DOCSLIB.ORG

Association of Hypertensive Status and Its Drug Treatment with Lipid and Haemostatic Factors in Middle-Aged Men: the PRIME Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Association of Hypertensive Status and Its Drug Treatment with Lipid and Haemostatic Factors in Middle-Aged Men: the PRIME Study Journal of Human Hypertension (2000) 14, 511–518 2000 Macmillan Publishers Ltd All rights reserved 0950-9240/00 $15.00 www.nature.com/jhh ORIGINAL ARTICLE Association of hypertensive status and its drug treatment with lipid and haemostatic factors in middle-aged men: the PRIME Study P Marques-Vidal1, M Montaye2, B Haas3, A Bingham4, A Evans5, I Juhan-Vague6, J Ferrie`res1, G Luc2, P Amouyel2, D Arveiler3, D McMaster5, JB Ruidavets1, J-M Bard2, PY Scarabin4 and P Ducimetie`re4 1INSERM U518, Faculte´ de Me´decine Purpan, Toulouse, France; 2MONICA-Lille, Institut Pasteur de Lille, Lille, France; 3MONICA-Strasbourg, Laboratoire d’Epide´miologie et de Sante´ Publique, Strasbourg, France; 4INSERM U258, Hoˆ pital Broussais, Paris, France; 5Belfast-MONICA, Department of Epidemiology, The Queen’s University of Belfast, UK; 6Laboratory of Haematology, La Timone Hospital, Marseille, France Aims: To assess the association of hypertensive status this effect remained after multivariate adjustment. Cal- and antihypertensive drug treatment with lipid and hae- cium channel blockers decreased total cholesterol and mostatic levels in middle-aged men. apoproteins A-I and B; those differences remained sig- Methods and results: Hypertensive status, antihyperten- nificant after multivariate adjustment. ACE inhibitors sive drug treatment, total and high-density lipoprotein decreased total cholesterol, triglycerides, apoprotein B (HDL) cholesterol, triglyceride, apoproteins A-I and B, and LpE:B; and this effect remained after multivariate lipoparticles LpA-I, LpE:B and Lp(a), fibrinogen, plas- adjustment. Analysis of the subjects on monotherapy minogen activator inhibitor-1 (PAI-1) activity and factor showed beta-blockers to decrease total cholesterol and VII were assessed in a sample of men 50–59 years living HDL parameters and angiotersin-converting enzyme ACE) inhibitors to decrease low-density lipoprotein) .(2374 ؍ and Northern Ireland (n (7050 ؍ in France (n After adjustment for age, body mass index, smoking (LDL)-related parameters, while no effect was found for status, educational level, country, alcohol drinking and the other antihypertensive drugs. hypolipidaemic drug treatment, untreated hypertensive Conclusions: Hypertensive status is associated with an subjects had higher levels of total cholesterol, triglycer- unfavourable lipid and haemostatic profile in middle- ide, apoproteins A-I and B and PAI-I activity than normo- aged men. Antihypertensive treatment with beta-block- tensive subjects. On univariate analysis, diuretics ers decreases HDL parameters, whereas treatment with decreased total and HDL-cholesterol and apoproteins A- ACE inhibitors appears to decrease total cholesterol I and B; those differences remained after multivariate and LDL-related parameters. adjustment. Treatment with beta-blockers decreased Journal of Human Hypertension (2000) 14, 511–518 total and HDL-cholesterol, apoprotein A-I and LpA-I, and Keywords: lipids; lipoproteins; drug treatment; haemostasis; epidemiology Introduction been shown that some of the most commonly used antihypertensive drugs tend to increase total choles- Cardiovascular diseases (CVD) are the leading cause 4,7,8 1 terol and triglyceride levels. This increase would of premature death in industrialised countries. The reduce the beneficial effects of blood pressure lower- association of hypertension with CVD is well docu- ing. Furthermore, although the effects of the older mented, and several clinical studies have shown antihypertensive drugs (thiazide diuretics and beta- that reduction in high levels of blood pressure leads blockers) on serum lipids are well documented,7 to a decrease in the incidence of stroke and myocar- there is still controversy on the effects of these drugs dial infarction (MI).2–5 Nevertheless, the decrease in in haemostatic variables.9 Finally, there is some myocardial infarction rates is somewhat less than expected from the magnitude of the decrease in controversy on the effects of the other classes of anti- blood pressure levels.4,6 A possible explanation for hypertensive drugs such