Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
High blood pressure [keywords]
- Efficacy and tolerability of fixed-combination bimatoprost/timolol versus fixed-combination dorzolamide/brimonidine/timolol in patients with primary open-angle glaucoma or ocular hypertension: a multicenter, prospective, crossover study. [JOURNAL ARTICLE]
- BMC Ophthalmol 2014 Dec 19; 14(1):161.
Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension.In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index(C) (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively.Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P < 0.01) and dorz/brim/tim (P < 0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P < 0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P = 0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim//tim at month 3, 38% had an IOP <14 mm Hg, which remained comparable after return to bim/tim. OSDI scores and incidence of adverse events were similar in both groups.In this first direct comparison of the efficacy of dorz/brim/tim and bim/tim, patients switched from dorz/brim/tim to bim/tim demonstrated improved/lower IOP; when returned to dorz/brim/tim, IOP increased to levels seen at study initiation, suggesting that once-daily bim/tim may have greater IOP-lowering efficacy. Both bim/tim and dorz/brim/tim were well tolerated with minimal ocular surface damage. Trial registration: ClinicalTrial.gov: NCT01737853 (registered October 9, 2012).
- Noninvasive assessment of pulse-wave velocity and flow-mediated vasodilation in anesthetized göttingen minipigs. [Journal Article]
- Comp Med 2014; 64(6):471-7.
Few methods for noninvasive assessment of arterial stiffness and endothelial dysfunction in porcine models are available. The aim of this study was to evaluate methods for assessment of arterial stiffness and endothelial dysfunction in anesthetized Göttingen minipigs. Pulse-wave velocity (PWV) was assessed in male Göttingen minipigs (n = 8; age approximately 60 wk) by using applanation tonometry of the carotid and femoral arteries. In addition, flow-mediated vasodilation (FMD) was assessed by using vascular ultrasonography of the brachial artery to evaluate endothelial dysfunction. To evaluate the reproducibility of the methods, minipigs were anesthetized by intravenous infusion of ketamine and midazolam and examined every other day for a total of 3 trials. Neither examination day nor systolic, diastolic, or mean arterial blood pressure statistically influenced PWV or FMD. The median interexamination coefficient of variation was 17% for PWV and 59% for FMD. Measured values of PWV corresponded largely to those in clinically healthy humans, but FMD values were lower than expected for lean, young animals. Although the ketamine-midazolam anesthesia we used has been associated with minor hemodynamic effects in vivo, in vitro studies suggest that both drugs are vasodilatory. Therefore anesthesia might have influenced the endothelial response, contributing to the modest FMD response and the concurrent high coefficients of variation that we noted. We conclude that PWV-but not FMD-showed acceptable interexamination variation for its potential application in porcine models.
- Autoantigen complementarity and its Contributions to hallmarks of autoimmune disease. [JOURNAL ARTICLE]
- J Theor Biol 2014 Dec 16.
The question considered is, "What causes the autoimmune response to begin and what causes it to worsen into autoimmune disease?" The theory of autoantigen complementarity posits that the initiating immunogen causing disease is a protein complementary (antisense) to the self-antigen, rather than a response to the native protein. The resulting primary antibody elicits an anti-antibody response or anti-idiotype, consequently producing a disease-inciting autoantibody. Yet, not everyone who developes self-reactive autoantibodies will manifest autoimmune disease. What is apparent is that manifestation of disease is governed by the acquisition of multiple immune-compromising traits that increase susceptibility and drive disease. Taking into account current cellular, molecular, and genetic information, six traits, or 'hallmarks', of autoimmune disease were proposed: 1) Autoreactive cells evade deletion, 2) Presence of asymptomatic autoantibodies, 3) Hyperactivity of Fc-FcR pathway, 4) Susceptibility to environmental impact, 5) Antigenic modifications of self-proteins, 6) Microbial Infections. Presented here is a discussion on how components delineated in the theory of autoantigen complementarity potentially promote the acquisition of multiple 'hallmarks' of disease.
- B-type natriuretic peptide secretion without change in intra-cardiac pressure. [JOURNAL ARTICLE]
- Clin Biochem 2014 Dec 16.
