astrocytes and pericytes, in which microenvironment the BCECs express restrictive tight junctional complexes that block the paracellular inward/outward traverse of biomolecules/compounds. These cells selectively/specifically control the transportation process through carrier and/or receptor mediated transport machineries that can also be exploited for the delivery of pharmaceuticals into the brain. Intelligent molecular therapies should be designed using such transport machineries for the efficient delivery of designated drugs into the brain. For better clinical outcomes, these smart pharmaceuticals should be engineered as seamless nanosystems to provide simultaneous imaging and therapy (multimodal theranostics. Conclusion: The exceptional functional presence of BBB selectively controls inward and outward transportation mechanisms, thus advanced smart multifunctional nanomedicines are needed for the effective brain drug delivery and targeting. Fully understanding the biofunctions of BBB appears to be a central step for engineering of intelligent seamless therapeutics consisting of homing device for targeting, imaging moiety for detecting, and stimuli responsive device for on-demand liberation of therapeutic agent.

  13. Dietary spermidine for lowering high blood pressure

    Science.gov (United States)

    Zimmermann, Andreas; Schroeder, Sabrina; Pendl, Tobias; Harger, Alexandra; Stekovic, Slaven; Schipke, Julia; Magnes, Christoph; Schmidt, Albrecht; Ruckenstuhl, Christoph; Dammbrueck, Christopher; Gross, Angelina S; Herbst, Viktoria; Carmona-Gutierrez, Didac; Pietrocola, Federico; Pieber, Thomas R; Sigrist, Stephan J; Linke, Wolfgang A; Mühlfeld, Christian; Sadoshima, Junichi; Dengjel, Joern; Kiechl, Stefan; Kroemer, Guido; Sedej, Simon; Madeo, Frank

    2017-01-01

    Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure. The high blood pressure-lowering effect likely results from improved global arginine bioavailability and protection from hypertension-associated renal damage. The polyamine spermidine is naturally present in human diets, though to a varying amount depending on food type and preparation. In humans, high dietary spermidine intake correlates with reduced blood pressure and decreased risk of cardiovascular disease and related death. Altogether, spermidine represents a cardio- and vascular-protective autophagy inducer that can be readily integrated in common diets. PMID:28118075

  14. 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...... Elut Certify columns. Screening was performed for 175 compounds (psychotropic, cardiovascular, designer, and abused drugs). The drugs were separated in 15 min using a UPLC system (Waters ACQUITY BEH C18, 1.7 µm, 2.1 mm × 100 mm column) coupled to an LCT Premier XE (Waters) instrument. Data were...... and effective screening method for basic drugs in whole blood....

  15. 78 FR 38994 - Implanted Blood Access Devices for Hemodialysis; Draft Guidance for Industry and Food and Drug...

    Science.gov (United States)

    2013-06-28

    ... HUMAN SERVICES Food and Drug Administration 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 and Drug Administration (FDA) is announcing...

  16. 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.

  17. [Uncontrolled factors of blood pressure in essential hypertension: from "patient's high blood pressure" to "hypertensive patient"].

    Science.gov (United States)

    Xiong, Xing-Jiang; Wang, Jie

    2014-04-01

    Hypertension is a significant medical and public health issue which puts an enormous burden on health care resources and the community. It is a chronic medical condition in which the systemic arterial blood pressure (BP) is elevated. Serious complications including cardiovascular and cerebrovascular diseases would be preventable if the rise in BP with age could be prevented or diminished. The majority of hypertensive patients require long-term treatment. Oral antihypertensive drugs, lifestyle modification including exercise and dietary modification are milestones for hypertension therapy. However, the control rate of hypertension hasn't reached the expected requirements currently. "Three lows" status quo, just low awareness, low treatment, and low control, are still the major problems confronting modern medicine. Recently, uncontrolled factors of blood pressure are widely concerned, which include insomnia, constipation, mood disorders, exogenous, etc. What's more, the control strategies of hypertension should not only pay close attention to "patient's high blood pressure", but also to "hypertensive patient". Therefore, the treatment of uncontrolled factors of blood pressure plays an important role in hypertensive therapy, which could be further research priorities.

  18. 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 in

  19. CDC Vital Signs: High Blood Pressure and Cholesterol

    Science.gov (United States)

    ... the MMWR Science Clips High Blood Pressure and Cholesterol Out of Control Recommend on Facebook Tweet Share ... cdc.gov/GISCVH2/ High Blood Pressure and High Cholesterol Among US Adults SOURCES: National Health and Nutrition ...

  20. High blood pressure in children and adolescents.

    Science.gov (United States)

    Riley, Margaret; Bluhm, Brian

    2012-04-01

    High blood pressure in children and adolescents is a growing health problem that is often overlooked by physicians. Normal blood pressure values for children and adolescents are based on age, sex, and height, and are available in standardized tables. Prehypertension is defined as a blood pressure in at least the 90th percentile, but less than the 95th percentile, for age, sex, and height, or a measurement of 120/80 mm Hg or greater. Hypertension is defined as blood pressure in the 95th percentile or greater. A secondary etiology of hypertension is much more likely in children than in adults, with renal parenchymal disease and renovascular disease being the most common. Overweight and obesity are strongly correlated with primary hypertension in children. A history and physical examination are needed for all children with newly diagnosed hypertension to help rule out underlying medical disorders. Children with hypertension should also be screened for other risk factors for cardiovascular disease, including diabetes mellitus and hyperlipidemia, and should be evaluated for target organ damage with a retinal examination and echocardiography. Hypertension in children is treated with lifestyle changes, including weight loss for those who are overweight or obese; a healthy, low-sodium diet; regular physical activity; and avoidance of tobacco and alcohol. Children with symptomatic hypertension, secondary hypertension, target organ damage, diabetes, or persistent hypertension despite nonpharmacologic measures should be treated with antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, and calcium channel blockers are safe, effective, and well tolerated in children.

  1. High-pressure processing for preservation of blood products

    NARCIS (Netherlands)

    Matser, A.M.; Ven, van der C.; Gouwerok, C.W.N.; Korte, de D.

    2005-01-01

    The possibilities of high pressure as a preservation method for human blood products were evaluated by examining the functional properties of blood fractions, after high-pressure processing at conditions which potentially inactivate micro-organisms and viruses. Blood platelets, red blood cells and

  2. 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.

  3. High-throughput screening in drug metabolism and pharmacokinetic support of drug discovery.

    Science.gov (United States)

    White, R E

    2000-01-01

    The application of rapid methods currently used for screening discovery drug candidates for metabolism and pharmacokinetic characteristics is discussed. General considerations are given for screening in this context, including the criteria for good screens, the use of counterscreens, the proper sequencing of screens, ambiguity in the interpretation of results, strategies for false positives and negatives, and the special difficulties encountered in drug metabolism and pharmacokinetic screening. Detailed descriptions of the present status of screening are provided for absorption potential, blood-brain barrier penetration, inhibition and induction of cytochrome P450, pharmacokinetics, biotransformation, and computer modeling. Although none of the systems currently employed for drug metabolism and pharmacokinetic screening can be considered truly high-throughput, several of them are rapid enough to be a practical part of the screening paradigm for modern, fast-moving discovery programs.

  4. Blood compatibility assessment of polymers used in drug eluting stent coatings.

    Science.gov (United States)

    Szott, Luisa Mayorga; Irvin, Colleen A; Trollsas, Mikael; Hossainy, Syed; Ratner, Buddy D

    2016-06-15

    Differences in thrombosis rates have been observed clinically between different drug eluting stents. Such differences have been attributed to numerous factors, including stent design, injury created by the catheter delivery system, coating application technologies, and the degree of thrombogenicity of the polymer. The relative contributions of these factors are generally unknown. This work focuses on understanding the thrombogenicity of the polymer by examining mechanistic interactions with proteins, human platelets, and human monocytes of a number of polymers used in drug eluting stent coatings, in vitro. The importance for blood interactions of adsorbed albumin and the retention of albumin was suggested by the data. Microscopic imaging and immunostaining enhanced the interpretation of results from the lactate dehydrogenase cell counting assay and provided insight into platelet interactions, total quantification, and morphometry. In particular, highly spread platelets may be surface-passivating, possibly inhibiting ongoing thrombotic events. In many of the assays used here, poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) showed a differentiated protein deposition pattern that may contribute to the explanation of the consistently thromboresistant blood-materials interaction for fluororpolymers cited in literature. These results are supportive of one of several possible factors contributing to the good thromboresistant clinical safety performance of PVDF-HFP coated drug eluting stents.

  5. Sleep Deprivation: A Cause of High Blood Pressure?

    Science.gov (United States)

    ... High blood pressure (hypertension) Is it true that sleep deprivation can cause high blood pressure? Answers from Sheldon ... Cirelli C, et al. Definition and consequences of sleep deprivation. http://www.uptodate.com/home. Accessed March 24, ...

  6. High Blood Pressure, Afib and Your Risk of Stroke

    Science.gov (United States)

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

  7. 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 ...

  8. High Blood Pressure Rates Have Doubled Worldwide Since 1975

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_162069.html High Blood Pressure Rates Have Doubled Worldwide Since 1975 Most of ... News) -- The number of people worldwide with high blood pressure has nearly doubled over the past 40 years, ...

  9. [Influence of Perftoran nanoemulsion on blood plasma concentrations of lipophilic drugs].

    Science.gov (United States)

    Pshenkina, N N

    2012-01-01

    The influence of perfluorocarbon blood substitute Perfloran on the plasma concentrations of bendazole, drotaverine, ketorolac and verapamil upon intravenous introduction after Perfloran infusion (5 ml/kg) has been investigated on rabbits. It has been found that the plasma concentrations of verapamil, drotaverine and bendazole (highly lipophilic drugs with log(P) = 4.5, 4.9 and 3.5, respectively) increased in the presence of Perfloran. The influence of Perfloran on the concentration of weakly lipophilic ketorolac was less significant. Perfloran effectively bound drotaverine, ketorolac and verapamil in vitro, whereas the binding of ketorolac by the emulsion particles was weak. Evidently, the infusion of hydrophobic nanoemulsion Perftoran elevates the sorption capacity of plasma and creates prerequisites for the redistribution drugs and favors increase in their concentrations.

  10. [High blood pressure and physical exercise].

    Science.gov (United States)

    Sosner, P; Gremeaux, V; Bosquet, L; Herpin, D

    2014-06-01

    High blood pressure is a frequent pathology with many cardiovascular complications. As highlighted in guidelines, the therapeutic management of hypertension relies on non-pharmacological measures, which are diet and regular physical activity, but both patients and physicians are reluctant to physical activity prescription. To acquire the conviction that physical activity is beneficial, necessary and possible, we can take into account some fundamental and clinical studies, as well as the feedback of our clinical practice. Physical inactivity is a major risk factor for cardiovascular morbidity and mortality, and hypertension contributes to increase this risk. Conversely, regular practice of physical activity decreases very significantly the risk by up to 60%. The acute blood pressure changes during exercise and post-exercise hypotension differs according to the dynamic component (endurance or aerobic and/or strength exercises), but the repetition of the sessions leads to the chronic hypotensive benefit of physical activity. Moreover, physical activity prescription must take into account the assessment of global cardiovascular risk, the control of the hypertension, and the opportunities and desires of the patient in order to promote good adherence and beneficial lifestyle change. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. What about African Americans and High Blood Pressure?

    Science.gov (United States)

    ... whites. • Heredity —A tendency to have high blood pressure runs in families. • Age — In general, the older you get, the greater your chance of developing high blood pressure. • Sex — Men tend to develop high blood pressure ...

  12. Let's Talk about High Blood Pressure and Stroke

    Science.gov (United States)

    ... stroke. How does high blood pressure increase stroke risk? High blood pressure is the single most important risk factor for ... vessel ruptures over time. Who is at higher risk for HBP? People with a family history of high blood pressure African-Americans People age 35 or older People ...

  13. 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

  14. Parallel artificial membrane permeability assay for blood-brain permeability determination of illicit drugs and synthetic analogues.

    Science.gov (United States)

    Clemons, Kristina; Kretsch, Amanda; Verbeck, Guido

    2014-09-01

    With the number of designer drugs on the streets rampantly on the rise, it's becoming more and more important to be able to rapidly characterize them in a biologically relevant way. Using a parallel artificial membrane permeability assay (PAMPA) to assess the blood brain barrier permeability has shown to be a high throughput way to compare new drugs with currently controlled substances via their effective permeability values. This combined with direct infusion electrospray ionization-mass spectrometry creates a rapid technique for characterization of new designer drugs. PAMPA has successfully determined the effective permeabilities of cocaine, methamphetamine, heroin, MDMA, and several tryptamine derivatives.

  15. The Effects Of Antiretroviral Drugs On The Absorbance Characteristics Of Blood Components

    Directory of Open Access Journals (Sweden)

    O. I. Ani

    2015-08-01

    Full Text Available Abstract The effects of antiretroviral drugs on the absorbance characteristics of blood components have been studied. The methodology involved the serial dilution of the five different antiretroviral drugs two HAARTFDC and three single drugs and the subsequent incubation with the blood samples collected from ten blood samples of HIV negative persons for the absorbance measurement using a digital Ultraviolet Visible MetaSpecAE1405031Pro Spectrophotometer. Reflectance Dielectric constant etc were derived from the absorbance data. For these drugs to be effective as HIV blockers they should be able to coat the surfaces of the lymphocytes. The question therefore arises as to what extent these drugs are able to coat the surfaces of the blood cells This was established using the extent of absorbance change. Models for coating effectiveness were formulated. The coating effectiveness was therefore calculated from peak absorbance values. Red blood cells were shown not to give reliable results. The results obtained however establish the fact that some coating of the drug had really occurred on the surfaces of the lymphocytes. The drug films were determined for lymphocytes and used to explain some observed clinical findings. The use of the findings of this work in drug design may be expected to yield good results.

  16. Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: a review.

    Science.gov (United States)

    Bicker, Joana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar

    2014-08-01

    During the research and development of new drugs directed at the central nervous system, there is a considerable attrition rate caused by their hampered access to the brain by the blood-brain barrier. Throughout the years, several in vitro models have been developed in an attempt to mimic critical functionalities of the blood-brain barrier and reliably predict the permeability of drug candidates. However, the current challenge lies in developing a model that retains fundamental blood-brain barrier characteristics and simultaneously remains compatible with the high throughput demands of pharmaceutical industries. This review firstly describes the roles of all elements of the neurovascular unit and their influence on drug brain penetration. In vitro models, including non-cell based and cell-based models, and in vivo models are herein presented, with a particular emphasis on their methodological aspects. Lastly, their contribution to the improvement of brain drug delivery strategies and drug transport across the blood-brain barrier is also discussed.

  17. Drug Transport by the Blood-Aqueous Humor Barrier of the Eye.

    Science.gov (United States)

    Lee, Jonghwa; Pelis, Ryan M

    2016-10-01

    The ocular barriers (cornea, blood-retinal barrier, and blood-aqueous humor barrier) make treating eye diseases with therapeutic drugs challenging. The tight capillary endothelium of the iris and the ciliary body epithelium form the blood-aqueous humor barrier. The iris and ciliary body (iris-ciliary body) express a variety of drug transporters in the ATP-binding cassette and solute carrier (SLC) families. ATP-binding cassette family drug transporters that are present in the iris-ciliary body include P-glycoprotein, breast cancer resistance protein, and several multidrug resistance-associated proteins. SLC family drug transporters that are present in the iris-ciliary body include organic anion transporters, organic anion transporting polypeptides, bile acid transporters (apical sodium-dependent bile salt transporter and sodium taurocholate cotransporter), organic cation transporters (novel organic cation transporter and multidrug and toxin extrusion transporter) and peptide transporters. Freshly dissected iris-ciliary body preparations actively accumulate a variety of substrates of SLC drug transporters that are expressed in the tissue. The ciliary body in vitro supports active transport in the aqueous humor-to-blood direction of several substrates of organic anion transporters and multidrug resistance-associated proteins, consistent with the subcellular localization of these transporters in the ciliary body epithelium. In vivo data suggest that drug transporters in the iris-ciliary body reduce the permeation of drugs in the direction of blood-to-aqueous humor, thereby reducing ocular drug bioavailability, and are also involved in active drug elimination from the aqueous humor. An understanding of the influence on pharmacokinetics of drug transporters in the blood-aqueous humor barrier should help improve drug delivery and efficacy in the eye. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Calcium Supplements: Do They Interfere with Blood Pressure Drugs?

    Science.gov (United States)

    ... some blood pressure medications. Interactions may occur with: Thiazide diuretics. Taking 1,500 milligrams (mg) or more of calcium with thiazide diuretics — such as chlorothiazide (Diuril), hydrochlorothiazide (Microzide, Oretic) and ...

  19. The Impact of Blood Rheology on Drug Transport in Stented Arteries: Steady Simulations

    Science.gov (United States)

    Vijayaratnam, Pujith R. S.; O’Brien, Caroline C.; Reizes, John A.; Barber, Tracie J.; Edelman, Elazer R.

    2015-01-01

    Background and Methods It is important to ensure that blood flow is modelled accurately in numerical studies of arteries featuring drug-eluting stents due to the significant proportion of drug transport from the stent into the arterial wall which is flow-mediated. Modelling blood is complicated, however, by variations in blood rheological behaviour between individuals, blood’s complex near-wall behaviour, and the large number of rheological models which have been proposed. In this study, a series of steady-state computational fluid dynamics analyses were performed in which the traditional Newtonian model was compared against a range of non-Newtonian models. The impact of these rheological models was elucidated through comparisons of haemodynamic flow details and drug transport behaviour at various blood flow rates. Results Recirculation lengths were found to reduce by as much as 24% with the inclusion of a non-Newtonian rheological model. Another model possessing the viscosity and density of blood plasma was also implemented to account for near-wall red blood cell losses and yielded recirculation length increases of up to 59%. However, the deviation from the average drug concentration in the tissue obtained with the Newtonian model was observed to be less than 5% in all cases except one. Despite the small sensitivity to the effects of viscosity variations, the spatial distribution of drug matter in the tissue was found to be significantly affected by rheological model selection. Conclusions/Significance These results may be used to guide blood rheological model selection in future numerical studies. The clinical significance of these results is that they convey that the magnitude of drug uptake in stent-based drug delivery is relatively insensitive to individual variations in blood rheology. Furthermore, the finding that flow separation regions formed downstream of the stent struts diminish drug uptake may be of interest to device designers. PMID:26066041

  20. Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugs.

    Science.gov (United States)

    Mossello, Enrico; Pieraccioli, Mariachiara; Nesti, Nicola; Bulgaresi, Matteo; Lorenzi, Chiara; Caleri, Veronica; Tonon, Elisabetta; Cavallini, M Chiara; Baroncini, Caterina; Di Bari, Mauro; Baldasseroni, Samuele; Cantini, Claudia; Biagini, Carlo A; Marchionni, Niccolò; Ungar, Andrea

    2015-04-01

    The prognostic role of high blood pressure and the aggressiveness of blood pressure lowering in dementia are not well characterized. To assess whether office blood pressure, ambulatory blood pressure monitoring, or the use of antihypertensive drugs (AHDs) predict the progression of cognitive decline in patients with overt dementia and mild cognitive impairment (MCI). Cohort study between June 1, 2009, and December 31, 2012, with a median 9-month follow-up of patients with dementia and MCI in 2 outpatient memory clinics. Cognitive decline, defined as a Mini-Mental State Examination (MMSE) score change between baseline and follow-up. We analyzed 172 patients, with a mean (SD) age of 79 (5) years and a mean (SD) MMSE score of 22.1 (4.4). Among them, 68.0% had dementia, 32.0% had MCI, and 69.8% were being treated with AHDs. Patients in the lowest tertile of daytime systolic blood pressure (SBP) (≤ 128 mm Hg) showed a greater MMSE score change (mean [SD], -2.8 [3.8]) compared with patients in the intermediate tertile (129-144 mm Hg) (mean [SD], -0.7 [2.5]; P = .002) and patients in the highest tertile (≥ 145 mm Hg) (mean [SD], -0.7 [3.7]; P = .003). The association was significant in the dementia and MCI subgroups only among patients treated with AHDs. In a multivariable model that included age, baseline MMSE score, and vascular comorbidity score, the interaction term between low daytime SBP tertile and AHD treatment was independently associated with a greater cognitive decline in both subgroups. The association between office SBP and MMSE score change was weaker. Other ambulatory blood pressure monitoring variables were not associated with MMSE score change. Low daytime SBP was independently associated with a greater progression of cognitive decline in older patients with dementia and MCI among those treated with AHDs. Excessive SBP lowering may be harmful for older patients with cognitive impairment. Ambulatory blood pressure monitoring can be useful to help

  1. What Are the Signs, Symptoms, and Complications of High Blood Pressure?

    Science.gov (United States)

    ... What Are the Signs, Symptoms, and Complications of High Blood Pressure? Because diagnosis is based on blood pressure readings, ... damaged from chronic high blood pressure. Complications of High Blood Pressure When blood pressure stays high over time, it ...

  2. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

    Science.gov (United States)

    Saraiva, Cláudia; Praça, Catarina; Ferreira, Raquel; Santos, Tiago; Ferreira, Lino; Bernardino, Liliana

    2016-08-10

    The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.

  3. Development of a blood-brain barrier model in a membrane-based microchip for characterization of drug permeability and cytotoxicity for drug screening.

    Science.gov (United States)

    Shao, Xiaojian; Gao, Dan; Chen, Yongli; Jin, Feng; Hu, Guangnan; Jiang, Yuyang; Liu, Hongxia

    2016-08-31

    Since most of the central nervous system (CNS) drug candidates show poor permeability across the blood-brain barrier (BBB), development of a reliable platform for permeability assay will greatly accelerate drug discovery. Herein, we constructed a microfluidic BBB model to mimic drug delivery into the brain to induce cytotoxicity at target cells. To reconstitute the in vivo BBB properties, human cerebral microvessel endothelial cells (hCMEC/D3) were dynamically cultured in a membrane-based microchannel. Sunitinib, a model drug, was then delivered into the microchannel and forced to permeate through the BBB model. The permeated amount was directly quantified by an electrospray ionization quadrupole time-of-flight mass spectrometer (ESI-Q-TOF MS) after on-chip SPE (μSPE) pretreatment. Moreover, the permeated drug was incubated with glioma cells (U251) cultured inside agarose gel in the downstream to investigate drug-induced cytotoxicity. The resultant permeability of sunitinib was highly correlated with literature reported value, and it only required 30 min and 5 μL of sample solution for each permeation experiment. Moreover, after 48 h of treatment, the survival rate of U251 cells cultured in 3D scaffolds was nearly 6% higher than that in 2D, which was in accordance with the previously reported results. These results demonstrate that this platform provides a valid tool for drug permeability and cytotoxicity assays which have great value for the research and development of CNS drugs.

  4. Massage-induced release of subcutaneously injected liposome-encapsulated drugs to the blood.

    Science.gov (United States)

    Trubetskoy, V S; Whiteman, K R; Torchilin, V P; Wolf, G L

    1998-01-01

    Liposome-based, externally regulated drug delivery system is described in which liposome-encapsulated bioactive molecules can be delivered into the blood in response to simple mechanical action. Without any mechanical stimulation, subcutaneously injected 200 mm liposomes are usually trapped in the interstitial for prolonged time. However, upon lymphotropic stimulation (such as manual massage of the injection site), the liposomes can be mobilized into the blood via lymphatic pathway. Up to 40% of the injection dose can be delivered to the blood via lymphatic pathway from the injection site at the rabbit's front paw dorsum during 5 min manual massage cycle. Using vasoconstricting hormone angiotensin II as liposome-encapsulated pharmacological marker, we demonstrated that physiological response to encapsulated drug (average blood pressure increase) can also induced and modulated by massage. Massage itself was found to have no effect on the blood pressure. Modification of liposome surface with polyethylene glycol was found to increase blood localization of the liposome-encapsulated drug presumably due to decreasing the uptake of the drug carrier by lymph node macrophages. Pressure-dependent gaps between lymphatic capillary endothelial cells are thought to play the role of the size discrimination device allowing larger particulates into the lymphatics and, eventually into the blood after increase of interstitial pressure caused by injection site massage.

  5. Preeclampsia and High Blood Pressure During Pregnancy

    Science.gov (United States)

    ... have certain medical conditions such as diabetes mellitus , thrombophilia , or lupus • are obese •had in vitro fertilization ... an abnormal amount of protein in the urine. Thrombophilia: A condition in which the blood does not ...

  6. Drug and light dose responses to focal photodynamic therapy of single blood vessels in vivo

    Science.gov (United States)

    Khurana, Mamta; Moriyama, Eduardo H.; Mariampillai, Adrian; Samkoe, Kimberley; Cramb, David; Wilson, Brian C.

    2009-11-01

    As part of an ongoing program to develop two-photon (2-γ) photodynamic therapy (PDT) for treatment of wet-form age-related macular degeneration (AMD) and other vascular pathologies, we have evaluated the reciprocity of drug-light doses in focal-PDT. We targeted individual arteries in a murine window chamber model, using primarily the clinical photosensitizer Visudyne/liposomal-verteporfin. Shortly after administration of the photosensitizer, a small region including an arteriole was selected and irradiated with varying light doses. Targeted and nearby vessels were observed for a maximum of 17 to 25 h to assess vascular shutdown, tapering, and dye leakage/occlusion. For a given end-point metric, there was reciprocity between the drug and light doses, i.e., the response correlated with the drug-light product (DLP). These results provide the first quantification of photosensitizer and light dose relationships for localized irradiation of a single blood vessel and are compared to the DLP required for vessel closure between 1-γ and 2-γ activation, between focal and broad-beam irradiation, and between verteporfin and a porphyrin dimer with high 2-γ cross section. Demonstration of reciprocity over a wide range of DLP is important for further development of focal PDT treatments, such as the targeting of feeder vessels in 2-γ PDT of AMD.

  7. 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...... to lower their blood pressure. METHODS: In our multicentre, partial-factorial trial, we randomly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure (systolic 140-220 mm Hg) to 7 days of transdermal glyceryl trinitrate (5 mg per day...

  8. 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.

  9. 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).

  10. 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

  11. 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

  12. 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

  13. 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

  14. Effectiveness of saliva and fingerprints as alternative specimens to urine and blood in forensic drug testing.

    Science.gov (United States)

    Kuwayama, Kenji; Miyaguchi, Hajime; Yamamuro, Tadashi; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Iwata, Yuko T; Inoue, Hiroyuki

    2016-07-01

    In forensic drug testing, it is important to immediately take biological specimens from suspects and victims to prove their drug intake. We evaluated the effectiveness of saliva and fingerprints as alternative specimens to urine and blood in terms of ease of sampling, drug detection sensitivity, and drug detection periods for each specimen type. After four commercially available pharmaceutical products were administered to healthy subjects, each in a single dose, their urine, blood, saliva, and fingerprints were taken at predetermined sampling times over approximately four weeks. Fourteen analytes (the administered drugs and their main metabolites) were extracted from each specimen using simple pretreatments, such as dilution and deproteinization, and were analyzed using liquid chromatography/mass spectrometry (LC/MS). Most of the analytes were detected in saliva and fingerprints, as well as in urine and blood. The time-courses of drug concentrations were similar between urine and fingerprints, and between blood and saliva. Compared to the other compounds, the acidic compounds, for example ibuprofen, acetylsalicylic acid, were more difficult to detect in all specimens. Acetaminophen, dihydrocodeine, and methylephedrine were detected in fingerprints at later sampling times than in urine. However, a relationship between the drug structures and their detection periods in each specimen was not found. Saliva and fingerprints could be easily sampled on site without using special techniques or facilities. In addition, fingerprints could be immediately analyzed after simple and rapid treatment. In cases where it would be difficult to immediately obtain urine and blood, saliva and fingerprints could be effective alternative specimens for drug testing. Copyright © 2015 John Wiley & Sons, Ltd.

  15. 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 essential hyperte

  16. 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

  17. Permeability analysis of neuroactive drugs through a dynamic microfluidic in vitro blood-brain barrier model.

    Science.gov (United States)

    Booth, R; Kim, H

    2014-12-01

    This paper presents the permeability analysis of neuroactive drugs and correlation with in vivo brain/plasma ratios in a dynamic microfluidic blood-brain barrier (BBB) model. Permeability of seven neuroactive drugs (Ethosuximide, Gabapentin, Sertraline, Sunitinib, Traxoprodil, Varenicline, PF-304014) and trans-endothelial electrical resistance (TEER) were quantified in both dynamic (microfluidic) and static (transwell) BBB models, either with brain endothelial cells (bEnd.3) in monoculture, or in co-culture with glial cells (C6). Dynamic cultures were exposed to 15 dyn/cm(2) shear stress to mimic the in vivo environment. Dynamic models resulted in significantly higher average TEER (respective 5.9-fold and 8.9-fold increase for co-culture and monoculture models) and lower drug permeabilities (average respective decrease of 0.050 and 0.052 log(cm/s) for co-culture and monoculture) than static models; and co-culture models demonstrated higher average TEER (respective 90 and 25% increase for static and dynamic models) and lower drug permeability (average respective decrease of 0.063 and 0.061 log(cm/s) for static and dynamic models) than monoculture models. Correlation of the resultant logP e values [ranging from -4.06 to -3.63 log(cm/s)] with in vivo brain/plasma ratios (ranging from 0.42 to 26.8) showed highly linear correlation (R (2) > 0.85) for all model conditions, indicating the feasibility of the dynamic microfluidic BBB model for prediction of BBB clearance of pharmaceuticals.

  18. Preeclampsia and High Blood Pressure During Pregnancy

    Science.gov (United States)

    ... help prevent seizures. If your condition or the baby’s condition worsens, prompt delivery will be needed. What steps can I take ... of the heart and blood vessels. Cesarean Delivery: Delivery of a baby through surgical incisions made in the mother’s abdomen ...

  19. Targeted blood-to-brain drug delivery --10 key development criteria.

    Science.gov (United States)

    Gaillard, Pieter J; Visser, Corine C; Appeldoorn, Chantal C M; Rip, Jaap

    2012-09-01

    Drug delivery to the brain remains challenging due to the presence of the blood-brain barrier. In this review, 10 key development criteria are presented that are important for successful drug development to treat CNS diseases by targeted drug delivery systems. Although several routes of delivery are being investigated, such as intranasal delivery, direct injections into the brain or CSF, and transient opening of the blood-brain barrier, the focus of this review is on physiological strategies aiming to target endogenous transport mechanisms. Examples from literature, focusing on targeted drug delivery systems that are being commercially developed, will be discussed to illustrate the 10 key development criteria. The first four criteria apply to the targeting of the blood-brain barrier: (1) a proven inherently safe receptor biology, (2) a safe and human applicable ligand, (3) receptor specific binding, and (4) applicable for acute and chronic indications. Next to an efficient and safe targeting strategy, as captured in key criteria 1 to 4, a favorable pharmacokinetic profile is also important (key criterion 5). With regard to the drug carriers, two criteria are important: (6) no modification of active ingredient and (7) able to carry various classes of molecules. The final three criteria apply to the development of a drug from lab to clinic: (8) low costs and straightforward manufacturing, (9) activity in all animal models, and (10) strong intellectual property (IP) protection. Adhering to these 10 key development criteria will allow for a successful brain drug development.

  20. Homeopathy effect on high blood pressure

    OpenAIRE

    Mahmoudian, A.

    2004-01-01

    There are many problems in the treatment of hypertension, so we use alternative medicine to achieve better results to solve these problems. In this article we describe a hypertensive patient resisted to conventional drugs and she had some other somatic and psychotic symptoms and was treated by homeopathy, a method of alternative medicine. Keywords: hypertension, homeopathy.

  1. Homeopathy effect on high blood pressure

    Directory of Open Access Journals (Sweden)

    A Mahmoudian

    2004-12-01

    Full Text Available There are many problems in the treatment of hypertension, so we use alternative medicine to achieve better results to solve these problems. In this article we describe a hypertensive patient resisted to conventional drugs and she had some other somatic and psychotic symptoms and was treated by homeopathy, a method of alternative medicine. Keywords: hypertension, homeopathy.