as calcium channel block- ers and angiotensin-converting enzyme (ACE) this discrepancy is a deleterious effect of antihyper- 9–12 tensive drug treatment on blood lipids, and it has inhibitors on lipid and haemostatic variables. Hence, we used the baseline data from the PRIME (Prospective Epidemiological Study of Myocardial Infarction) Study to assess the association of hyper- Correspondence: Jean Ferrie`res, INSERM U518, Faculte´ de Me´de- cine, De´partment d’Epide´miologie, ler e´t., 37, Alle´es Jules tensive status and of different antihypertensive Guesde, 31073 Toulouse cedex, France. Tel: +33 5 61 52 18 70, drugs with serum lipid and haemostatic variables. Fax: +33562264240 Received 26 November 1999; revised and accepted 6 May 2000 Lipids and haemostasis in hypertension P Marques-Vidal et al 512 Patients and methods subjects for which SBP у160 mm Hg or DBP у95 mm Hg, who had been told that they were hyperten- Population sampling sive, but without antihypertensive drug therapy. The PRIME Study was established in 1991 in the Category 4: Treated hypertensive subjects: subjects populations of four WHO-MONICA collaborating currently on antihypertensive drug therapy. centres in Belfast (UK), Lille, Strasbourg and Toul- ouse (France). The target was to recruit 2500 men, aged 50–59 years, in each centre and to follow them Blood sampling and assay procedures for a minimum of 5 years. The sample was recruited to broadly match the social class structure of the Venous blood was collected between 9 and 10 am background population. The sampling frame was into siliconised vacutainer tubes (Vacutainer, based on industry and various employment groups, Becton Dickinson, Franklin Lakes, NJ, USA) con- and on health screening centres and general prac- taining 0.11 M trisodium citrate. Platelet-poor plasma was obtained by centrifugation at 3000 g and tice. Participation was voluntary. Subjects were ° ° informed of the aim of the study and those who 4 C (PAI-1 activity measurements) or 20 C agreed to take part were given a morning appoint- (fibrinogen and factor VII assay) for 15 min. Aliquots ment and asked to fast for a minimum of 10 h. of plasma were immediately transferred into plastic tubes and frozen at −80°C. The frozen aliquots were then shipped in batches to the central laboratory Personal and medical history in Lille. Self-administered questionnaires relating to demo- Haemostatic variables were measured in the cen- graphic, socio-economic factors and diet were com- tral haemostasis laboratory of La Timone Hospital at pleted at home by the participants and checked by Marseille, France. Fibrinogen was measured accord- the interviewer at the clinic. Additional question- ing to the method of Clauss (Fibriprest automate, naires on medical history were administered by the Diagnostica Stago, Asnie`res, France). Factor VIIc interviewers at the clinic. Data on level of education, was assayed in a regular one-stage system using rab- occupational activity, personal and family history, bit thromboplastin. Factor VII-deficient substrate tobacco and alcohol consumption, drug intake and plasma was prepared from absorbed bovine plasma physical activity were also collected. and concentrate of human factors IX, X and II as described previously.13 Results were expressed as a percentage of reference plasma. PAI-1 activity was Definition of hypertension measured by a two-stage amidolytic method using a Blood pressure was measured once at the end of the commercially available kit (Spectrolyse/pl, Biopool, examination after a 5-min rest in the sitting position. Umea, Sweden). All the haemostatic tests were per- Measurements were performed with an automatic formed between January 1991 and January 1994. device (Spengler SP9), which also recorded heart Accuracy and precision of haemostatic assays were rate. A standard cuff size was used, but a large cuff assured by a strict internal quality control pro- was available when necessary. At least three meas- gramme. A single batch of normal plasma pool pre- uring devices were available at any time in each pared from 50 healthy subjects was used as control centre and all three were used equally. In order to material. For each assay, two to four controls were avoid systematic differences between centres, the included in each run of PRIME study samples. devices were circulated between them. The devices Analysis of internal quality control data showed that were also recalibrated every 3 months in the co- the laboratory coefficient of variation ranged from ordinating centre in Paris. 