In clinical cardiology, B-type natriuretic peptide (BNP) is used as a non-invasive surrogate marker for intra-cardiac filling pressures, particularly in patients with heart failure. It is unknown, whether and to what extent increase in intravascular volume and/or sympathetic tone while maintaining constant intra-cardiac pressures leads to an increase in levels of BNP in vivo.We aimed to test this hypothesis in an experimental in-vivo model of patients directly after off-pump coronary artery bypass grafting admitted to the intensive care unit. These patients require high volumes of intravenous fluids titrated to keep intra-cardiac filling pressures and arterial blood pressure in the normal range while awakening from deep general anesthesia. In 27 consecutive patients intra-cardiac filling pressures (using a pulmonary artery catheter) and levels of BNP were measured simultaneously every 6hours.At 0, 6, 12, and 18hours, the pulmonary capillary wedge pressure remained constant (12±4, 13±3, 12±3, and 13±3mmHg, respectively; p=0.351). Similarly, right heart filling pressures did not change during the study period. In contrast, BNP levels increased significantly during the study period: Median levels were 82 [IQR 37-162] pg/ml at 0hour, 153 [92-246] pg/ml at 6hours, 274 [156-392] pg/ml at 12hours, and 320 [200-528] pg/ml at 18hours (p<0.001). No significant correlation between BNP levels and pulmonary capillary wedge pressures was found (r=0.052; p=0.604).After cardiac surgery BNP cannot be considered a reliable non-invasive surrogate for PCWP. In vivo, substantial BNP secretion occurs independently of PCWP in a setting of increasing intravascular volume and consciousness/sympathetic tone.
- Identifying associations between sedentary time and cardio-metabolic risk factors in working adults using objective and subjective measures: a cross-sectional analysis. [JOURNAL ARTICLE]
- BMC Public Health 2014 Dec 19; 14(1):1307.
Sedentary behavior has been reported to be associated with metabolic and vascular health independent of moderate-to-vigorous physical activity (MVPA). In order to select appropriate options to measure sedentary behavior in practice and research settings, it is worthwhile to characterize the extent to which objective and subjective measures of sedentary behavior quantify adverse health risks in the same population. This cross-sectional analysis compared accelerometer-derived and self-reported sedentary time to identify their association with cardio-metabolic risk factors.Cross-sectional analysis was conducted using data from 661 Japanese workers (145 women) aged 20-64 years. Participants wore a tri-axial accelerometer device for 10 consecutive days and completed the Japan Atherosclerosis Longitudinal Study Physical Activity Questionnaire. Data on body mass index, waist circumference, resting blood pressure, triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, total:HDL cholesterol ratio, blood glucose, and glycosylated hemoglobin (HbA1c) were obtained from annual health examinations.Both accelerometer-derived and self-reported sedentary time were deleteriously associated with triglycerides, HDL-cholesterol, total:HDL ratio, and HbA1c after adjustment for potential confounders including MVPA. There were no significant differences in regression coefficients between the two measures. Thus, the magnitude of the associations of both measures with cardio-metabolic risk factors was similar, despite poor agreement between them. Occupational sedentary time was correlated with both measures of total sedentary time, and more consistently associated with cardio-metabolic risk factors than sedentary leisure time.Both accelerometer and self-report measurements are similarly associated with cardio-metabolic risk factors in a Japanese working adult population. Subjective and objective measures of sedentary behaviors appear to capture different aspects of behaviors. Further efforts to establish data processing methods integrating objective and subjective measures are needed to more effectively assess sedentary time's relationship to health outcomes.
- Improving drug delivery to solid tumors: Priming the tumor microenvironment. [REVIEW]
- J Control Release 2014 Dec 16.