  2. Dirty Air, High Blood Pressure Linked

    Institute of Scientific and Technical Information of China (English)

    应树道

    2001-01-01

    贵刊去年第6期曾刊登一短文,题目是:盐,迫升血压之元凶。读了该文,我开始严格控制每日的食盐摄入量,再附以药物治疗,血压果然趋于平稳。近日上网,遇一奇文,意思是人的血压与空气污染状况有涉!根据对2600个成年人的调查,得出了这样的结论:Pollution may cause changes in the part of the nervous system that controls blood pressure.文章又同时说明:Exactly how pollution might cause blood pressure to climb remains unclear.人体之奥妙由此可见一斑。

  3. Effects of Blood-Activating and Stasis-Resolving Drugs on Tumor Formation and Metastasis

    Institute of Scientific and Technical Information of China (English)

    QIAN Yan-fang; WANG Xiao-jing; DUAN Shu-min

    2009-01-01

    @@ In order to summarize and analyze the internal relations of tumor formation and metastasis to blood-stasis syndrome and the influential factors of blood-activating and stasis-resolving drugs (BASRD) on tumor inhibition and metastasis, and to grasp the opportunity of selecting and using BASRD, the authors have retrieved by the computer the relative literature published from 1985 to 2006 in Full-text Database of Chinese Periodicals with "BASRD" and "cancer" as retrieval words.

  4. 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....

  5. High Blood Pressure, Afib and Your Risk of Stroke

    Science.gov (United States)

    ... atrial fibrillation has more than five times the risk of stroke.” “Because high blood pressure is so frequent, affecting tens of millions of ... is a more potent risk factor.” The two risk factors are also related to each other: High blood pressure is a risk factor for atrial fibrillation. Middle- ...

  6. 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 ...

  7. Heart and Artery Damage and High Blood Pressure

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More How High Blood Pressure Can Lead to a Heart Attack Updated:Dec ... sheet This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

  8. Americans with High Blood Pressure Still Eating Too Much Salt

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_163977.html Americans With High Blood Pressure Still Eating Too Much Salt Average sodium intake ... March 8, 2017 (HealthDay News) -- For Americans with high blood pressure, cutting back on salt is an important way ...

  9. Changes You Can Make to Manage High Blood Pressure

    Science.gov (United States)

    ... Aneurysm More Changes You Can Make to Manage High Blood Pressure Updated:Mar 10,2017 Fighting back against the “ ... Follow us on Twitter Follow us on Facebook High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

  10. 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.

  11. Dried blood spot analysis for therapeutic drug monitoring of pazopanib.

    Science.gov (United States)

    de Wit, Djoeke; den Hartigh, Jan; Gelderblom, Hans; Qian, Yanwen; den Hollander, Margret; Verheul, Henk; Guchelaar, Henk-Jan; van Erp, Nielka P

    2015-12-01

    Dried blood spot (DBS) sampling is potentially a more patient-friendly and flexible alternative to venous sampling of pazopanib. This study determined the agreement between pazopanib DBS and plasma concentrations to facilitate implementation of pazopanib DBS sampling into clinical practice. Paired DBS and plasma samples were collected in 12 patients. Pazopanib plasma concentrations were calculated from DBS concentrations using the formula: plasma concentration = DBSconcentration /(1 - hematocrit). Passing-Bablok and Bland-Altman analyses were used to determine the agreement between calculated and measured plasma concentrations. We predefined a clinical acceptance limit of 25% for the Bland-Altman analysis. Passing-Bablok analysis showed a small constant (intercept estimate, -8.53 [95%CI, -12.22 to -4.41]) and slightly proportional (slope estimate, 1.15 [95%CI, 1.04-1.24]) bias between calculated and measured concentrations. This bias was clinically nonrelevant, as shown by Bland-Altman analysis; the mean ratio of calculated to measured concentrations was 0.94 (95%CI, 0.65-1.23). The clinical acceptance limits were well within these 95% limits of agreement. More specifically, 92.6% of the data points were within the predefined acceptance limits. Pazopanib plasma concentrations can be accurately calculated from DBS concentrations. Although validation of DBS cards prepared by patients themselves is required, these results show that DBS sampling can be used to monitor pazopanib therapy in clinical practice.

  12. Drug-induced blood consumption: the impact of adverse drug reactions on demand for blood components in German departments of internal medicine.

    Science.gov (United States)

    Rottenkolber, Dominik; Schmiedl, Sven; Rottenkolber, Marietta; Thuermann, Petra A; Hasford, Joerg

    2012-10-01

    Therapy for adverse drug reactions (ADRs) often results in the application of blood components. This study aims to assess the demand for blood components and the resulting economic burden (hospital perspective) in German hospitals induced by ADRs leading to admissions to departments of internal medicine. In this prospective study, ADRs leading to hospitalization were surveyed in four regional pharmacovigilance centres in Germany during the years 2000-2007. ADRs assessed as 'possible', 'likely' or 'very likely' were included. Market prices for blood components and hospitalization data were determined by desktop research. A probabilistic sensitivity analysis was performed. A total of 6099 patients were admitted to internal medicine departments because of an outpatient ADR of whom 1165 patients (19.1%; mean age, 73.0 ± 13.0 years) required treatment with blood components owing to major bleeding events. Overall consumption was 4185 erythrocyte concentrates (EC), 426 fresh frozen plasma (FFP) and 48 thrombocyte (TC) units. On the basis of statistical hospital data, we estimated a nationwide demand of approximately 132,020 EC, 13,440 FFP and 1515 TC units, resulting in total costs of €12.66 million per year for all German hospitals. Some 19.2% of all ADR cases were assessed as preventable. Theoretically, a nationwide decreased demand for blood components and a savings potential of €2.43 million per year could be achieved by preventing ADRs in Germany. Blood components are used in one-fifth (mainly gastrointestinal bleeding) of all ADRs, leading to hospitalizations in internal medicine departments. Both blood demand and hospital procurement costs can be significantly lowered by preventing ADRs.

  13. Modeling Superparamagnetic Particles in Blood Flow for Applications in Magnetic Drug Targeting

    Directory of Open Access Journals (Sweden)

    Iris Rukshin

    2017-06-01

    Full Text Available Magnetic drug targeting is a technique that involves the binding of medicine to magnetizable particles to allow for more specific transport to the target location. This has recently come to light as a method of drug delivery that reduces the disadvantages of conventional, systemic treatments. This study developed a mathematical model for tracking individual superparamagnetic nanoparticles in blood flow in the presence of an externally applied magnetic field. The model considers the magnetic attraction between the particles and the external magnet, influence of power law flow, diffusive interaction between the particles and blood, and random collisions with red blood cells. A stochastic system of differential equations is presented and solved numerically to simulate the paths taken by particles in a blood vessel. This study specifically focused on localized cancer treatment, in which a surface tumor is accessed through smaller blood vessels, which are more conducive to this delivery method due to slower flow velocities and smaller diameters. The probability of the particles reaching the tumor location is found to be directly dependent on ambient factors; thus, diffusion through Brownian motion and red blood cell collisions, different magnetic field and force models, blood viscosities, and release points are considered.

  14. Using Mindfulness to Develop Health Education Strategies for Blood Borne Virus Prevention in Injecting Drug Use

    Science.gov (United States)

    Treloar, Carla; Laybutt, Becky; Carruthers, Susan

    2010-01-01

    Aims: Prevention education has had limited success in reducing transmission of blood borne virus among people who inject drugs. Innovative approaches to prevention education are required. Method: This study used video recordings of injecting episodes and interviews with participants reviewing their video recordings to explore the concept of…

  15. 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 cros

  16. Stability of dried blood spots for HIV-1 drug resistance analysis.

    Science.gov (United States)

    Hearps, Anna C; Ryan, Claire E; Morris, Lisa M; Plate, Megan M; Greengrass, Vicki; Crowe, Suzanne M

    2010-03-01

    The wide scale application of dried blood spots (DBS) as a collection tool for low-cost HIV drug resistance testing requires a greater understanding of the accuracy of DBS for genotype analysis and the stability of DBS under various environmental conditions. Analysis of a 50microl DBS via a single amplicon, nested PCR-based in-house assay (the Burnet genotyping assay) showed an average nucleotide concordance of 98.9% with plasma samples, although only 65% of nucleotide mixtures detected in plasma were also detected within DBS. The analysis of three DBS resulted in the detection of a greater number of nucleotide mixtures (72 and 109 mixtures detected within one and three DBS, respectively, n=10). Two DBS extraction protocols (silica particle; NucliSENS, bioMerieux and spin column extraction; High Pure, Roche) were assessed and found to be equivalent (79% and 84% recovery success respectively, n=19). FTA Elute paper (Whatman) was an inferior DBS collection medium compared to Whatman 903 paper. DBS appeared relatively tolerant to multiple freeze/thaw cycles, with 79% of DBS subjected to ten freeze/thaw cycles successfully amplified compared to 93% of DBS defrosted once (n=14). High temperature (37 degrees C) and high humidity (>90%) substantially impaired DBS recovery within two weeks of storage (38%, n=8), whilst storage at -20 degrees C or 4 degrees C adequately preserved DBS for this period (100% recovery, n=8). Therefore, whilst DBS are suitable for HIV drug resistance surveillance, the use of multiple DBS may be required to ensure accurate detection of minor HIV quasispecies and short-term storage of samples at either 4 degrees C or -20 degrees C is recommended.

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

    DEFF Research Database (Denmark)

    Tornabene, Erica; Brodin, Birger

    2016-01-01

    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...... 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...

  18. 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 st

  19. Motivating Factors and Potential Deterrents to Blood Donation in High School Aged Blood Donors

    Directory of Open Access Journals (Sweden)

    Rachel Finck

    2016-01-01

    Full Text Available Background. To ensure an adequate supply of blood, collection centers must design campaigns that successfully recruit and maintain an active donor pool. Understanding factors that motivate and deter individuals from donating may help centers develop targeted recruitment campaigns. These factors among high school aged blood donors have not yet been fully investigated. Study Design and Methods. A voluntary, anonymous survey was administered to student donors at high school mobile blood drives. The survey instrument asked the students to rate several potential motivating factors in their importance in the decision to donate blood and several potential deterring factors in their future decision whether or not to donate blood again. The survey also asked the students to rate the desirability of several potential incentives. Results. Motivating factors that reflected prosocial, empathetic, and altruistic thoughts and beliefs were rated highly by students. Pain from phlebotomy was most commonly chosen as potential deterrent. Movie tickets and cookies/snacks at the drive were rated as the most attractive incentives. Conclusion. High school aged blood donors are similar to other donor groups in their expressed motives for donating blood. This group may be unique in the factors that deter them from donating and in their preferences for different incentives.

  20. 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.

  1. The effect of drugs on the labeling of blood elements with technetium-99m.

    Science.gov (United States)

    Braga, A C; Oliveira, M B; Feliciano, G D; Reiniger, I W; Oliveira, J F; Silva, C R; Bernardo-Filho, M

    2000-07-01

    The influence of drugs on the labeling of red blood cells and plasma proteins with 99mTc has been reported. Any drug, which alters the labeling of the tracer, could be expected to modify the disposition of the radiopharmaceuticals. Red blood cells (RBC) labeled with technetium-99m (99mTc) are used for several evaluations in nuclear medicine. We have evaluated the effect of Thuya occidentalis, Peumus boldus and Nicotiana tabacum (tobacco) extracts on the labeling of RBC and plasma and cellular proteins with 99mTc. Blood was incubated with the drugs. Stannous chloride (SnCl2) solutions and 99mTc were added. Plasma (P) and blood cells (BC) were separated. The percentage of radioactivity (%ATI) bound to P and BC was determined. The %ATI on the plasma and cellular proteins was also evaluated by precipitation of P and BC samples with trichloroacetic acid (TCA) and isolation of soluble (SF) and insoluble (IF) fractions. The analysis of the results shows that there is a decrease in %ATI (from 97.64 to 75.89 percent) in BC with Thuya occidentalis extract. The labeling of RBC and plasma proteins can be decreased in presence of tobacco. This can be due either a direct or indirect effect (reactive oxygen species) of tobacco. The analysis of radioactivity in samples of P and BC isolated from samples of whole blood treated with Peumus boldus showed a rapid uptake of the radioactivity by blood cells in the presence of the Peumus boldus, whereas there was a slight decrease in the amount of 99mTc radioactivity in the TCA-insoluble fraction of plasma. This study shows that extracts of some medicinal plants can affect the radiolabeling of red blood cells with 99mTc using an in vitro technique.

  2. 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

  3. DASH diet to lower high blood pressure

    Science.gov (United States)

    ... that are naturally low in salt, cholesterol, and saturated fats. You will also include foods that are high ... AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of ...

  4. How Is High Blood Cholesterol Diagnosed?

    Science.gov (United States)

    ... for total and HDL cholesterol does not require fasting. If your total cholesterol is 200 mg/dL ... triglyceride level include: Overweight and obesity Lack of physical activity Cigarette smoking Excessive alcohol use A very high ...

  5. Can aerobic exercise complement antihypertensive drugs to achieve blood pressure control in individuals with essential hypertension?

    Science.gov (United States)

    Maruf, Fatai A; Salako, Babatunde L; Akinpelu, Aderonke O

    2014-06-01

    Achieving adequate blood pressure (BP) control with antihypertensive medication remains an elusive goal for many patients. The advances in knowledge of hypertension and the increasingly improved upon therapeutic strategies seem not to guarantee even sustainable control rates at the population level. In addition, patients who either discontinue their medications or are non-adherent to drug therapy run the risk of developing uncontrolled BP. Number of daily tablets more than two and number of daily drug administration at least three have been associated with poor adherence with drug therapy. However, BP control seems to go beyond adherence with drug therapy as there are other associated factors. Studies have demonstrated beneficial effect of aerobic exercise in the prevention and management of hypertension. It appears, however, that the majority of these studies failed to explore the possible additive or synergistic effect of aerobic exercise on antihypertensive drugs such that fewer drugs would be required to achieve BP control or that the BP control rate would be increased with the same number of drugs. This review presents the evidence for poor BP control in the general population, and the possible means and process of aerobic exercise complementing antihypertensive drug therapy in order to achieve higher BP control rates.

  6. How Potassium Can Help Control High Blood Pressure

    Science.gov (United States)

    ... natural sources of potassium. For example, a medium banana has about 420 mg of potassium and half ... high blood pressure. Learn more Get a fact sheet on following a heart-healthy diet: English | Spanish ...

  7. Solid and solution NMR studies of the complexation of Ag + with the trans isomer of captopril: Biological activities of this high blood pressure drug along with its Ag + complex

    Science.gov (United States)

    Isab, Anvarhusein A.; Wazeer, Mohamed I. M.

    2006-09-01

    Complexation of Ag + with captopril, 1-[(2 S)-3-mercapto-2-methylpropionyl]- L-proline, has been studied by 1H and 13C-NMR spectroscopy. The equilibrium constants for the trans to cis isomers of captopril bound to Ag + were measured by 1H NMR spectroscopy. It is observed that the trans isomer of the drug binds more strongly to Ag + between pH 5 and 8, as shown by the broadening of the trans isomer's resonances in 13C NMR spectra on complexation. A monodentate complexation of the trans captopril with Ag + via the thiol site is proposed based on the solid-state NMR and IR data. A superior antimicrobial activity is exhibited by the Cap-Ag(I) complex compared to captopril ligand itself against Heterotrotropic Plate Counts (HPC), Pseudomonas aeruginosa and Fecal streptococcus bacteria.

  8. Blood-Vessel-on-a-Chip Platforms for Evaluating Nanoparticle Drug Delivery Systems.

    Science.gov (United States)

    Li, Yuancheng; Zhu, Kai; Liu, Xiao; Zhang, Y Shrike

    2017-09-24

    Nanoparticle-based drug delivery systems hold great promise for the treatment of major diseases. However, their slow translation from bench to the clinic posts a serious concern. It is mainly attributed to the lack of suitable in vitro platforms for rapid and accurate screening of nanomedicine. Recent developments in microfluidic technologies have provided the possibility to reproduce the biomimetic blood vessel microenvironments outside the body, thus offering a convenient means to characterize the in vivo dynamics and biological responses of nanoparticles. In this review, we discuss the challenges facing the field of nanoparticle drug delivery and highlight the urgent need for construction of blood-vessel-on-a-chip platforms for testing nanomedicine. We subsequently illustrate advances in fabricating various well-controlled blood-vessel-on-a-chip platforms, covering a few examples that have used such models for evaluating nanoparticles behaviors. We then summarize with conclusions and perspectives. We anticipate that, further development of these blood-vessel-on-a-chip platforms with improved biomimetic parameters, tissue specificity, and personalization, will enable their wide applications in drug screening including nanomedicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. 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

  10. 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

    2012-01-17

    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 that 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 Whatman ET31 paper used for blood cards. Analysis using a hand-held 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.

  11. High blood pressure in older subjects with cognitive impairment.

    Science.gov (United States)

    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.

  12. Classification of High Blood Pressure Persons Vs Normal Blood Pressure Persons Using Voice Analysis

    Directory of Open Access Journals (Sweden)

    Saloni

    2013-11-01

    Full Text Available The human voice is remarkable, complex and delicate. All parts of the body play some role in voice production and may be responsible for voice dysfunction. The larynx contains muscles that are surrounded by blood vessels connected to circulatory system. The pressure of blood in these vessels should be related with dynamic variation of vocal cord parameters. These parameters are directly related with acoustic properties of speech. Acoustic voice analysis can be used to characterize the pathological voices. This paper presents the classification of high blood pressure and normal with the aid of voice signal recorded from the patients. Various features have been extracted from the voice signal of healthy persons and persons suffering from high blood pressure. Simulation results show differences in the parameter values of healthy and pathological persons. Then an optimum feature vector is prepared and kmean classification algorithm was implemented for data classification. The 79% classification efficiency was obtained.

  13. Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat.

    Science.gov (United States)

    Igreja, Bruno; Pires, Nuno Miguel; Bonifácio, Maria João; Loureiro, Ana Isabel; Fernandes-Lopes, Carlos; Wright, Lyndon Christopher; Soares-da-Silva, Patrício

    2015-01-01

    Hyperactivation of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. This study evaluated the efficacy of etamicastat, a dopamine-β-hydroxylase (DβH) inhibitor, in controlling high blood pressure in the spontaneously hypertensive rat (SHR), either alone or in combination with other classes of antihypertensives. SHRs were administered with etamicastat by gavage, and its pharmacodynamic and pharmacokinetic properties were evaluated. Etamicastat induced a time-dependent decrease in noradrenaline-to-dopamine ratios in the heart and kidney, and had no effect on catecholamine levels in the frontal cortex of SHRs. Cardiovascular pharmacodynamic effects following administration of etamicastat alone or in combination with other classes of antihypertensive drugs were assessed by telemetry. Etamicastat was evaluated in combination with captopril, losartan, hydrochlorothiazide, metoprolol, prazosin and/or diltiazem. Etamicastat monotherapy induced a dose-dependent reduction in blood pressure without reflex tachycardia. Combination therapy amplified the antihypertensive effects of all tested drugs. In conclusion, inhibition of peripheral DβH with etamicastat, as a monotherapy or combination therapy, may constitute a valid alternative treatment for high blood pressure.

  14. Identification of highly active flocculant proteins in bovine blood.

    Science.gov (United States)

    Piazza, George J; Nuñez, Alberto; Garcia, Rafael A

    2012-03-01

    Synthetic polymeric flocculants are used extensively for wastewater remediation, soil stabilization, and reduction in water leakage from unlined canals. Sources of highly active, inexpensive, renewable flocculants are needed to replace synthetic flocculants. High kaolin flocculant activity was documented for bovine blood (BB) and blood plasma with several anticoagulant treatments. BB serum also had high flocculant activity. To address the hypothesis that some blood proteins have strong flocculating activity, the BB proteins were separated by SEC. Then, the major proteins of the flocculant-active fractions were separated by SDS-PAGE. Identity of the major protein components was determined by tryptic digestion and peptide analysis by MALDI TOF MS. The sequence of selected peptides was confirmed using TOF/TOF-MS/MS fragmentation. Hemoglobin dimer (subunits α and β) was identified as the major protein component of the active fraction in BB; its high flocculation activity was confirmed by testing a commercial sample of hemoglobin. In the same manner, three proteins from blood plasma (fibrinogen, γ-globulin, α-2-macroglobulin) were found to be highly active flocculants, but bovine serum albumin, α-globulin, and β-globulin were not flocculants. On a mass basis, hemoglobin, γ-globulin, α-2-macroglobulin were as effective as anionic polyacrylamide (PAM), a widely used synthetic flocculant. The blood proteins acted faster than PAM, and unlike PAM, the blood proteins flocculants did not require calcium salts for their activity.

  15. High Fibrinogen in Peripheral Blood Correlates with Poorer Hearing Recovery in Idiopathic Sudden Sensorineural Hearing Loss

    Science.gov (United States)

    Kanzaki, Sho; Sakagami, Masafumi; Hosoi, Hiroshi; Murakami, Shingo; Ogawa, Kaoru

    2014-01-01

    Objectives We used hearing tests and peripheral blood sample analyses to characterize the pathology of idiopathic sudden sensorineural hearing loss (ISSNHL) and to identify possible prognostic factors for predicting recovery of hearing loss. Study Design A retrospective, multicenter trial was conducted. Methods Two hundred three patients examined within 7 days after the onset of ISSNHL received prednisone with lipo-prostaglandin E1. Pure-tone auditory tests were performed before and after treatment with these drugs. Blood tests were performed on blood samples collected during the patients’ initial visit to our clinic. Results In all patients, elevated white blood cell (WBC) counts, fasting blood sugar levels, HgbA1c, and erythrocyte sedimentation rate (ESR) significantly correlated with high hearing threshold measurements obtained on the initial visit. High fibrinogen levels, WBC counts, ESR, and low concentrations of fibrinogen degradation products (FDP) were associated with lower hearing recovery rates. Additionally, different audiogram shapes correlated with different blood test factors, indicating that different pathologies were involved. Conclusions High fibrinogen levels measured within seven days after ISSNHL onset correlated with poorer hearing recovery. This may be a consequence of ischemia or infections in the inner ear. The high WBC counts also observed may therefore reflect an immune response to inner ear damage induced by ischemic changes or infections. Our data indicate that therapeutic strategies should be selected based on the timing of initial treatment relative to ISSNHL onset. PMID:25166620

  16. High fibrinogen in peripheral blood correlates with poorer hearing recovery in idiopathic sudden sensorineural hearing loss.

    Directory of Open Access Journals (Sweden)

    Sho Kanzaki

    Full Text Available OBJECTIVES: We used hearing tests and peripheral blood sample analyses to characterize the pathology of idiopathic sudden sensorineural hearing loss (ISSNHL and to identify possible prognostic factors for predicting recovery of hearing loss. STUDY DESIGN: A retrospective, multicenter trial was conducted. METHODS: Two hundred three patients examined within 7 days after the onset of ISSNHL received prednisone with lipo-prostaglandin E1. Pure-tone auditory tests were performed before and after treatment with these drugs. Blood tests were performed on blood samples collected during the patients' initial visit to our clinic. RESULTS: In all patients, elevated white blood cell (WBC counts, fasting blood sugar levels, HgbA1c, and erythrocyte sedimentation rate (ESR significantly correlated with high hearing threshold measurements obtained on the initial visit. High fibrinogen levels, WBC counts, ESR, and low concentrations of fibrinogen degradation products (FDP were associated with lower hearing recovery rates. Additionally, different audiogram shapes correlated with different blood test factors, indicating that different pathologies were involved. CONCLUSIONS: High fibrinogen levels measured within seven days after ISSNHL onset correlated with poorer hearing recovery. This may be a consequence of ischemia or infections in the inner ear. The high WBC counts also observed may therefore reflect an immune response to inner ear damage induced by ischemic changes or infections. Our data indicate that therapeutic strategies should be selected based on the timing of initial treatment relative to ISSNHL onset.

  17. 75 FR 18849 - Food and Drug Administration/National Heart Lung and Blood Institute/National Science Foundation...

    Science.gov (United States)

    2010-04-13

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/National Heart Lung and Blood Institute/National Science Foundation Workshop on Computer Methods for Cardiovascular Devices: The Integration of Nonclinical and Clinical Models; Public Workshop AGENCY: Food and Drug Administration,...

  18. 76 FR 49775 - Food and Drug Administration/National Heart, Lung, and Blood Institute/National Science...

    Science.gov (United States)

    2011-08-11

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/National Heart, Lung, and Blood Institute/National Science Foundation Public Workshop on Computer Methods for Medical Devices AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and...

  19. Highly sensitive detection of Staphylococcus aureus directly from patient blood.

    Directory of Open Access Journals (Sweden)

    Padmapriya P Banada

    Full Text Available BACKGROUND: Rapid detection of bloodstream infections (BSIs can be lifesaving. We investigated the sample processing and assay parameters necessary for highly-sensitive detection of bloodstream bacteria, using Staphylococcus aureus as a model pathogen and an automated fluidic sample processing-polymerase chain reaction (PCR platform as a model diagnostic system. METHODOLOGY/PRINCIPAL FINDINGS: We compared a short 128 bp amplicon hemi-nested PCR and a relatively shorter 79 bp amplicon nested PCR targeting the S. aureus nuc and sodA genes, respectively. The sodA nested assay showed an enhanced limit of detection (LOD of 5 genomic copies per reaction or 10 colony forming units (CFU per ml blood over 50 copies per reaction or 50 CFU/ml for the nuc assay. To establish optimal extraction protocols, we investigated the relative abundance of the bacteria in different components of the blood (white blood cells (WBCs, plasma or whole blood, using the above assays. The blood samples were obtained from the patients who were culture positive for S. aureus. Whole blood resulted in maximum PCR positives with sodA assay (90% positive as opposed to cell-associated bacteria (in WBCs (71% samples positive or free bacterial DNA in plasma (62.5% samples positive. Both the assays were further tested for direct detection of S. aureus in patient whole blood samples that were contemporaneous culture positive. S. aureus was detected in 40/45 of culture-positive patients (sensitivity 89%, 95% CI 0.75-0.96 and 0/59 negative controls with the sodA assay (specificity 100%, 95% CI 0.92-1. CONCLUSIONS: We have demonstrated a highly sensitive two-hour assay for detection of sepsis causing bacteria like S. aureus directly in 1 ml of whole blood, without the need for blood culture.

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

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Holly H. (Bethel Island, CA); Hirschfeld, deceased, Tomas B. (late of Livermore, CA)

    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.

  1. Effect of anticoagulants on the protein corona-induced reduced drug carrier adhesion efficiency in human blood flow.

    Science.gov (United States)

    Sobczynski, Daniel J; Eniola-Adefeso, Omolola

    2017-01-15

    Plasma proteins rapidly coat the surfaces of particulate drug carriers to form a protein corona upon their injection into the bloodstream. The high presence of immunoglobulins in the corona formed on poly(lactic-co-glycolic acid) (PLGA) vascular-targeted carrier (VTC) surfaces was recently shown to negatively impact their adhesion to activated endothelial cells (aECs) in vitro. Here, we characterized the influence of anticoagulants, or their absence, on the binding efficiency of VTCs of various materials via modulation of their protein corona. Specifically, we evaluated the adhesion of PLGA, poly(lactic acid) (PLA), polycaprolactone (PCL), silica, and polystyrene VTCs to aECs in heparinized, citrated, and non-anticoagulated (serum and whole) blood flows relative to buffer control. Particle adhesion is substantially reduced in non-anticoagulated blood flows regardless of the material type while only moderate to minimal reduction is observed for VTCs in anticoagulant-containing blood flow depending on the anticoagulant and material type. The substantial reduction in VTC adhesion in blood flows was linked to a high presence of immunoglobulin-sized proteins in the VTC corona via SDS-PAGE analysis. Of all the materials evaluated, PLGA was the most sensitive to plasma protein effects while PCL was the most resistant, suggesting particle hydrophobicity is a critical component of the observed negative plasma protein effects. Overall, this work demonstrates that anticoagulant positively alters the effect of plasma proteins in prescribing VTC adhesion to aECs in human blood flow, which has implication in the use of in vitro blood flow assays for functional evaluation of VTCs for in vivo use.

  2. Focused ultrasound-mediated drug delivery through the blood-brain barrier.

    Science.gov (United States)

    Burgess, Alison; Shah, Kairavi; Hough, Olivia; Hynynen, Kullervo

    2015-05-01

    Despite recent advances in blood-brain barrier (BBB) research, it remains a significant hurdle for the pharmaceutical treatment of brain diseases. Focused ultrasound (FUS) is one method to transiently increase permeability of the BBB to promote drug delivery to specific brain regions. An introduction to the BBB and a brief overview of the methods, which can be used to circumvent the BBB to promote drug delivery, is provided. In particular, we discuss the advantages and limitations of FUS technology and the efficacy of FUS-mediated drug delivery in models of disease. MRI for targeting and evaluating FUS treatments, combined with administration of microbubbles, allows for transient, reproducible BBB opening. The integration of a real-time acoustic feedback controller has improved treatment safety. Successful clinical translation of FUS has the potential to transform the treatment of brain disease worldwide without requiring the development of new pharmaceutical agents.

  3. Antileishmanial High-Throughput Drug Screening Reveals Drug Candidates with New Scaffolds

    OpenAIRE

    Siqueira-Neto, Jair L; Ok-Ryul Song; Hyunrim Oh; Jeong-Hun Sohn; Gyongseon Yang; Jiyoun Nam; Jiyeon Jang; Jonathan Cechetto; Chang Bok Lee; Seunghyun Moon; Auguste Genovesio; Eric Chatelain; Thierry Christophe; Freitas-Junior, Lucio H.

    2010-01-01

    International audience; Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assa...

  4. Nanoparticle mediated P-glycoprotein silencing for improved drug delivery across the blood-brain barrier: a siRNA-chitosan approach.

    Directory of Open Access Journals (Sweden)

    Jostein Malmo

    Full Text Available The blood-brain barrier (BBB, composed of tightly organized endothelial cells, limits the availability of drugs to therapeutic targets in the central nervous system. The barrier is maintained by membrane bound efflux pumps efficiently transporting specific xenobiotics back into the blood. The efflux pump P-glycoprotein (P-gp, expressed at high levels in brain endothelial cells, has several drug substrates. Consequently, siRNA mediated silencing of the P-gp gene is one possible strategy how to improve the delivery of drugs to the brain. Herein, we investigated the potential of siRNA-chitosan nanoparticles in silencing P-gp in a BBB model. We show that the transfection of rat brain endothelial cells mediated effective knockdown of P-gp with subsequent decrease in P-gp substrate efflux. This resulted in increased cellular delivery and efficacy of the model drug doxorubicin.

  5. Racial differences in hypertension: implications for high blood pressure management.

    Science.gov (United States)

    Lackland, Daniel T

    2014-08-01

    The racial disparity in hypertension and hypertension-related outcomes has been recognized for decades with African Americans with greater risks than Caucasians. Blood pressure levels have consistently been higher for African Americans with an earlier onset of hypertension. Although awareness and treatment levels of high blood pressure have been similar, racial differences in control rates are evident. The higher blood pressure levels for African Americans are associated with higher rates of stroke, end-stage renal disease and congestive heart failure. The reasons for the racial disparities in elevated blood pressure and hypertension-related outcomes risk remain unclear. However, the implications of the disparities of hypertension for prevention and clinical management are substantial, identifying African American men and women with excel hypertension risk and warranting interventions focused on these differences. In addition, focused research to identify the factors attributed to these disparities in risk burden is an essential need to address the evidence gaps.

  6. Highly sensitive optical sensor system for blood leakage detection

    Science.gov (United States)

    Ueda, Masahiro; Ishikawa, Kazuhiko; Jie, Chen; Sanae, Mizuno; Touma, Yasunori

    A highly sensitive method for the detection of blood leakage has been developed, and a practical sensor system for blood concentration measurement has been constructed. The present method is based on the attenuation of laser light by blood cells. The effects of the fluctuations of the incident laser light power are eliminated by normalizing the attenuated light intensity by the incident light intensity. A part of the incident laser light is reflected by a beam splitter mounted at the entrance of the test cell, of which the power is measured to provide base data for normalization. The optical path is extended to enhance sensitivity by using a pair of side mirrors. This multi-reflection method is very effective to increase sensitivity; the maximum sensitivity obtained for blood concentration is about 4 X 10 -6 by volume, which is significantly higher than that of the conventional sensors.

  7. An ex Vivo Model for Evaluating Blood-Brain Barrier Permeability, Efflux, and Drug Metabolism

    DEFF Research Database (Denmark)

    Hellman, Karin; Aadal Nielsen, Peter; Ek, Fredrik

    2016-01-01

    , risperidone, citalopram, fluoxetine, and haloperidol were studied, and one preselected metabolite for each drug was analyzed, identified, and quantified. Metabolite identification studies of clozapine and midazolam showed that the locust brain was highly metabolically active, and 18 and 14 metabolites...