4.3% (fibrinogen) to 9.5% (PAI-1). Hypertension was defined according to WHO cri- Plasma prepared with EDTA was used for analysis teria, ie, when a subject had a systolic blood press- of lipids. Plasma total cholesterol and triglycerides ure (SBP) у160 mm Hg and/or a diastolic blood were measured by enzymatic methods using pressure (DBP) у95 mm Hg and/or was taking anti- reagents from Boerhinger Mannheim (Mannheim, hypertensive drugs. Awareness of hypertension was Germany). The inter-assay coefficient of variation for defined by a positive answer to the question: ‘Did a total cholesterol and triglyceride were 2% and 3%, doctor ever tell you that you had high blood press- respectively. High density lipoprotein (HDL) choles- ure levels?’ Medical treatment was considered if the terol was measured after precipitation of apoprotein subject answered positively to the question: ‘Are B-containing lipoproteins with
Load more

Recommended publications
  • Still an Important Cause of Heart Failure?
    Journal of Human Hypertension (2005) 19, 267–275 & 2005 Nature Publishing Group All rights reserved 0950-9240/05 $30.00 www.nature.com/jhh REVIEW ARTICLE Hypertension — still an important cause of heart failure? E Kazzam1, BA Ghurbana2, EN Obineche1 and MG Nicholls1 1Department of Internal Medicine, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates; 2Department of Medicine, Al Ain Hospital, Al Ain, United Arab Emirates Hypertension has been the single most important risk from highly selected study groups in tertiary referral factor for heart failure until the last few decades. Now, it centres to patients with heart failure in primary and is frequently claimed that atherosclerotic coronary secondary care, may not be justified. Finally, the artery disease dominates as the major underlying cause, situation of heart failure primarily due to impaired left and hypertension is of lesser importance. We here ventricular diastolic function, where hypertension is a review evidence regarding the contribution of hyperten- frequent precursor, is often ignored in discussions of sion to heart failure in the recent decades. It is not aetiology. Our view is that hypertension remains and possible, in our view, to be confident of the relative probably is the single most, important modifiable risk importance of hypertension and coronary artery disease factor for cardiac failure in some races and countries, since there are significant limitations in the available where the dominant cardiac abnormality is left ventri- data. The often-questionable diagnostic criteria used in cular diastolic dysfunction. The situation is less clear for defining heart failure is one such limitation.
    [Show full text]
  • The Role of Intercalated Cell Nedd4–2 in BP Regulation, Ion Transport, and Transporter Expression
    BASIC RESEARCH www.jasn.org The Role of Intercalated Cell Nedd4–2 in BP Regulation, Ion Transport, and Transporter Expression Masayoshi Nanami,1 Truyen D. Pham,1 Young Hee Kim,1 Baoli Yang,2 Roy L. Sutliff,3 Olivier Staub,4,5 Janet D. Klein,1 Karen I. Lopez-Cayuqueo,6,7 Regine Chambrey,8 Annie Y. Park,1 Xiaonan Wang,1 Vladimir Pech,1 Jill W. Verlander,9 and Susan M. Wall1,10 Due to the number of contributing authors, the affiliations are listed at the end of this article. ABSTRACT Background Nedd4–2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a corre- lation between Nedd4–2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4–2 gene ablation on IC transporter abundance and function and on BP. Methods We generated IC Nedd4–2 knockout mice using Cre-lox technology and produced global pen- 2/2 drin/Nedd4–2 null mice by breeding global Nedd4–2 null (Nedd4–2 ) mice with global pendrin null 2/2 (Slc26a4 ) mice. Mice ate a diet with 1%–4% NaCl; BP was measured by tail cuff and radiotelemetry. We 2 measured transepithelial transport of Cl and total CO2 and transepithelial voltage in cortical collecting ducts perfused in vitro. Transporter abundance was detected with immunoblots, immunohistochemistry, and immunogold cytochemistry. 2 2 Results IC Nedd4–2 gene ablation markedly increased electroneutral Cl /HCO3 exchange in the cortical col- lecting duct, although benzamil-, thiazide-, and bafilomycin-sensitive ion flux changed very little.
