体积 5, 问题 2 (2016)


Erectile Function in Cardiovascular Disease and Hypertension: the Role of Nebivolol

Athanasios Manolis and Michael Doumas

Beta blockers are used for the management of arterial hypertension and are gold standard treatment for coronary artery disease and heart failure, medical conditions that affect large numbers of older patients and are associated with very high morbidity and mortality rates.

Lifelong therapy in primary and secondary prevention (without and with established cardiovascular disease, respectively) is limited by low adherence to drugs which is accompanied by increased mortality. Drug adverse events and impaired quality of life are among the main causes of poor adherence to therapy. Erectile dysfunction is the ‘prima ballerina’ of drug-induced life quality impairment. Beta blockers exert detrimental effects on erectile function. In contrast, nebivolol (a third generation beta blocker with vasodilating properties and proven efficacy in patients with hypertension and heart failure) does not share the unfavourable effects of other beta blockers on erectile function due to increased nitric oxide bioavailability.

Therefore, Nebivolol represents an attractive option for patients with hypertension, heart failure, and other related diseases who need to be treated with beta blockers.


Renal Denervation Improves Cardiac Diastolic Dysfunction by Restoring Serca2a Transcription in Uninephrectomized Rats

Hirohama D, Kawakami-Mori F, Ogura S, Mu S, Jimbo R, Uetake U, Yatomi Y, Nangaku M, Fujita T and Shimosawa T

Background: The mortality and morbidity of heart failure with preserved ejection fraction has increased. Sarcoplasmic reticulum Ca2+-ATPase type 2a (SERCA2a) regulates cardiac functions, and a reduction in SERCA2a expression has been documented in left ventricular (LV) diastolic dysfunction. By contrast, SERCA2a overexpression improves LV diastolic dysfunction. Thus, transcriptional regulation of SERCA2a may be a new therapeutic target. The aim of this study was to determine whether renal denervation, a treatment for resistant hypertension, is a regulator of SERCA2a transcription in vivo.

Methods: Uninephrectomy and 6-week salt loading in three-week-old male Sprague-Dawley rats were used to devise a cardiac diastolic dysfunction model, and mechanical renal denervation was performed. The expression of SERCA2a and related molecules was evaluated with quantitative polymerase chain reaction and western blot analyses. The maximal positive LV pressure development (+dP/dtmax) and time constant at the isovolumic relaxation phase (Tau) were determined with cardiac catheters.

Results: Uninephrectomy combined with a high-salt diet significantly reduced the messenger RNA expression and protein abundance of SERCA2a, which were restored by renal denervation. In accordance with changes in SERCA2a transcription, uninephrectomy and the high-salt diet decreased LV diastolic function, which was evaluated by Tau and restored by renal denervation. LV systolic function, measured with +dp/dtmax, was preserved. Renal denervation did not lower blood pressure, urinary protein levels, cardiac hypertrophy, or fibrosis.

Conclusions: We found that renal denervation is a regulator of SERCA2a transcription in vivo. Our data may provide new therapeutic insights into LV diastolic dysfunction and warrant further study.


Granulomatosis with Polyangiitis Presenting as Postoperative Gastrointestinal Stromal Tumors: A Case Report

Ye Rui-hai, Yang Li, Yang Jun-chao, Mao Yu-ping, Zhang Chun-li, Xu Jun, Zhu Yuan-hong and Wang Zhen

Introduction: Granulomatosis with polyangiitis (GPA) is a systemic vasculitis syndrome, previously known as Wegener’s granulomatosis, characterized by necrotizing granulomatous inflammation of the respiratory tracts, systemic necrotizing vasculitis, and necrotizing glomerulonephritis. This disorder represents a significant diagnostic dilemma due its diverse presentations, although presentation in the form of postoperative gastrointestinal stromal tumors is uncommon. Here, we report one of the first identified cases of GPA presenting as postoperative gastrointestinal stromal tumors (GISTs).

Case presentation: A 78-year-old Chinese man presented to our Respiratory Department in Zhejiang Hospital of Traditional Chinese Medicine with a history of progressively worsening fever and pulmonary nodules. He had history of postoperative gastrointestinal stromal tumors. Because of failed treatment with antibiotics, he had been diagnosed with a fungal infection of the lung, which was empirically treated with voriconazole for approximately two months. However, the condition did not improve until the patient was successfully treated with moderate-dose steroids. His clinical course was fever, pulmonary nodules and nasosinusitis, which are associated with granulomatosis with polyangiitis.

Conclusion: The recognition of a multisystem disease is critical for diagnosing GPA. Postoperative GISTs may be associated with manifestations of the disease, in which case, immediate and aggressive treatment with steroids can be life-saving.


Non-Hypersplenism Causes of Peripheral Cytopenias in Patients with Cirrhotic Portal Hypertension: A Review

Yunfu Lv, Wan Yee Lau, Jie Deng, YeJuan Li and Yonghong Dong

Hypersplenism and non-hypersplenism factors, either alone or in combination, can cause peripheral cytopenias in patients with cirrhotic portal hypertension. Although non-hypersplenism factors account for only a small proportion of patients, they do exist. When peripheral cytopenias do not improve, or fail to improve adquately, or even become worse after splenectomy in these patients, non-hypersplenism factors should be considered. This review aims to provide an overview of non-hypersplenism factors.