Malignant transformation and growth of the tumor mass tends to induce changes in the surrounding microenvironment. Abnormality of the tumor microenvironment provides a driving force leading not only to tumor progression, including invasion and metastasis, but also to acquisition of drug resistance, including pharmacokinetic (drug delivery-related) and pharmacodynamic (sensitivity-related) resistance. Drug delivery systems exploiting the enhanced permeability and retention (EPR) effect and active targeting moieties were expected to be able to cope with delivery-related drug resistance. However, recent evidence supports a considerable barrier role of tumors via various mechanisms, which results in imperfect or inefficient EPR and/or targeting effect. The components of the tumor microenvironment such as abnormal tumor vascular system, deregulated composition of the extracellular matrix, and interstitial hypertension (for example, elevated interstitial fluid pressure collectively or cooperatively hinder the drug distribution, which is prerequisite to the efficacy of nanoparticles and small-molecule drugs used in cancer medicine. Hence, the abnormal tumor microenvironment has recently been suggested to be a promising target for the improvement of drug delivery to improve therapeutic efficacy. Strategies to modulate the abnormal tumor microenvironment, referred to here as "solid tumor priming" (vascular normalization and/or solid stress alleviation leading to improvement in blood perfusion and convective molecular movement), have shown promising results in the enhancement of drug delivery and anticancer efficacy. These strategies may provide a novel avenue for the development of new chemotherapeutics and combination chemotherapeutic regimens as well as reassessment of previously ineffective agents.
- Androgen-Induced Hypertension in Angiotensinogen Deficient Mice: Role of 20-Hete and Eets. [JOURNAL ARTICLE]
- Prostaglandins Other Lipid Mediat 2014 Dec 16.
20-HETE is a potent inducer of endothelial ACE in vitro and administration of lisinopril or losartan attenuates blood pressure in models of 20-HETE-dependent hypertension. The present study was undertaken to further define the relationship between 20-HETE and the renin-angiotensin system in hypertension using an angiotensinogen-deficient mouse (Agt+/-). Treatment of male AGT+/- with 5α-dihydrotestosterone (DHT) increased systolic BP from 102±2 to 125±3mmHg; in comparison, the same treatment raised BP in wild type (WT) from 110±2 to 138±2mmHg. DHT increased vascular 20-HETE levels in AGT+/- and WT from 1.5±0.7 and 2.1±0.6 to 13.0±2.0 and 15.8±4.0ng/mg, respectively. Concurrent treatment with the 20-HETE antagonist, 20-hydroxyeicosa-6(Z), 15(Z)-dienoic acid (20-HEDE) prevented the increases in BP in both AGT+/- and WT mice. Administration of 20-HEDE at the peak of the DHT-induced BP increase (12 days) reduced BP to basal levels after 48hours. Interestingly, basal levels of renal microvascular EETs were higher in AGT+/- compared to WT (55.2±9.7 vs 20.0±4.1ng/mg) and treatment of AGT+/- with DHT decreased the levels of EETs (28.4±5.1ng/mg). DHT-mediated changes in vascular EET level were not observed in WT mice. Vascular Cyp4a12 and ACE protein levels were increased in both AGT+/- and WT by 30-40% and decreased with concomitant administration of 20-HEDE. Lisinopril was as effective as 20-HEDE in preventing DHT-mediated increases in BP in both AGT+/- and WT mice. This study substantiates our previous findings that the RAS plays an important role in 20-HETE-mediated hypertension. It also proposes a novel interaction between 20-HETE and EETs.
- Health outcomes of vitamin D. Part II. Role in prevention of diseases. [JOURNAL ARTICLE]
- Rocz Panstw Zakl Hig 2014; 65(4):273-279.
Apart from the classic role of vitamin D, its hormonal active form, calcitriol is also characterized by pleiotropic effects on various organs and tissues. For the last several years, many researchers have shown an association between deficiency of vitamin D and the risk of type 2 diabetes mellitus (T2DM). Recent investigations suggested the need of vitamin D supplementation in T2DM prevention. It was shown that vitamin D deficiency decreases insulin secretion. It was also observed that proper vitamin D supplementation may improve the ability of the cells of the islets of Langerhans to synthesize many proteins de novo and to convert proinsulin to insulin. Apart from regulating bone metabolism and also calcium and phosphate homeostasis, 1,25(OH)2D3 exerts antiproliferative and pro-differentiating effects on a wide variety of cell types. It also induces apoptosis of cancer cells and slows their proliferation. In a number of major studies the relationship between low vitamin D levels and increased risk of various cancers was observed. It concerns colorectal, lung, prostate, breast and ovarian cancer. It was observed that in patients with low serum vitamin D concentrations such disorders as ischemic heart disease, heart attack, stroke, cardiac arrhythmia, and hypertension were more frequent and mortality was significantly higher. These results led the researchers to consider vitamin D deficiency as a potential risk factor for cardiovascular diseases. The possible mechanism in the pathogenesis of cardiovascular diseases that may be related to low levels of vitamin D, is its adverse effect on the renin-angiotensin-aldosterone system (RAAS). Calcitriol is also an important determinant of muscle cell proliferation and differentiation, as well as inhibition of apoptosis. Vitamin D is synthesized in the skin. However, there are only a few food products that are rich in vitamin D3, e.g.: fish oils, fish and fortified-products, such as dairy products and margarines. Individuals who are vulnerable to vitamin D deficiency should be supplemented.vitamin D, diabetes mellitus, deficiency of vitamin D, cancer, cardiovascular diseases, muscle physiology.