    [Show full text]
  • Sharon R. Roseman, MD, FACP Practice Limited to Gastroenterology
    Sharon R. Roseman, MD, FACP Practice Limited to Gastroenterology 701 Broad Street, Suite 411 Sewickley, PA 15143 (412) 749-7160 Fax: (412) 749-7388 http://www.heritagevalley.org/sharonrosemanmd Patient Drug Education for Diltiazem / Nifedipine Ointment Diltiazem/Nifedipine ointment is used to help heal anal fissures. The ointment relaxes the smooth muscle around the anus and promotes blood flow which helps heal the fissure (tear). The ointment reduces anal canal pressure, which diminishes pain and spasm. We use a diluted concentration of Diltiazem/Nifedipine compared to what is typically used for heart patients, and this is why you need to obtain the medication from a pharmacy which will compound your prescription. It is also prescribed to treat anal sphincter spasm, painful hemorrhoids and pelvic floor spasm. The Diltiazem/Nifedipine ointment should be applied 3 times per day, or as directed. A pea-sized drop should be placed on the tip of your finger and then gently placed inside the anus. The finger should be inserted 1/3 – 1/2 its length and may be covered with a plastic glove or finger cot. You may use Vaseline ® to help coat the finger or dilute the ointment. (If you are unable or hesitant to use your finger to administer the ointment TELL U S and we will order you a suppository to use as an “applicator”.) If you are advised to mix the Diltiazem/Nifedipine with steroid ointment, limit the steroids to one to two weeks. The first few applications should be taken lying down, as mild light- headedness or a brief headache may occur.
    [Show full text]
  • Valproate-Olanzapine-Nifedipine Interaction Related Pedal Edema
    Letter-to-the Editor Taiwanese Journal of Psychiatry (Taipei) Vol. 28 No. 3 2014 • 181 • Valproate-olanzapine-nifedipine Interaction Related Pedal Edema Patient’s bilateral pedal pitting edema did not Case Report resolve spontaneously after discontinuing olan- zapine until he received diuretics with furosemide A 45-year-old single male patient with bipo- 40 mg/day and spironolactone 75 mg/day on the lar I disorder was admitted to acute ward of our 21st day of pitting edema. He required further hospital due to depressive mood with irritability treatment, and had normal fi ndings in physical ex- for more than one month. The fi nding of physical amination and repeated laboratory tests. examination at admission revealed no bilateral pedal edema under long-term usage of valproate Comment 700 mg/day as mood stabilizer, nifedipine 30 mg/ day for essential hypertension, and allopurinol There have been some clinical reports to as- 100 mg/day for gouty arthritis before hospitaliza- sociate olanzapine treatment with bilateral lower tion. The results of laboratory tests for electro- extremity edema since 2000 [1]. Pre-clinical trials lytes, renal function, liver function, chest X-ray, of oral olanzapine (doses being equal or greater and electrocardiography were also within normal than 2.5 mg/day) have also reported peripheral limits. edema as a rare adverse event. The pathophysio- During this hospitalization, we added olan- logical mechanism of low extremity edema re- zapine 5 mg/day to control manic symptoms. Five mains unknown, although some mechanisms days later, he reported bilateral swelling over low- could be proposed, such as olanzapine’s blockage er legs and ankles, a bilateral 2+ pitting edema in of α1, M1, M3 and 5-HT2 receptors [2, 3].