Angiotensinogen M235T, β2 Adrenergic Receptor Arg16Gly and Aldosterone Synthase C-344T Gene Polymorphisms and Essential Hypertension among Han Population Living at High Altitude in China

Xinghui Li, Yan Qiao, Yingdong Li, Hui Cai, Jin He, Yan Huang, Ping Xie, Haizhong Ma and R Devasundaram

We explored the association of angiotensinogen (AGT) M235T, β2 adrenergic receptor (β2-AR) Arg16Gly and aldosterone synthase (CYP11B2) C-344T genes polymorphisms with essential hypertension (EH) in Han population living at high altitude in China. A total of 390 hypertensive subjects (males, 207; females, 183) and 424 normal healthy individuals (males, 251; females, 173) were enrolled in this study based on the inclusion and exclusion criteria. The polymorphisms of AGT M235T, β2-AR Arg16Gly, CYP11B2 C-344T genes were analyzed by Snapshot mini sequencing method. The frequencies of CC genotype and C allele of AGT M235T in EH group were higher than in control (p<0.05), gender wise analysis revealed that the genotype and allele patterns between patients and controls were found to be significantly different (p<0.05). However, genotype and allele frequencies of the distribution of β2-AR Arg16Gly and CYP11B2 C-344T between EH patients and normotensive controls were not significantly different (p>0.05, respectively), in gender-specific analysis, the differences were also not found (p>0.05, respectively). This finding suggests that the polymorphism of AGT M235T was correlated with EH in Han population living at high altitude in China, however, β2-AR Arg16Gly and CYP11B2 C-344T polymorphism were unlikely to associated with hypertensive subjects of this population.


A Review of Arterial Stiffness and HIV Infection in Adult Africans

Kofoworola Olajire Awotedu and Jehu Iputo

Aim: To review the impact of the human immunodeficiency virus and antiretroviral therapy on the vasculature.

Objectives: This review seeks to identify the burden which the human immunodeficiency virus and antiretroviral therapy have on the vasculature.

Method: Medline/PubMed and Google scholar were searched. There were over 100 publications reviewed. Some people who worked in similar fields were also contacted. The present review summarized current understanding of Human immunodeficiency virus, antiretroviral therapy and effect on the vasculature such as arterial stiffness. Atherosclerosis, endothelial dysfunction, the strengths and weaknesses of current testing strategies, and their potential applications in clinical research and patient care. The association of inflammatory biomarkers, blood pressure and ageing with arterial stiffness were also reviewed.

Conclusion: Available literature shows that HIV and antiretroviral agents have a great impact on the vasculature and its progression.


Antioxidant and Antiproliferative Activities of Purslane Seed Oil

Gai Guo, Li Yue, Shaoli Fan, Siqun Jing and Liang-Jun Yan

The aim of this study was to evaluate the antioxidant and antiproliferative activities of PSO in vitro and its application in horse oil storage. We determined the reducing power of PSO and its scavenging effects on hydroxyl (•OH) and 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH•) and tested its stabilizing effects on horse oil storage. The results showed that PSO had remarkable, dose-dependent antioxidant activities, and it effectively prevented horse oil lipid oxidation. We treated cervical cancer HeLa cells, esophageal cancer Eca-109 cells and breast cancer MCF-7 cells with PSO using non-neoplastic monkey kidney Vero cells as controls. The results indicate that PSO significantly inhibited tumor cell growth in a time- and dose-dependent fashion. Our studies suggest that PSO may be used as a substitute for synthetic antioxidants in food preservation and may be potentially useful as a food and cosmetic ingredient. Meanwhile, the oxidative stress can cause hypertension, so PSO is expected to develop a health care products for the prevention and mitigation hypertensive symptoms.


Change of Blood Pressure Control and Related Factors in Three Types of Heart Failure Based on the Jnc 7, 8 Hyprertension Guidelines

Hong Seok Lee, Belen Nunez, Ferdinnd Visco, Savi Mushiyev and Gerald Pekler

The Joint National Committee (JNC) 8 hypertension guidelines were released in 2014 targeting higher blood pressure (BP) goals and it may allow the less antihypertensive medications. We will determine how BP was affected in different types of heart failure according to JNC 7, 8.732 patients enrolled in our heart failure program were analyzed retrospectively. And 688 patients who had been followed since March, 2014 were included. Based on ACC/AHA guidelines, heart failure is classified as a reduced ejection fraction (HFrEF, EF < 40), preserved ejection fraction (HFpEF, EF > 50) and heart failure with an improved ejection fraction (HFpEF (i), EF ≥ 40). 70.6% (486/688) patients were controlled based on the new guidelines, on the contrary, previous guideline revealed 58.7% BP control. Mean systolic BP was 128.9 ± 18 mmHg in heart failure with reduced EF and 125.1 ± 17 mmHg in heart failure with preserved EF. Obesity [Odds ratio (OR): 0.119, 95%, Confidence Interval (CI): 0.048-0.284], ACE inhibitor [OR: 2.659, 95% CI: 1.500-3.415] and Diuretics [OR: 1.904, 95%, CI: 1.068-3.394] were noted to significantly differentiate the controlled versus the uncontrolled BP group in reduced EF group. And obesity (BMI ≥ 30) was associated with BP control in HFrEF [OR: 0.180, 95% CI: 0.090-0.341]. The control rate according to JNC 8 was more increased compared to one based on JNC 7 even with the same medication. In each type of heart failure, there were medication related differences of risk factors related to BP control by two different guidelines. Patients may need change types of medication to control BP according to types of heart failure.