  8. Viral metagenomics applied to blood donors and recipients at high risk for blood-borne infections

    Science.gov (United States)

    Sauvage, Virginie; Laperche, Syria; Cheval, Justine; Muth, Erika; Dubois, Myriam; Boizeau, Laure; Hébert, Charles; Lionnet, François; Lefrère, Jean-Jacques; Eloit, Marc

    2016-01-01

    Background Characterisation of human-associated viral communities is essential for epidemiological surveillance and to be able to anticipate new potential threats for blood transfusion safety. In high-resource countries, the risk of blood-borne agent transmission of well-known viruses (HBV, HCV, HIV and HTLV) is currently considered to be under control. However, other unknown or unsuspected viruses may be transmitted to recipients by blood-derived products. To investigate this, the virome of plasma from individuals at high risk for parenterally and sexually transmitted infections was analysed by high throughput sequencing (HTS). Materials and methods Purified nucleic acids from two pools of 50 samples from recipients of multiple transfusions, and three pools containing seven plasma samples from either HBV−, HCV− or HIV-infected blood donors, were submitted to HTS. Results Sequences from resident anelloviruses and HPgV were evidenced in all pools. HBV and HCV sequences were detected in pools containing 3.8×103 IU/mL of HBV-DNA and 1.7×105 IU/mL of HCV-RNA, respectively, whereas no HIV sequence was found in a pool of 150 copies/mL of HIV-RNA. This suggests a lack of sensitivity in HTS performance in detecting low levels of virus. In addition, this study identified other issues, including laboratory contaminants and the uncertainty of taxonomic assignment of short sequence. No sequence suggestive of a new viral species was identified. Discussion This study did not identify any new blood-borne virus in high-risk individuals. However, rare and/or viruses present at very low titre could have escaped our protocol. Our results demonstrate the positive contribution of HTS in the detection of viral sequences in blood donations. PMID:27136432

  9. C. elegans in high-throughput drug discovery

    OpenAIRE

    O’Reilly, Linda P.; Cliff J Luke; Perlmutter, David H.; Silverman, Gary A.; Pak, Stephen C.

    2013-01-01

    C. elegans has proven to be a useful model organism for investigating molecular and cellular aspects of numerous human diseases. More recently, investigators have explored the use of this organism as a tool for drug discovery. Although earlier drug screens were labor-intensive and low in throughput, recent advances in high-throughput liquid workflows, imaging platforms and data analysis software have made C. elegans a viable option for automated high-throughput drug screens. This review will ...

  10. Leisure-Time Exercise Could Lower Your Risk of High Blood Pressure

    Science.gov (United States)

    ... Leisure-time exercise could lower your risk of high blood pressure American Heart Association Rapid Access Journal Report September ... copyright American Heart Association Download (1.4 MB) High Blood Pressure A high blood pressure reading. copyright American Heart ...

  11. High blood pressure in a semi-urban community in south-south ...

    African Journals Online (AJOL)

    EB

    High blood pressure (BP) is a leading cause of global burden of disease ... (9%), high blood glucose and physical inactivity (6% each) ... When the burden of high blood pressure disease was ... C was information on activity and sleep pattern,.

  12. Effect of spiritual therapy on blood pressure, anxiety and quality of life in patients with high blood pressure

    OpenAIRE

    2014-01-01

    Background: High blood pressure is the most important risk factor of cardiovascular diseases. This study was conducted to evaluate the efficacy of spiritual therapy on blood pressure, anxiety and quality of life in patients with high blood pressure. Method: This study was quasi-experimentalwith apretest-posttest and control group design. The sample consisted of 30 patients with high blood pressure refering to Kangavar Healthcare center that were selected through convenience sampling and...

  13. 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 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.

  14. 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.

  15. Polymeric nanoparticles assembled with microfluidics for drug delivery across the blood-brain barrier

    Science.gov (United States)

    Tavares, M. R.; de Menezes, L. R.; do Nascimento, D. F.; Souza, D. H. S.; Reynaud, F.; Marques, M. F. V.; Tavares, M. I. B.

    2016-07-01

    The blood-brain barrier (BBB) is a challenge in the treatment of some diseases, since it prevents many drugs from reaching therapeutic concentrations in the brain. In this context, there is a growing interest in nanoparticles for drug delivery, since they are able to cross this barrier and target the brain. The use of polymeric materials in the development of these nanoparticles has been extensively studied. It has already been demonstrated that these nanosystems have the ability to cross the BBB, which allows effective drug release into the brain. Biodegradable polymers provide a great advantage in the development of nanosystems, but modifications of the nanoparticles' surface is essential. The traditional batch methods lack precise control over the processes of nucleation and growth, resulting in poor control over final properties of the nanoparticles. Therefore, microfluidics could be used to achieve a better production environment for the fabrication of nano- structured drug delivery systems. This study provides a brief review of: the BBB, the polymeric nanoparticles with the ability to overcome the barrier, the properties of the most used polymeric matrices, and the nanostructured drug delivery systems assembled with microfluidics.

  16. 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.

  17. 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.

  18. Adiposopathy: sick fat causes high blood sugar, high blood pressure and dyslipidemia.

    Science.gov (United States)

    Bays, Harold; Abate, Nicola; Chandalia, Manisha

    2005-01-01

    Adiposopathy is defined as pathological adipose tissue function that may be promoted and exacerbated by fat accumulation (adiposity) and sedentary lifestyle in genetically susceptible patients. Adiposopathy is a root cause of some of the most common metabolic diseases observed in clinical practice, including Type 2 diabetes mellitus, hypertension and dyslipidemia. The most common term for the metabolic consequences of adiposopathy is currently 'the metabolic syndrome'. Drug usage to treat the metabolic syndrome has focused on the safety and efficacy of treatments directed towards individual components of the metabolic syndrome, and not so much upon adiposopathy itself. However, enough is known about the pathophysiology of adiposopathy to propose diagnostic criteria. Regulatory issues are important obstacles to the research and development of new drug treatments for the metabolic syndrome. It is hoped that these obstacles can, to some extent, be addressed and overcome by clearly defining and increasing our understanding of adiposopathy.

  19. Drug delivery strategies to enhance the permeability of the blood-brain barrier for treatment of glioma.

    Science.gov (United States)

    Zhang, Fang; Xu, Chun-Lei; Liu, Chun-Mei

    2015-01-01

    Gliomas are amongst the most insidious and destructive types of brain cancer and are associated with a poor prognosis, frequent recurrences, and extremely high lethality despite combination treatment of surgery, radiotherapy, and chemotherapy. The existence of the blood-brain barrier (BBB) restricts the delivery of therapeutic molecules into the brain and offers the clinical efficacy of many pharmaceuticals that have been demonstrated to be effective for other kinds of tumors. This challenge emphasizes the need to be able to deliver drugs effectively across the BBB to reach the brain parenchyma. Enhancement of the permeability of the BBB and being able to transport drugs across it has been shown to be a promising strategy to improve drug absorption and treatment efficacy. This review highlights the innovative technologies that have been introduced to enhance the permeability of the BBB and to obtain an optimal distribution and concentration of drugs in the brain to treat gliomas, such as nanotechniques, hyperthermia techniques, receptor-mediated transport, cell-penetrating peptides, and cell-mediated delivery.

  20. Hierarchical zwitterionic modification of a SERS substrate enables real-time drug monitoring in blood plasma

    Science.gov (United States)

    Sun, Fang; Hung, Hsiang-Chieh; Sinclair, Andrew; Zhang, Peng; Bai, Tao; Galvan, Daniel David; Jain, Priyesh; Li, Bowen; Jiang, Shaoyi; Yu, Qiuming

    2016-11-01

    Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive analytical technique with molecular specificity, making it an ideal candidate for therapeutic drug monitoring (TDM). However, in critical diagnostic media including blood, nonspecific protein adsorption coupled with weak surface affinities and small Raman activities of many analytes hinder the TDM application of SERS. Here we report a hierarchical surface modification strategy, first by coating a gold surface with a self-assembled monolayer (SAM) designed to attract or probe for analytes and then by grafting a non-fouling zwitterionic polymer brush layer to effectively repel protein fouling. We demonstrate how this modification can enable TDM applications by quantitatively and dynamically measuring the concentrations of several analytes--including an anticancer drug (doxorubicin), several TDM-requiring antidepressant and anti-seizure drugs, fructose and blood pH--in undiluted plasma. This hierarchical surface chemistry is widely applicable to many analytes and provides a generalized platform for SERS-based biosensing in complex real-world media.

  1. Risk of cardiovascular events among women with high normal blood pressure or blood pressure progression: prospective cohort study

    OpenAIRE

    Conen, David; Ridker, Paul M.; Buring, Julie E.; Glynn, Robert J.

    2007-01-01

    Objective To compare cardiovascular risk among women with high normal blood pressure (130-9/85-9 mm Hg) against those with normal blood pressure (120-9/75-84 mm Hg) and those with baseline hypertension.

  2. Risk of cardiovascular events among women with high normal blood pressure or blood pressure progression: prospective cohort study

    OpenAIRE

    Conen, David; Ridker, Paul M.; Buring, Julie E.; Glynn, Robert J.

    2007-01-01

    Objective To compare cardiovascular risk among women with high normal blood pressure (130-9/85-9 mm Hg) against those with normal blood pressure (120-9/75-84 mm Hg) and those with baseline hypertension.

  3. National High Blood Pressure 12-Month Kit. May 1988.

    Science.gov (United States)

    National Heart and Lung Inst. (DHHS/NIH), Bethesda, MD. National High Blood Pressure Education Program.

    Part I of this kit provides information for program planners and health professionals on ways to overcome barriers to health care among the medically underserved, promote high blood pressure control through the media and other community channels, and improve adherence to treatment among hypertensive patients. It lists additional resources for…

  4. Abnormal blood flow in the sublingual microcirculation at high altitude

    NARCIS (Netherlands)

    Martin, D.S.; Ince, C.; Goedhart, P.; Levett, D.Z.H.; Grocott, M.P.W.

    2009-01-01

    We report the first direct observations of deranged microcirculatory blood flow at high altitude, using sidestream dark-field imaging. Images of the sublingual microcirculation were obtained from a group of 12 volunteers during a climbing expedition to Cho Oyu (8,201 m) in the Himalayas.

  5. 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.

  6. High speed optical holography of retinal blood flow

    CERN Document Server

    Pellizzari, Mathilde; Degardin, Julie; Sahel, Jose-Alain; Fink, Mathias; Paques, Michel; Atlan, Michael

    2016-01-01

    We performed non-invasive video imaging of retinal blood flow in a pigmented rat by holographic interferometry of near-infrared laser light backscattered by retinal tissue, beating against an off-axis reference beam sampled at a frame rate of 39 kHz with a high throughput camera. Local Doppler contrasts emerged from the envelopes of short-time Fourier transforms and the phase of autocorrelation functions of holograms rendered by Fresnel transformation. This approach permitted imaging of blood flow in large retinal vessels (30 microns diameter) over 400 by 400 pixels with a spatial resolution of 8 microns and a temporal resolution of 6.5 ms.

  7. The Knowledge About Drugs, Attitudes Towards Them And Drug Use Rates Of High School Students

    Science.gov (United States)

    Fejer, Dianne; Smart, Reginald G.

    1973-01-01

    A survey of attitudes towards drugs, knowledge about them and the use of alcohol, tobacco, illicit and psychoactive drugs was conducted among 4,693 high school students. Knowledge level and permissive attitudes tended to increase with grade level. Knowledge scores also increased, but attitudes became less permissive with increasing academic…

  8. Antihypertensive drug classes have different effects on short-term blood pressure variability in essential hypertension.

    Science.gov (United States)

    Levi-Marpillat, Natacha; Macquin-Mavier, Isabelle; Tropeano, Anne-Isabelle; Parati, Gianfranco; Maison, Patrick

    2014-06-01

    Increased blood pressure variability (BPV) contributes to end-organ damage, cardiovascular events and mortality associated with hypertension. In a cohort of 2780 hypertensive patients treated by either calcium channel blockers (CCBs), diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) or β-blockers alone or in combination, we compared indices of short-term BPV according to the different treatments. Short-term BPV was calculated as the standard deviation (s.d.) of 24 h, daytime or nighttime systolic blood pressure and diastolic blood pressure (SBP and DBP). Short-term BPV was compared between patients treated with a given antihypertensive class of interest (alone or in combination) and those not treated with this class, after controlling for ambulatory average blood pressure, heart rate, age, gender, propensity scores and carotid-femoral pulse wave velocity. Patients treated with CCBs (n=1247) or diuretics (n=1486) alone, or in addition to other drugs had significant lower s.d. of 24-h SBP compared with those not treated with these classes (mean differences in s.d. -0.50±0.50 mm Hg, P=0.001 and -0.17±0.15 mm Hg, P=0.05, respectively). There was no significant difference regarding treatment with or without ARBs, ACEIs and β-blockers. The combinations of CCBs with diuretics or ARBs on top of other treatments resulted in a lower 24-h SBP variability (mean differences in s.d. -0.43±0.17 mm Hg, P=0.02 and -0.44±0.19 mm Hg, P=0.005 vs. other combination uses, respectively). Antihypertensive drug classes have differential effects on short-term BPV with a greater reduction in patients treated with CCBs and diuretics. The combinations of CCBs with diuretics may be the most efficient treatments in lowering BPV.

  9. TARGETING OF DRUGS TO VARIOUS BLOOD-CELL TYPES USING (NEO-)GLYCOPROTEINS, ANTIBODIES AND OTHER PROTEIN CARRIERS

    NARCIS (Netherlands)

    MOLEMA, G; MEIJER, DKF

    1994-01-01

    The current problems in controlling severe viral infections of blood cells such as in AIDS as well as the lack of effective and safe pharmacotherapeutic measures for such diseases have renewed interest in the options of targeting of drugs and genes to various blood cell types. The design and develop

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. A patient-centric goal in time to blood pressure control from drug therapy initiation.

    Science.gov (United States)

    Hong, Song Hee; Wang, Junling; Tak, Sunghee

    2013-02-01

    A time frame in which newly diagnosed hypertensive patients attain blood pressure (BP) goal would guide patients through uncertainty associated with initiating drug therapy for hypertension control. This study estimates time to BP goal resulting from drug therapy initiation among real-world hypertensive patients and identifies factors associated with variations in time to BP goal. The study uses a historical cohort design. Hypertensive patients who had initiated antihypertensive drug therapy between July 1, 2002, and December 31, 2003, were followed up to 12 months until the end of 2004. Electronic medical records from a medical group were linked with pharmacy claims, as well as with medical claims. Survival analyses were used to compare lengths of time needed to reach BP goals. A total of 223 patients from a real world practice setting had initiated antihypertensive drug therapy. The patients took 3.25 months (95% CI: 2.49-4.82) to reach BP goal. The patient-centric time to BP goal was 7.1 weeks longer than those reported in controlled experimental settings. This finding highlights the gap between results of controlled clinical trials and their application to clinical practice, and informs healthcare practitioners of the importance of setting a patient-centric goal in pharmacological treatment of hypertension.

  15. Efficacy of flavonoids in the management of high blood pressure.

    Science.gov (United States)

    Clark, Jaime L; Zahradka, Peter; Taylor, Carla G

    2015-12-01

    Plant compounds such as flavonoids have been reported to exert beneficial effects in cardiovascular disease, including hypertension. Information on the effects of isolated individual flavonoids for management of high blood pressure, however, is more limited. This review is focused on the flavonoids, as isolated outside of the food matrix, from the 5 main subgroups consumed in the Western diet (flavones, flavonols, flavanones, flavan-3-ols, and anthocyanins), along with their effects on hypertension, including the potential mechanisms for regulating blood pressure. Flavonoids from all 5 subgroups have been shown to attenuate a rise in or to reduce blood pressure during several pathological conditions (hypertension, metabolic syndrome, and diabetes mellitus). Flavones, flavonols, flavanones, and flavanols were able to modulate blood pressure by restoring endothelial function, either directly, by affecting nitric oxide levels, or indirectly, through other pathways. Quercetin had the most consistent blood pressure-lowering effect in animal and human studies, irrespective of dose, duration, or disease status. However, further research on the safety and efficacy of the flavonoids is required before any of them can be used by humans, presumably in supplement form, at the doses required for therapeutic benefit.

  16. 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.

  17. 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.

  18. Drug Use Patterns among High School Athletes and Nonathletes.

    Science.gov (United States)

    Naylor, Adam H.; Gardner, Doug; Zaichkowsky, Len

    2001-01-01

    High school students (N=1,515) in Massachusetts were surveyed about whether participation in athletics promoted a healthier lifestyle and decreased use of recreational drugs. Participation in athletics did promote a healthier lifestyle and athletes were significantly less likely to use cocaine, psychedelic drugs, or smoke cigarettes. However, work…

  19. The elusiveness of population-wide high blood pressure control.

    Science.gov (United States)

    Whelton, Paul K

    2015-03-18

    High blood pressure (hypertension) is a leading risk factor for cardiovascular disease. It is highly prevalent in the US general population, especially in those who are old, African American, or socially disadvantaged. Prevalence is also high and increasing worldwide. Awareness, treatment, and control of hypertension have improved over time, but there is still considerable room for improvement. The optimal solution to this health challenge varies by country. Several nonpharmacologic and pharmacologic interventions are well proven as effective means to prevent hypertension and improve control rates in those with established hypertension. Better prevention and control of hypertension will yield substantial general population health benefits and remain high priorities in public health.

  20. Prevalence of sedentary lifestyle in individuals with high blood pressure.

    Science.gov (United States)

    Guedes, Nirla Gomes; Lopes, Marcos Venícios de Oliveira; Moreira, Rafaella Pessoa; Cavalcante, Tahissa Frota; de Araujo, Thelma Leite

    2010-01-01

    To identify the prevalence of a sedentary lifestyle in individuals with high blood pressure. This cross-sectional study was conducted among 310 individuals with high blood pressure. The prevalence of the diagnosis of sedentary lifestyle was 60%. The more common defining characteristics were "lack of physical conditioning" and "lack of practice for physical exercises." The nursing diagnosis was associated with age and presence of diabetes. Individuals who presented with a sedentary lifestyle related to lack of motivation were significantly younger. This study showed a high prevalence of "sedentary lifestyle" and its associations with age and the presence of diabetes. IMPLICATIONS TO NURSING PRACTICE: The acknowledgement of "sedentary lifestyle" contributes to the choice for nursing interventions that promote physical activity centered on the subject and the surroundings.

  1. Patents associated with high-cost drugs in Australia.

    Directory of Open Access Journals (Sweden)

    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.

  2. Commentary on “Alzheimer’s disease drug development and the problem of the blood-brain barrier”

    OpenAIRE

    Simpkins, James W.

    2009-01-01

    The perspective by Dr. William Pardridge entitled “Alzheimer’s Disease Drug Discovery and the Problem of the Blood-Brain Barrier” makes a strong case for the imbalance in resource distribution to the drug-discovery and brain drug delivery processes, where the latter received less than 1% of the investment of the former. My own calculations are consistent with this striking imbalance. Dr. Pardridge predicts that current trials of passive immunity against β-amyloid peptide wil...

  3. Quantitative dynamic nuclear polarization‐NMR on blood plasma for assays of drug metabolism

    DEFF Research Database (Denmark)

    Lerche, Mathilde Hauge; Meier, Sebastian; Jensen, Pernille Rose

    2011-01-01

    Analytical platforms for the fast detection, identification and quantification of circulating drugs with a narrow therapeutic range are vital in clinical pharmacology. As a result of low drug concentrations, analytical tools need to provide high sensitivity and specificity. Dynamic nuclear...... polarization‐NMR (DNP‐NMR) in the form of the hyperpolarization–dissolution method should afford the sensitivity and spectral resolution for the direct detection and quantification of numerous isotopically labeled circulating drugs and their metabolites in single liquid‐state NMR transients. This study......‐scan 13C DNP‐NMR. An internal standard is used for the accurate quantification of drug and metabolite. Comparison of quantitative DNP‐NMR data with an established analytical method (liquid chromatography‐mass spectrometry) yields a Pearson correlation coefficient r of 0.99. Notably, all DNP...

  4. Trends in occurrence of drugs of abuse in blood and urine of arrested drivers and drug traffickers in the border region of Aachen.

    Science.gov (United States)

    Schiwy-Bochat, K H; Bogusz, M; Vega, J A; Althoff, H

    1995-01-21

    The region of Aachen is located in a triangle on the German, Dutch and Belgian borders and is heavily exposed to drug traffic, due to the differences in national drug policies. The analysis of toxicological casework in the Institute of Forensic Medicine in Aachen was undertaken for the period 1987-1993, i.e. 6 years before and 1 year after the partial suspension of the border control due to the Maastricht Treaty; 2653 cases were registered, among them 988 automobile drivers. The profile of the casework has changed after the opening of the border: up to 1992 most cases were obtained from the customs. In 1993 the prevalence of police samples was noticed. In the population of drivers, blood samples were only taken in 30% of all the cases. In other cases, concerning mainly motorized drug smugglers, only urine samples or seized drugs have been sent for examination. The urine samples in this group were mostly drug-positive. Drug-smuggling drivers appeared to be a risk-generating group for road traffic safety. The analyses of blood and urine samples revealed multiple drug use in most of the cases. Since 1992, a steep increase in the frequency of cocaine-positive blood samples among drivers was noticed. The results of the study indicate that the abolition of the border control affected the road traffic safety in the region of Aachen.

  5. 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.

  6. Transport of carbamazepine and drug interactions at blood-brain barrier

    Institute of Scientific and Technical Information of China (English)

    Jing-jing SUN; Lin XIE; Xiao-dong LIU

    2006-01-01

    Aim: To investigate the characteristics of carbamazepine (CBZ) transport and drug interactions at the blood-brain barrier. Methods: Cultured rat brain microvascular endothelial cells (rBMEC) were used as an in vitro model of the blood-brain barrier (BBB). When cells became confluent, CBZ uptake over time was recorded by incubation of the cells in a medium containing 10 mg/L CBZ at 37 ℃. The steady-state uptake of CBZ by rBMEC was tested for different CBZ concentrations at 37 ℃. The effects of various agents on the steady-state uptake of CBZ and efflux of CBZ from rBMEC were also studied. Results: The uptake of CBZ by rBMEC was time- and concentration-dependent. The steady-state uptake occurred at 30 min for incubation. The steady-state uptake was significantly increased (P<0.01) by treatment with dinitrophenol. The co-administration of cyclosporine A significantly increased the steady-state uptake of CBZ by the rBMEC, whereas co-administration of olanzapine significantly decreased the uptake in a concentration- and temperature-dependent manner. The efflux of CBZ from rBMEC was inhibited by CsA. Conclusion: The transport of CBZ at the BBB is mediated by many transporters. Some specific ABC (ATP-binding cassette,ABC ) efflux transporters may be involved in the transport of CBZ. Drugs influence the transport of CBZ at the BBB in different ways.

  7. Increased Risk of Drug-Induced Hyponatremia during High Temperatures

    Directory of Open Access Journals (Sweden)

    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

  8. Increased Risk of Drug-Induced Hyponatremia during High Temperatures

    Science.gov (United States)

    Jönsson, Anna K.; Lövborg, Henrik; Lohr, Wolfgang; Ekman, Bertil; Rocklöv, Joacim

    2017-01-01

    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. PMID:28737683

  9. 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.

  10. 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

    2016-01-01

    ABSTRACT OBJECTIVE To analyze the access to and use of medicines for high blood pressure among the Brazilian population according to social and demographic conditions. METHODS 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. RESULTS 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. CONCLUSIONS Access to

  11. Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals.

    Science.gov (United States)

    Johnson, Andrew D; Newton-Cheh, Christopher; Chasman, Daniel I; Ehret, Georg B; Johnson, Toby; Rose, Lynda; Rice, Kenneth; Verwoert, Germaine C; Launer, Lenore J; Gudnason, Vilmundur; Larson, Martin G; Chakravarti, Aravinda; Psaty, Bruce M; Caulfield, Mark; van Duijn, Cornelia M; Ridker, Paul M; Munroe, Patricia B; Levy, Daniel

    2011-05-01

    We previously conducted genome-wide association meta-analysis of systolic blood pressure, diastolic blood pressure, and hypertension in 29,136 people from 6 cohort studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Here we examine associations of these traits with 30 gene regions encoding known antihypertensive drug targets. We find nominal evidence of association of ADRB1, ADRB2, AGT, CACNA1A, CACNA1C, and SLC12A3 polymorphisms with 1 or more BP traits in the Cohorts for Heart and Aging Research in Genomic Epidemiology genome-wide association meta-analysis. We attempted replication of the top meta-analysis single nucleotide polymorphisms for these genes in the Global BPgen Consortium (n=34,433) and the Women's Genome Health Study (n=23,019) and found significant results for rs1801253 in ADRB1 (Arg389Gly), with the Gly allele associated with a lower mean systolic blood pressure (β: 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=4.7×10(-10)), diastolic blood pressure (β: 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P=9.5×10(-10)), and prevalence of hypertension (β: 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P=3.3×10(-4)). Variation in AGT (rs2004776) was associated with systolic blood pressure (β: 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=3.8×10(-6)), as well as diastolic blood pressure (P=5.0×10(-8)) and hypertension (P=3.7×10(-7)). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (β: 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P=3.0×10(-5)). Two loci, ADRB1 and AGT, contain single nucleotide polymorphisms that reached a genome-wide significance threshold in meta-analysis for the first time. Our findings suggest that these genes warrant further studies of their genetic effects on blood pressure, including pharmacogenetic interactions.

  12. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

    Directory of Open Access Journals (Sweden)

    Jose A Santiago

    Full Text Available Early diagnosis of Parkinson's disease (PD continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson's Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009 when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS and Montreal Cognitive Assessment (MoCA score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN compared to cognitively impaired PD patients (PD-MCI. Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.

  13. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

    Science.gov (United States)

    Santiago, Jose A; Potashkin, Judith A

    2015-01-01

    Early diagnosis of Parkinson's disease (PD) continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson's Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009) when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA) score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN) compared to cognitively impaired PD patients (PD-MCI). Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes) compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.

  14. Enhanced drug loading on magnetic nanoparticles by layer-by-layer assembly using drug conjugates: blood compatibility evaluation and targeted drug delivery in cancer cells.

    Science.gov (United States)

    Manju, S; Sreenivasan, K

    2011-12-06

    Drug targeting using magnetic nanoparticles (MNPs) under the action of an external magnetic field constitutes an important mode of drug delivery. Low cargo capacity, particularly in hydrophobic drugs, is one limitation shown by MNPs. This article describes a simple strategy to enhance the drug-loading capacity of MNPs. The approach was to use polymer-drug conjugates to modify MNPs by layer-by-layer assembly (LbL). Curcumin (CUR) has shown remarkably high cytotoxicity toward various cancer cell lines. However, the drug shows low anticancer activity in vivo because of its reduced systemic bioavailability acquired from its poor aqueous solubility and instability. To address this issue, we synthesized cationic and anionic CUR conjugates by anchoring CUR onto poly(vinylpyrroidone) (PVP-Cur) and onto hyaluronic acid (HA-Cur). We used these oppositely charged conjugates to modify MNPs by layer-by-layer (LbL) assembly. Six double layers of curcumin conjugates were constructed on positively charged amino-terminated magnetic nanoparticles, TMSPEDA@MNPs. Finally, HA was coated onto the outer surface to form HA (HA-Cur/PVP-Cur)(6)@MNPs. Cellular viability studies showed the dose-dependent antiproliferative effect of HA (HA-Cur/PVP-Cur)(6)@MNPs in two cancer cell lines (glioma cells and Caco-2 cells). HA (HA-Cur/PVP-Cur)(6)@MNPs exhibited more cytotoxicity than did free curcumin, which was attributed to the enhanced solubility along with better absorption via hyaluronic acid receptor-mediated endocytosis. Flow cytometry showed enhanced intake of the modified MNPs by cells. Confocal microscope images also confirmed the uptake of HA (HA-Cur/PVP-Cur)(6)@MNPs with greater efficacy. Thus, the strategy that we adopted here appears to have substantial potential in carrying enhanced payloads of hydrophobic drugs to specified targets. © 2011 American Chemical Society

  15. Examination of nanoparticles as a drug carrier on blood flow through catheterized composite stenosed artery with permeable walls.

    Science.gov (United States)

    Ijaz, S; Nadeem, S

    2016-09-01

    In this paper, we have discussed the influence of copper nanoparticles on a blood flow through composite stenosed artery with permeable walls. The nature of blood is discussed mathematically by considering it as viscous nanofluid. The study is carried out for a blood vessel under mild stenosis approximations and expressions of the temperature, velocity, resistance impedance to flow, wall shear stress and the pressure gradient is obtained by using corresponding boundary conditions. Results for the effects of permeability on blood flow through composite stenosis have been discussed graphically. The considered analysis also summarizes that the drug copper nanoparticles are efficient to reduce hemodynamics of stenosis and could be helpful to predict important uses for biomedical applications. Results indicate that nanoparticles are helpful as drug carriers to minimize the effects of resistance impedance to blood flow or coagulation factors due to stenosis.

  16. Blood coagulation using High Intensity Focused Ultrasound (HIFU)

    Science.gov (United States)

    Nguyen, Phuc V.; Oh, Junghwan; Kang, Hyun Wook

    2014-03-01

    High Intensity Focused Ultrasound (HIFU) technology provides a feasible method of achieving thermal coagulation during surgical procedures. One of the potential clinical benefits of HIFU can induce immediate hemostasis without suturing. The objective of this study was to investigate the efficiency of a HIFU system for blood coagulation on severe vascular injury. ngHIFU treatment was implemented immediately after bleeding in artery. The ultrasound probe was made of piezoelectric material, generating a central frequency of 2.0 MHz as well as an ellipsoidal focal spot of 2 mm in lateral dimension and 10 mm in axial dimension. Acoustic coagulation was employed on a perfused chicken artery model in vitro. A surgical incision (1 to 2 mm long) was made with a scapel on the arterial wall, and heparinized autologous blood was made to leak out from the incision with a syringe pump. A total of 5 femoral artery incisions was treated with the HIFU beam. The intensity of 4500 W/cm2 at the focus was applied for all treatments. Complete hemostasis was achieved in all treatments, along with the treatment times of 25 to 50 seconds. The estimated intraoperative blood loss was from 2 to 5 mL. The proposed HIFU system may provide an effective method for immediate blood coagulation for arteries and veins in clinical applications.

  17. Erythrocyte membranes from slaughterhouse blood as potential drug vehicles: Isolation by gradual hypotonic hemolysis and biochemical and morphological characterization.

    Science.gov (United States)

    Kostić, Ivana T; Ilić, Vesna Lj; Đorđević, Verica B; Bukara, Katarina M; Mojsilović, Slavko B; Nedović, Viktor A; Bugarski, Diana S; Veljović, Đorđe N; Mišić, Danijela M; Bugarski, Branko M

    2014-10-01

    The present study was aimed at investigating the effect of isolation process-gradual hypotonic hemolysis on chosen parameters of the erythrocyte membranes (ghosts) originating from bovine and porcine slaughterhouse blood. The estimation of the gradual hypotonic hemolysis as a drug loading procedure for the erythrocyte ghosts was performed as well. Based on the results derived from analysis of the osmotic properties of the erythrocytes, the gradual hemolysis was performed with high volume of erythrocytes and 35mM hypotonic sodium-phosphate/NaCl, enabling >90% of hemolysis for both types of erythrocytes. Detailed insight into ghosts' morphology by field emission-scanning electron microscopy revealed a distortion from erythrocyte shape and an altered surface texture with increased bilayer curvature for both samples. Compared to erythrocytes, an average diameter of ghosts from both type of erythrocytes decreased for only about 10%. The reported unidispersity of the isolated ghosts is of great importance for their potential application as vehicles of active compounds. Gradual hemolysis did not lead to substantial loss of cholesterol and membrane/cytoskeleton proteins. This result indicated the ghosts' possibility to mimic the chemical and structural anisotropic environment of in vivo cell membranes, which is of significance for drug diffusion and partition coefficients. Induced shift of phosphatidylserine to external surface of the ghosts demonstrated their potential application as vehicles for targeted drug delivery to cells of reticuloendothelial system. Ultra high-performance liquid chromatography and Fourier transform infrared spectroscopy revealed the presence of a drug model - dexamethasone-sodium phosphate, and its interaction with structural components in both types of erythrocyte ghosts. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Advances of Studies on Mechanisms of Drugs for Activating Blood Circulation and Removing Blood Stasis in Treatment of Primary Liver Cancer

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Primary liver cancer is mainly characterized by the mass in hypochondriac region, stabbing pain at a fixative region, tenderness, dim complexion,vascular spider, vein exposure, livid tongue,ecchymosis, taut and uneven pulse and other symptoms of blood stasis. Experimental studies have found that the patient with liver cancer is often accompanied with disturbance of microcirculation,increase of blood viscosity and high blood agglutinative state. Therefore, activating blood circulation to remove blood stasis is clinically an important therapy for primary liver cancer. A great number of studies on the mechanisms have been carried out in China and other countries. The follow is a review about the mechanisms.