    [Show full text]
  • Nifedipine Adalat, Adalat PA, Adalat XL, Apo-Nifed, Nu-Nifed
    Nifedipine Adalat, Adalat PA, Adalat XL, Apo-Nifed, Nu-Nifed Information for patients and families Why am I taking this drug? Nifedipine helps to: Control high blood pressure (hypertension) Reduce how often you have chest pains (angina) How does nifedipine work? Nifedipine belongs to a class of drugs called calcium channel blockers. It relaxes the muscles in your blood vessels so that they will open wider. This lowers your blood pressure and makes it easier for your heart to pump blood. Nifedipine also opens the blood vessels in your heart (coronary arteries) wider so that more blood and oxygen can get to the heart muscle. This is helpful for angina, which happens when the heart muscle is not getting enough blood and oxygen for the amount of work it is doing. How should I take this medicine? Never chew or crush nifedipine tablets. It is best to take nifedipine on an empty stomach. Avoid taking it with grapefruit juice. Take your pills at the same time every day. Do not stop taking this drug unless you check with your doctor first. You may need to gradually take less and less instead of stopping all at once. What should I do if I miss a dose? If you are late taking a dose and it is almost time for the next one, skip the late dose then follow your regular schedule. Never take more than 1 dose at a time. If you do not know what to do, ask your pharmacist, doctor or nurse practitioner. What should I expect from this medicine? Nifedipine usually starts to work within 30 to 60 minutes after you take it.
    [Show full text]
  • Comparing the Efficacy of Angiotensin Converting Enzyme In- Hibitors with Calcium Channel Blockers on the Treatment of Di- Abetic Nephropathy: a Meta-Analysis
    Iran J Public Health, Vol. 48, No.2, Feb 2019, pp.189-197 Review Article Comparing the Efficacy of Angiotensin Converting Enzyme In- hibitors with Calcium Channel Blockers on the Treatment of Di- abetic Nephropathy: A Meta-Analysis *Zhaowei ZHANG 1, Chunlin CHEN 2, Shiwen LV 1, Yalan ZHU 1, Tianzi FANG 1 1. Department of Pharmacy, Jin Hua Municipal Central Hospital, Jin Hua 32100, China 2. College of Chemistry and Bio-Engineering, Yi Chun University, Yi Chun 336000, China *Corresponding Author: Email: [email protected] (Received 21 Mar 2018; accepted 11 Jun 2018) Abstract Background: The angiotensin-converting enzyme inhibitors (ACEIs) could improve the symptoms of diabetic nephropathy. Whether the calcium channel blockers (CCBs) could be as effective as ACEIs on treating diabetic nephropathy is controversial. Here, we aimed to compare the efficacy of ACEIs with CCBs on the treatment of diabetic nephropathy by performing a meta-analysis of randomized controlled trials (RCTs). Methods: The Pubmed, Medline, Embase and The Cochrane Database were searched up to July 2017 for eli- gible randomized clinical trials studies. Effect sizes were summarized as mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (P-value<0.05). Results: Seven RCTs involving 430 participants comparing ACEIs with CCBs were included. No benefit was seen in comparative group of ACEIs on systolic blood pressure（SBP） (MD=1.05 mmHg; 95% CI: -0.97 to 3.08, P=0.31), diastolic blood pressure (DBP) (MD= -0.34 mmHg; 95% CI: -1.2 to 0.51, P=0.43), urinary al- bumin excretion rates (UAER) (MD=1.91μg/min; 95% CI: -10.3 to 14.12, P=0.76), 24-h urine protein (24-UP) (SMD=-0.26; 95%CI: -0.55 to 0.03, P=0.08), glomerular filtration rate (GFR) (SMD=0.01; 95% CI: -0.38 to 0.41, P=0.95).
