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Abdulla Shehab Asim A. Elnour Adel Sadik Mahmoud Abu Mandil Ali AlShamsi Aesha Al Suwaidi AkshayaSrikanth Bhagavathula Pinar Erkekoglu Farah Hamad Saif K. Al Nuaimi 《Saudi medical journal》2015,36(11):1290-1298
Objectives:
To provide early data regarding clinical utility of dabigatran in Al-Ain, United Arab Emirates (UAE).Methods:
This was an ethics approved retrospective cross sectional study. We retrieved a total of 76 patients who were using dabigatran from September to December 2014 in the Cardiology Clinic at Al-Ain Hospital, Al-Ain, UAE. The primary analysis was designed to test the frequency of bleeding events (rate) with dabigatran 75, 110, and 150 mg.Results:
The mean age ± standard deviation of cohort was 67.9 ± 1.5 years (range; 29-98 years), composed of males (52.6%) with mean age of 66.3 ± 1.7 years, and females (47.4%) with mean age of 69.6 ± 1.1 years. The highest age group was those between 61-80 years (60.5%). Most comprised the age strata of ≤75 years (73.7%). The main indication for dabigatran use was atrial fibrillation. The rate of bleeding with dabigatran was 18/76 (23.7%), and melena was the leading cause of bleeding 8/76 (10.7%). The hospitalization rate was 67.1%, dabigatran withdrawal rate was 0.01%, and mortality rate was 6.5%. The cohort had exhibited incidences of minor bleeding with one fatal major bleeding, high co-morbidities, admission, and readmission, which was not directly linked to dabigatran. We did not identify any relation of death due to dabigatran.Conclusion:
Dabigatran is a suitable alternative to warfarin obviating the need for repetitive international normalized ratio monitoring, however, it may need plasma drug monitoring.Atrial fibrillation (AF) is the most common cardiac arrhythmia that affects 1-1.5% of population worldwide.1 Atrial fibrillation prevalence increases with age, and rises from 0.7% in those between 55-59 years to 17.8% in those ≥85 years. Nearly 85% of patients with AF are aged >65 years old.2 The lifetime risk for the development of AF as demonstrated in the Framingham study was one in 4 for men and women aged ≥40 years,3 which pose certain concerns in countries with aging populations.4,5 In addition to this, hospitalization related to AF is alarmingly increasing.6 The risk of stroke in patients with AF is 5 folds, and systemic thromboembolism is 3 folds.7,8 Banerjee, et al9 has deployed stroke prevention score in patients with AF, however, the predictive value is of less magnitude. The European Society of Cardiology set estimation of stroke risk in patients with AF as per CHA2DS2-VASc score to determine the recommendation for initiating an oral anticoagulant,10 whereas in patients with CHA2DS2-VASc ≥2, HAS-BLED score can be used to assess the risk of bleeding, and commencement of anticoagulant.11Warfarin (vitamin K antagonist [VKA]) has proven efficacy in reducing the risk of stroke in patients with AF, however, it poses high bleeding incidences, emergency hospitalizations, unpredictable therapeutic effect, and multiple international normalized ratio (INR) tests leading to many limitations in its clinical utility.12 Novel oral anticoagulants (NOACs) are proved as effective anticoagulants in prevention of stroke in patients with AF. Novel oral anticoagulants were preferred in non-valvular AF, and do not require coagulation monitoring, however, strict adherence to approved indication is highly warranted.13 Dabigatran (Pradaxa®), a competitive inhibitor of thrombin was approved in October 2010 by the United States of America Food and Drug Administration to reduce the risk of stroke, and systemic embolism in patients with non-valvular AF.14 A systematic review incorporated 6 economic reviews from diverse healthcare systems (USA, Canada, and United Kingdom) utilizing different economic models. It has suggested the benefit of dabigatran in patients with high-risk of stroke, high-risk of intra-cerebral hemorrhage, or suboptimal use of warfarin. The review outlined concerns on tolerability of dabigatran, adherence issues, and adverse consequences.15In comparison with warfarin, dabigatran 150 mg has shown low rates of stroke, and systemic embolism (dabigatran p<0.001 for superiority). However, both drugs exhibited comparable rates of major hemorrhage.16-18 Greater fatal, and non fatal bleeding events were reported with dabigatran than warfarin.19,20 A recent (2015) retrospective Medicare data analysis study20 on dabigatran’s safety highlighted that the incidence of bleeding was higher than with warfarin (33% versus 27%), major bleeding (9% versus 6%), and gastrointestinal bleeding (17% versus 10%). Intracranial hemorrhage occurred more often with warfarin than dabigatran (1.8% versus 0.6%).20 It has been documented that risks of major bleeding from dabigatran is high for patients with chronic kidney disease, and in African Americans.20 The Randomized Evaluation of Long-term Anticoagulant Therapy: Dabigatran versus warfarin-RE-LY studies18 have showed similar risk of bleeding with warfarin versus dabigatran in patients with non-valvular AF. This dictated the importance of age sub-group analysis in studies. In real clinical practice, patients from different countries may have more co-morbid conditions than those in the RE-LY study.21 The current available data around bleeding incidences from dabigatran is relevant to populations with diverse characteristics. Revealing the clinical utility of dabigatran in our Emirati population may demonstrate different perspectives. Therefore, we intend to provide early data around the clinical utility of dabigatran in United Arab Emirates (UAE) Emirati population. 相似文献3.