  19. Analytical sample preparation strategies for the determination of antimalarial drugs in human whole blood, plasma and urine

    DEFF Research Database (Denmark)

    Casas, Monica Escolà; Hansen, Martin; Krogh, Kristine A;

    2014-01-01

    Antimalarial drugs commonly referred to as antimalarials, include a variety of compounds with different physicochemical properties. There is a lack of information on antimalarial distribution in the body over time after administration, e.g. the drug concentrations in whole blood, plasma, and urin...... summarized. Finally, the main problems that the researchers have dealt with are highlighted. This information will aid analytical chemists in the development of novel methods for determining existing antimalarials and upcoming new drugs.......Antimalarial drugs commonly referred to as antimalarials, include a variety of compounds with different physicochemical properties. There is a lack of information on antimalarial distribution in the body over time after administration, e.g. the drug concentrations in whole blood, plasma, and urine...

  20. Comparison the prevalence of isolated Hepatitis B core antibody among injection drug users with blood donors in central province in IRAN

    Directory of Open Access Journals (Sweden)

    Masoomeh Soufian

    2011-09-01

    Full Text Available Background: In healthy blood donors, 2%–5% have isolated anti-HBc. Prevalence of hepatitis B, C and co- infection (HBV +HCV among injection drug user is high. Hepatitis C suppress of HB SAg and may be hepatitis B presented only with isolated anti HBC. This study determined of prevalence of isolated anti HBC among injection drug users and compare with blood donors in Arak city. Methods: A total 684 subjects (531voluntary blood donors and 153 injection drug users in Arak, Iran were included in this study. Hepatitis B surface antigen (HBsAg, hepatitis B surface antibody (anti-HBs, anti-HBc, and hepatitis C antibody (anti-HCV were tested in all subjects. Results: A total of 531 voluntary blood donors living in the city of Arak, in the Central Province of Iran, with a mean age of 36 ± 10.18 years (range 16–60 years were enrolled in the study. Ninety-three percent of patients were male and 7% were female. Of the 531 cases, 11 subjects (2.1% had isolated anti-HBc. A total of 153 injection drug users of Arak, in the Central Province of Iran, with a mean age of 30.66 ± 5.92 years (range 20-50 years were enrolled in the study. All of them were male. Of the 153 cases, 12 subjects (7.84% had isolated anti-HBc. All of 12 cases were HCV positive. Conclusion: Prevalence of isolated anti-HBc among injection drug users was 3. 73 fold in comparison with blood donors. For diagnosis of hepatitis B in this group test for anti-HBc will be done. Evaluation of occult hepatitis B in subject with isolated anti-HBc by exact method such as real time PCR is necessary.

  1. High blood pressure: the foundation for epidemic cardiovascular disease in African populations.

    Science.gov (United States)

    Cooper, Richard S; Amoah, Albert G B; Mensah, George A

    2003-01-01

    High-blood pressure is a powerful independent risk factor for death from heart disease and stroke. It is also a common clinical condition affecting more than 600 million persons worldwide and seen in nearly all populations. Although reliable, large-scale, population-based data on high blood pressure in sub-Saharan Africa (SSA) are limited, recent studies provide important and worrisome findings in both epidemiology and clinical outcomes. Although overall hypertension prevalence is between 10%-15%, prevalence rates as high as 30%-32% have been reported in middle-income urban and some rural areas. Importantly, hypertension awareness, treatment, and control rates as low as 20%, 10%, and 1%, respectively have also been found. Stroke has been by far the most common clinical sequela. In most SSA settings, hypertension control assumes a relatively low priority and little experience exists in implementing sustainable and successful programs for drug treatment. Rapid urbanization and transition from agrarian life to the wage-earning economy of city life continue to fuel increases in average blood pressure levels and prevalence of hypertension. Although the true burden of high blood pressure in sub-Saharan Africa remains largely unmeasured, compelling preliminary evidence suggests that it is the foundation for epidemic cardiovascular disease in Africa and already contributes substantively to death and disability from stroke, heart failure, and kidney failure in this region. Success in limiting this epidemic in SSA will depend heavily on the implementation of sustainable and aggressive population-based programs for high blood pressure awareness, prevention, treatment, and control. It will be critical to obtain investments in improved surveillance and program-relevant research to provide the evidence base for policy development and effective hypertension prevention and control.

  2. Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma

    Science.gov (United States)

    Kraft, John C.; McConnachie, Lisa A.; Koehn, Josefin; Kinman, Loren; Collins, Carol; Shen, Danny D.; Collier, Ann C.; Ho, Rodney J.Y.

    2017-01-01

    Objective: The aim of the present study was to determine whether a combination of anti-HIV drugs – tenofovir (TFV), lopinavir (LPV) and ritonavir (RTV) – in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma. Design: Four macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analysed using a validated combination LC-MS/MS assay. Results: For the two active drugs (TFV, LPV), plasma and PBMC intracellular drug levels persisted for over 2 weeks; PBMC drug exposures were three- to four-fold higher than those in plasma. Apparent terminal half-lives (t1/2) of TFV and LPV were 65.3 and 476.9 h in plasma, and 169.1 and 151.2 h in PBMCs. At 24 and 192 h, TFV and LPV drug levels in LNMCs were up to 79-fold higher than those in PBMCs. Analysis of PBMC intracellular TFV and its active metabolite TFV-diphosphate (TFV-DP) indicated that intracellular exposures of total TFV and TFV-DP were markedly higher and persisted longer than in humans and macaques dosed with oral TFV prodrugs, tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). Conclusions: A simple, scalable three-drug combination, lipid-stabilized nanosuspension exhibited persistent drug levels in cells of lymph nodes and the blood (HIV host cells) and in plasma. With appropriate dose adjustment, TLC-ART101 may be a useful HIV treatment with a potential to impact residual virus in lymph nodes. PMID:28099191

  3. Vitamin D and high blood pressure: causal association or epiphenomenon?

    Science.gov (United States)

    Kunutsor, Setor K; Burgess, Stephen; Munroe, Patricia B; Khan, Hassan

    2014-01-01

    High plasma levels of vitamin D are associated with a reduced risk of high blood pressure, but whether this association is causal remains to be ascertained. We performed a meta-analysis of randomized clinical trials, to examine the effect of vitamin D supplementation on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) and supplemented these results with a Mendelian randomization analysis to investigate the causal relationship between vitamin D status (25-hydroxyvitamin D [25(OH)D]) and BP. Pooled random effects meta-analysis of weighted mean differences across 16 trials of vitamin D supplementation showed a non-significant reduction in SBP (-0.94, 95% CI -2.98, 1.10 mmHg) and DBP (-0.52, 95% CI -1.18, 0.14 mmHg), with evidence of heterogeneity (I(2) = 67.9%, P causal effects of a doubling of genetically-elevated risk of vitamin D deficiency were 0.14 mmHg (95% CI -0.19, 0.47, P = 0.42), and 0.12 mmHg (95% CI -0.09, 0.33, P = 0.25) on SBP and DBP respectively. Additional evidence from genetic data are directionally consistent with clinical trial data, though underpowered to reliably demonstrate a strong causal effect of vitamin D status on BP. Further investigation may be warranted.

  4. High speed optical holography of retinal blood flow.

    Science.gov (United States)

    Pellizzari, M; Simonutti, M; Degardin, J; Sahel, J-A; Fink, M; Paques, M; Atlan, M

    2016-08-01

    We performed noninvasive video imaging of retinal blood flow in a pigmented rat by holographic interferometry of near-infrared laser light backscattered by retinal tissue, beating against an off-axis reference beam sampled at a frame rate of 39 kHz with a high throughput camera. Local Doppler contrasts emerged from the envelopes of short-time Fourier transforms and the phase of autocorrelation functions of holograms rendered by Fresnel transformation. This approach permitted imaging of blood flow in large retinal vessels (∼30 microns diameter) over 400×400  pixels with a spatial resolution of ∼8 microns and a temporal resolution of ∼6.5  ms.

  5. Raltegravir permeability across blood-tissue barriers and the potential role of drug efflux transporters.

    Science.gov (United States)

    Hoque, M Tozammel; Kis, Olena; De Rosa, María F; Bendayan, Reina

    2015-05-01

    The objectives of this study were to investigate raltegravir transport across several blood-tissue barrier models and the potential interactions with drug efflux transporters. Raltegravir uptake, accumulation, and permeability were evaluated in vitro in (i) P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1), or MRP4-overexpressing MDA-MDR1 (P-gp), HEK-ABCG2, HeLa-MRP1, or HEK-MRP4 cells, respectively; (ii) cell culture systems of the human blood-brain (hCMEC/D3), mouse blood-testicular (TM4), and human blood-intestinal (Caco-2) barriers; and (iii) rat jejunum and ileum segments using an in situ single-pass intestinal perfusion model. [(3)H]Raltegravir accumulation by MDA-MDR1 (P-gp) and HEK-ABCG2-overexpressing cells was significantly enhanced in the presence of PSC833 {6-[(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoic acid]-7-L-valine-cyclosporine}, a P-gp inhibitor, or Ko143 [(3S,6S,12aS)-1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester], a BCRP inhibitor, suggesting the inhibition of a P-gp- or BCRP-mediated efflux process, respectively. Furthermore, [(3)H]raltegravir accumulation by human cerebral microvessel endothelial hCMEC/D3 and mouse Sertoli TM4 cells was significantly increased by PSC833 and Ko143. In human intestinal Caco-2 cells grown on Transwell filters, PSC833, but not Ko143, significantly decreased the [(3)H]raltegravir efflux ratios. In rat intestinal segments, [(3)H]raltegravir in situ permeability was significantly enhanced by the concurrent administration of PSC833 and Ko143. In contrast, in the transporter inhibition assays, raltegravir (10 to 500 μM) did not increase the accumulation of substrate for P-gp (rhodamine-6G), BCRP ([(3)H]mitoxantrone), or MRP1 [2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)] by MDA-MDR1 (P-gp)-, HEK-ABCG2-, or HeLa-MRP1-overexpressing

  6. Charge-Reversal APTES-Modified Mesoporous Silica Nanoparticles with High Drug Loading and Release Controllability.

    Science.gov (United States)

    Wang, Yifeng; Sun, Yi; Wang, Jine; Yang, Yang; Li, Yulin; Yuan, Yuan; Liu, Changsheng

    2016-07-13

    In this study, we demonstrate a facile strategy (DL-SF) for developing MSN-based nanosystems through drug loading (DL, using doxorubicin as a model drug) followed by surface functionalization (SF) of mesoporous silica nanoparticles (MSNs) via aqueous (3-aminopropyl)triethoxysilane (APTES) silylation. For comparison, a reverse functionalization process (i.e., SF-DL) was also studied. The pre-DL process allows for an efficient encapsulation (encapsulation efficiency of ∼75%) of an anticancer drug [doxorubicin (DOX)] inside MSNs, and post-SF allows in situ formation of an APTES outer layer to restrict DOX leakage under physiological conditions. This method makes it possible to tune the DOX release rate by increasing the APTES decoration density through variation of the APTES concentration. However, the SF-DL approach results in a rapid decrease in drug loading capacity with an increase in APTES concentration because of the formation of the APTES outer layer hampers the inner permeability of the DOX drug, resulting in a burst release similar to that of undecorated MSNs. The resulting DOX-loaded DL-SF MSNs present a slightly negatively charged surface under physiological conditions and become positively charged in and extracellular microenvironment of solid tumor due to the protonation effect under acidic conditions. These merits aid their maintenance of long-term stability in blood circulation, high cellular uptake by a kind of skin carcinoma cells, and an enhanced intracellular drug release behavior, showing their potential in the delivery of many drugs beyond anticancer chemotherapeutics.

  7. 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.

  8. Distribution of certain drug products by registered blood establishments and comprehensive hemophilia diagnostic treatment centers that qualify as health care entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements and administrative procedures. Final rule.

    Science.gov (United States)

    2008-10-09

    The Food and Drug Administration (FDA) is amending its regulations to allow certain registered blood establishments and comprehensive hemophilia diagnostic treatment centers that are also health care entities to distribute certain drug products. The final rule amends limited provisions of the regulations implementing the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA). These regulations, among other things, restrict the sale, purchase, or trade of, or the offer to sell, purchase, or trade, prescription drugs purchased by hospitals and other health care entities.

  9. Bone Mineral Density Changes Among Women Initiating Blood Pressure Lowering Drugs: A SWAN Cohort Study

    Science.gov (United States)

    Solomon, Daniel H.; Ruppert, Kristine; Zhao, Zhenping; Lian, YinJuan; Kuo, I-Hsin; Greendale, Gail A.; Finkelstein, Joel S.

    2016-01-01

    Purpose Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women’s Health Across the Nation. Methods We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14-years of observation were compared with non-users. Results Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of non-users. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (−0.28% vs −0.88%; p = 0.008) and the spine (−0.74% vs −1.0%; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in non-users. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (−0.35% vs −0.60%; p = 0.08) and a similar trend at the FN (−0.39% vs −0.64%; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (−0.48% vs −0.82%; p = 0.02), but not at the spine (−0.40% vs −0.56%; p = 0.23). Conclusions Neither ACEi nor BB were associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with non-users, as well as compared with ACEi and BB. PMID:26449354

  10. Cyclosporine-inhibitable Blood-Brain Barrier Drug Transport Influences Clinical Morphine Pharmacodynamics

    Science.gov (United States)

    Meissner, Konrad; Avram, Michael J.; Yermolenka, Viktar; Francis, Amber M.; Blood, Jane; Kharasch, Evan D.

    2013-01-01

    Background The blood-brain barrier is richly populated by active influx and efflux transporters influencing brain drug concentrations. Morphine, a drug with delayed clinical onset, is a substrate for the efflux transporter P-glycoprotein in vitro and in animals. This investigation tested whether morphine is a transporter substrate in humans. Methods Fourteen healthy volunteers received morphine (0.1 mg/kg, 1 h intravenous infusion) in a crossover study after nothing (control) or the validated P-glycoprotein inhibitor cyclosporine (5 mg/kg, 2 h infusion). Plasma and urine morphine and morphine glucuronide metabolite concentrations were measured by mass spectrometry. Morphine effects were measured by miosis and analgesia. Results Cyclosporine minimally altered morphine disposition, increasing the area under the plasma morphine concentration versus time curve to 100 ± 21 versus 85 ± 24 ng/ml•hr (p Cyclosporine enhanced (3.2 ± 0.9 vs. 2.5 ± 1.0 mm peak) and prolonged miosis, and increased the area under the miosis-time curve (18 ± 9 vs. 11 ± 5 mm-hr), plasma-effect site transfer rate constant (ke0, median 0.27 vs. 0.17 hr−1), and maximum calculated effect site morphine concentration (11.5 ± 3.7 vs. 7.6 ± 2.9 ng/ml) (all p cyclosporine-related pain. Conclusions Morphine is a transporter substrate at the human blood-brain barrier. Results suggest a role for P-glycoprotein or other efflux transporters in brain morphine access, although the magnitude of the effect is small, and unlikely to be a major determinant of morphine clinical effects. Efflux may explain some variability in clinical morphine effects. PMID:23851346

  11. Blood

    Science.gov (United States)

    ... Also, blood is either Rh-positive or Rh-negative. So if you have type A blood, it's either A positive or A negative. Which type you are is important if you need a blood transfusion. And your Rh factor could be important ...

  12. High altitude hypoxia and blood pressure dysregulation in adult chickens.

    Science.gov (United States)

    Herrera, E A; Salinas, C E; Blanco, C E; Villena, M; Giussani, D A

    2013-02-01

    Although it is accepted that impaired placental perfusion in complicated pregnancy can slow fetal growth and programme an increased risk of cardiovascular dysfunction at adulthood, the relative contribution of reductions in fetal nutrition and in fetal oxygenation as the triggering stimulus remains unclear. By combining high altitude (HA) with the chick embryo model, we have previously isolated the direct effects of HA hypoxia on embryonic growth and cardiovascular development before hatching. This study isolated the effects of developmental hypoxia on cardiovascular function measured in vivo in conscious adult male and female chickens. Chick embryos were incubated, hatched and raised at sea level (SL, nine males and nine females) or incubated, hatched and raised at HA (seven males and seven females). At 6 months of age, vascular catheters were inserted under general anaesthesia. Five days later, basal blood gas status, basal cardiovascular function and cardiac baroreflex responses were investigated. HA chickens had significantly lower basal arterial PO2 and haemoglobin saturation, and significantly higher haematocrit than SL chickens, independent of the sex of the animal. HA chickens had significantly lower arterial blood pressure than SL chickens, independent of the sex of the animal. Although the gain of the arterial baroreflex was decreased in HA relative to SL male chickens, it was increased in HA relative to SL female chickens. We show that development at HA lowers basal arterial blood pressure and alters baroreflex sensitivity in a sex-dependent manner at adulthood.

  13. Administration of Traditional Chinese Blood Circulation Activating Drugs for Microvascular Complications in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Lisha He

    2016-01-01

    Full Text Available Traditional Chinese medicine (TCM is an important complementary strategy for treating diabetes mellitus (DM in China. Traditional Chinese blood circulation activating drugs are intended to guide an overall approach to the prevention and treatment of microvascular complications of DM. The core mechanism is related to the protection of the vascular endothelium and the basement membrane. Here, we reviewed the scientific evidence underpinning the use of blood circulation activating drugs to prevent and treat DM-induced microvascular complications, including diabetic nephropathy (DN, diabetic peripheral neuropathy (DPN, and diabetic retinopathy (DR. Furthermore, we summarized the effects and mechanism of TCM on improving blood rheology, inhibiting aggregation of platelet, forming advanced glycation end products (AGEs, regulating oxidative stress, reducing blood fat, and improving lipid metabolism. The paper provides a new theoretical basis for the clinical practice of TCM in the prevention and treatment of DM and its microvascular complications.

  14. Blood pressure percentile charts to identify high or low blood pressure in children.

    Science.gov (United States)

    Banker, Ashish; Bell, Cynthia; Gupta-Malhotra, Monesha; Samuels, Joshua

    2016-07-19

    The goal was to develop familiar blood pressure (BP) charts representing BP percentile curves similar to CDC growth charts to improve screening of both high and low BP in children. Since height accounts for substantially more BP variability than age and is a more direct measure of body size and maturation in children, height-specific BP percentile curves were drawn separately for males and females. We used the 2004 Fourth Report data source and equations to calculate the BP threshold value for each gender and 5 cm height group. By slightly underestimating a child's BP percentile for high BP and slightly overestimating a child's BP percentile for low BP, these charts guarantee 100 % sensitivity in detecting abnormal BP. Sensitivity and specificity of the chart cut-offs were confirmed in a sample of 1254 healthy children from a school-based blood pressure screening program. The 1st, 5th, 25th, 50th, 75th, 90th, 95th, and 99th BP percentile curves are depicted in the chart for each corresponding gender and height from 85 to 190 cm, mimicking the ubiquitous CDC "growth charts". Shaded areas of the chart differentiate abnormal BP status categories: hypotension, normal BP, prehypertension, Stage 1 hypertension, and Stage 2 hypertension. Sensitivity was confirmed to be 100 % with specificity above 94 %. These simplified BP charts improve upon currently available BP screening reference with the following features: (a) tracking BP longitudinally in an individual child, (b) full physiological range of BP percentiles represented in percentile curve format for rapid identification both high and low BP, (c) easy to use with absolute height alone avoiding the additional step of determining height percentile, (d) incorporation of adult threshold for pre-hypertension to assist in accurate transition from adolescence into adulthood, (e) high sensitivity and specificity to ensure all children at risk are identified with very few false positives.

  15. Thirty-two Cases of Acne Treated with Blood-letting Puncture,Cupping and Chinese-Drug Facemask

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To observe the therapeutic effect on acne treated with blood-letting puncture, cupping and Chinese-drug facemask. Thirty-two patients with acne were treated with above-mentioned therapeutic method. Cure,improvement and ineffectiveness were respectively found in 24, 7 and 1 case, with a curative rate of 75.0% and a total effective rate of 96.8%. The combination of blood-letting puncture, cupping and external application of Chinese-drug facemask is effective in treating acne.

  16. Chronic Diarrhea Associated with High Teriflunomide Blood Concentration

    OpenAIRE

    Duquette, André; Frenette, Anne Julie; Doré, Maxime

    2016-01-01

    Objective To report the case of a patient treated with leflunomide that presented with chronic diarrhea associated with high teriflunomide blood concentration. Case Summary An 84-year-old woman taking leflunomide 20 mg once daily for the past 2 years to treat rheumatoid arthritis (RA) was investigated for severe chronic diarrhea that had been worsening for the past 5 months. The patient’s general condition progressively deteriorated and included electrolyte imbalances and a transient loss of ...

  17. Characterization of blood donors with high haemoglobin concentration

    DEFF Research Database (Denmark)

    Magnussen, K; Hasselbalch, H C; Ullum, H;

    2013-01-01

    Background and Objectives  The literature contains little on the prevalence and causes of high predonation haemoglobin levels among blood donors. This study aimed to characterize and develop an algorithm to manage would-be donors with polycythaemia. Materials and Methods  Between November 2009......, erythropoietin, ferritin, platelet count and leucocyte count, JAK2 V617 and JAK2 exon12 analysis, as well as other routine measurements. Results  Among 46 such donors, 39 had a history of smoking, which contributes to erythrocytosis. Two had PV, five had severe hypertension, one of them because of renal artery...

  18. Gamma-hydroxybutyrate concentrations in the blood of impaired drivers, users of illicit drugs, and medical examiner cases.

    Science.gov (United States)

    Jones, A Wayne; Holmgren, Anita; Kugelberg, Fredrik C

    2007-01-01

    Gamma-hydroxybutyrate (GHB) was determined in blood samples from impaired drivers, people arrested for petty drug offenses (non-traffic cases), and GHB-related deaths. The method of analysis involved conversion of GHB into gamma-butyrolactone and determination of the latter by gas chromatography with a flame ionization detector, and with gamma-valerolactone as the internal standard. The mean and median concentrations of GHB in blood from impaired drivers (N=473) were 90 and 84 mg/L, respectively, and offenders were predominantly men (96%) with an average age of 26 year (range 15-50 year). In 185 cases, GHB was the only drug present in blood at mean and median concentrations of 92 and 86 mg/L, respectively. People arrested for petty drug offenses (N=1061) had slightly higher GHB concentrations in their blood: median 118 mg/L for men and 111 mg/L for women. In GHB-related deaths (N=33), the mean and median concentrations were considerably higher: 307 mg/L and 190 mg/L, respectively, and the highest was 2200 mg/L. The typical signs of drug influence noted by the arresting police officers included sedation, agitation, slurred speech, irrational behaviour, jerky movements, and spitting. The short elimination half-life of GHB means that the concentrations in blood decrease rapidly and are probably a lot lower than at the time of driving, which was 30-90 min earlier.

  19. How will the growing threat of resistant hypertension impact the future treatment of high blood pressure?

    Science.gov (United States)

    Lackland, Daniel T

    2013-11-01

    Hypertension treatment and control efforts represent a major component of primary care with dedicated clinical guidelines and recommendations. However, high blood pressure (BP) control rates are complicated with the difficult to treat and resistant hypertensive patients. This category of patient, therefore, affects the development and implementation of the clinical guidelines. The recommendations of specific algorithms for resistant hypertension and difficult-to-treat patients with elevated BPs have been developed in consideration of new therapies and combination drug treatment. Hypertension treatment guidelines include and will continue to grade evidence from randomized clinical trials with detailed strategies on the management of these high-risk patients. Although resistant hypertension affects high BP control rates, the inclusion of refined pharmaceutical and device treatment strategies in evidence-based guidelines will be expected to have a significant impact on the clinical management of this high-risk patient population.

  20. A Screening Method Using LC-MS MS for Illicit Drugs in Postmortem Blood an Application to 62 Postmortem Cases

    Directory of Open Access Journals (Sweden)

    Serap Annette Akgür

    2007-04-01

    Full Text Available Screening of biological specimens in the presence of illicit drugs is of great importance, particularly in criminal cases. The most relevant matrices to be analyzed for this purpose are plasma or blood, due to providing a good correlation between their concentration and pharmacological effects. For majority of laboratories, a common method for screening illicit drugs has been immunoassay methods and Gas Chromatography-coupled with Mass Spectrometry (GC-MS that is widely employed for confirmation purposes. However, the widespread use of liquid chromatography coupled single-stage or tandem mass spectrometry (LC-MS, LC-MS/MS is becoming increasingly significant for both qualitative and quantitative analysis of target analyse which could be polar and thermally labile. This assay method, consisted of morphine, (±-amphetamine, (±-methamphetami-ne, cocaine, benzoylecgonine, cocaethylene and (--ll-nor-9-car-boxy-c9-THC was based on the detection of LC-ESI-MS. In this study, LC-MS/MS method for illicit drugs in postmortem blood was developed. These data provided a documentation to use LC-MS/MS technique without any precipitation for postmortem blood to detect low concentrations of some illicit drugs and applied to 62 postmortem forensic cases. Key words: Illicit drug, screening, LC-MS/MS, postmortem blood

  1. Multiprofessional Treatment of High Blood Pressure in Very Elderly Patients

    Science.gov (United States)

    Jardim, Luciana Muniz Sanches Siqueira Veiga; Jardim, Thiago Veiga; de Souza, Weimar Kunz Sebba Barroso; Pimenta, Camila Dutra; Sousa, Ana Luiza Lima; Jardim, Paulo César Brandão Veiga

    2017-01-01

    Background As the world population ages, patients older than 80 years, known as very elderly, are more frequently found. There are no studies in this age group aimed at analyzing the multidisciplinary intervention in the treatment of systemic arterial hypertension (SAH) and some comorbidities. Objectives To assess the effect of a multidisciplinary approach in very elderly hypertensives cared for at a specialized service. Methods Longitudinal retrospective cohort study in a multidisciplinary service specialized in the SAH treatment in the Brazilian West-Central region. Patients aged 80 years and older by June 2015 were included. Data from the first (V1) and last visit (Vf) were assessed. Anthropometric variables, blood pressure (BP), renal function, pharmacological treatment, lifestyle, comorbidities and cardiovascular events were studied, comparing data from V1 and Vf. Controlled BP was defined as systolic blood pressure (SBP) lower than 140 mm Hg and diastolic blood pressure (DBP) lower than 90 mm Hg. Statistical analyses were performed with SPSSR software, version 21.0. Values of p<0,05 were considered significant. Results Data of 71 patients were assessed with a mean follow-up time of 15,22 years. Their mean age at V1 was 69.2 years, and, at Vf, 84.53 years, and 26.8% of them were males. There was a significant reduction in mean SBP (157.3 x 142.1 mm Hg; p<0.001) and DBP (95.1 x 77.8 mm Hg; p<0.001), with an increase in BP control rates from V1 to Vf (36.6 x 83.1%; p<0.001). The number of antihypertensive drugs used increased (1.49 x 2.85; p<0.001), with an increase in the use of angiotensin-converting enzyme inhibitors (22.5 x 46.5%; p=0.004), angiotensin II receptor blockers (4.2 x 35.2%; p<0.001) and calcium-channel blockers (18.3 x 67.6%; p<0.001). There was a reduction in total cholesterol (217.9 x 191 mg/dL; p<0.001) and LDL-cholesterol (139.6 x 119.0 mg/dL; p<0.001), but worsening of the glomerular filtration rate (62.5 x 45.4 mL/min; p<0.001). Conclusion

  2. Contribution of parental blood pressures to association between low birth weight and adult high blood pressure: cross sectional study

    Science.gov (United States)

    Walker, Brian R; McConnachie, Alex; Noon, Joseph P; Webb, David J; Watt, Graham C M

    1998-01-01

    Objective: To examine the possibility that low birth weight is a feature of the inherited predisposition to high blood pressure. Design: Cross sectional study. Setting: Primary care medical centre in Edinburgh. Subjects: One offspring of 452 families (231 men and 221 women aged 16-26 years) in whom blood pressure, weight, and height were measured in 1986 and whose parents had blood pressure measured in 1979. Birth weights were obtained from case records (270 offspring) or by questionnaires sent to the mothers (182 offspring). Main outcome measures: Birth weight and adult systolic blood pressure in offspring in relation to parental blood pressure. Results: If parental blood pressures were not considered, a 1 kg decrease in birth weight was associated with a 2.24 mm Hg increase in systolic blood pressure of offspring (P=0.06) after correction for current weight and sex. However, parental blood pressures correlated positively with blood pressure of offspring, and higher maternal blood pressure was associated with lower birth weight (−3.03 g/mm Hg, Ppressures, a 1 kg decrease in birth weight was associated with only a 1.71 mm Hg increase in the systolic blood pressure of the offspring (P=0.15). Conclusions: Low birth weight is a feature of the inherited predisposition to hypertension, perhaps because it is associated with higher maternal blood pressure during pregnancy. Parental blood pressure may be an important confounding factor in the relation between low birth weight and subsequent hypertension. Key messages Hypertension has both inherited and environmental causes The relation between low birth weight and hypertension in later life may result from the mother’s nutritional environment during pregnancy This study found that mothers who have higher blood pressure in later life deliver babies with lower birth weight, who also develop higher blood pressure Hereditary factors therefore explain part of the relation between low birth weight and adult

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

    Directory of Open Access Journals (Sweden)

    Benjamin S Bleier

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  5. Stretching Behavior of Red Blood Cells at High Strain Rates

    Science.gov (United States)

    Mancuso, Jordan; Ristenpart, William

    2016-11-01

    Most work on the mechanical behavior of red blood cells (RBCs) has focused on simple shear flows. Relatively little work has examined RBC deformations in the physiologically important extensional flow that occurs at the entrance to a constriction. In particular, previous work suggests that RBCs rapidly stretch out and then retract upon entering the constriction, but to date no model predicts this behavior for the extremely high strain rates typically experienced there. In this work, we use high speed video to perform systematic measurements of the dynamic stretching behavior of RBCs as they enter a microfluidic constriction. We demonstrate that a simple viscoelastic model captures the observed stretching dynamics, up to strain rates as high as 1000 s-1. The results indicate that the effective elastic modulus of the RBC membrane at these strain rates is an order of magnitude larger than moduli measured by micropipette aspiration or other low strain rate techniques.

  6. 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.

  7. Microfluidic cell chips for high-throughput drug screening.

    Science.gov (United States)

    Chi, Chun-Wei; Ahmed, Ah Rezwanuddin; Dereli-Korkut, Zeynep; Wang, Sihong

    2016-05-01

    The current state of screening methods for drug discovery is still riddled with several inefficiencies. Although some widely used high-throughput screening platforms may enhance the drug screening process, their cost and oversimplification of cell-drug interactions pose a translational difficulty. Microfluidic cell-chips resolve many issues found in conventional HTS technology, providing benefits such as reduced sample quantity and integration of 3D cell culture physically more representative of the physiological/pathological microenvironment. In this review, we introduce the advantages of microfluidic devices in drug screening, and outline the critical factors which influence device design, highlighting recent innovations and advances in the field including a summary of commercialization efforts on microfluidic cell chips. Future perspectives of microfluidic cell devices are also provided based on considerations of present technological limitations and translational barriers.

  8. Molecularly imprinted solid-phase extraction for the selective determination of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs in human whole blood by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Kumazawa, Takeshi; Hasegawa, Chika; Hara, Kenji; Uchigasaki, Seisaku; Lee, Xiao-Pen; Seno, Hiroshi; Suzuki, Osamu; Sato, Keizo

    2012-03-01

    A novel method is described for the extraction of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxy-methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine, and 3,4-(methylenedioxyphenyl)-2-butanamine, from human whole blood using molecularly imprinted solid-phase extraction as highly selective sample clean-up technique. Whole blood samples were diluted with 10 mmol/L ammonium acetate (pH 8.6) and applied to a SupelMIP-Amphetamine molecularly imprinted solid-phase extraction cartridge. The cartridge was then washed to eliminate interferences, and the amphetamines of interest were eluted with formic acid/methanol (1:100, v/v). After derivatization with trifluoroacetic anhydride, the analytes were quantified using gas chromatography-mass spectrometry. Recoveries of the seven amphetamines spiked into whole blood were 89.1-102%. The limits of quantification for each compound in 200 μL of whole blood were between 0.25 and 1.0 ng. The maximum intra- and inter-day coefficients of variation were 9.96 and 13.8%, respectively. The results show that methamphetamine, amphetamine, and methylenedioxyphenylalkyl-amine designer drugs can be efficiently extracted from crude biological samples such as whole blood by molecularly imprinted solid-phase extraction with good reproducibility. This extraction method will be useful for the pretreatment of human samples before gas chromatography-mass spectrometry.