    [Show full text]
  • Print This Article
    Print ISSN: 2319-2003 | Online ISSN: 2279-0780 IJBCP International Journal of Basic & Clinical Pharmacology DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20174634 Original Research Article Anticonvulsant effect of nifedipine, dizepam and in combination on pentylenetetrazol induced experimental models of epilepsy on albino rats Muralidhar C.1, Vijay Prasad S.2*, Sridhar I.3 ABSTRACT Background: In many patients, the presently available antiepileptic drugs such 1Medical Officer, Under as phenobarbital, phenytoin, benzodiazepines, sodium valproate, etc., are unable DMHO, Medak, Telangana, to control seizures efficiently and the problem of adverse effects has also not been India circumvented completely and approximately 30% of the patients continue to have 2Department of Pharmacology, seizures with current antiepileptic drugs therapy. Hence, search should continue Dr Vithalrao Vikhe Patil to develop newer, more effective, and safer neuro-protective agents for treatment Foundation's Medical College, of epilepsy. Aim of the study was to investigate the activity of nifedipine, the Ahmednagar, Maharashtra, dihydropyridine calcium channel blocker, diazepam, the benzodiazepine anti- India convulsant of established efficacy and their combinations against rat models of 3Department of Pharmacology, pentylenetetrazol (PTZ) induced convulsions. Method: Wister albino rats of Government Medical College, either sex, weighing between 150-220gm were used. Rats were divided into 10 Nizamabad, Telangana, India groups, in each group n=6 total N=60. Methods: PTZ was administration 30 min after test drug administration. Received: 17 September 2017 Intraperitoneal injection of PTZ at the dose of 80mg/Kg body weight were Accepted: 22 September 2017 administered to the rats to produce chemically-induced seizure. The effect of nifedipine and diazepam were assessed on such seizure model.
    [Show full text]
  • In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
    applied sciences Article Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts Dorina Lauritano 1,*,† , Giulia Moreo 1,†, Fedora Della Vella 2 , Annalisa Palmieri 3, Francesco Carinci 4 and Massimo Petruzzi 2 1 Centre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy; [email protected] 2 Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy; [email protected] (F.D.V.); [email protected] (M.P.) 3 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmoro 8, 40126 Bologna, Italy; [email protected] 4 Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] * Correspondence: [email protected] † These authors contribute equally to this work. Abstract: Background: It has been proven that the antihypertensive agent nifedipine can cause gingi- val overgrowth as a side effect. The aim of this study was to analyze the effects of pharmacological treatment with nifedipine on human gingival fibroblasts activity, investigating the possible patho- genetic mechanisms that lead to the onset of gingival enlargement. Methods: The expression profile of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway, fibroblasts’ viability at different drug concentrations, and E-cadherin levels in treated fibroblasts were assessed using real-time Polymerase Chain Reaction, PrestoBlue™ cell viability test, and an enzyme-linked immunoassay (ELISA), respectively. Results: Metalloproteinase 24 and 8 (MMP24, MMP8) showed Citation: Lauritano, D.; Moreo, G.; significant upregulation in treated cells with respect to the control group, and cell adhesion gene Vella, F.D.; Palmieri, A.; Carinci, F.; CDH1 (E-cadherin) levels were recorded as increased in treated fibroblasts using both real-time Petruzzi, M.
    [Show full text]
  • Actual Place of Diuretics in Hypertension Treatment
    Mini Review J Cardiol & Cardiovasc Ther Volume 3 Issue 4 - March 2017 Copyright © All rights are reserved by Farouk Abcha DOI: 10.19080/JOCCT.2017.03.555616 Actual Place of Diuretics in Hypertension Treatment Farouk Abcha, Marouane Boukhris*, Zied Ibn Elhadj, Lobna Laroussi, Faouzi Addad, Afef Ben Halima and Salem Kachboura Cardiology Department of Abderrahmen Mami Hospital, University of Tunis El Manar, Tunisia Submission: February 03, 2017; Published: March 07, 2017 *Corresponding author: Marouane Boukhris, Cardiology Department of Abderrahmen Mami Hospital, Ariana, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia, Tel: ; Email: Abstract Diuretics represent a large and heterogeneous class of drugs, differing from each other by structure, site and mechanism of action. Diuretics are widely used, and have several indications in different cardiovascular disorders, particularly in hypertension and heart failure. Despite the large number of available anti-hypertensive drugs, diuretics remained a cornerstone of hypertension treatment. In the current editorial, we assessed the actual place of different diuretics in the hypertension guidelines focusing on the concept of tailored approach in prescribing them for hypertensive patients. Keywords: Diuretics; Hypertension; Hydrochlorothiazide; Indapamide; Guidelines Introduction Diuretics represent a large and heterogeneous class of drugs, differing from each other by structure, site and mechanism of action. Diuretics are widely used, and have several indications in different cardiovascular disorders, particularly in hypertension and heart failure. Despite the large number of available anti-hypertensive drugs, diuretics remained a cornerstone of hypertension treatment [1]. Indeed, they are the second most commonly prescribed class of antihypertensive medication. For instance, 12% of US adults were prescribed a diuretic, and the relative increase in prescriptions from 1999 through 2012 was 1.4 [2].