Summative Evaluation of Physician-Pharmacist Collaboration Management

Rachel J. Finkelstein, Natalie D. Blaine, Christopher P. Parker, Mark W. Vander Weg, Barry L. Carter

Background: Studies have shown physician-pharmacist collaboration can improve outcomes and management of chronic disease states; however, there is limited knowledge of the barriers to implementing these models.
To evaluate the perceived effectiveness of and barriers to physician-pharmacist collaborative management (PPCM) in diverse primary care medical offices.
Prospective cluster-randomized mixed methods trial in 32 primary care offices. Each medical office was randomized to a 9 or 24 month hypertension intervention or a 9 month asthma intervention with usual care hypertension management. A post study summative evaluation of physician and pharmacists was conducted to identify obstacles and suggest facilitators for implementation of PPCM in primary care offices.
A total of 63 physicians and 26 pharmacists from 27 (84%) and 26 (81%) offices, respectively, completed the summative evaluation. Collaboration for the duration of the Collaboration Among Pharmacists and Physicians To Improve Outcomes Now (CAPTION) Trial resulted in expanded clinical pharmacy services for the management of chronic diseases. Both physicians and pharmacists participating in the study reported that physicians at their sites were generally receptive to pharmacist’s recommendations both prior to and following the study. Physicians appear to be confident in the expertise of pharmacists and their ability to manage chronic diseases. Over 98% of physicians reported accepting pharmacist recommendations. In addition, 100% of responding physicians and pharmacists believed the model implemented in the CAPTION Trial could be expanded to disease states beyond blood pressure (BP) and asthma. Collaboration reportedly increased as physician workload became heavier. A major reported barrier to collaboration was access to pharmacists including conflicts with other non-clinical responsibilities. Collaboration had a positive impact on patient-provider relationships and 100% of the surveyed physicians responded that they believe a pharmacist’s involvement in chronic disease management improved patient outcomes. When asked if pharmacists should be recognized as healthcare providers, 95% of physicians responded affirmatively.
The results of this summative evaluation indicate both physicians and pharmacists perceived collaboration in primary care settings as a means to improve the quality of patient care and treatment outcomes. Physicians and pharmacists perceived collaborative care as well received by patients and that it strengthened patient-provider relationships. Physicians’ desire to collaborate with pharmacists to manage chronic diseases is promising but will require ongoing efforts to develop and maintain positive professional relationships as well as reimbursement strategies for clinical services provided by pharmacists.


Effects of Dichloromethane-Methanolic Leaf Extracts of Carissa edulis (Forssk) Vahl on Serum Lipid Profiles in Normal Rat Models

Obel H. Jorum, Alex K. Machocho, Ngugi M. Piero

Assessment of serum lipid profile is required for wellbeing of every individual since the blood can act as pathological reflector and also as an indicator of the physiological state of an animal. Disorders arising from lipid components imbalance are approaching epidemic levels while the methods used to conventionally manage them are not improving hence the need to continually seek alternative methods of management. Carissa edulis (Forssk.) Vahl belongs to the Apocynaceae family. This plant has been used extensively in traditional medicine to manage various diseases including those that are lipids related. This study, therefore, was designed to investigate the effects of Dichloromethane-Methanolic leaf extract of C. edulis on serum lipid profiles. The plant leaves were collected from Siakago-Mbeere North Sub-County, Embu County, Kenya. The samples were prepared and extraction of the active compounds carried out using organic solvents; dichloromethane and methanol in the ratio of 1:1. Experimental rats were divided into four groups each consisting of five normal rats. The groups received oral doses of 50, 75 and 100 mg/kgbw of the extract while one group was used as control and did not receive any dosage. Blood samples were drawn from the rats at intervals of seven days then the serum lipid profiles were analysed using an auto-analyzer machine. Screening for plants phytochemicals was conducted using the standard recommended procedures. The results of this study showed that DCM-MeOH leaf extract of C. edulis induced general changes in serum lipid profiles of normal rats. The triglycerides, total cholesterol and low density lipoprotein cholesterol levels decreased significantly at all the dose levels (p<0.05), while high density lipoprotein cholesterol levels increased significantly during this study (p<0.05). Qualitative phytochemical screening confirmed the presence of various phytochemicals which included alkaloid, flavonoids, tannins, phenols, terpenes and traces of steroids which have the ability to alter lipid metabolism. It was concluded that the plant extract may be useful in the management of lipid related disorders.



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