  9. 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.

  10. 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.

  11. BCS class IV drugs: Highly notorious candidates for formulation development.

    Science.gov (United States)

    Ghadi, Rohan; Dand, Neha

    2017-02-28

    BCS class IV drugs (e.g., amphotericin B, furosemide, acetazolamide, ritonavir, paclitaxel) exhibit many characteristics that are problematic for effective oral and per oral delivery. Some of the problems associated include low aqueous solubility, poor permeability, erratic and poor absorption, inter and intra subject variability and significant positive food effect which leads to low and variable bioavailability. Also, most of the class IV drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP3A4 (extensive pre systemic metabolism) which further potentiates the problem of poor therapeutic potential of these drugs. A decade back, extreme examples of class IV compounds were an exception rather than the rule, yet today many drug candidates under development pipeline fall into this category. Formulation and development of an efficacious delivery system for BCS class IV drugs are herculean tasks for any formulator. The inherent hurdles posed by these drugs hamper their translation to actual market. The importance of the formulation composition and design to successful drug development is especially illustrated by the BCS class IV case. To be clinically effective these drugs require the development of a proper delivery system for both oral and per oral delivery. Ideal oral dosage forms should produce both a reasonably high bioavailability and low inter and intra subject variability in absorption. Also, ideal systems for BCS class IV should produce a therapeutic concentration of the drug at reasonable dose volumes for intravenous administration. This article highlights the various techniques and upcoming strategies which can be employed for the development of highly notorious BCS class IV drugs. Some of the techniques employed are lipid based delivery systems, polymer based nanocarriers, crystal engineering (nanocrystals and co-crystals), liquisolid technology, self-emulsifying solid dispersions and miscellaneous techniques addressing the P

  12. Evaluation of sphingomyelin, cholester, and phosphatidylcholine-based immobilized artificial membrane liquid chromatography to predict drug penetration across the blood-brain barrier.

    Science.gov (United States)

    De Vrieze, Mike; Verzele, Dieter; Szucs, Roman; Sandra, Pat; Lynen, Frédéric

    2014-10-01

    Over the past decades, several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier. So far, in high-performance liquid chromatography, most attention has been paid to micellar liquid chromatography and immobilized artificial membrane (IAM) LC. IAMLC has been described as a viable approach, since the stationary phase emulates the lipid environment of a cell membrane. However, research in IAMLC has almost exclusively been limited to phosphatidylcholine (PC)-based stationary phases, even though PC is only one of the lipids present in cell membranes. In this article, sphingomyelin and cholester stationary phases have been tested for the first time towards their ability to predict drug penetration across the blood-brain barrier. Upon comparison with the PC stationary phase, the sphingomyelin- and cholester-based columns depict similar predictive performance. Combining data from the different stationary phases did not lead to improvements of the models.

  13. [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.

  14. Nanotech revolution for the anti-cancer drug delivery through blood-brain barrier.

    Science.gov (United States)

    Caraglia, M; De Rosa, G; Salzano, G; Santini, D; Lamberti, M; Sperlongano, P; Lombardi, A; Abbruzzese, A; Addeo, R

    2012-03-01

    Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the bloodbrain- barrier (BBB) that protects brain from toxicological injuries but, at the same time, makes impossible for most of the pharmacological agents with anti-cancer activity to reach tumour cells placed in the brain and derived from either primary tumours or metastases. In fact, only highly lipophilic molecules can passively diffuse through BBB to reach central nervous system (CNS). Another possibility is to use nanotechnological approaches as powerful tools to across BBB, by both prolonging the plasma half-life of the drugs and crossing fenestrations of BBB damaged by brain metastases. Moreover, modifications of nanocarrier surface with specific endogenous or exogenous ligands can promote the crossing of intact BBB as in the case of primary brain tumours. This aim can be achieved through the binding of the nanodevices to carriers or receptors expressed by the endothelial cells of BBB and that can favour the internalization of the nanostructured devices delivering anti-cancer drugs. This review summarizes the most meaningful advances in the field of nanotechnologies for brain delivery of drugs.

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

    Science.gov (United States)

    McDannold, Nathan; Zhang, Yongzhi; Power, Chanikarn; Arvanitis, Costas D.; Vykhodtseva, Natalia; Livingstone, Margaret

    2015-05-01

    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. The method presents new opportunities for the use of drugs and for the study of the brain.

  16. Highly active ozonides selected against drug resistant malaria

    Science.gov (United States)

    Lobo, Lis; de Sousa, Bruno; Cabral, Lília; Cristiano, Maria LS; Nogueira, Fátima

    2016-01-01

    Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART), artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites. PMID:27276364

  17. Highly active ozonides selected against drug resistant malaria

    Directory of Open Access Journals (Sweden)

    Lis Lobo

    2016-01-01

    Full Text Available Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART, artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites.

  18. More Folic Acid in Pregnancy May Protect Kids from High Blood Pressure

    Science.gov (United States)

    ... Folic Acid in Pregnancy May Protect Kids From High Blood Pressure If mothers have heart disease risk factors, nutrient ... levels during pregnancy may reduce the risk of high blood pressure in children if their mothers have heart disease ...

  19. Many People Don't Take Their High Blood Pressure Meds

    Science.gov (United States)

    ... 163928.html Many People Don't Take Their High Blood Pressure Meds: Study Failure to follow doctors' orders leads ... 20 percent of patients seeking care for stubborn high blood pressure take all the medicine they're supposed to, ...

  20. 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...... 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...... may affect the normal physiology of the animals....

  1. Rapid screening of 10 drugs in blood using ultra performance liquid chromatography with high resolution quadrupole-time-of-flight mass spectrometry%超高效液相色谱-四极杆-飞行时间质谱法快速筛查血液中10种常见毒物

    Institute of Scientific and Technical Information of China (English)

    石银涛; 王绘军; 郭璟琦; 丁静; 王俊伟

    2016-01-01

    A high-throughput method was developed for rapid screening of 10 drugs in blood by ultra performance liquid chromatography with high resolution quadrupole-time-of-flight mass spectrometry( UPLC-Q-TOF/MS). The sample was extracted by ethyl acetate,the extraction solution was concentrated to near dryness,and dissolved with methanol. Then the sample was passed through a 0. 22 μm membrane. The separation of the 10 target compounds was per-formed on a Waters ACQUITY UPLC@BEH C18 column(100 mm×2. 1 mm,1. 7 μm)with gra-dient elution using methanol and 0. 1%( v/v)formic acid aqueous solution as mobile phases, and analyzed by UPLC-Q-TOF/MS under electrospray ionization ( ESI ) mode with scanning range of m/z 50-1 000. Rapid screening can be achieved using MS matching scores,deviation of retention time,measured mass,isotopic abundance matching scores,isotope spacing match scores and MS/MS matching scores. Good linearities were observed in the range of 10. 0-500. 0μg/L with the correlation coefficients from 0. 990 8 to 0. 995 8. The limits of detection and the limits of quantification were 1. 0-2. 0 μg/L and 4. 0-8. 0 μg/L,respectively. The spiked recov-eries were 56. 7% -83. 0% with the relative standard deviations of 3. 6% -8. 9%. The result screening database was built using Agilent Mass Hunter PCDL Manager software and then used for the analysis of spiked samples. MS matching scores,isotopic abundance matching scores, isotope spacing matching scores(all > 90 points)and MS/MS matching scores(> 70 points) were applied to identify the drugs. The results showed that all the spiked drugs could be cor-rectly identified with low deviations of retention time(< 0. 1 min)and mass(< 1 mDa). The developed method is suitable for the screening and confirmation of the drugs in forensic and clinical analytical toxicology.%建立了超高效液相色谱-四极杆-飞行时间串联质谱( UPLC-Q-TOF/MS)快速筛查血液中10种毒物的检测方法。用乙酸乙酯提取

  2. High throughput screening for anti-Trypanosoma cruzi drug discovery.

    Science.gov (United States)

    Alonso-Padilla, Julio; Rodríguez, Ana

    2014-12-01

    The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease, stands as a fundamental need. Currently, there are only two drugs available to treat this neglected disease, which represents a major public health problem in Latin America. Both available therapies, benznidazole and nifurtimox, have significant toxic side effects and their efficacy against the life-threatening symptomatic chronic stage of the disease is variable. Thus, there is an urgent need for new, improved anti-T. cruzi drugs. With the objective to reliably accelerate the drug discovery process against Chagas disease, several advances have been made in the last few years. Availability of engineered reporter gene expressing parasites triggered the development of phenotypic in vitro assays suitable for high throughput screening (HTS) as well as the establishment of new in vivo protocols that allow faster experimental outcomes. Recently, automated high content microscopy approaches have also been used to identify new parasitic inhibitors. These in vitro and in vivo early drug discovery approaches, which hopefully will contribute to bring better anti-T. cruzi drug entities in the near future, are reviewed here.

  3. High throughput screening for anti-Trypanosoma cruzi drug discovery.

    Directory of Open Access Journals (Sweden)

    Julio Alonso-Padilla

    2014-12-01

    Full Text Available The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease, stands as a fundamental need. Currently, there are only two drugs available to treat this neglected disease, which represents a major public health problem in Latin America. Both available therapies, benznidazole and nifurtimox, have significant toxic side effects and their efficacy against the life-threatening symptomatic chronic stage of the disease is variable. Thus, there is an urgent need for new, improved anti-T. cruzi drugs. With the objective to reliably accelerate the drug discovery process against Chagas disease, several advances have been made in the last few years. Availability of engineered reporter gene expressing parasites triggered the development of phenotypic in vitro assays suitable for high throughput screening (HTS as well as the establishment of new in vivo protocols that allow faster experimental outcomes. Recently, automated high content microscopy approaches have also been used to identify new parasitic inhibitors. These in vitro and in vivo early drug discovery approaches, which hopefully will contribute to bring better anti-T. cruzi drug entities in the near future, are reviewed here.

  4. 中药活血化淤法改善脑出积压患者运动功能疗效观察%Observation of improvement of movement function by Chinese drugs through promoting circulation by removing blood stasis in patients with brain hemorrhage

    Institute of Scientific and Technical Information of China (English)

    尹德铭; 高聪; 沈岩松

    2002-01-01

    @@ Background:Disability rate following brain hemorrhage is high.Rcovery and improvement of movement function is closely related to management of brain hemorrhage during acute phage,absorption of hematoma.According to traditional medicine principle,Chinese drugs promote absorption and functional recovery through promoting blood circulation by removing blood stasis.The Chinese drugs are safe in clinic

  5. 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.

    2015-01-01

    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 p

  6. Quantitative analysis of antiretroviral drugs in lysates of peripheral blood mononuclear cells using MALDI-triple quadrupole mass spectrometry.

    NARCIS (Netherlands)

    Kampen, JJ van; Burgers, P.C.; Gruters, R.A.; Osterhaus, A.D.; Groot, R. de; Luider, T.M.; Volmer, D.A.

    2008-01-01

    We report here on the use of a prototype matrix-assisted laser desorption/ionization (MALDI)-triple quadrupole mass spectrometer for quantitative analysis of six antiretroviral drugs in lysates of peripheral blood mononuclear cells (PBMC). Of the five investigated MALDI matrixes, 2,5-dihydroxybenzoi

  7. High throughput electrophysiology: new perspectives for ion channel drug discovery.

    Science.gov (United States)

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter; Jensen, Bo Skaaning; Korsgaard, Mads P G; Christophersen, Palle

    2003-01-01

    Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels. A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion channel targets accessible for drug screening. Specifically, genuine HTS parallel processing techniques based on arrays of planar silicon chips are being developed, but also lower throughput sequential techniques may be of value in compound screening, lead optimization, and safety screening. The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery.

  8. High blood pressure in school children: prevalence and risk factors

    Directory of Open Access Journals (Sweden)

    Rivers Patrick A

    2006-11-01

    Full Text Available Abstract Background The purpose of this study was to determine the prevalence of high blood pressure (HBP and associated risk factors in school children 8 to 13 years of age. Methods Elementary school children (n = 1,066 were examined. Associations between HBP, body mass index (BMI, gender, ethnicity, and acanthosis nigricans (AN were investigated using a school based cross-sectional study. Blood pressure was measured and the 95th percentile was used to determine HBP. Comparisons between children with and without HBP were utilized. The crude and multiple logistic regression adjusted odds ratios were used as measures of association. Results Females, Hispanics, overweight children, and children with AN had an increased likelihood of HBP. Overweight children (BMI ≥ 85th percentile and those with AN were at least twice as likely to present with HBP after controlling for confounding factors. Conclusion Twenty one percent of school children had HBP, especially the prevalence was higher among the overweight and Hispanic group. The association identified here can be used as independent markers for increased likelihood of HBP in children.

  9. Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis

    Directory of Open Access Journals (Sweden)

    Hunter Kerry

    2012-03-01

    Full Text Available Abstract Background Type 2 diabetes is a risk factor for Alzheimer's disease (AD, most likely linked to an impairment of insulin signalling in the brain. Therefore, drugs that enhance insulin signalling may have therapeutic potential for AD. Liraglutide (Victoza and exenatide (Byetta are novel long-lasting analogues of the GLP-1 incretin hormone and are currently available to treat diabetes. They facilitate insulin signalling via the GLP-1 receptor (GLP-1R. Numerous in vitro and in vivo studies have shown that GLP-1 analogues have a range of neuroprotective properties. GLP-1Rs are expressed in the hippocampal area of the brain an important site of adult neurogenesis and maintenance of cognition and memory formation. Therefore, if GLP-1 analogues can cross the blood brain barrier, diffuse through the brain to reach the receptors and most importantly activate them, their neuroprotective effects may be realized. Results In the present study we profiled the GLP-1 receptor agonists liraglutide (Victoza and lixisenatide (Lyxumia. We measured the kinetics of crossing the blood brain barrier (BBB, activation of the GLP-1R by measuring cAMP levels, and physiological effects in the brain on neuronal stem cell proliferation and neurogenesis. Both drugs were able to cross the BBB. Lixisenatide crossed the BBB at all doses tested (2.5, 25, or 250 nmol/kg bw ip. when measured 30 min post-injection and at 2.5-25 nmol/kg bw ip. 3 h post-injection. Lixisenatide also enhanced neurogenesis in the brain. Liraglutide crossed the BBB at 25 and 250 nmol/kg ip. but no increase was detectable at 2.5 nmol/kg ip. 30 min post-injection, and at 250 nmol/kg ip. at 3 h post-injection. Liraglutide and lixisenatide enhanced cAMP levels in the brain, with lixisenatide being more effective. Conclusions Our results suggest that these novel incretin analogues cross the BBB and show physiological activity and neurogenesis in the brain, which may be of use as a treatment of

  10. Novel, high-yield red blood cell production methods from CD34-positive cells derived from human embryonic stem, yolk sac, fetal liver, cord blood, and peripheral blood.

    Science.gov (United States)

    Olivier, Emmanuel; Qiu, Caihong; Bouhassira, Eric E

    2012-08-01

    The current supply of red blood cells expressing rare blood groups is not sufficient to cover all the existing transfusion needs for chronically transfused patients, such as sickle cell disease homozygous carriers, because of alloimmunization. In vitro production of cultured red blood cells is slowly emerging as a possible complement to the existing collection-based red blood cell procurement system. The yield of cultured red blood cells can theoretically be maximized by amplifying the stem, progenitor, or precursor compartment. Here, we combined methods designed to expand these three compartments to optimize the yield of cultured red blood cells and found that exposing CD34(+) cells to a short pulse of cytokines favorable for erythroid differentiation prior to stem cell expansion followed by progenitor expansion produced the highest yield of erythroid cells. This novel serum-free red blood cell production protocol was efficient on CD34(+) cells derived from human embryonic stem cells, 6-8-week yolk sacs, 16-18-week fetal livers, cord blood, and peripheral blood. The yields of cells obtained with these new protocols were larger by an order of magnitude than the yields observed previously. Globin expression analysis by high-performance liquid chromatography revealed that these expansion protocols generally yielded red blood cells that expressed a globin profile similar to that expected for the developmental age of the CD34(+) cells.

  11. How to Prevent High Blood Pressure: MedlinePlus Health Topic

    Science.gov (United States)

    ... medicines that are causing it. Who is at risk for high blood pressure? Anyone can develop high blood pressure, but there ... it. Lifestyle - Certain lifestyle habits can raise your risk for high blood pressure, such as eating too much sodium or not ...

  12. Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs.

    Science.gov (United States)

    Evans, Brian C; Nelson, Christopher E; Yu, Shann S; Beavers, Kelsey R; Kim, Arnold J; Li, Hongmei; Nelson, Heather M; Giorgio, Todd D; Duvall, Craig L

    2013-03-09

    Phospholipid bilayers that constitute endo-lysosomal vesicles can pose a barrier to delivery of biologic drugs to intracellular targets. To overcome this barrier, a number of synthetic drug carriers have been engineered to actively disrupt the endosomal membrane and deliver cargo into the cytoplasm. Here, we describe the hemolysis assay, which can be used as rapid, high-throughput screen for the cytocompatibility and endosomolytic activity of intracellular drug delivery systems. In the hemolysis assay, human red blood cells and test materials are co-incubated in buffers at defined pHs that mimic extracellular, early endosomal, and late endo-lysosomal environments. Following a centrifugation step to pellet intact red blood cells, the amount of hemoglobin released into the medium is spectrophotometrically measured (405 nm for best dynamic range). The percent red blood cell disruption is then quantified relative to positive control samples lysed with a detergent. In this model system the erythrocyte membrane serves as a surrogate for the lipid bilayer membrane that enclose endo-lysosomal vesicles. The desired result is negligible hemolysis at physiologic pH (7.4) and robust hemolysis in the endo-lysosomal pH range from approximately pH 5-6.8.

  13. Getting to the Root of High Prescription Drug Prices.

    Science.gov (United States)

    Waxman, Henry; Corr, Bill; Martin, Kristi; Duong, Sophia

    2017-07-01

    ISSUE: Historic increases in prescription drug prices and spending are contributing to unsustainable health care costs in the United States. There is widespread public support for elected officials to address the problem. GOAL: To document the drivers of high U.S. prescription drug prices and offer a broad range of feasible policy actions. METHODS: Interviews with experts and organizations engaged with prescription drug development and utilization, pricing, regulation, and clinical practice. Review of policy documents, proposals, and position statements from a variety of stakeholders. FINDINGS AND CONCLUSIONS: Congress and regulators can undertake a wide range of policy actions to begin to rebalance incentives for innovation and price competition, prioritize patient access and affordability, and maximize the availability of information to patients, providers, and payers.

  14. High throughput screening for drug discovery of autophagy modulators.

    Science.gov (United States)

    Shu, Chih-Wen; Liu, Pei-Feng; Huang, Chun-Ming

    2012-11-01

    Autophagy is an evolutionally conserved process in cells for cleaning abnormal proteins and organelles in a lysosome dependent manner. Growing studies have shown that defects or induced autophagy contributes to many diseases including aging, neurodegeneration, pathogen infection, and cancer. However, the precise involvement of autophagy in health and disease remains controversial because the theories are built on limited assays and chemical modulators, indicating that the role of autophagy in diseases may require further verification. Many food and drug administration (FDA) approved drugs modulate autophagy signaling, suggesting that modulation of autophagy with pharmacological agonists or antagonists provides a potential therapy for autophagy-related diseases. This suggestion raises an attractive issue on drug discovery for exploring chemical modulators of autophagy. High throughput screening (HTS) is becoming a powerful tool for drug discovery that may accelerate screening specific autophagy modulators to clarify the role of autophagy in diseases. Herein, this review lays out current autophagy assays to specifically measure autophagy components such as LC3 (mammalian homologue of yeast Atg8) and Atg4. These assays are feasible or successful for HTS with certain chemical libraries, which might be informative for this intensively growing field as research tools and hopefully developing new drugs for autophagy-related diseases.

  15. Blood-brain barrier pathology in Alzheimer's and Parkinson's disease: implications for drug therapy.

    Science.gov (United States)

    Desai, Brinda S; Monahan, Angela J; Carvey, Paul M; Hendey, Bill

    2007-01-01

    The blood-brain barrier (BBB) is a tightly regulated barrier in the central nervous system. Though the BBB is thought to be intact during neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD), recent evidence argues otherwise. Dysfunction of the BBB may be involved in disease progression, eliciting of peripheral immune response, and, most importantly, altered drug efficacy. In this review, we will give a brief overview of the BBB, its components, and their functions. We will critically evaluate the current literature in AD and PD BBB pathology resulting from insult, neuroinflammation, and neurodegeneration. Specifically, we will discuss alterations in tight junction, transport and endothelial cell surface proteins, and vascular density changes, all of which result in altered permeability. Finally, we will discuss the implications of BBB dysfunction in current and future therapeutics. Developing a better appreciation of BBB dysfunction in AD and PD may not only provide novel strategies in treatment, but will prove an interesting milestone in understanding neurodegenerative disease etiology and progression.

  16. [THE TREATMENT OF HIGH BLOOD PRESSURE MUST BE TAILOR-MADE].

    Science.gov (United States)

    Krzesinski, J-M

    2015-01-01

    Hypertension has a high world-wide prevalence, affecting more than 25 % of the population; it remains the silent killer number one in cardiovascular pathology. Although lowering high blood pressure is protective, perfect control of hypertension is far from being optimal in spite of many international guidelines regularly updated according to published scientific studies. A personalized approach of hypertension management is an attractive way to improve this situation. Tools are developing (pharmacogenetics, pharmacometabolomics), but their use in daily clinical practice seems premature. At the present time, it is the physician experience which offers the best opportunity to propose the best treatment to the best patient. The management of hypertension remains a difficult task in some cases. Patient education is also crucial to improve drug compliance.

  17. Rapid Identification of Psychoactive Drugs in Drained Gastric Lavage Fluid and Whole Blood Specimens of Drug Overdose Patients Using Ambient Mass Spectrometry.

    Science.gov (United States)

    Lee, Chi-Wei; Su, Hung; Cai, You-Da; Wu, Ming-Tsang; Wu, Den-Chyang; Shiea, Jentaie

    2017-01-01

    Psychoactive drug overdoses are life-threatening and require prompt and proper treatment in the emergency room to minimize morbidity and mortality. Prompt identification of the ingested psychoactive drugs is challenging, since witness recall is unreliable and patients' symptoms do not necessarily explain their loss of consciousness. Gas and liquid chromatography mass spectrometric analyses have been the traditionally employed methods to detect and identify abused substances; however, these techniques are time-consuming and labor-intensive. In this study, thermal desorption electrospray ionization mass spectrometry, an ambient mass spectrometric technique, was applied to rapidly characterize flunitrazepam, lysergic acid diethylamide, and 3,4-methylenedioxy-methamphetamine in drained gastric lavage fluid, and ketamine, cocaine, amphetamine and norketamine in whole blood samples. No pretreatment of the gastric lavage fluid specimens was required and the entire analytical process took less than 30 s per specimen. Liquid-liquid extraction, followed by centrifugation, was performed on the whole blood samples. The corresponding compounds were identified through matching the obtained mass spectrometric data with those provided by commercial databases. The limits-of-detection of the tested drugs in both drained gastric lavage fluid and whole blood samples are at sub ppm levels. This is sensitive enough for emergency medical application, since the quantities of medications ingested by overdosed abusers are much higher than the amounts that were tested.

  18. Instability and "Sausage-String" Appearance in Blood Vessels during High Blood Pressure

    CERN Document Server

    Alstrøm, P; Colding-Jorgensen, M; Gustafsson, F; Holstein-Rathlou, N H; Alstrom, Preben; Eguiluz, Victor M.; Colding-Jorgensen, Morten; Gustafsson, Finn; Holstein-Rathlou, Niels-Henrik

    1999-01-01

    A new Rayleigh-type instability is proposed to explain the `sausage-string' pattern of alternating constrictions and dilatations formed in blood vessels under influence of a vasoconstricting agent. Our theory involves the nonlinear elasticity characteristics of the vessel wall, and provides predictions for the conditions under which the cylindrical form of a blood vessel becomes unstable.

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

    Science.gov (United States)

    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…

  20. In vivo wound healing activity of Dragon's Blood (Croton spp.), a traditional South American drug, and its constituents.

    Science.gov (United States)

    Pieters, L; De Bruyne, T; Van Poel, B; Vingerhoets, R; Totté, J; Vanden Berghe, D; Vlietinck, A

    1995-07-01

    The wound healing activity of dragon'sblood (Croton spp.), in Spanish 'sangre de drago‛ or 'sangre de grado‛, a traditional South American drug, and some of its constituents, including the alkaloid taspine (1), the dihydrobenzufuran lignan 3',4-O-dimethylcedrusin (2) and proantho-cyanidins, was evaluated in vivo on rats, and compared with the wound healing actitivy of synthetic proanthocyanidins. The beneficial effect of dragon's blood on wound healing was confirmed. Dragon's blood stimulated contraction of the wound, formation of a crust, formation of new collagen, and regeneration of the epithelial layer. 3',4-O-Dimethylcedrusin also improved wound healing in vivo by stimulating the formation of fibroblasts and collagen, but crude dragon's blood was more effective. This was due to the proanthocyanidins, present in dragon's blood, which stimulate contraction of the wound and precipitate with proteins forming a dark crust covering the wound, but which delay wound repair by a decreased formation of new fibroblasts.

  1. Drug-loaded bubbles with matched focused ultrasound excitation for concurrent blood-brain barrier opening and brain-tumor drug delivery.

    Science.gov (United States)

    Fan, Ching-Hsiang; Ting, Chien-Yu; Chang, Yuan-Chih; Wei, Kuo-Chen; Liu, Hao-Li; Yeh, Chih-Kuang

    2015-03-01

    Focused ultrasound (FUS) with microbubbles has been used to achieve local blood-brain barrier opening (BBB opening) and increase the penetration of therapeutic drugs into brain tumors. However, inertial cavitation of microbubbles during FUS-induced BBB opening causes intracerebral hemorrhaging (ICH), leading to acute and chronic brain injury and limiting the efficiency of drug delivery. Here we investigated whether induction of drug (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU)-loaded bubbles (BCNU bubbles) to oscillate at their resonant frequency would reduce inertial cavitation during BBB opening, thereby eliminating ICH and enhancing drug delivery in a rat brain model. FUS was tested at 1 and 10 MHz, over a wide range of pressure (mechanical index ranging from 0.16 to 1.42) in the presence of BCNU bubbles. Excitation of BCNU bubbles by resonance frequency-matched FUS (10 MHz) resulted in predominantly stable cavitation and significantly reduced the occurrence of potential hazards of exposure to biological tissues during the BBB opening process. In addition, the drug release process could be monitored by acoustic emission obtained from ultrasound imaging. In tumor-bearing animals, BCNU bubbles with FUS showed significant control of tumor progression and improved maximum survival from 26 to 35 days. This study provides useful advancements toward the goal of successfully translating FUS theranostic bubble-enhanced brain drug delivery into clinical use.

  2. 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

  3. 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 ...

  4. 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.

  5. Blood-Brain Barrier Changes in High Altitude.

    Science.gov (United States)

    Lafuente, José V; Bermudez, Garazi; Camargo-Arce, Lorena; Bulnes, Susana

    2016-01-01

    Cerebral syndromes related to high-altitude exposure are becoming more frequent as the number of trips to high altitudes has increased in the last decade. The commonest symptom is headache, followed by acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), which can be fatal. The pathophysiology of these syndromes is not fully understood. The classical "tight-fit hypothesis" posits that there are some anatomical variations that would obstruct the sinovenous outflow and worsen vasogenic edema and intracranial hypertension reactive to hypoxia. This could explain microhemorrhages seen in autopsies. However, recent magnetic resonance imaging studies have demonstrated some components of cytotoxic edema in HACE absent in AMS, suggesting a dysfunction in water balance at the cellular level. Currently, the "red-ox theory" supports trigemino-vascular system activation by free radicals formed after hypoxia and the consequent oxidative stress cascades. Apart from trigemino-vascular system activation, free radicals can also provoke membrane destabilisation mediated by lipid peroxidation, inflammation, and local hypoxia inducible factor-1α and vascular endothelial growth factor activation, resulting in gross blood-brain barrier (BBB) dysfunction. Besides alterations in endothelial cells such as increased pinocytotic vesicles and disassembly of interendothelial tight junction proteins, capillary permeability may also increase with subsequent swelling of astrocyte end-feet. In conclusion, although the pathophysiology of AMS and HACE is not completely understood, recent evidence proposes a multifactorial entity, with brain swelling and compromise of the BBB considered to play an important role. A fuller comprehension of these processes is crucial to reduce and prevent BBB alterations during high-altitude exposure.

  6. High throughput electrophysiology: new perspectives for ion channel drug discovery

    DEFF Research Database (Denmark)

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter

    2003-01-01

    characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion....... The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery.......Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels...

  7. High-Tech Blood Sugar Monitors May Help People with Type 1 Diabetes

    Science.gov (United States)

    ... gov/news/fullstory_163211.html High-Tech Blood Sugar Monitors May Help People With Type 1 Diabetes ... need insulin shots every day manage their blood sugar levels safely, two new studies suggest. Also known ...

  8. 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.

  9. 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

    2010-11-01

    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.

  10. Are Peripheral Blood Mononuclear Cells Derived from Patients with Certain Myopathies Suitable for Personalized Drug Screening?

    Directory of Open Access Journals (Sweden)

    Andriy V. Shatillo

    2014-12-01

    Full Text Available Background: Limb girdle muscular dystrophies (LGMDs and several other disorders which share their specific phenotype are rare, predominantly hereditary conditions with no curative treatment. Differential diagnosis of these myopathies is quite challenging and expensive in many cases. Therefore, a significant proportion of patients remains undiagnosed and untreated for a long time. At the same time there is a huge amount of drugs and supplements potentially able to modify the course of some of these muscular dystrophies. That is why a simple empirical approach able to define a patient’s reaction to a specific compound seems rational. Because most common basic pathogenetic mechanisms for these quite different disorders increase the vulnerability of muscle cells (or decrease ability for reparation during mechanical stress, we propose a simple, noninvasive and inexpensive approach for individualized drug screening based on the drug’s influence on the mechanical vulnerability of peripheral blood mononuclear cells (PBMC. Methods: PBMC derived from 8 patients with Duchenne muscular dystrophy (DMD, 2 patients with LGMD2A, 1 patient with LGMD2B, 1 with MERRF syndrome, 1 with facioscapulohumeral muscular dystrophy (FSHD and 13 matched control subjects were irradiated by ultrasound in the presence of several compounds (lisinopril, vitamin D3, prednisolon, tocopherol, topiramate, glutargin, α-lipoic acid, essentiale, and physiological solution. Then viability indexes of the samples were detected by citotoxic assays based on vital dye (neutral red and resazurin metabolism. Results: In cytotoxicity tests with active transport of neutral red into PBMC derived from DMD patients, the cells showed signs of destruction at 1.06±0.52 minutes of ultrasounding compared to 1.75±0.6 minutes in control. PBMCs from patients with other myopathies have either normal or decreased resistance to ultrasound. The addition of tocopherol significantly changes the PBMC

  11. Detection of EPO-Fc fusion protein in human blood: screening and confirmation protocols for sports drug testing.

    Science.gov (United States)

    Reichel, Christian; Thevis, Mario

    2012-11-01

    The neonatal Fc receptor (FcRn) has been under investigation for several years as a pharmaceutical drug target. Clinical studies have shown that fusion proteins consisting of human recombinant erythropoietin (rhEPO) and the Fc-part of IgG can be transported after pulmonary administration via FcRn across the airway epithelium to the blood stream. So far, no clinically approved pharmaceutical formulation of EPO-Fc is available. Since various forms of recombinant erythropoietins have been frequently misused by athletes as performance-enhancing agents, EPO-Fc might play a similar role in sports in the future. In order to investigate the detectability of EPO-Fc in human blood, different strategies were tested and developed. Only two of them fulfilled the necessary requirements regarding sensitivity and specificity. A rapid protocol useful for screening purposes first enriches EPO-Fc from human serum via high capacity protein A beads and subsequently detects EPO-Fc in the eluate with a commercial EPO ELISA kit. The limit of detection (LOD) of the method is about 5 pg (45 amol) EPO-Fc and is independent of the serum volume used. For screening and/or confirmation purposes a second protocol was evaluated, which consists of a fast EPO immunopurification step followed by sodium dodecyl sulfate or sarcosyl polyacrylamide gel electrophoresis (SDS-PAGE, SAR-PAGE) and Western double-blotting with chemiluminescence detection - a method already established in routine EPO anti-doping control. The latter strategy allows the detection of EPO-Fc in serum together with all other recombinant erythropoietins and with an identical LOD (5 pg/45 amol) as for the rapid screening protocol.