    [Show full text]
  • The Role of Intercalated Cell Nedd4–2 in BP Regulation, Ion Transport, and Transporter Expression
    BASIC RESEARCH www.jasn.org The Role of Intercalated Cell Nedd4–2 in BP Regulation, Ion Transport, and Transporter Expression Masayoshi Nanami,1 Truyen D. Pham,1 Young Hee Kim,1 Baoli Yang,2 Roy L. Sutliff,3 Olivier Staub,4,5 Janet D. Klein,1 Karen I. Lopez-Cayuqueo,6,7 Regine Chambrey,8 Annie Y. Park,1 Xiaonan Wang,1 Vladimir Pech,1 Jill W. Verlander,9 and Susan M. Wall1,10 Due to the number of contributing authors, the affiliations are listed at the end of this article. ABSTRACT Background Nedd4–2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a corre- lation between Nedd4–2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4–2 gene ablation on IC transporter abundance and function and on BP. Methods We generated IC Nedd4–2 knockout mice using Cre-lox technology and produced global pen- 2/2 drin/Nedd4–2 null mice by breeding global Nedd4–2 null (Nedd4–2 ) mice with global pendrin null 2/2 (Slc26a4 ) mice. Mice ate a diet with 1%–4% NaCl; BP was measured by tail cuff and radiotelemetry. We 2 measured transepithelial transport of Cl and total CO2 and transepithelial voltage in cortical collecting ducts perfused in vitro. Transporter abundance was detected with immunoblots, immunohistochemistry, and immunogold cytochemistry. 2 2 Results IC Nedd4–2 gene ablation markedly increased electroneutral Cl /HCO3 exchange in the cortical col- lecting duct, although benzamil-, thiazide-, and bafilomycin-sensitive ion flux changed very little.
    [Show full text]
  • Initial Medication Selection for Treatment of Hypertension in an Open-Panel HMO
    J Am Board Fam Pract: first published as 10.3122/jabfm.8.1.1 on 1 January 1995. Downloaded from Initial Medication Selection For Treatment Of Hypertension In An Open-Panel HMO Micky jerome, PharmD, MBA, George C. Xakellis, MD, Greg Angstman, MD, and Wayne Patchin, MBA Background: During the past 25 years recommendations for treating hypertension have evolved from a stepped-care approach to monotherapy or sequential monotherapy as experience has been gained and new antihypertensive agents have been introduced. In an effort to develop a disease management strategy for hypertension, we investigated the prescribing patterns of initial medication therapy for newly treated hypertensive patients. Methods: We examined paid claims data of an open-panel HMO located in the midwest. Charts from 377 patients with newly treated hypertension from a group of 12,242 hypertenSive patients in a health insurance population of 85,066 persons were studied. The type of medication regimen received by patients newly treated for hypertension during an 18-month period was categorized into monotherapy, sequential monotherapy, stepped care, and initial treatment with multiple agents. With monotherapy, the class of medication was also reported. Associations between use of angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, or (3-blockers and presence of comorbid conditions were reported. Results: Fifty-five percent of patients received monotherapy, 22 percent received stepped care, and 18 percent received sequential monotherapy. Of those 208 patients receiving monotherapy, 30 percent were prescribed a calcium channel blocker, 22 percent an ACE inhibitor, and 14 percent a f3-blocker. No customization of treatment for comorbid conditions was noted.
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]