Muhammad Nadeem Aslam Roscoe L. Warner Narasimharao Bhagavathula Isaac Ginsburg James Varani 《Archives of dermatological research》2010,302(9):669-677
PADMA 28 is a multi-component herbal mixture formulated according to an ancient Tibetan recipe. PADMA 28 is known to stimulate
collagen production and reduced levels of collagen-degrading matrix metalloproteinases (MMPs). The goal of the present study
was to determine whether topical treatment of rat skin with PADMA 28 would improve skin structure/function, and whether subsequently
induced abrasion wounds would heal more rapidly in skin that had been pretreated with PADMA 28. Hairless rats were exposed
to a potent topical corticosteroid (Temovate) in combination with either DMSO alone or with PADMA 28 given topically. At the
end of the treatment period, superficial wounds were created in the skin, and time to wound closure was assessed. Collagen
production and matrix-degrading MMPs were assessed. Abrasion wounds in skin that had been pretreated with PADMA 28 healed
more rapidly than did wounds in Temovate plus DMSO-treated skin. Under conditions in which improved wound healing was observed,
there was an increased collagen production and decreased MMP expression, but no significant epidermal hyperplasia and no evidence
of skin irritation. The ability to stimulate collagen production and inhibit collagen-degrading enzymes in skin and facilitate
more rapid wound closure without irritation should provide a rationale for development of the herbal preparation as a “skin-repair”
agent. 相似文献
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Yellajyosula Lakshmi Narasimha Murthy Boddeti Govindh Bhagavathula S. Diwakar Karthikeyan Nagalakshmi Kothagorla Venkata Raghava Rao 《Medicinal chemistry research》2012,21(10):3104-3110
Isatin (2,3-dioxindole) and its derivatives show a wide range of biological activities. In the present study, a series of Schiff and Mannich bases of isatin derivatives were prepared using 4-amino-5-benzyl-2,4-dihydro-3H-1,2,4-triazole-3-thione. The structures of these derivatives were characterized by IR, 1H NMR and elemental analysis. In vitro antimicrobial activities were evaluated by agar dilution method and the zone of inhibition values of these derivatives were compared with ciprofloxacin and fluconazole. Chloro and Bromo groups at fifth position of isatin broaden the spectrum of antibacterial activity against S. aures, P. aeruginoa, and E. coli, respectively. For the antifungal activity, the compound 6h showed equipotent activity against A. niger. The remaining majority of the compounds were found active in the biological screening. The efforts were also made to establish structure activity relationships among synthesized compounds. 相似文献
5.