  12. The determination of phenazone in blood plasma for obtained sistem suitable test of monitoring drug level

    OpenAIRE

    Mochamad Lazuardi

    2007-01-01

    The determining of Phenazone to human blood plasma from healthy man after separated by solid phase extraction (SPE) and spectroscopic measurements has been investigated. The objective of that research was to obtain system suitable test for determine the Phenazone level in biological fluids (human blood plasma), for new performed dosage regimented in clinical dentistry. The method can be divided into the following four steps. 1. Centrifugation the blood sample, 2. Extraction from blood plasma ...

  13. [Mass spectrometry analysis of blood plasma lipidome as method of disease diagnostics, evuation of effectiveness and optimization of drug therapy].

    Science.gov (United States)

    Lokhov, P G; Maslov, D L; Balashova, E E; Trifonova, O P; Medvedeva, N V; Torkhovskaya, T I; Ipatova, O M; Archakov, A I; Malyshev, P P; Kukharchuk, V V; Shestakova, E A; Shestakova, M V; Dedov, I I

    2015-01-01

    A new method for the analysis of blood lipid based on direct mass spectrometry of lipophilic low molecular weight fraction of blood plasma has been considered. Such technique allows quantification of hundreds of various types of lipids and this changes existing concepts on diagnostics of lipid disorders and related diseases. The versatility and quickness of the method significantly simplify its wide use. This method is applicable for diagnostics of atherosclerosis, diabetes, cancer and other diseases. Detalization of plasma lipid composition at the molecular level by means of mass spectrometry allows to assess the effectiveness of therapy and to optimize the drug treatment of cardiovascular diseases by phospholipid preparations.

  14. Predictive value of ambulatory blood pressure shortly after withdrawal of antihypertensive drugs in primary care patients

    NARCIS (Netherlands)

    Beltman, FW; Heesen, WF; Smit, AJ; May, JF; deGraeff, PA; Havinga, TK; Schuurman, FH; vanderVeur, E; Lie, KI; MeyboomdeJong, B

    1996-01-01

    Objective-To determine whether ambulatory blood pressure eight weeks after withdrawal of antihypertensive medication is a more sensitive measure than seated blood pressure to predict blood pressure in the long term. Design-Patients with previously untreated diastolic hypertension were treated with a

  15. High throughput miniature drug-screening platform using bioprinting technology.

    Science.gov (United States)

    Rodríguez-Dévora, Jorge I; Zhang, Bimeng; Reyna, Daniel; Shi, Zhi-dong; Xu, Tao

    2012-09-01

    In the pharmaceutical industry, new drugs are tested to find appropriate compounds for therapeutic purposes for contemporary diseases. Unfortunately, novel compounds emerge at expensive prices and current target evaluation processes have limited throughput, thus leading to an increase of cost and time for drug development. This work shows the development of the novel inkjet-based deposition method for assembling a miniature drug-screening platform, which can realistically and inexpensively evaluate biochemical reactions in a picoliter-scale volume at a high speed rate. As proof of concept, applying a modified Hewlett Packard model 5360 compact disc printer, green fluorescent protein expressing Escherichia coli cells along with alginate gel solution have been arrayed on a coverslip chip under a repeatable volume of 180% ± 26% picoliters per droplet; subsequently, different antibiotic droplets were patterned on the spots of cells to evaluate the inhibition of bacteria for antibiotic screening. The proposed platform was compared to the current screening process, validating its effectiveness. The viability and basic function of the printed cells were evaluated, resulting in cell viability above 98% and insignificant or no DNA damage to human kidney cells transfected. Based on the reduction of investment and compound volume used by this platform, this technique has the potential to improve the actual drug discovery process at its target evaluation stage.

  16. [Influence of probiotic drugs BPS-44 and BPS-L on the acid-base balance in the calf blood].

    Science.gov (United States)

    Aheiev, V O; Diachenko, H M; Derev'ianko, S V; Bozhok, L V

    2010-01-01

    Research of influence of the probiotic drugs BPS-44 and BPS-L on the state of the antioxidation system by means of experiments on young animals of cattle. The authors have established that the effective functioning of antioxidation system of cattles' blood (a decrease of the products of lipids' peroxidation level and activation of the primary enzymes of antioxidation defense) is provided by the prophylactic use of these probiotics. The most evident positive influence on the antioxidation system of cattle young animals was made by the associate drug BPS-L that causes the essential decrease of malonic dialdehyde, activation of catalase and increase of antioxidation factor value.

  17. Chinese Drugs That Invigorate Spleen to Remove Dampness and Activate Blood Circulation to Eliminate Turbid for Retarding Progression of Chronic Renal Failure

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the effect of Chinese drugs (CD) that invigorate Spleen to remove Dampness and activate the blood circulation to eliminate Turbid for retarding progression of chronic renal failure (CRF). Methods: Thirty-nine patients with CRF were divided into two groups at random: the 18 patients in group A (the control group) were treated with low protein diet and controlling blood pressure and 21 patients in group B (the treatment group) were treated similarly with that of the control group and additional CD. Levels of serous creatinine (SCr), blood urea nitrogen (BUN), blood albumin (Alb), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and hemoglobin (Hb) were checked every two months and the rate of progression of CRF was estimated by slope of the creatinine reciprocal (1/SCr) with time (months). Results: Levels of SCr and BUN in group B were lower and HDL higher than those in group A significantly, P<0.05. Mean slopes of the creatinine reciprocal with time in the two groups were markedly different, P<0.01. Conclusion: Additional CD treatment based upon the low protein diet and controlling blood pressure could retard the rate of progression of CRF evidently.

  18. Intensive trapping of blood-fed Anopheles darlingi in Amazonian Peru reveals unexpectedly high proportions of avian blood-meals

    Science.gov (United States)

    Saavedra, Marlon P.; Bickersmith, Sara A.; Prussing, Catharine; Michalski, Adrian; Tong Rios, Carlos; Vinetz, Joseph M.; Conn, Jan E.

    2017-01-01

    Anopheles darlingi, the main malaria vector in the Neotropics, has been considered to be highly anthropophilic. However, many behavioral aspects of this species remain unknown, such as the range of blood-meal sources. Barrier screens were used to collect resting Anopheles darlingi mosquitoes from 2013 to 2015 in three riverine localities (Lupuna, Cahuide and Santa Emilia) in Amazonian Peru. Overall, the Human Blood Index (HBI) ranged from 0.58–0.87, with no significant variation among years or sites. Blood-meal analysis revealed that humans are the most common blood source, followed by avian hosts (Galliformes-chickens and turkeys), and human/Galliforme mixed-meals. The Forage Ratio and Selection Index both show a strong preference for Galliformes over humans in blood-fed mosquitoes. Our data show that 30% of An. darlingi fed on more than one host, including combinations of dogs, pigs, goats and rats. There appears to be a pattern of host choice in An. darlingi, with varying proportions of mosquitoes feeding only on humans, only on Galliformes and some taking mixed-meals of blood (human plus Galliforme), which was detected in the three sites in different years, indicating that there could be a structure to these populations based on blood-feeding preferences. Mosquito age, estimated in two localities, Lupuna and Cahuide, ranged widely between sites and years. This variation may reflect the range of local environmental factors that influence longevity or possibly potential changes in the ability of the mosquito to transmit the parasite. Of 6,204 resting An. darlingi tested for Plasmodium infection, 0.42% were infected with P. vivax. This study provides evidence for the first time of the usefulness of barrier screens for the collection of blood-fed resting mosquitoes to calculate the Human Blood Index (HBI) and other blood-meal sources in a neotropical malaria endemic setting. PMID:28231248

  19. Self-measurement of blood pressure at home reduces the need for antihypertensive drugs: a randomized, controlled trial.

    Science.gov (United States)

    Verberk, Willem J; Kroon, Abraham A; Lenders, Jacques W M; Kessels, Alfons G H; van Montfrans, Gert A; Smit, Andries J; van der Kuy, Paul-Hugo M; Nelemans, Patricia J; Rennenberg, Roger J M W; Grobbee, Diederick E; Beltman, Frank W; Joore, Manuela A; Brunenberg, Daniëlle E M; Dirksen, Carmen; Thien, Theo; de Leeuw, Peter W

    2007-12-01

    It is still uncertain whether one can safely base treatment decisions on self-measurement of blood pressure. In the present study, we investigated whether antihypertensive treatment based on self-measurement of blood pressure leads to the use of less medication without the loss of blood pressure control. We randomly assigned 430 hypertensive patients to receive treatment either on the basis of self-measured pressures (n=216) or office pressures (OPs; n=214). During 1-year follow-up, blood pressure was measured by office measurement (10 visits), ambulatory monitoring (start and end), and self-measurement (8 times, self-pressure group only). In addition, drug use, associated costs, and degree of target organ damage (echocardiography and microalbuminuria) were assessed. The self-pressure group used less medication than the OP group (1.47 versus 2.48 drug steps; P<0.001) with lower costs ($3222 versus $4420 per 100 patients per month; P<0.001) but without significant differences in systolic and diastolic OP values (1.6/1.0 mm Hg; P=0.25/0.20), in changes in left ventricular mass index (-6.5 g/m(2) versus -5.6 g/m(2); P=0.72), or in median urinary microalbumin concentration (-1.7 versus -1.5 mg per 24 hours; P=0.87). Nevertheless, 24-hour ambulatory blood pressure values at the end of the trial were higher in the self-pressure than in the OP group: 125.9 versus 123.8 mm Hg (P<0.05) for systolic and 77.2 versus 76.1 mm Hg (P<0.05) for diastolic blood pressure. These data show that self-measurement leads to less medication use than office blood pressure measurement without leading to significant differences in OP values or target organ damage. Ambulatory values, however, remain slightly elevated for the self-pressure group.

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

    Directory of Open Access Journals (Sweden)

    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

  1. High HCV seroprevalence and HIV drug use risk behaviors among injection drug users in Pakistan

    Directory of Open Access Journals (Sweden)

    Zafar Tariq

    2006-08-01

    Full Text Available Abstract Introduction HIV and HCV risk behaviors among injection drug users (IDUs in two urban areas in Pakistan were identified. Methods From May to June 2003, 351 IDUs recruited in harm-reduction drop-in centers operated by a national non-governmental organization in Lahore (Punjab province and Quetta (Balochistan province completed an interviewer-administered survey and were tested for HIV and HCV. Multivariable logistic regression identified correlates of seropositivity, stratifying by site. All study participants provided written, informed consent. Results All but two were male; median age was 35 and Discussion Despite no HIV cases, overall HCV prevalence was very high, signaling the potential for a future HIV epidemic among IDUs across Pakistan. Programs to increase needle exchange, drug treatment and HIV and HCV awareness should be implemented immediately.

  2. High Throughput Screening for Drugs that Modulate Intermediate Filament Proteins

    Science.gov (United States)

    Sun, Jingyuan; Groppi, Vincent E.; Gui, Honglian; Chen, Lu; Xie, Qing; Liu, Li

    2016-01-01

    Intermediate filament (IF) proteins have unique and complex cell and tissue distribution. Importantly, IF gene mutations cause or predispose to more than 80 human tissue-specific diseases (IF-pathies), with the most severe disease phenotypes being due to mutations at conserved residues that result in a disrupted IF network. A critical need for the entire IF-pathy field is the identification of drugs that can ameliorate or cure these diseases, particularly since all current therapies target the IF-pathy complication, such as diabetes or cardiovascular disease, rather than the mutant IF protein or gene. We describe a high throughput approach to identify drugs that can normalize disrupted IF proteins. This approach utilizes transduction of lentivirus that expresses green-fluorescent-protein-tagged keratin 18 (K18) R90C in A549 cells. The readout is drug ‘hits’ that convert the dot-like keratin filament distribution, due to the R90C mutation, to a wildtype-like filamentous array. A similar strategy can be used to screen thousands of compounds and can be utilized for practically any IF protein with a filament-disrupting mutation, and could therefore potentially target many IF-pathies. ‘Hits’ of interest require validation in cell culture then using in vivo experimental models. Approaches to study the mechanism of mutant-IF normalization by potential drugs of interest are also described. The ultimate goal of this drug screening approach is to identify effective and safe compounds that can potentially be tested for clinical efficacy in patients. PMID:26795471

  3. Drug-adherence questionnaires not valid for patients taking blood-pressure-lowering drugs in a primary health care setting.

    NARCIS (Netherlands)

    Steeg, N. van de; Sielk, M.; Pentzek, M.; Bakx, C.; Altiner, A.

    2009-01-01

    PURPOSE: To validate two established questionnaires [Morisky and Medication Adherence Report Scale (MARS-5)] for the measurement of medical adherence of patients treated with antihypertensive drugs in primary care in Germany. SETTING: General practitioners (GPs) and their patients in North Rhine-Wes

  4. Patterns and Correlates of Drug Use Among Urban High School Students

    Science.gov (United States)

    Mc Killip, Jack; And Others

    1973-01-01

    A drug-use survey was administered in a large metropolitan, middle class high school to test two hypotheses: a. drug users can be divided according to the types of drugs used (tobacco, alcohol, and marijuana vs. opiates, LSD, amphetamines, etc.); and, b. respondents' drug use is significantly related to their peers drug use. Both hypotheses were…

  5. Patterns and Correlates of Drug Use Among Urban High School Students

    Science.gov (United States)

    Mc Killip, Jack; And Others

    1973-01-01

    A drug-use survey was administered in a large metropolitan, middle class high school to test two hypotheses: a. drug users can be divided according to the types of drugs used (tobacco, alcohol, and marijuana vs. opiates, LSD, amphetamines, etc.); and, b. respondents' drug use is significantly related to their peers drug use. Both hypotheses were…

  6. 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

  7. Evaluation of Mutual Drug-Drug Interaction within Geneva Cocktail for Cytochrome P450 Phenotyping using Innovative Dried Blood Sampling Method.

    Science.gov (United States)

    Bosilkovska, Marija; Samer, Caroline; Déglon, Julien; Thomas, Aurélien; Walder, Bernhard; Desmeules, Jules; Daali, Youssef

    2016-09-01

    Cytochrome P450 (CYP) activity can be assessed using a 'cocktail' phenotyping approach. Recently, we have developed a cocktail (Geneva cocktail) which combines the use of low-dose probes with a low-invasiveness dried blood spots (DBS) sampling technique and a single analytical method for the phenotyping of six major CYP isoforms. We have previously demonstrated that modulation of CYP activity after pre-treatment with CYP inhibitors/inducer could be reliably predicted using Geneva cocktail. To further validate this cocktail, in this study, we have verified whether probe drugs contained in the latter cause mutual drug-drug interactions. In a randomized, four-way, Latin-square crossover study, 30 healthy volunteers received low-dose caffeine, flurbiprofen, omeprazole, dextromethorphan and midazolam (a previously validated combination with no mutual drug-drug interactions); fexofenadine alone; bupropion alone; or all seven drugs simultaneously (Geneva cocktail). Pharmacokinetic profiles of the probe drugs and their metabolites were determined in DBS samples using both conventional micropipette sampling and new microfluidic device allowing for self-sampling. The 90% confidence intervals for the geometric mean ratios of AUC metabolite/AUC probe for CYP probes administered alone or within Geneva cocktail fell within the 0.8-1.25 bioequivalence range indicating the absence of pharmacokinetic interaction. The same result was observed for the chosen phenotyping indices, that is metabolic ratios at 2 hr (CYP1A2, CYP3A) or 3 hr (CYP2B6, CYP2C9, CYP2C19, CYP2D6) post-cocktail administration. DBS sampling could successfully be performed using a new microfluidic device. In conclusion, Geneva cocktail combined with an innovative DBS sampling device can be used routinely as a test for simultaneous CYP phenotyping. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  8. High-content analysis for drug delivery and nanoparticle applications.

    Science.gov (United States)

    Brayden, David J; Cryan, Sally-Ann; Dawson, Kenneth A; O'Brien, Peter J; Simpson, Jeremy C

    2015-08-01

    High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents.

  9. Performance-Enhancing Drugs and the High School Athlete.

    Science.gov (United States)

    Franckowiak, Bonnie

    2015-07-01

    A performance-enhancing drug (PED) is any substance that is used to increase muscle mass, dull pain, reduce weight, or ease stress. The use of PEDs is a growing concern among adolescents, due in part to the pressures to perform, the influence of professional role models, and a general lack of education about the dangers of these substances. Use of performance enhancers has been identified in middle school as well as high school age students. This article details the school nurse's role in identifying youth who are using a PED, providing education for students and families, and referring for treatment if needed. Although PED use is not as prevalent as use of other illicit drugs, PEDs still pose a threat to adolescent physical and mental health. Discussion about PED use can open the door to discussion about use of other substances.

  10. Blood pressure reductions following catheter-based renal denervation are not related to improvements in adherence to antihypertensive drugs measured by urine/plasma toxicological analysis.

    Science.gov (United States)

    Ewen, Sebastian; Meyer, Markus R; Cremers, Bodo; Laufs, Ulrich; Helfer, Andreas G; Linz, Dominik; Kindermann, Ingrid; Ukena, Christian; Burnier, Michel; Wagenpfeil, Stefan; Maurer, Hans H; Böhm, Michael; Mahfoud, Felix

    2015-12-01

    Renal denervation can reduce blood pressure in patients with uncontrolled hypertension. The adherence to prescribed antihypertensive medication following renal denervation is unknown. This study investigated adherence to prescribed antihypertensive treatment by liquid chromatography-high resolution tandem mass spectrometry in plasma and urine at baseline and 6 months after renal denervation in 100 patients with resistant hypertension, defined as baseline office systolic blood pressure ≥140 mmHg despite treatment with ≥3 antihypertensive agents. At baseline, complete adherence to all prescribed antihypertensive agents was observed in 52 patients, 46 patients were partially adherent, and two patients were completely non-adherent. Baseline office blood pressure was 167/88 ± 19/16 mmHg with a corresponding 24-h blood pressure of 154/86 ± 15/13 mmHg. Renal denervation significantly reduced office and ambulatory blood pressure at 6-month follow-up by 15/5 mmHg (p treatment was significantly reduced from 85.0 % at baseline to 80.7 %, 6 months after renal denervation (p = 0.005). The blood pressure decrease was not explained by improvements in adherence following the procedure. Patients not responding to treatment significantly reduced their drug intake following the procedure. Adherence was highest for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta blockers (>90 %) and lowest for vasodilators (21 %). In conclusion, renal denervation can reduce office and ambulatory blood pressure in patients with resistant hypertension despite a significant reduction in adherence to antihypertensive treatment after 6 months.

  11. Cost Evaluation of Dried Blood Spot Home Sampling as Compared to Conventional Sampling for Therapeutic Drug Monitoring in Children

    Science.gov (United States)

    Martial, Lisa C.; Aarnoutse, Rob E.; Schreuder, Michiel F.; Henriet, Stefanie S.; Brüggemann, Roger J. M.; Joore, Manuela A.

    2016-01-01

    Dried blood spot (DBS) sampling for the purpose of therapeutic drug monitoring can be an attractive alternative for conventional blood sampling, especially in children. This study aimed to compare all costs involved in conventional sampling versus DBS home sampling in two pediatric populations: renal transplant patients and hemato-oncology patients. Total costs were computed from a societal perspective by adding up healthcare cost, patient related costs and costs related to loss of productivity of the caregiver. Switching to DBS home sampling was associated with a cost reduction of 43% for hemato-oncology patients (€277 to €158) and 61% for nephrology patients (€259 to €102) from a societal perspective (total costs) per blood draw. From a healthcare perspective, costs reduced with 7% for hemato-oncology patients and with 21% for nephrology patients. Total savings depend on the number of hospital visits that can be avoided by using home sampling instead of conventional sampling. PMID:27941974

  12. A Method for Gray-Scale Imaging of Blood Flow Using High-Frequency Ultrasound.

    Science.gov (United States)

    Yang, Jun; Pang, Chao; Song, Xue-Dong; Gao, Xuan

    2017-07-01

    This paper presents a new method that complements current techniques available in the high-frequency blood imaging field. A comprehensive scattering model was established to determine the feasibility and frequency range of the blood flow imaging of superficial organs and tissues using high-frequency ultrasound. The transmitting and receiving modes and an algorithm were designed to obtain blood flow information based on differentiation between tissues and blood flow. The system was created and tested first with a model that simulates blood flow and was then used on human tissue. A fine-scale image of a blood vessel could be obtained with this system. Moreover, this method can obtain weak blood flow signal using single pulse rather than the traditional pulse-code method and maintains a high resolution that can be matched to high-frequency structural imaging. This study provides a reliable method for further applications related to diagnoses of superficial organs.

  13. Development of high drug-loading nanomicelles targeting steroids to the brain.

    Science.gov (United States)

    Zheng, Sijia; Xie, Yanqi; Li, Yuan; Li, Ling; Tian, Ning; Zhu, Wenbo; Yan, Guangmei; Wu, Chuanbin; Hu, Haiyan

    2014-01-01

    The objective of this research was to develop and evaluate high drug-loading ligand-modified nanomicelles to deliver a steroidal compound to the brain. YC1 (5α-cholestane-24-methylene-3β, 5α, 6β, 19-tetraol), with poor solubility and limited access to the brain, for the first time, has been proved to be an effective neuroprotective steroid by our previous studies. Based on the principle of 'like dissolves like', cholesterol, which shares the same steroidal parent nucleus with YC1, was selected to react with sodium alginate, producing amphiphilic sodium alginate- cholesterol derivatives (SACDs). To increase the grafting ratio and drug loading, cholesterol was converted to cholesteryl chloroformate, for the first time, before reacting with sodium alginate. Further, lactoferrin was conjugated on SACDs to provide lactoferrin-SACDs (Lf-SACD), which was established by immune electron microscopy (IEM) and self-assembled into brain-targeting nanomicelles. These nanomicelles were negatively charged and spherical in nature, with an average size of drug loading was increased due to the cholesteryl inner cores of the nanomicelles, and the higher the grafting ratio was, the lower the critical micelle concentration (CMC) value of SACD, and the higher drug loading. The in vitro drug release, studied by bulk-equilibrium dialysis in 20 mL of 6% hydroxypropyl-β-cyclodextrin solution at 37°C, indicated a prolonged release profile. The YC1 concentration in mouse brain delivered by lactoferrin-modified nanomicelles was higher than in those delivered by non-modified nanomicelles and YC1 solution. The unique brain-targeting nanomicelle system may provide a promising carrier to deliver hydrophobic drugs across the blood-brain barrier for the treatment of brain diseases.

  14. Ultrasound-assisted dispersive liquid-liquid microextraction for the determination of seven recreational drugs in human whole blood using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Lin, Zebin; Li, Jiaolun; Zhang, Xinyu; Qiu, Meihong; Huang, Zhibin; Rao, Yulan

    2017-03-01

    Recreational drugs have large impact on public health and security, and to monitor them is of urgent demand. In the present study, ultrasound-assisted dispersive liquid-liquid microextraction combined with the detection of gas chromatography-mass spectrometry was applied to the determination of seven common recreational drugs, including amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, meperidine, methadone and ketamine in 200μL of human whole blood. A series of factors which would affect the extraction efficiency were systematically investigated, including the nature and the volume of extraction and dispersing solvents, ultrasonication time, salting-out effect and pH value. The method consumed small amount of sample. The limits of detection and limits of quantification for each analyte were 10 and 40ng/mL, respectively, and the linearity was in the range of 0.04-25μg/mL (R(2) higher than 0.99). Good specificity, precision (1.5-8.2% for the intra-day study and 2.6-12.8% for the inter-day study), satisfactory accuracy (85.0-117.1%) and extraction recovery (77.0-92.4%) were obtained, which makes it a high performance method for the determination of recreational drugs in human whole blood samples.

  15. Methodological aspects of blood pressure measurement and adherence to antihypertensive drug therapy

    NARCIS (Netherlands)

    Braam, R.L.

    2007-01-01

    Hypertension is an important risk-factor for cardiovascular disease. Accurate blood pressure measurements are very important to diagnose hypertension. Nowadays these blood pressure measurements are often performed using automatic devices. One can wonder whether these devices are accurate enough. In

  16. Methodological aspects of blood pressure measurement and adherence to antihypertensive drug therapy

    NARCIS (Netherlands)

    Braam, R.L.

    2007-01-01

    Hypertension is an important risk-factor for cardiovascular disease. Accurate blood pressure measurements are very important to diagnose hypertension. Nowadays these blood pressure measurements are often performed using automatic devices. One can wonder whether these devices are accurate enough. In

  17. 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.

  18. 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.

  19. High Blood Glucose: What It Means and How To Treat It

    Science.gov (United States)

    ... leave this field empty High Blood Glucose: What It Means and How To Treat It What is high blood glucose? People who do ... glucose, also called 'hyperglycemia', is considered "high" when it is 160 mg/dl or above your individual ...

  20. 17 Million U.S. Adults May Have Tough-to-Spot High Blood Pressure

    Science.gov (United States)

    ... Million U.S. Adults May Have Tough-to-Spot High Blood Pressure 'Masked' hypertension doesn't show up in a ... Health and Human Services. More Health News on: High Blood Pressure Recent Health News Related MedlinePlus Health Topics High ...

  1. Aliskiren improves blood pressure control and prevents cardiac damage in high-risk hypertensive subjects.

    Science.gov (United States)

    Mazza, A; Montemurro, D; Zuin, M; Schiavon, L; Zorzan, S; Chondrogiannis, S; Ferretti, A; Ramazzina, E; Rubello, D

    2013-08-01

    Longitudinal study aimed to evaluate the antihypertensive efficacy, safety and the effect on cardiac damage of Aliskiren, administered to a group of high-risk hypertensive patients with mild impairment of renal function and uncontrolled blood pressure (BP) despite a two-drug antihypertensive treatment. One hundred and six patients (56 men and 50 females) aged 61.9±12.7 years, were assigned to receive Aliskiren 150-300 mg once-daily for 12 months. Clinic BP measurements were taken at every follow-up visit (1st, 6th and 12th month), while biochemical tests, estimated glomerular filtration rate (eGFR), 24-hours ambulatory BP measurements (ABMP) and echocardiography were evaluated at baseline and at the end of follow-up. Analysis of variance for repeated measures compared BP, left ventricular mass index (LVMI) and eGFR values changes. A significant reduction (all P0.05). Putative adverse events caused withdrawal of 7 subjects (6 for gastrointestinal disturbances, 1 for alopecia). Aliskiren was effective in decreasing both clinical and ABPM values and in reducing LVMI in both genders without any influence on eGFR. The treatment resulted safe, even in combination with ACE-inhibitors and angiotensin II receptor blockers. A significant reduction in the use of concomitant antihypertensive drugs was observed.

  2. Polymer brushes interfacing blood as a route toward high performance blood contacting devices.

    Science.gov (United States)

    Surman, František; Riedel, Tomáš; Bruns, Michael; Kostina, Nina Yu; Sedláková, Zdeňka; Rodriguez-Emmenegger, Cesar

    2015-05-01

    In the current study, well-defined polymer brushes are shown as an effective surface modification to resist the adhesion of whole blood and its components. Poly[oligo(ethylene glycol)methylether methacrylate] (poly(MeOEGMA)), poly(hydroxyethyl methacrylate) (poly(HEMA)), poly[N-(2-hydroxypropyl) methacrylamide] (poly(HPMA)), and poly(carboxybetaine acrylamide) (poly(CBAA)) brushes were grown by surface initiated atom transfer radical polymerization (SI-ATRP) and subsequently characterized by Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), dynamic contact angle measurements, atomic force microscopy (AFM), and surface plasmon resonance (SPR) spectroscopy. All brushes decreased the fouling from blood plasma over 95% and prevented the adhesion of platelets, erythrocytes, and leukocytes as evidenced by SPR and SEM measurements.

  3. Unexpectedly high injection drug use, HIV and hepatitis C prevalence among female sex workers in the Republic of Mauritius.

    Science.gov (United States)

    Johnston, Lisa Grazina; Corceal, Sewraz

    2013-02-01

    Female sex workers (FSW) often have a disproportionately high prevalence of HIV infection and they, along with their clients, are considered a core group contributing to the transmission of HIV in many countries. In 2010, females who reported having vaginal/anal/oral sex in the last 6 months with a male in exchange for money or gifts, aged ≥15 years, and living in Mauritius were recruited into a survey using respondent driven sampling. Consenting females (n = 299) completed a behavioral questionnaire and provided venous blood for HIV, HCV and HBV testing. HIV seroprevalence among FSW was 28.9 % and 43.8 % were infected with HCV; among HIV seropositive FSW, 88.2 % were also infected with HCV. Almost 40 % of FSW reported injecting drugs sometime in their lives and 30.5 % of all FSW reported doing so in the previous 3 months. Among those who ever injected drugs, 82.5 % did so in the past 3 months and among those 60 % reported injecting drugs at least once a day. Among FSW who ever injected drugs, 17.5 % reported sharing a needle at last injection. Regression analyses found injection drug use behaviors to be positively associated with HIV seroprevalence. These findings indicate that FSW, especially those who inject drugs, are at high risk for HIV and HCV infection and transmission and illustrates the need for gender responsive HIV and injection drug use prevention and treatment models that respond to the unique situations that affect this population.

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Getting into the brain: liposome-based strategies for effective drug delivery across the blood-brain barrier.

    Science.gov (United States)

    Vieira, Débora B; Gamarra, Lionel F

    This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood-brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer's, Parkinson's, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood-brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. A Prediction Method for P-glycoprotein-Mediated Drug-Drug Interactions at the Human Blood-Brain Barrier From Blood Concentration-Time Profiles, Validated With PET Data.

    Science.gov (United States)

    Matsuda, Akihiro; Karch, Rudolf; Bauer, Martin; Traxl, Alexander; Zeitlinger, Markus; Langer, Oliver

    2017-09-01

    The purpose of this study was to establish physiologically based pharmacokinetic models to predict in humans the brain concentration-time profiles and P-glycoprotein (Pgp)-mediated brain drug-drug interactions between the model Pgp substrate (R)-[(11)C]verapamil (VPM), the model dual Pgp/breast cancer resistance protein (BCRP) substrate [(11)C]tariquidar (TQD), and the Pgp inhibitor tariquidar. The model predictions were validated with results from positron emission tomography studies in humans. Using these physiologically based pharmacokinetic models, the differences between predicted and observed areas under the concentration-time curves (AUC) of VPM and TQD in the brain were within a 1.2-fold and 2.5-fold range, respectively. Also, brain AUC increases of VPM and TQD after Pgp inhibitor administration were predicted with 2.5-fold accuracy when in vitro inhibition constant or half-maximum inhibitory concentration values of tariquidar were used. The predicted rank order of the magnitude of AUC increases reflected the results of the clinical positron emission tomography studies. Our results suggest that the established models can predict brain exposure from the respective blood concentration-time profiles and rank the magnitude of the Pgp-mediated brain drug-drug interaction potential for both Pgp and Pgp/BCRP substrates in humans. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. Measurement of HIV-1 viral load for drug resistance surveillance using dried blood spots: literature review and modeling of contribution of DNA and RNA.

    Science.gov (United States)

    Parkin, Neil T

    2014-01-01

    World Health Organization-recommended surveys of acquired HIV-1 drug resistance include assessment of HIV-1 viral load suppression to levels below 1,000 copies/ml and drug resistance-associated mutation patterns in subjects on antiretroviral therapy. Surveys are being conducted in regions of the world that cannot support the collection, storage, and shipping of frozen plasma. Therefore, dried blood spots are often the specimen type of choice for both genotyping and viral load measurement. Furthermore, viral load testing for individual patient management in these regions is being scaled-up in accordance with WHO 2013 Guidelines for Antiretroviral Treatment. Technical issues related to the adaptation of viral load assays to dried blood spots, especially with respect to sensitivity (limit of detection), specificity (cell-free RNA vs. cell-associated DNA or RNA), and assay method, affect the interpretation of a viral load result from dried blood spots. Amongst published studies of commercial assay performance with dried blood spots, the bioMérieux EasyQ® and Abbott RealTime assays tended to show high (> 90%) specificity and sensitivity; the Biocentric Generic or Roche TaqMan® assays tended to show high sensitivity but lower specificity, using a 1,000 copies/ml threshold. The relative contribution of cell-associated DNA or RNA to a viral load measurement is likely to vary between patients, depending on clinical parameters and treatment status. A model was developed that predicts that in patients on antiretroviral therapy with low plasma viral load, cellular DNA is the predominant source of non-plasma virus-derived nucleic acid in dried blood spots. The extent of viral load overestimation from dried blood spots becomes less important when plasma viral load is over about 5,000 copies/ml. To avoid misclassifying subjects with plasma viral load suppression, the World Health Organization-recommended threshold of 1,000 copies/ml can be applied only when an assay that can

  10. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration.