- Teenage pregnancy antenatal and perinatal morbidity: Results from a tertiary centre in Greece. [JOURNAL ARTICLE]
- J Obstet Gynaecol 2014 Dec 19.:1-5.
We present the experience of a tertiary referral hospital in Greece, evaluating obstetric and perinatal outcomes among teenage and average maternal age (AMA) women. We retrospectively assessed all singleton pregnancies during a twelve-month period (January-December 2012). A total of 1,704 cases were reviewed and divided into two groups: one of AMA mothers (20-34 years old) (1,460 women) and the other of teenage mothers (12-19 years old) (244 women). We observed significantly higher incidence rates of preterm births (p < 0.001), preterm premature rupture of the membranes (p < 0.001), gestational hypertension (p < 0.001), preeclampsia (p = 0.043) and Apgar scores < 7 at 5 min (p = 0.015) among teenage mothers. Antenatal surveillance was decreased among teenage mothers (p < 0.001), while rates of anaemia were higher (p < 0.001). Teenage pregnancy is accompanied by significant antenatal and perinatal complications that need specific obstetrical attention. Obstetricians should be aware of these complications in order to ameliorate the antenatal outcome of childbearing teenagers.
- Interaction between Angiotensin-converting enzyme gene insertion/deletion polymorphism and Angiotensin-converting enzyme inhibition on survival in hemodialyzed patients. [Journal Article]
- Medicine (Baltimore) 2014 Dec; 93(28):e315.
The association between ACE (angiotensin-converting enzyme) gene insertion/deletion (I/D) polymorphism and mortality has been inconsistently observed in earlier studies in patients on maintenance hemodialysis. We hypothesized that the effect of ACE gene I/D polymorphism on mortality may be influenced by concurrent ACE inhibitor therapy in this population.In this prospective, multicenter cohort, observational study, data was collected from 716 prevalent chronic hemodialysis patients, blood samples were genotyped for I/D single nucleotide polymorphism. Patient mortality was assessed in tree genotype groups insertion/insertion, insertion/deletion and deletion/deletion (I/I, I/D, and D/D) using multivariate Cox proportional hazard models.The most frequent genotype was I/D (42.6%), followed by D/D (37.7%) and I/I (19.7%) genotypes. The mean age was 54.9 ± 15.5 years, 53.2% of all patients were male and in the total group the prevalence of diabetes was 19.3%. ACE inhibitor therapy was prescribed for 47.9% of all patients. The median duration of dialysis before blood sampling was 23.8 months (IQR 11.2-47.1). Patients were followed for 10 years, the median follow-up time was 29.8 months (IQR 12.6-63.4). Patient characteristics were well balanced among the genotype groups. D/D genotype, was associated with inferior survival (I/I vs D/D: log-rank test: P = 0.04) in patients not receiving ACE inhibitor therapy, and the presence of this therapy diminished this difference. There was no difference in survival among unselected patients with different genotypes. In multivariate Cox regression models, D/D genotype (compared to I/I) was a significant predictor of mortality only in patients without ACE inhibitor therapy (HR 0.67, 95% CI 0.46-0.97, P = 0.03).Our data suggests that hemodialyzed patients with the deletion/deletion (D/D) genotype might have inferior outcome, and ACE inhibitor therapy may be associated with improved survival in this subgroup.