Muhammad Nadeem Aslam Narasimharao Bhagavathula Tejaswi Paruchuri Xin Hu Subhas Chakrabarty James Varani 《Cancer letters》2009,283(2):186-192
Proliferation and differentiation were assessed in a series of human colon carcinoma cell lines in response to a mineral-rich extract derived from the red marine algae, Lithothamnion calcareum. The extract contains 12% Ca2+, 1% Mg2+, and detectable amounts of 72 trace elements, but essentially no organic material. The red algae extract was as effective as inorganic Ca2+ alone in suppressing growth and inducing differentiation of colon carcinoma cells that are responsive to a physiological level of extracellular Ca2+ (1.4 mM). However, with cells that are resistant to Ca2+ alone, the extract was still able to reduce proliferation and stimulate differentiation. 相似文献
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Hao Li Airong Chen Li Zhao Akshaya S. Bhagavathula Palanisamy Amirthalingam Jamal Rahmani Ammar Salehisahlabadi Hebatullah M. Abdulazeem Oladimeji Adebayo Xiao Yin 《Phytotherapy research : PTR》2020,34(8):1956-1965
Tomato (Solanum lycopersicum) phytochemicals, which include phytoene, phytofluene, beta‐carotene, flavonoids, lycopene, and polyphenols, have been shown to improve the effects of fasting on plasma triglyceride (TG), low‐density lipoprotein cholesterol (LDL), high‐density lipoprotein cholesterol (HDL), total cholesterol (TC), and fasting blood sugar (FBS). The aim of this study was to systematically evaluate the effects of Tomato TC, TG, HDL, LDL, and FBS in humans. A systematic literature search was conducted in PubMed/MEDLINE, Web of sciences, and SCOPUS databases by two researchers for studies published until August of 2019 without language and time limitations. Results were combined with random effect models. Six studies were included in this meta‐analysis. Combined results reveal a significant reduction in cholesterol (weighted mean difference [WMD]: ?4.39 mg/dl, 95% CI: ?7.09, ?1.68, I2 = % 48, p heterogeneity: .05), TG (WMD: ?3.94 mg/dl, 95% CI: ?7.67, ?0.21, I2 = % 90, p heterogeneity: .001), LDL levels (WMD: ?2.09 mg/dl, 95% CI: ?3.73, ?0.81, I2 = % 78, p heterogeneity: .001), and increasing in HDL levels (WMD: 2.25 mg/dl, 95% CI: 0.41, 4.10, I2 = % 97, p heterogeneity: .001). Tomato was found to have a higher reduction effect on TG and LDL in younger participants. While pooled results indicate no significant effect on FBS levels (WMD: 0.59 mg/dl, 95% CI: ?0.28, 1.46, I2 = % 95, p heterogeneity: .001). In conclusion, the results indicate a significant reduction in total cholesterol, TG, and LDL and increase in HDL levels that is caused by tomato consumption. 相似文献
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Zhifang Xiao Hui Chen Yu Zhang Hui Deng KunWei Wang Akshaya Srikanth Bhagavathula Shamma Jauaan Almuhairi Paul M. Ryan Jamal Rahmani Minyan Dang Vasileios Kontogiannis Andrew Vick Yuhe Wei 《Phytotherapy research : PTR》2020,34(6):1237-1247
Water‐soluble dietary fibers have been shown to improve lipid profile and glucose metabolism in diabetes. The aim of this study was to review the effects of psyllium consumption on weight, body mass index, lipid profiles, and glucose metabolism in diabetic patients in randomized controlled trials. A comprehensive systematic search was performed in PubMed/MEDLINE, Web of Sciences, Cochrane, and Scopus by two independent researchers up to August 2019 without any time and language restrictions. The DerSimonian and Laird random‐effects model method performed to calculate the pooled results. Inclusion criteria were randomized controlled trial design, adult subjects, and studies reporting the mean differences with the 95% confidence interval for outcome. Eight studies containing nine arms with 395 participants were identified and included in final analysis. Combined results found a significant reduction in triglycerides, low‐density lipoprotein, fasting blood sugar, and hemoglobin A1c following psyllium consumption (weighted mean differences [WMD]: ?19.18 mg/dl, 95% CI [?31.76, ?6.60], I2 = 98%), (WMD: ?8.96 mg/dl, 95% CI [?13.39, ?4.52], I2 = 97%), (WMD: ?31.71 ml/dl, 95% CI [?50.04, ?13.38], I2 = 97%), and (WMD: ?0.91%, 95% CI [?1.31, ?0.51], I2 = 99%), respectively. There was no significant change in high‐density lipoprotein, body mass index, cholesterol, and weight. In conclusion, the results demonstrated a significant reduction in triglycerides, low‐density lipoprotein, fasting blood sugar, and hemoglobin A1c by psyllium intervention among diabetic patients. 相似文献
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Varani J Bhagavathula N Aslam MN Fay K Warner RL Hanosh A Barron AG Miller RA 《Archives of dermatological research》2008,300(1):27-35
Mice on a calorie-restricted (CR) diet (total calories restricted to 70% of ad libitum; AL) for periods of time ranging from
3 to 18 months were examined for response to topical treatment with all-trans retinoic acid (RA). Daily application of a 0.1%
solution of RA to the shaved skin of UM-HET3 mice on an AL diet produced a severe irritation that was evident by day 4, maximal
at day 7–8 and still detectable at day 14. Skin irritation was characterized by redness, dryness, flaking and failure of the
hair to grow at the treated site. In CR mice, the same treatment produced little detectable irritation. Animals were sacrificed
at the end of the retinoid-treatment period (day 7 or day 14) and skin from these animals was examined histologically. In
both AL and CR mice, a similar degree of epidermal hyperplasia was observed. Numerous inflammatory cells (mononuclear cells
and granulocytes) were present in the skin of both groups. Occasional S100-positive cells (presumably Langerhans cells) were
also observed in the epidermis of skin from both groups. S100-positive cells were also observed in the dermis. When skin from
CR and AL mice was incubated in organ culture for 3 days (on day 7 after initiation of RA treatment), similar levels of four
different pro-inflammatory cytokines were found in the conditioned medium. Soluble type I collagen levels were also similar.