    Science.gov (United States)

    Rodrigues, Stephen F; Fiel, Luana A; Shimada, Ana L; Pereira, Natalia R; Guterres, Silvia S; Pohlmann, Adriana R; Farsky, Sandra H

    2016-05-01

    Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration.

  11. 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

  12. 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.

  13. High-throughput screening technologies for drug glucuronidation profiling.

    Science.gov (United States)

    Trubetskoy, Olga; Finel, Moshe; Trubetskoy, Vladimir

    2008-08-01

    A significant number of endogenous and exogenous compounds, including many therapeutic agents, are metabolized in humans via glucuronidation, catalysed by uridine diphosphoglucuronosyltransferases (UGTs). The study of the UGTs is a growing field of research, with constantly accumulated and updated information regarding UGT structure, purification, substrate specificity and inhibition, including clinically relevant drug interactions. Development of reliable UGT assays for the assessment of individual isoform substrate specificity and for the discovery of novel isoform-specific substrates and inhibitors is crucial for understanding the function and regulation of the UGT enzyme family and its clinical and pharmacological relevance. High-throughput screening (HTS) is a powerful technology used to search for novel substrates and inhibitors for a wide variety of targets. However, application of HTS in the context of UGTs is complicated because of the poor stability, low levels of expression, low affinity and broad substrate specificity of the enzymes, combined with difficulties in obtaining individual UGT isoforms in purified format, and insufficient information regarding isoform-specific substrates and inhibitors. This review examines the current status of HTS assays used in the search for novel UGT substrates and inhibitors, emphasizing advancements and challenges in HTS technologies for drug glucuronidation profiling, and discusses possible avenues for future advancement of the field.

  14. 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 eleva

  15. 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

  16. For People with Diabetes or High Blood Pressure: Get Checked for Kidney Disease

    Science.gov (United States)

    ... Language URL Español For People with Diabetes or High Blood Pressure: Get Checked for Kidney Disease Page Content Make ... I be checked for kidney disease? Diabetes and high blood pressure can damage the kidneys and lead to kidney ...

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

    Science.gov (United States)

    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.

  18. EVALUATION OF BLOOD SAMPLING TIMES AND INDICATIONS FOR THERAPEUTIC DRUG MONITORING SERVICES

    Directory of Open Access Journals (Sweden)

    AISHAH HAMZAH

    2008-01-01

    Full Text Available The appropriateness of sampling times and indications for monitoring of serum drug concentrations for the purpose of therapeutic drug monitoring (TDM were evaluated at three hospitals on the east coast of Malaysia. Appropriateness criteria for indication and sampling were adapted from previously published criteria and with input from local TDM pharmacists. Six drugs were chosen, namely gentamicin, digoxin, carbamazepine, phenobarbital, phenytoin, and valproic acid. A total of 265 TDM requests were evaluated. Appropriateness of the indication for TDM ranged from 77.4% to 82%, while that for sampling ranged from 34.2% to 62.1%. There were no significant differences between the three hospitals in both categories of appropriateness. Among different drug groups, the percentage of appropriate indication was found to be highest with antiepileptic drugs. Antiepileptic drugs, however, had the lowest rate of appropriate sampling. Overall, findings from the three hospitals showed very encouraging results with almost 80% of the requests considered as appropriately indicated. However, the percentage of appropriateness of sampling was lower, and thus may require further investigation.

  19. 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

    2016-04-21

    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.

  20. Construction and expression of retroviruses encoding dual drug resistance genes in human umbilical cord blood CD34+ cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of retroviral vectors encoding human mdr1 gene alone as well as in combination with either human mgmt gene or human mutant Ser31-dhfr gene are engineered. The resultant retroviruses are used to transduce human umbilical cord blood CD34+ cells. It has been shown that expression of dual drug resistance genes in transduced cells confers a broad range of resistance to both kinds of corresponding drugs. These data suggest a rationale for the use of such double chemoresistance gene constructs in an in vivo model in which transduced hematopoietic cells will acquire multiple protection against the cytotoxic side effects of combination chemotherapy and may have future application in chemoprotection of normal tissues, thus killing tumor cells more effectively.

  1. 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.

  2. The use of dried blood spot specimens for HIV-1 drug resistance genotyping in young children initiating antiretroviral therapy

    Science.gov (United States)

    Salimo, Anna T.; Ledwaba, Johanna; Coovadia, Ashraf; Abrams, Elaine J.; Technau, Karl-Günter; Kuhn, Louise; Morris, Lynn; Hunt, Gillian M.

    2015-01-01

    Paired plasma and dried blood spots (DBS) from 232 South African HIV-infected children initiating antiretroviral therapy (ART) were genotyped for drug resistance mutations, most of who had prior exposure to ART for prevention-of-mother-to-child-transmission. Non-nucleoside reverse transcriptase inhibitor mutations were most commonly detected in both specimen types, particularly Y181C/I and K103N/S. Resistance interpretation concordance was achieved in 97% of pairs with 7 children having mutations detected in DBS only. These results validate the preferential use of DBS specimens for HIVDR genotyping in this patient group. PMID:26192603

  3. High-Resolution Crystal Structures Elucidate the Molecular Basis of Cholera Blood Group Dependence.

    Science.gov (United States)

    Heggelund, Julie Elisabeth; Burschowsky, Daniel; Bjørnestad, Victoria Ariel; Hodnik, Vesna; Anderluh, Gregor; Krengel, Ute

    2016-04-01

    Cholera is the prime example of blood-group-dependent diseases, with individuals of blood group O experiencing the most severe symptoms. The cholera toxin is the main suspect to cause this relationship. We report the high-resolution crystal structures (1.1-1.6 Å) of the native cholera toxin B-pentamer for both classical and El Tor biotypes, in complexes with relevant blood group determinants and a fragment of its primary receptor, the GM1 ganglioside. The blood group A determinant binds in the opposite orientation compared to previously published structures of the cholera toxin, whereas the blood group H determinant, characteristic of blood group O, binds in both orientations. H-determinants bind with higher affinity than A-determinants, as shown by surface plasmon resonance. Together, these findings suggest why blood group O is a risk factor for severe cholera.

  4. PET studies on P-glycoprotein function in the blood-brain barrier : How it affects uptake and binding of drugs within the CNS

    NARCIS (Netherlands)

    Elsinga, PH; Hendrikse, Nelis; Bart, J; Vaalburg, W; van Waarde, A

    2004-01-01

    Permeability of the blood-brain barrier (BBB) is one of the factors determining the bioavailability of therapeutic drugs. The BBB only allows entry of lipophilic compounds with low molecular weights by passive diffusion. However, many lipophilic drugs show negligible brain uptake. They are substrate

  5. Self-Reported Drug and Alcohol Use and Attitudes toward Drug Testing in High Schools with Random Student Drug Testing

    Science.gov (United States)

    DuPont, Robert L.; Campbell, Michael D.; Campbell, Teresa G.; Shea, Corinne L.; DuPont, Helen S.

    2013-01-01

    Many schools implement random student drug testing (RSDT) programs as a drug prevention strategy. This study analyzes self-report surveys of students in eight secondary schools with well-established RSDT programs, comparing students who understood they were subject to testing and students who understood they were not subject to testing. Students…

  6. Self-Reported Drug and Alcohol Use and Attitudes toward Drug Testing in High Schools with Random Student Drug Testing

    Science.gov (United States)

    DuPont, Robert L.; Campbell, Michael D.; Campbell, Teresa G.; Shea, Corinne L.; DuPont, Helen S.

    2013-01-01

    Many schools implement random student drug testing (RSDT) programs as a drug prevention strategy. This study analyzes self-report surveys of students in eight secondary schools with well-established RSDT programs, comparing students who understood they were subject to testing and students who understood they were not subject to testing. Students…

  7. Experimental investigation on blood magnetic contamination in the presence of drug molecules

    Energy Technology Data Exchange (ETDEWEB)

    Creanga, D E; Nadejde, C [' Al. I. Cuza' University, Faculty of Physics, 11A Blvd. Carol I, RO-700506, Iasi (Romania); Iacob, G H [' Gr. T. Popa' University, Faculty of Biomedical Engineering, Kogalniceanu Street, No. 9-13, RO-700454, Iasi (Romania)], E-mail: nadej_dia@yahoo.com

    2009-05-01

    The purpose of the present project was to study the interference of magnetic nanoparticles with drug molecules - rifampicin, used in lung infectious disease and respectively, sodium diclofenac, an antiinflammatory steroid. The controlled magnetic contamination was accomplished using colloidal nanoparticles supplied from diluted magnetic fluids. Various concentrations of diluted aqueous magnetic fluids, based on magnetite cores coated with citric acid and respectively sodium oleate, were tested. The experiment was focused on the capacity of the magnetic nanoparticles to form reversible complexes with the drug molecules, as well as on the monitoring of the nanoparticle-drug complex dynamics, under the action of external magnetic field. The level of released rifampicin ranged between 4 mg/100 ml and 7 mg/100 ml for the magnetic exposure of 20 mT, while the sodium diclofenac decomplexation level was not higher than 2.5 mg/100 ml under magnetic exposure of 60 mT. The experimental arrangement was proved to be an adequate model for the dynamical study of magnetite reversible complexation with drug molecules, evidencing certain specific values of drug concentration and magnetic field induction that favour such interactions.

  8. Manipulation of magnetic carriers for drug delivery using pulsed-current high T {sub c} superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Yung [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States)]. E-mail: yscha@anl.gov; Chen, Lihua [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI 48824 (United States); Askew, Thomas [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Physics Department, Kalamazoo College, Kalamazoo, MI 49006 (United States); Veal, Boyd [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Hull, John [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States)

    2007-04-15

    An innovative method of manipulating magnetic carriers is proposed, and its feasibility for drug delivery and therapy is demonstrated experimentally. The proposed method employs pulsed-field solenoid coils with high-critical- temperature (T {sub c}) superconductor inserts. Pulsed current is used to magnetize and de-magnetize the superconductor insert. The proposed method was demonstrated to be able to (1) move magnetic particles, ranging in size from a few millimeters to 10 {mu}m, with strong enough forces over a substantial distance, (2) hold the particles at a designated position as long as needed, and (3) reverse the processes and retrieve the particles. We further demonstrated that magnetic particles can be manipulated in a stationary environment, in water flow, and in simulated blood (water/glycerol mixture) flow.

  9. Manipulation of magnetic carriers for drug delivery using pulsed-current high Tc superconductors

    Science.gov (United States)

    Cha, Yung; Chen, Lihua; Askew, Thomas; Veal, Boyd; Hull, John

    2007-04-01

    An innovative method of manipulating magnetic carriers is proposed, and its feasibility for drug delivery and therapy is demonstrated experimentally. The proposed method employs pulsed-field solenoid coils with high-critical- temperature ( Tc) superconductor inserts. Pulsed current is used to magnetize and de-magnetize the superconductor insert. The proposed method was demonstrated to be able to (1) move magnetic particles, ranging in size from a few millimeters to 10 μm, with strong enough forces over a substantial distance, (2) hold the particles at a designated position as long as needed, and (3) reverse the processes and retrieve the particles. We further demonstrated that magnetic particles can be manipulated in a stationary environment, in water flow, and in simulated blood (water/glycerol mixture) flow.

  10. The determination of phenazone in blood plasma for obtained sistem suitable test of monitoring drug level

    Directory of Open Access Journals (Sweden)

    Mochamad Lazuardi

    2007-09-01

    Full Text Available The determining of Phenazone to human blood plasma from healthy man after separated by solid phase extraction (SPE and spectroscopic measurements has been investigated. The objective of that research was to obtain system suitable test for determine the Phenazone level in biological fluids (human blood plasma, for new performed dosage regimented in clinical dentistry. The method can be divided into the following four steps. 1. Centrifugation the blood sample, 2. Extraction from blood plasma and, 3. Separation by SPE with manual pressured, 4. Elution to SPE followed by the measurement on a spectrophotometer in the ultra violet region. The critical value of  │t │at the 5% confidence level indicates that there is no systematic error in the linearity proposed method. Recoveries for this research were obtained at ranging 93.460 to 95.598%. The coefficient variation precision of this procedure was clearly good at smallest than 2%. The analytical procedure can be carried out in one working operation as a monitored therapeutic activity.

  11. Baseline albuminuria predicts the efficacy of blood pressure-lowering drugs in preventing cardiovascular events

    NARCIS (Netherlands)

    Boersma, C.; Postma, M.J.; Visser, S.T.; Atthobari, J.; de Jong, P.E.; de Jong-van den Berg, L.T.; Gansevoort, R.T.

    2008-01-01

    AIMS Albuminuria has been proven to be associated with cardiovascular (CV) events in specific patient populations, but also in the general population. This study aimed to investigate whether the efficacy of blood pressure-lowering agents in preventing CV events depends on baseline urinary albumin ex

  12. Blood compatibility studies of Swarna bhasma (gold bhasma), an Ayurvedic drug.

    Science.gov (United States)

    Paul, Willi; Sharma, Chandra Prakash

    2011-01-01

    Swarna bhasma (gold bhasma) preparations are widely utilized as therapeutic agents. However, in vitro biological evaluations of bhasma preparations are needed along with the physicochemical characterization for present day standardization of metallic bhasma preparations to meet the criteria that supports its use. Therefore, an attempt has been made to evaluate the protein adsorption, blood compatibility and complement activation potential of two batches of Swarna bhasma preparation, along with its physicochemical characterization. The particle size, morphology, elemental analysis, and in vitro cytotoxicity were evaluated initially. Red blood cell hemolysis, aggregation studies with blood cells, protein adsorption, complement C3 adsorption, platelet activation and tight junction permeability in Caco-2 cell line were investigated. The Swarna bhasma preparations with a crystallite size of 28-35 nm did not induce any blood cell aggregation or protein adsorption. Activation potential of these preparations towards complement system or platelets was negligible. These particles were also non-cytotoxic. Swarna bhasma particles opened the tight junctions in Caco-2 cell experiments. The results suggest the application of Swarna bhasma preparations as a therapeutic agent in clinical medicine from the biological safety point of view.

  13. Natural killer cells in highly exposed hepatitis C-seronegative injecting drug users.

    Science.gov (United States)

    Mina, M M; Cameron, B; Luciani, F; Vollmer-Conna, U; Lloyd, A R

    2016-06-01

    Injecting drug use remains the major risk factor for hepatitis C (HCV) transmission. A minority of long-term injecting drug users remain seronegative and aviraemic, despite prolonged exposure to HCV - termed highly exposed seronegative subjects. Natural killer (NK) cells have been implicated in this apparent protection. A longitudinal nested, three group case-control series of subjects was selected from a prospective cohort of seronegative injecting drug users who became incident cases (n = 11), remained seronegative (n = 11) or reported transient high-risk behaviour and remained uninfected (n = 11). The groups were matched by age, sex and initial risk behaviour characteristics. Stored peripheral blood mononuclear cells were assayed in multicolour flow cytometry to enumerate natural killer cell subpopulations and to assess functional activity using Toll-like receptor ligands before measurement of activation, cytokine production and natural cytotoxicity receptor expression. Principal components were derived to describe the detailed phenotypic characteristics of the major NK subpopulations (based on CD56 and CD16 co-expression), before logistic regression analysis to identify associations with exposed, seronegative individuals. The CD56(dim) CD16(+) (P = 0.05, OR 6.92) and CD56(dim) CD16(-) (P = 0.05, OR 6.07) principal components differed between exposed, seronegative individuals and pre-infection samples of the other two groups. These included CD56(dim) CD16(+) and CD56(dim) CD16(-) subsets with CD56(dim) CD16(+) IFN-γ and TNF-α on unstimulated cells, and CD56(dim) CD16(-) CD69(+) , CD107a(+) , IFN-γ and TNF-α following TLR stimulation. The cytotoxic CD56(dim) NK subset thus distinguished highly exposed, seronegative subjects, suggesting NK cytotoxicity may contribute to protection from HCV acquisition. Further investigation of the determinants of this association and prospective assessment of protection against HCV infection are warranted.

  14. Miniaturized blood sampling techniques to benefit reduction in mice and refinement in nonhuman primates: applications to bioanalysis in toxicity studies with antibody-drug conjugates.

    Science.gov (United States)

    Caron, Alexis; Lelong, Christine; Pascual, Marie-Hélène; Benning, Véronique

    2015-03-01

    Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development of miniaturized blood sampling methods (including microsampling and dried blood spots) applicable to toxicokinetic determinations of small-molecule drugs. Implementation of miniaturized blood sampling methods in the context of biotherapeutic drugs is desirable because a limitation to this type of medicine remains the total blood volume needed from a single animal to support toxicokinetic determinations of several analytes (parent drug, metabolites[s], antidrug antibodies, and so forth). We describe here the technical details, applicability, and relevance of new miniaturized blood sampling procedures in mice and nonhuman primates in the context of the toxicologic evaluation of biotherapeutic drugs consisting of antibody-drug conjugates developed for oncology indications. These examples illustrate how these techniques can benefit the reduction of animal usage in mouse toxicity studies by decreasing the number of animals dedicated to toxicokinetic determinations and the refinement of practices in nonhuman primate toxicity studies by decreasing the blood volume repeatedly drawn for toxicokinetic determinations.

  15. Miniaturized Blood Sampling Techniques to Benefit Reduction in Mice and Refinement in Nonhuman Primates: Applications to Bioanalysis in Toxicity Studies with Antibody–Drug Conjugates

    Science.gov (United States)

    Caron, Alexis; Lelong, Christine; Pascual, Marie-Hélène; Benning, Véronique

    2015-01-01

    Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development of miniaturized blood sampling methods (including microsampling and dried blood spots) applicable to toxicokinetic determinations of small-molecule drugs. Implementation of miniaturized blood sampling methods in the context of biotherapeutic drugs is desirable because a limitation to this type of medicine remains the total blood volume needed from a single animal to support toxicokinetic determinations of several analytes (parent drug, metabolites[s], antidrug antibodies, and so forth). We describe here the technical details, applicability, and relevance of new miniaturized blood sampling procedures in mice and nonhuman primates in the context of the toxicologic evaluation of biotherapeutic drugs consisting of antibody–drug conjugates developed for oncology indications. These examples illustrate how these techniques can benefit the reduction of animal usage in mouse toxicity studies by decreasing the number of animals dedicated to toxicokinetic determinations and the refinement of practices in nonhuman primate toxicity studies by decreasing the blood volume repeatedly drawn for toxicokinetic determinations. PMID:25836960

  16. High Blood Cholesterol Q&A Dr. Michael Lauer | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... high cholesterol research. Dr. Michael Lauer and his wife, Dr. Robin Avery, agree on the health benefits ... trial of the drug methotrexate in high-risk patients with vascular disease. We have come to appreciate ...

  17. The Transferrin Receptor at the Blood-Brain Barrier - exploring the possibilities for brain drug delivery

    NARCIS (Netherlands)

    Visser, Corine

    2005-01-01

    There are many diseases of the central nervous system (CNS), like Parkinson's disease, Alzheimer's disease, depression, schizophrenia, epilepsy, migraine headache, and HIV infection in the brain. However, treatment is difficult since many drugs cannot reach the brain in sufficient quantities due to

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

    African Journals Online (AJOL)

    EB

    Department of Medical Rehabilitation, Faculty of Health Sciences and Technology, Nnamdi Azikiwe ... drug therapy seems to have been investigated in only laboratory animals. ... Methods: This open label randomised-controlled trial involved .... completed the study. ... not and whether each number in a set should remain.

  19. Benzodiazepines and sedative-hypnotics in blood of drivers under the influence and their association with other common illegal drug use and national sales figures.

    Science.gov (United States)

    Blencowe, Tom; Raaska, Kari; Lillsunde, Pirjo

    2011-02-01

    The authors examined benzodiazepine and sedative-hypnotic positive cases of drivers under the influence (DUI) in Finland from 1997 to 2008. Factors studied were the number of cases positive for the most commonly encountered of these pharmaceuticals, simultaneous use of amphetamine and/or cannabis, and the relationship between the number of DUI cases and overall sales in Finland for the individual pharmaceuticals. Data for 20037 cases positive for the relevant drugs were retrieved from the laboratory database of the Alcohol and Drug Analytics Unit, National Institute for Health and Welfare. Toxicological results were from blood analysis. Drug sales figures for each pharmaceutical were obtained from the Finnish Medicines Agency. An increase in DUI cases that were positive for the drugs studied was evident, which reflected the overall increase in positive DUI cases detected annually. The proportion of relevant cases was typically 75% or higher of all positive DUI cases up to 2003, the year that the Finnish zero tolerance law was introduced, and then decreased to 66.2% in 2008. Diazepam was consistently the most commonly detected nonmetabolite drug. The prevalence of clonazepam and alprazolam increased sharply from 2004 onward. Metabolites of diazepam, nordiazepam, temazepam, and oxazepam, were other common findings. Associated use of amphetamine and/or cannabis was also common in these DUI cases, typically between 56% and 66% of cases. An increase in the number of DUI cases showing combined use of benzodiazepines and sedative-hypnotics with amphetamines in particular was apparent after zero tolerance legislation and the introduction in 2005 of an effective on-site screening device for the stimulant. Ratios of DUI cases to sales figures showed an increase in detection of clonazepam-positive DUI cases from 2003. Diazepam, midazolam, and alprazolam also exhibited relatively high ratios, which increased from 1997 to 2008.

  20. Drug: D06912 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nese Medicine in Japan [BR:br08304] Crude Drugs Drugs for blood Drugs for removing blood stasis D06912 *Quercus cortex; Bokusoku Drug...s for external use Drugs for external use D06912 *Quercu

  1. Gold nanoparticles generated and stabilized by water soluble curcumin-polymer conjugate: blood compatibility evaluation and targeted drug delivery onto cancer cells.

    Science.gov (United States)

    Manju, S; Sreenivasan, K

    2012-02-15

    Curcumin (Cur) shows low anticancer activity in vivo due to its reduced systemic bioavailability stemmed from its poor aqueous solubility and instability. Suitably functionalized nanocarriers designed to empty the drug specifically at tumor sites can potentially enhance the antitumor activity of Cur. We devised a simple method for the fabrication of water soluble Cur conjugated gold nanoparticles to target various cancer cell lines. Cur was conjugated to hyaluronic acid (HA) to get a water soluble conjugate (HA-Cur). We generated gold nanoparticles (AuNPs) by reducing chloroauric acid using HA-Cur, which played the dual role of a reducing and stabilizing agent and subsequently anchored folate conjugated PEG. These entities were probed using different analytical techniques, assayed the blood compatibility and cytotoxicity. Their interaction with cancer cell lines (HeLa cells, glyoma cells and Caco 2 cells) was followed by flow cytometry and confocal microscopy. Blood-materials interactions studies showed that the nanoparticles are highly hemocompatible. Flow cytometry and confocal microscopy results showed significant cellular uptake and internalization of the particles by cells. HA-Cur@AuNPs exhibited more cytotoxicity comparing to free Cur. The strategy, we adopted here, resulted the formation blood compatible Cur conjugated AuNPs with enhanced targeting and improved efficacy. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Anthropometric indicators of obesity as screening tools for high blood pressure in the elderly.

    Science.gov (United States)

    Leal Neto, João de Souza; Coqueiro, Raildo da Silva; Freitas, Roberta Souza; Fernandes, Marcos Henrique; Oliveira, Daniela Sousa; Barbosa, Aline Rodrigues

    2013-08-01

    The study objectives were to investigate the indicators of obesity most associated with high blood pressure in community-dwelling elderly and identify among these which one best discriminates high blood pressure. This is an epidemiological, population, cross-sectional and home-based study of elderly people (≥ 60 years, n = 316) residing in northeastern Brazil. The results showed that the body mass index and the body adiposity index were the indicators more closely associated with high blood pressure in both sexes. Both in female and male genders, body mass index showed high values of specificity and low sensitivity values for discriminating high blood pressure, whereas the body adiposity index showed high sensitivity and moderate specificity values. In clinical practice and health surveillance, it is suggested that both indicators be used as screening tools for hypertension in the elderly.

  3. Suitability of blood-pressure-to-height ratio as the criterion for high blood pressure in children in an environmental study.

    Science.gov (United States)

    Paunović, Katarina; Jakovljević, Branko

    2017-01-01

    Blood-pressure-to-height ratio is considered a simple, accurate, inexpensive and non-age-dependent index for screening high blood pressure in a clinical setting, but its suitability in epidemiological surveys was not taken into consideration. The aim of this study was to test the suitability of blood-pressure-to-height ratio against blood pressure for age percentiles for the identification of high blood pressure in an environmental study. The sample consisted of 2195 children, aged 3 to 15 years, whose blood pressure was measured as part of an environmental study in Belgrade, Serbia. High blood pressure was estimated using percentiles (gold standard) and blood-pressure-to-height ratios for systolic and diastolic pressures separately (proposed criterion). The optimal cut-offs of the blood-pressure-to-height ratio (BPHR) were selected based on Youden's index (sensitivity + specificity - 1) calculated from the receiver operator characteristic curve analysis. The proposed criterion identified five times more cases of high blood pressure in the investigated children of all age groups in comparison to the gold standard. The optimal cut-off values were selected based on the sensitivity and specificity values by age groups and gender. Blood-pressure-to-height ratio can be a reliable criterion for the estimation of high blood pressure in epidemiological studies. This is the first study on the applicability of blood-pressure-to-height ratio in Serbian children, but it may not be easily generalized to other populations due to small sample size across the examined age groups and potential diversities in risk factors for high blood pressure. Applied in epidemiological studies, BPHR would help researchers estimate the role of certain environmental factors on blood pressure in children.

  4. Hispanics, Blacks Less Likely to Get High Blood Pressure Treatment: Study

    Science.gov (United States)

    ... Hispanics, Blacks Less Likely to Get High Blood Pressure Treatment: Study Less than half from any group had BP under good control To use the ... and what differences exist across racial and ethnic groups," Argulian said in ... blood pressure treatment. But, "There are multiple factors that contribute ...

  5. Obesity promotes oxidative stress and exacerbates blood-brain barrier disruption after high-intensity exercise

    Directory of Open Access Journals (Sweden)

    Hee-Tae Roh

    2017-06-01

    Conclusion: Our study suggests that episodic vigorous exercise can increase oxidative stress and blood neurotrophic factor levels and induce disruption of the BBB. Moreover, high levels of neurotrophic factor in the blood after exercise in the obese group may be due to BBB disruption, and it is assumed that oxidative stress was the main cause of this BBB disruption.

  6. Herb-Drug Pharmacokinetic Interaction of a Traditional Chinese Medicine Jia-Wei-Xiao-Yao-San with 5-Fluorouracil in the Blood and Brain of Rat Using Microdialysis

    Directory of Open Access Journals (Sweden)

    Meng-Hsuan Chiang

    2015-01-01

    Full Text Available According to a survey from the National Health Insurance Research Database (NHIRD, Jia-Wei-Xiao-Yao-San (JWXYS is the most popular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU is a general anticancer drug for the chemotherapy. To investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a microdialysis technique coupled with a high-performance liquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel groups, one of which was treated with 5-FU (100 mg/kg, i.v. alone and the remaining three groups were pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days followed by a combination with 5-FU. This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day has no significant effect on the pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day coadministered with 5-FU extends the elimination half-life and increases the volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance. This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS.

  7. Herb-Drug Pharmacokinetic Interaction of a Traditional Chinese Medicine Jia-Wei-Xiao-Yao-San with 5-Fluorouracil in the Blood and Brain of Rat Using Microdialysis

    Science.gov (United States)

    Chiang, Meng-Hsuan; Chang, Li-Wen; Wang, Ju-Wen; Lin, Lie-Chwen; Tsai, Tung-Hu

    2015-01-01

    According to a survey from the National Health Insurance Research Database (NHIRD), Jia-Wei-Xiao-Yao-San (JWXYS) is the most popular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU) is a general anticancer drug for the chemotherapy. To investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a microdialysis technique coupled with a high-performance liquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel groups, one of which was treated with 5-FU (100 mg/kg, i.v.) alone and the remaining three groups were pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days) followed by a combination with 5-FU. This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day) coadministered with 5-FU extends the elimination half-life and increases the volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance. This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS. PMID:25861367

  8. Analysis on Drug Resistance and Experienced Medication in Blood Culture%血培养药敏结果与经验用药的调查分析

    Institute of Scientific and Technical Information of China (English)

    陈丽丹; 黄晓燕

    2011-01-01

    目的 提高临床医生在血培养结果出来前经验性用药的准确率.方法 对2009年11月-2010年10月我院血培养阳性菌株的耐药性进行分析,对相关病例进行回顾性分析.结果 178份血培养阳性的菌株耐药率较高;血培养结果出来前经验用药率达94.94%,与药敏试验结果的符合率为43.82%.使用率最高的抗菌药为喹诺酮类药物,使用率为41.86%.结论 临床医生应根据医院耐药谱合理选择用药,提高经验用药的准确率.%Objective To improve the veracity of experienced medication in clinical treatment of septicaemia before the outcome of blood culture. Methods 178 patients with positive blood culture from November 2009 to October 2010 were retrospectively analyzed. Results Drug resistance rate was high. 94. 94% of medication were used before the outcome of blood culture , only 43. 82% were coincident with the outcome. Quinolone was the most frequently used medication, with a use ratio of 41. 86% . Conclusion Doctors should select medication reasonably in accordance with the drug resistance to improve the accuracy of experienced medication.

  9. 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.

  10. Comparison of Clinic and Ambulatory Blood Pressure in Response to Antihypertensive Drugs in Chinese Patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To compare the difference between 24-h ambulatory blood pressure (ABP) and trough clinic blood pressure (CBP) after 8 weeks of therapy. Methods The study used meta-regression analysis to summarize three randomized,double-blind, active controlled trials in order to compare the difference between the magnitude of the reduction in 24-h average ABP and CBP Patients. Chinese patients with seated diastolic blood pressure (SDBP) 95-115 mmHg and ambulatory diastolic blood pressure (ADBP) ≥85 mmHg. Results The average age of 126 patients was 47.7±8.3 years, ranging from 25 to 67 (95 males and 31 females). All regimens reduced 24-h ABP and CBP after 8 weeks of treatment. In the 126 patients the baseline 24-h SBP and DBP values (142.7/94.4 mmHg) were markedly lower than those for clinic values (152.6/102.6 mmHg;P<0.0001). Similarly, the 24-h SBP and DBP values (132.7/87.7 mmHg) in week 8 were markedly lower than the clinic values (138.9/92.7 mmHg; P<0.0001). The differences between the treatment-induced reductions in 24-h ABP and CBP were statistically significant (the difference was 3.7/3.3 mmHg for SBP/DBP, P=0.0069/P<0.0001). Conclusion All regimens significantly reduced seated CBP and ABP. The effect of antihypertensive treatment was greater on CBP than that on ABP,suggesting that assessment on effectiveness of an antihypertensive treatment using CBP readings only has to be carefully interpreted, and a more systematic application of ABP monitoring should be adopted.

  11. Polytherapy with two or more antihypertensive drugs to lower blood pressure in elderly Ontarians. Room for improvement

    Science.gov (United States)

    Campbell, Norman RC; McAlister, Finlay A; Duong-Hua, Minh; Tu, Karen

    2007-01-01

    BACKGROUND: Although guidelines now recommend polytherapy to achieve blood pressure targets, little is know about which antihypertensive drugs are combined in clinical practice. OBJECTIVE: To examine current practices for the coprescribing of antihypertensive agents. METHODS: A population-based cohort study was performed using linked administrative databases on all Ontario residents 66 years of age or older who were newly treated for hypertension between July 1, 1994, and March 31, 2002, and did not have diabetes or other relevant comorbidities. All patients were followed for two years to determine which antihypertensives were prescribed concurrently. RESULTS: Of the 166,018 patients in the described cohort, 1819 (1%) were prescribed a combination therapy tablet as their first-line therapy. The number of patients prescribed antihypertensive polytherapy within the first two years of diagnosis increased from 2071 (21%) of the 9825 hypertensive patients starting treatment in the second half of 1994 to 2578 (37%) of the 6988 hypertensive patients beginning treatment in the first quarter of 2002 (P<0.0001). Overall, 11,003 (27%) of polytherapy prescriptions were for drugs without additive hypotensive effects when combined and this proportion did not change over time. CONCLUSIONS: Although there has been an increase in the use of polytherapy in elderly hypertensive patients without comorbidities in Ontario over the past decade, more than one-quarter of the two drugs prescribed together have not been proven to have additive hypotensive effects. Because this likely contributes to suboptimal blood pressure control rates, future guidelines and educational programs should devote increased attention to the choice of optimal polytherapy combinations. PMID:17703255

  12. Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

    Directory of Open Access Journals (Sweden)

    Timothy Robinson

    Full Text Available Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity.