In contrast, the level of matrix metalloproteinase-9 was lower in the conditioned medium of skin from CR mice than in conditioned
medium from skin cultures of AL mice. Taken together, these studies suggest that CR may provide a way to mitigate the irritation
that normally accompanies RA treatment without compromising the beneficial effects of retinoid use. CR appears to exert a
protective effect at the target tissue level rather than by a reduction in pro-inflammatory events, per se. 相似文献
9.
Muhammad Nadeem Aslam Jaclynn M. Kreider Tejaswi Paruchuri Narasimharao Bhagavathula Marissa DaSilva Ronald F. Zernicke Steven A. Goldstein James Varani 《Calcified tissue international》2010,86(4):313-324
The purpose of this study was to determine whether a mineral-rich extract derived from the red marine algae Lithothamnion calcareum could be used as a dietary supplement for prevention of bone mineral loss. Sixty C57BL/6 mice were divided into three groups
based on diet: the first group received a high-fat Western-style diet (HFWD), the second group was fed the same HFWD along
with the mineral-rich extract included as a dietary supplement, and the third group was used as a control and was fed a low-fat
rodent chow diet (AIN76A). Mice were maintained on the respective diets for 15 months. Then, long bones (femora and tibiae)
from both males and females were analyzed by three-dimensional micro-computed tomography (micro-CT) and (bones from female
mice) concomitantly assessed in bone strength studies. Tartrate-resistant acid phosphatase (TRAP), osteocalcin, and N-terminal
peptide of type I procollagen (PINP) were assessed in plasma samples obtained from female mice at the time of sacrifice. To
summarize, female mice on the HFWD had reduced bone mineralization and reduced bone strength relative to female mice on the
low-fat chow diet. The bone defects in female mice on the HFWD were overcome in the presence of the mineral-rich supplement.
In fact, female mice receiving the mineral-rich supplement in the HFWD had better bone structure/function than did female
mice on the low-fat chow diet. Female mice on the mineral-supplemented HFWD had higher plasma levels of TRAP than mice of
the other groups. There were no differences in the other two markers. Male mice showed little diet-specific differences by
micro-CT. 相似文献
10.
Bhagavathula N Nerusu KC Hanosh A Aslam MN Sundberg TB Opipari AW Johnson K Kang S Glick GD Varani J 《The Journal of pharmacology and experimental therapeutics》2008,324(3):938-947
7-Chloro-5-(4-hydroxyphenyl)-1-methyl-3-(naphthalen-2-ylmethyl)-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one (Bz-423) is a benzodiazepine that has cytotoxic and cytostatic activity against a variety of cells in vivo and in vitro. In the present study, we demonstrate that Bz-423 (formulated for topical delivery) reduces epidermal hyperplasia in human psoriatic skin after transplantation to severe, combined immunodeficient (scid) mice. Bz-423 also suppresses the hyperplasia that develops in nonpsoriatic human skin as a consequence of transplantation to scid mice. Proliferation of human epidermal keratinocytes in monolayer culture was suppressed by Bz-423 at concentrations of 0.5 to 2.0 muM (noncytotoxic concentrations). Keratinocyte growth inhibition was accompanied by increased oxidant generation in Bz-423-treated cells, and treatment with vitamin E along with Bz-423 reversed the growth inhibition. Growth inhibition was accompanied by a redistribution of beta-catenin from a cytoplasmic pool to the cell membrane and by reduced levels of c-myc and cyclin D1 (two molecules associated with Wnt pathway signaling). Several analogs of Bz-423 were examined for antiproliferative activity against human epidermal keratinocytes and human dermal fibroblasts in monolayer culture. Each of the analogs tested suppressed growth of both cell types, but in all cases, keratinocytes were more sensitive than fibroblasts. Two of the compounds were found to suppress epidermal hyperplasia induced with all-trans retinoic acid in organ cultures of human skin. Taken together, these data show that Bz-423 and certain analogs produce biological responses in skin cells in vitro and in vivo that are consistent with therapeutic goals for treating psoriasis or epidermal hyperplasia resulting from other causes. 相似文献