  13. Addressing the challenge of high-priced prescription drugs in the era of precision medicine: A systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks.

    Science.gov (United States)

    Gronde, Toon van der; Uyl-de Groot, Carin A; Pieters, Toine

    2017-01-01

    Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. A systematic review of Pubmed, the Financial Times, the New York Times, the Wall Street Journal and the Guardian was performed to identify articles related to the pricing of medicines. Changes in drug life cycles have dramatically affected patent medicine markets, which have long been considered a self-evident and self-sustainable source of income for highly profitable drug companies. Market failure in combination with high merger and acquisition activity in the sector have allowed price increases for even off-patent drugs. With market interventions and the introduction of QALY measures in health care, governments have tried to influence drug prices, but often encounter unintended consequences. Patent reform legislation, reference pricing, outcome-based pricing and incentivizing physicians and pharmacists to prescribe low-cost drugs are among the most promising short-term policy options. Due to the lack of systematic research on the effectiveness of policy measures, an increasing number of ad hoc decisions have been made with counterproductive effects on the availability of essential drugs. Future challenges demand new policies, for which recommendations are offered. A fertile ground for high-priced drugs has been created by changes in drug life-cycle dynamics, the unintended effects of patent legislation, government policy measures and orphan drug programs. There is an urgent need for regulatory reform to curtail prices and safeguard equitable access to innovative medicines.

  14. Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations

    Directory of Open Access Journals (Sweden)

    Romero EL

    2013-08-01

    Full Text Available Eder Lilia Romero, Maria Jose Morilla Nanomedicine Research Program, Department of Science and Technology, National University of Quilmes, Bernal, Buenos Aires, Argentina Abstract: Vesicles that are specifically designed to overcome the stratum corneum barrier in intact skin provide an efficient transdermal (systemic or local drug delivery system. They can be classified into two main groups according to the mechanisms underlying their skin interaction. The first group comprises those possessing highly deformable bilayers, achieved by incorporating edge activators to the bilayers or by mixing with certain hydrophilic solutes. The vesicles of this group act as drug carriers that penetrate across hydrophilic pathways of the intact skin. The second group comprises those possessing highly fluid bilayers, owing to the presence of permeation enhancers. The vesicles of this group can act as carriers of drugs that permeate the skin after the barrier of the stratum corneum is altered because of synergistic action with the permeation enhancers contained in the vesicle structure. We have included a detailed overview of the different mechanisms of skin interaction and discussed the most promising preclinical applications of the last five years of Transfersomes® (IDEA AG, Munich, Germany, ethosomes, and invasomes as carriers of antitumoral and anti-inflammatory drugs applied by the topical route. Keywords: Transfersomes, ethosomes, antitumoral, anti-inflammatory, topical delivery

  15. Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations

    Science.gov (United States)

    Romero, Eder Lilia; Morilla, Maria Jose

    2013-01-01

    Vesicles that are specifically designed to overcome the stratum corneum barrier in intact skin provide an efficient transdermal (systemic or local) drug delivery system. They can be classified into two main groups according to the mechanisms underlying their skin interaction. The first group comprises those possessing highly deformable bilayers, achieved by incorporating edge activators to the bilayers or by mixing with certain hydrophilic solutes. The vesicles of this group act as drug carriers that penetrate across hydrophilic pathways of the intact skin. The second group comprises those possessing highly fluid bilayers, owing to the presence of permeation enhancers. The vesicles of this group can act as carriers of drugs that permeate the skin after the barrier of the stratum corneum is altered because of synergistic action with the permeation enhancers contained in the vesicle structure. We have included a detailed overview of the different mechanisms of skin interaction and discussed the most promising preclinical applications of the last five years of Transfersomes® (IDEA AG, Munich, Germany), ethosomes, and invasomes as carriers of antitumoral and anti-inflammatory drugs applied by the topical route. PMID:23986634

  16. High-Throughput Screening of Ototoxic and Otoprotective Pharmacological Drugs

    Science.gov (United States)

    Kalinec, Federico

    2005-01-01

    Drug ototoxicity research has relied traditionally on animal models for the discovery and development of therapeutic interventions. More than 50 years of research, however, has delivered few--if any--successful clinical strategies for preventing or ameliorating the ototoxic effects of common pharmacological drugs such as aminoglycoside…

  17. Possible involvement of cationic-drug sensitive transport systems in the blood-to-brain influx and brain-to-blood efflux of amantadine across the blood-brain barrier.

    Science.gov (United States)

    Suzuki, Toyofumi; Fukami, Toshiro; Tomono, Kazuo

    2015-03-01

    The purpose of this study was to characterize the brain-to-blood efflux transport of amantadine across the blood-brain barrier (BBB). The apparent in vivo efflux rate constant for [(3) H]amantadine from the rat brain (keff ) was found to be 1.53 × 10(-2) min(-1) after intracerebral microinjection using the brain efflux index method. The efflux of [(3) H]amantadine was inhibited by 1-methyl-4-phenylpyridinium (MPP(+) ), a cationic neurotoxin, suggesting that amantadine transport from the brain to the blood across the BBB potentially involves the rat plasma membrane monoamine transporter (rPMAT). On the other hand, other selected substrates for organic cation transporters (OCTs) and organic anion transporters (OATs), as well as inhibitors of P-glycoprotein (P-gp), did not affect the efflux transport of [(3) H]amantadine. In addition, in vitro studies using an immortalized rat brain endothelial cell line (GPNT) showed that the uptake and retention of [(3) H]amantadine by the cells was not changed by the addition of cyclosporin, which is an inhibitor of P-gp. However, cyclosporin affected the uptake and retention of rhodamine123. Finally, the initial brain uptake of [(3) H]amantadine was determined using an in situ mouse brain perfusion technique. Notably, the brain uptake clearance for [(3) H]amantadine was significantly decreased with the co-perfusion of quinidine or verapamil, which are cationic P-gp inhibitors, while MPP(+) did not have a significant effect. It is thus concluded that while P-gp is not involved, it is possible that rPMAT and the cationic drug-sensitive transport system participate in the brain-to-blood efflux and the blood-to-brain influx of amantadine across the BBB, respectively.

  18. Clinical applications of high-speed blood flow measurements with diffuse correlation spectroscopy

    Science.gov (United States)

    Parthasarathy, Ashwin B.; Baker, Wesley B.; Gannon, Kimberly; Mullen, Michael T.; Detre, John A.; Yodh, Arjun G.

    2017-02-01

    Diffuse Correlation Spectroscopy (DCS) is an increasingly popular non-invasive optical technique to clinically measure deep tissue blood flow, albeit at slow measurement rates of 0.5-1 Hz. We recently reported the development of a new `fast' DCS instrument that continuously measures blood flow at 50-100 Hz (simultaneously from 8 channels), using conventional DCS sources/detectors, and optimized software computations. A particularly interesting result was our ability to optically record pulsatile micro-vascular blood flow waveforms, and therein readily identify high frequency features such as the dicrotic notch. Here, we showcase the utility and potential of high-speed measurements of blood flow (and arterial blood pressure) in a few clinical applications. First, we employ the fast-DCS instrumentation to measure cerebral autoregulation (CVAR) dynamics. Cerebral autoregulation refers to the mechanism by which cerebral blood flow (CBF) is maintained during fluctuations in blood pressure; CVAR is impaired in the injured brain. We derive an index of autoregulation by measuring the rates of decrease (and recovery) of blood flow and blood pressure following a sudden, induced change in systemic blood pressure (e.g., bilateral thigh cuff deflation). Our pilot experiments in healthy volunteers show that DCS measured rates of micro-vascular regulation are comparable to conventional large vessel regulatory metrics (e.g., measured with transcranial Doppler ultrasound). Second, we utilized pulsatile blood flow oscillations in cerebral arteries to estimate the critical closing pressure (CrCP), i.e., the arterial blood pressure at which CBF approaches zero. Pilot experiments in healthy subjects show good agreement between CrCP measured with DCS and transcranial Doppler ultrasound.

  19. Factors Governing P-Glycoprotein-Mediated Drug-Drug Interactions at the Blood-Brain Barrier Measured with Positron Emission Tomography.

    Science.gov (United States)

    Wanek, Thomas; Römermann, Kerstin; Mairinger, Severin; Stanek, Johann; Sauberer, Michael; Filip, Thomas; Traxl, Alexander; Kuntner, Claudia; Pahnke, Jens; Bauer, Florian; Erker, Thomas; Löscher, Wolfgang; Müller, Markus; Langer, Oliver

    2015-09-01

    The adenosine triphosphate-binding cassette transporter P-glycoprotein (ABCB1/Abcb1a) restricts at the blood-brain barrier (BBB) brain distribution of many drugs. ABCB1 may be involved in drug-drug interactions (DDIs) at the BBB, which may lead to changes in brain distribution and central nervous system side effects of drugs. Positron emission tomography (PET) with the ABCB1 substrates (R)-[(11)C]verapamil and [(11)C]-N-desmethyl-loperamide and the ABCB1 inhibitor tariquidar has allowed direct comparison of ABCB1-mediated DDIs at the rodent and human BBB. In this work we evaluated different factors which could influence the magnitude of the interaction between tariquidar and (R)-[(11)C]verapamil or [(11)C]-N-desmethyl-loperamide at the BBB and thereby contribute to previously observed species differences between rodents and humans. We performed in vitro transport experiments with [(3)H]verapamil and [(3)H]-N-desmethyl-loperamide in ABCB1 and Abcb1a overexpressing cell lines. Moreover we conducted in vivo PET experiments and biodistribution studies with (R)-[(11)C]verapamil and [(11)C]-N-desmethyl-loperamide in wild-type mice without and with tariquidar pretreatment and in homozygous Abcb1a/1b((-/-)) and heterozygous Abcb1a/1b((+/-)) mice. We found no differences for in vitro transport of [(3)H]verapamil and [(3)H]-N-desmethyl-loperamide by ABCB1 and Abcb1a and its inhibition by tariquidar. [(3)H]-N-Desmethyl-loperamide was transported with a 5 to 9 times higher transport ratio than [(3)H]verapamil in ABCB1- and Abcb1a-transfected cells. In vivo, brain radioactivity concentrations were lower for [(11)C]-N-desmethyl-loperamide than for (R)-[(11)C]verapamil. Both radiotracers showed tariquidar dose dependent increases in brain distribution with tariquidar half-maximum inhibitory concentrations (IC50) of 1052 nM (95% confidence interval CI: 930-1189) for (R)-[(11)C]verapamil and 1329 nM (95% CI: 980-1801) for [(11)C]-N-desmethyl-loperamide. In homozygous Abcb1a/1b

  20. Hypothesis testing in high-throughput screening for drug discovery.

    Science.gov (United States)

    Prummer, Michael

    2012-04-01

    Following the success of small-molecule high-throughput screening (HTS) in drug discovery, other large-scale screening techniques are currently revolutionizing the biological sciences. Powerful new statistical tools have been developed to analyze the vast amounts of data in DNA chip studies, but have not yet found their way into compound screening. In HTS, characterization of single-point hit lists is often done only in retrospect after the results of confirmation experiments are available. However, for prioritization, for optimal use of resources, for quality control, and for comparison of screens it would be extremely valuable to predict the rates of false positives and false negatives directly from the primary screening results. Making full use of the available information about compounds and controls contained in HTS results and replicated pilot runs, the Z score and from it the p value can be estimated for each measurement. Based on this consideration, we have applied the concept of p-value distribution analysis (PVDA), which was originally developed for gene expression studies, to HTS data. PVDA allowed prediction of all relevant error rates as well as the rate of true inactives, and excellent agreement with confirmation experiments was found.

  1. Hot punching of high-aspect-ratio 3D polymeric microstructures for drug delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh; Keller, Stephan Sylvest; Boisen, Anja

    2015-01-01

    Hot punching: a highly versatile method of fabricating high-aspect-ratio 3D microstructures for drug delivery with good replication fidelity and yield.......Hot punching: a highly versatile method of fabricating high-aspect-ratio 3D microstructures for drug delivery with good replication fidelity and yield....

  2. Drug resistance of 115 Staphylococcus aureus strains isolated from blood culture%155例血培养金黄色葡萄球菌耐药分析

    Institute of Scientific and Technical Information of China (English)

    郝秀红; 赵强元; 郭建巍; 李艳君; 钱扬会; 刘力娟

    2013-01-01

    Objective To provide the evidence for treatment of Staphylococcus aureus infection by investigating its drug resistance in 2003-2011. Methods Blood samples of Staphylococcus aureus were taken using the blood culture bottle provided by Beijing Botai Technique Development Center and cultured in BacT/ALERT 3D automated blood culture system. The isolated bacteria were identified with the VITEK system, their drug sensitivity was tested by BIOMIC and their drug resistance was analyzed by WHONET 5.4 software. Results Of the 155 Staphylococcus aureus strains isolated from January 2003 to December 2011, 110 were methicillin-resistant S.aureus (MRSA), accounting for 70.9%. No resistance of Staphylococcus aureus to LNZ and VAN was found. The resistance of Staphylococcus aureus was below 30%to NIT and SXT, above 50%to TCY, LVX, CLX, CIP, CZO, AZM, ERY and PEN, 21.6%to 7 commonly used antibiotics and 34.6%to 8 commonly used antibiotics, respectively. Conclusion Staphylococcus aureus isolated from blood culture is highly resistant to drugs. The MRSA is resistant to multiple drugs and its drug resistance monitoring should be strengthened.%  目的了解2003-2011年血培养中金黄色葡萄球菌的耐药性变迁,为临床治疗提供依据.方法采用北京伯泰技术开发中心血培养瓶采样,BacT/ALERT 3D全自动血培养仪进行培养,VITEK微生物仪进行鉴定,BIOMIC仪进行药敏测试,WHONET5.4软件进行耐药性分析.结果2003年1月-2011年12月从临床送检的血培养标本分离出金葡菌155株,其中耐甲氧西林金黄色葡萄球菌(methicillin resistant staphylococcus aureus,MRSA)110株,MRSA在金葡菌中平均发生率为70.9%;9年间金葡菌对万古霉素、利奈唑胺未发现耐药株;对呋喃妥因、复方新诺明敏感性尚好,耐药率<30%;对四环素、左氧氟沙星、克林霉素、环丙沙星、头孢唑啉、阿齐霉素、红霉素、青霉素耐药率均达50%以上,且表现为

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

    Science.gov (United States)

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

    2011-12-01

    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 glucose levels in nectar-feeding bats (Glossophaga soricina) in experiments in which we varied the amount of dietary sugar or flight time. Blood glucose levels increased with the quantity of glucose ingested and exceeded 25 mmol l(-1) blood in resting bats, which is among the highest values ever recorded in mammals fed sugar quantities similar to their natural diet. During normal feeding, blood glucose values decreased with increasing flight time, but only fell to expected values when bats spent 75 per cent of their time airborne. Either nectar-feeding bats have evolved mechanisms to avoid negative health effects of hyperglycaemia, or high activity is key to balancing blood glucose levels during foraging. We suggest that the coevolutionary specialization of bats towards a nectar diet was supported by the high activity and elevated metabolic rates of these bats. High activity may have conferred benefits to the bats in terms of behavioural interactions and foraging success, and is simultaneously likely to have increased their efficiency as plant pollinators.

  4. Course of Untreated High Blood Pressure in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Daniel J Feaster

    2011-05-01

    Full Text Available Introduction: No clear understanding exists about the course of a patient’s blood pressure (BP during an emergency department (ED visit. Prior investigations have demonstrated that BP can be reduced by removing patients from treatment areas or by placing patients supine and observing them for several hours. However, modern EDs are chaotic and noisy places where patients and their families wait for long periods in an unfamiliar environment. We sought to determine the stability of repeated BP measurements in the ED environment. Methods: A prospective study was performed at an urban ED. Research assistants trained and certified in BP measurement obtained sequential manual BPs and heart rates on a convenience sample of 76 patients, beginning with the patient arrival in the ED. Patients were observed through their stay for up to 2 hours, and BP was measured at 10-minute intervals. Data analysis with SAS PROC MIXED (SAS Institute, Cary, North Carolina for regression models with correlated data determined the shape of the curve as BP changed over time. Patients were grouped on the basis of their presenting BP as normal (less than 140/90, elevated (140–160/90–100, or severely elevated (greater than 160/100 for the regression analysis. Results: A statistically significant downward trend in systolic and diastolic BP was observed only for those patients presenting with severely elevated BPs (ie, greater than 160/100. Conclusion: We demonstrate a statistically significant decline in systolic and diastolic BP over time spent in the ED only for patients with severely elevated presenting BPs. [West J Emerg Med. 2011;12(4:421–425.

  5. High glucose impairs superoxide production from isolated blood neutrophils

    DEFF Research Database (Denmark)

    Perner, A; Nielsen, S E; Rask-Madsen, J

    2003-01-01

    Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This stud...... measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils....

  6. High-normal blood pressure and the risk of cardiovascular disease.

    Science.gov (United States)

    Kokubo, Yoshihiro; Kamide, Kei

    2009-08-01

    The guidelines of the Joint National Committee 7 from the USA on hypertension have unified the normal and high-normal blood pressure categories into a single entity termed ;prehypertension'. In contrast, The European Guidelines for the management of hypertension in 2007 considered ;prehypertensive' to be divided into normal and high-normal blood pressure. These patients with high-normal blood pressure or prehypertension might progress to hypertension over time. Previous studies have shown that high-normal blood pressure is a risk factor for cardiovascular disease (CVD) in Western countries and Japan. The combination of high-normal blood pressure and other cardiovascular risk factors increases the risks of CVD. Recently, metabolic syndrome has also been shown to be a risk factor for CVD. In Japan, the association between metabolic syndrome and CVD was also found to be significant. The risks for CVD incidence were similar among participants who had the same number of components, regardless of the presence of abdominal obesity. In the Japanese guidelines for the management of hypertension published in 2009, patients are considered to be in a high-risk group if they have diabetes, chronic kidney disease, 3 or more risk factors, target organ damage or CVD, even if they have only high-normal blood pressure, and appropriate antihypertensive therapy should be initiated.

  7. More Young Adults at Risk for High Blood Pressure | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... develop high blood pressure without preventative measures. Today, clinical guidelines recommend that physicians work with patients to keep ... is the Dietary Approaches to Stop Hypertension (DASH) clinical study, which ... the importance of lowering sodium (salt) intake. Most Americans consume ...

  8. [Effect of 5 warm-hot nature Chinese drugs for promoting blood circulation and removing blood stasis on 5-HT, NE, and endocrine hormones of rats of cold coagulation and blood stasis syndrome].

    Science.gov (United States)

    Wang, Peng; Fu, Xian-Jun; Zhou, Yang; Wang, Zhen-Guo

    2014-11-01

    To study the mechanism of warm-hot nature Chinese drugs (WHNCD) for promoting blood circulation and removing blood stasis (PBCRBS) for intervening model rats of cold coagulation and blood stasis syndrome (CCBSS). CCBSS rat model was set up in outbred SD rats using ice water immersion method. Totally 300 successfully modeled CCBSS rats were randomly divided into 5 groups according to the principle of balance weight, 60 in each group. Contents of triothyrone (T3), tetraiodothyroine (T4), progesterone (P), 5-hydroxytryptamine (5-HT), and noradrenalin (NE) were paralleledly detected in all groups. Then rats in each group were subdivided into 6 subgroups as the model group, the curcuma group, the Ligsticum Chuanxiong group, the safflower group, the Rhizoma Corydalis group, and the Olibanumg group. Besides, 5 normal control groups were set up for 5 indices, 50 rats in total. We need 70 rats (7 groups) to finish observing 1 index, 350 rats in total for 5 indices. Except those in the model group and the normal control group, rats were administered with corresponding decoction at 20 g crude drugs/kg body weight by gastrogavage, 3 mL each time, once daily for 7 successive days. Equal volume of normal saline was given to rats in the normal control group and the model group. Contents of T3, T4, P, 5-HT, and NE were detected before treatment and 1 week after treatment. Compared with before treatment in the same group, T3 increased in the Ligsticum Chuanxiong group and the Olibanumg group, 5-HT increased in the Ligsticum Chuanxiong group, T4, NE, and P increased in all medicated groups (P endocrine system, which might be one of the pharmacodynamic mechanism of WHNCD for PBCRBS in intervening CCBSS.

  9. The Distribution and Drug Resistance of Pathogenic Bacteria in Blood Culture%血培养中的病原菌分布及耐药性分析

    Institute of Scientific and Technical Information of China (English)

    李玲; 张群智

    2015-01-01

    Objective: To understand the distribution and drug resistance of pathogenic bacteria in blood culture, and provide a reference basis for clinical treatment of infectious diseases. Methods: Bact/Alert 3D system was used for blood culture, the identification of bacteria and susceptibility test were performed by VITEK-2 Compact identification system and the Kirby-Bauer method; the distribution and drug resistance of pathogenic bacteria were analyzed statistically. Results: 391 strains of pathogenic bacteria were isolated in 4 758 specimens of blood culture, with the positive rate of 8.22%. Of 391 strains were 197 strains of Gram-negative bacillus, with the highest positive rate of E. coli(131 strains), followed by Pneumonia klebsiella bacteria(21 strains)and Onion burkholderia bacteria(10 strains), and 182 strains of Gram-positive coccus, with three highest positive rate of bacteria in order i.e. Staphylococcus epidermidis(53 strains), Staphylococcus hominis(39 strains)and Staphylococcus aureus(22 strains). The resistant rates of E. coli to ampicillin, ceftriaxone were 94.92%, 81.36%, 63.49%respectively. The resistant rates of Staphylococcus epidermidis to penicillin G, erythromycin, compound sulfamethoxazole were as high as 95.65%, 75.51%. Conclusion: A variety of pathogenic bacteria in blood culture were found, of which E. coli and Coagulase negative staphylococci were dominant and they had a high drug resistant rate to the common antibiotics. The monitoring of the drug resistance should be strengthened and antibiotics should be reasonably selected based on the result of drug sensitivity test.%目的:了解血培养病原菌分布及耐药情况,为临床感染性疾病的治疗提供参考依据。方法:采用Bact/Alert3D血培养仪、VITEK-2 Compact鉴定系统及K-B法进行血培养、细菌鉴定和药敏试验,统计、分析病原菌分布及药敏结果。结果:4758份血培养标本分离出病原菌391株(8.22%

  10. The influence of drug kinetics in blood on the calculation of oral bioavailability in linear pharmacokinetics: the traditional equation may considerably overestimate the true value.

    Science.gov (United States)

    Berezhkovskiy, Leonid M

    2006-04-01

    A common calculation of oral bioavailability is based on the comparison of the areas under the concentration-time curves after intravenous and oral drug administration. It does not take into account that after the oral dosing a drug enters the systemic circulation in different states, that is, as free fraction, protein bound and partitioned into blood cells, and plasma lipids, while after intravenous input it is introduced into the systemic circulation only as a free fraction. Consideration of this difference leads to a novel equation for the oral bioavailability. In general, the traditional calculation overestimates the oral bioavailability. For a widely applied model of a linear pharmacokinetic system with central (plasma) drug elimination it is shown that the traditional calculation of the oral bioavailability could substantially overestimate the true value. If the existence of an immediate equilibrium between different drug fractions in blood is assumed, the obtained equation becomes identical to the traditional one. Thus the deviation of oral bioavailability from the value given by a common calculation appears to be a kinetic phenomenon. The difference could be significant for the drugs with the rate constant of elimination from plasma of the same order of magnitude or greater than the dissociation rate constant of drug-protein complexes, or the off-rate constant of partitioning from the blood cells, if the blood concentration profiles were used to calculate the oral bioavailability.

  11. [Unfavorable outcome of aggressive lowering of high blood pressure. Case report].

    Science.gov (United States)

    Kuperczkó, Diána; Csécsei, Péter; Komáromy, Hedvig; Szapáry, László; Fehér, Gergely

    2014-10-19

    Cerebral autoregulation is essential in the maintenance of cerebral blood flow. Due to this autoregulation, cerebral perfusion is constant in healthy subjects if blood pressure values are between 50-150 mmHg. In hypertensive patients the curve is right-shifted towards higher blood pressure values (pathological autoregulation). Aggressive blood pressure reduction can lead to severe ischaemia. The authors report the history of a 73-year-old man with the background history of widespread atherosclerotic disease. The patient complained about headache and dizziness and was found to have high blood pressure (160/100 mmHg) and increased blood glucose (14.8 mmol/l). Prior to his admission an aggressive blood pressure and blood sugar reduction was carried out and, within a short period of time he became unconscious and was transferred to the department of the authors with the possible diagnosis of brainstem stroke. On admission the patient was unresponsive, comatose with brainstem symptoms. Urgent brain computed tomography failed to show any acute alterations. However, repeat CT scan revealed extensive bilateral space occupying ischemic changes involving in territories of both internal carotid arteries with consequent brainstem compression. Computed tomography angiography confirmed bilateral internal carotid artery occlusion. The authors conclude that intensive blood pressure reduction result in ischemic lesions via hypoperfusion especially in patients with widespread atherosclerotic disease and significant carotid vessel pathology.

  12. New guidelines for high blood pressure and dyslipidemia: beyond the controversy, are they reliable guides?

    OpenAIRE

    2014-01-01

    Updates to the Guidelines for the Management of High Blood Pressure and the Guidelines for the Management of Dyslipidemia have been recently published in the eighth report of the Joint National Committee. Both are evidence-based and rely on clinical trial results, leaving aside, when possible, recommendations made by experts. Both have introduced important methodological changes in the form of cataloging and summarizing the evidence used. The High Blood Pressure Guideline is considered to be ...

  13. The effects of different beverage intake on blood components during exercise under high-temperature environment

    OpenAIRE

    Baek, Soon Gi

    2013-01-01

    High temperature environment causes detrimental effects on health. In the present study, the effects of intake of several kinds of beverage on blood components during exercise under the high temperature environment were evaluated. The 10 subjects were student of the H University. Exercise intensity was 50–60% O2maxx and treadmill exercise was continued for 1 h. The kinds of beverage were water, ion beverage, cucumber drink. Blood sampling was performed before the exercise, immediately finishi...

  14. Optimal Blood Pressure Goals in Patients With Hypertension at High Risk for Cardiovascular Events.

    Science.gov (United States)

    Aronow, Wilbert S

    2016-01-01

    Existing epidemiologic and clinical trial data suggest that the blood pressure in patients with hypertension at high risk for cardiovascular events because of coronary artery disease, diabetes mellitus, chronic kidney disease, stroke, or heart failure should be reduced to blood pressure be reduced to 140-145 mm Hg if tolerated in patients aged 80 years and older. Studies from patients with coronary artery disease, diabetes mellitus, chronic kidney disease, stroke, and heart failure will be discussed that support a blood pressure goal of high risk for cardiovascular events.

  15. Triggered Drug Release from Superhydrophobic Meshes using High-Intensity Focused Ultrasound

    OpenAIRE

    Yohe, Stefan T.; Kopechek, Jonathan A.; Porter, Tyrone M; Colson, Yolonda L.; Grinstaff, Mark W.

    2013-01-01

    Application of high-intensity focused ultrasound to drug-loaded superhydrophobic meshes affords triggered drug release by displacing an entrapped air layer. The air layer within the superhydrophobic meshes is characterized using direct visualization and B-mode imaging. Drug-loaded superhydrophobic meshes are cytotoxic in an in vitro assay after ultrasound treatment.

  16. Highlights from Drug Use Among American High School Students 1975-1977.

    Science.gov (United States)

    Johnston, Lloyd D.; And Others

    The current prevalence of drug use among American high school seniors and the trends in use since 1975 are the two major topics treated. Also reported are prevailing attitudes and beliefs among seniors concerning various types of drug use. Eleven separate classes of drugs are distinguished: marihuana (including hashish), inhalants, hallucinogens,…

  17. Internal filtration, filtration fraction, and blood flow resistance in high- and low-flux dialyzers.

    Science.gov (United States)

    Schneditz, Daniel; Zierler, Edda; Vanholder, Raymond; Eloot, Sunny

    2014-01-01

    It was the aim to examine the fluid flow in blood and dialysate compartments of highly permeable hollow fiber dialyzers where internal filtration contributes to solute removal but where excessive filtration bears a risk of cell activation and damage. Flow characteristics of high- (HF) and low-flux (LF) dialyzers were studied in lab-bench experiments using whole bovine blood. Measurements obtained under different operating conditions and under zero net ultrafiltration were compared to theoretical calculations obtained from a mathematical model. Experimental resistances in the blood compartment were within ±2% of those calculated from the model when dialysate was used as a test fluid. With whole blood, the experimental resistances in the blood compartment were only 81.8 ± 2.8% and 83.7 ± 4.3% of those calculated for the LF and HF dialyzer, respectively. Surprisingly, measured blood flow resistance slightly but significantly decreased with increasing flow rate (p filtration fraction, while overall internal filtration increased. The increase in internal filtration when increasing blood flow is associated with a beneficial reduction in internal filtration fraction. Concerns of increased hemoconcentration when increasing blood flow therefore appear to be unwarranted.

  18. Risk factors for high blood pressure in low income children aged 3-4 years.

    Science.gov (United States)

    Vitolo, Márcia Regina; da Costa Louzada, Maria Laura; Rauber, Fernanda; Campagnolo, Paula Dal Bó

    2013-08-01

    This study aimed to evaluate the effect of dietary sodium intake on blood pressure among low income children aged 3-4 years. Data were collected during a randomized trial conducted in São Leopoldo, Brazil, with 500 mother-child pairs recruited from the maternity ward of a local hospital. Breastfeeding data were obtained during the children's first year of life. At 3 to 4 years of age, children's anthropometric, dietary, and blood pressure assessments were obtained. Sodium intake was estimated from two multiple-pass 24-h dietary recalls. Systolic blood pressure > 90th percentile for age, sex, and height was classified as high systolic blood pressure, according to the population-based percentiles provided by the Task Force on Hypertension Control in Children and Adolescents. Blood pressure data were obtained from 331 children at 3 to 4 years. The mean value of systolic blood pressure was 91.31 mmHg (SD = 8.30 mmHg) and 5.2% (n = 17) presented high systolic blood pressure. The results of the multivariable analyses showed that children who consumed more than 1,200 mg of sodium/day and with waist-to-height ratio higher than 0.5 presented, respectively, 3.32 (95%CI 0.98-11.22) and 8.81 (95%CI 2.13-36.31) greater risk of having high systolic blood pressure. Exclusive breastfeeding, child overweight and change in body mass index z score during the first year of life were not associated with the outcome. The results of this study suggest that at preschool age sodium intake and high waist-to-height ratio are risk factors for high systolic blood pressure.

  19. High glucose impairs superoxide production from isolated blood neutrophils

    DEFF Research Database (Denmark)

    Perner, A; Nielsen, S E; Rask-Madsen, J

    2003-01-01

    Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study...

  20. Reporting of consistency of blood pressure control in randomized controlled trials of antihypertensive drugs: a systematic review of 1372 trial reports.

    Science.gov (United States)

    Fischer, Urs; Webb, Alastair J S; Howard, Sally C; Rothwell, Peter M

    2012-07-01

    Hypertension is a powerful treatable risk factor for stroke. Reports of randomized controlled trials (RCTs) of antihypertensive drugs rightly concentrate on clinical outcomes, but control of blood pressure (BP) during follow-up is also important, particularly given that inconsistent control is associated with a high risk of stroke and that antihypertensive drug classes differ in this regard. We performed a systematic review of reporting of BP control in RCTs of antihypertensive drugs. We searched bibliographic databases (1950-2009) for systematic reviews of RCTs of BP-lowering and identified the main report of all trials. We identified 94 larger trials (>100 participants/arm, >1-year follow-up) and 1278 smaller/shorter trials. Ninety-one (96.8%) larger trials reported some data on mean BP during follow-up, but none reported effects on the consistency of control of BP over time. Although 81 (86.2%) larger trials reported group distribution of BP at baseline (usually SD), only 22 (23.4%) reported such data at any follow-up visit. Eleven (11.7%) larger trials reported group distribution of the change in BP from baseline to follow-up, but 61 (64.9%) reported no data at all on group distribution of BP at follow-up. Thirty-nine (41.5%) trials reported the proportion of patients reaching some BP target during follow-up, but no trial reported data on the consistency of control to target within individuals over time. Similar proportions were observed in the 1278 smaller/short trials. Reporting of BP control is limited in RCTs of BP-lowering drugs. We suggest reporting guidelines.