Nebivolol: haemodynamic effects and clinical significance of combined beta-blockade and nitric oxide release.

Nebivolol is a third-generation beta-adrenergic receptor antagonist (beta-blocker) with high selectivity for beta(1)-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional beta-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available beta-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with beta-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional beta-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardioprotective activity and a good tolerability profile

Old and new intravenous inotropic agents in the treatment of advanced heart failure

Inotropic agents are administered to improve cardiac output and peripheral perfusion in patients with systolic dysfunction and low cardiac output. However, there is evidence of increased mortality and adverse effects associated with current inotropic agents. These adverse outcomes may be ascribed to patient selection, increased myocardial energy expenditure and oxygen consumption, or to specific mechanisms of action. Both sympathomimetic amines and type III phosphodiesterase inhibitors act through an increase in intracellular cyclic adenosine monophoshate and free calcium concentrations, mechanisms that increase oxygen consumption and favor arrhythmias. Concomitant peripheral vasodilation with some agents (phosphodiesterase inhibitors and levosimendan) may also lower coronary perfusion pressure and favor myocardial damage. New agents with different mechanisms of action might have a better benefit to risk ratio and allow an improvement in tissue and end-organ perfusion with less untoward effects. We have summarized the characteristics of the main inotropic agents for heart failure treatment, the data from randomized controlled trials, and future perspectives for this class of drugs

School Reforms in Ontario: The "Marketization of Education" and the Resulting Silence on Equity

Market dynamics have begun to entrench themselves in educational systems around the world. Although this phenomenon has been addressed in several recent writings (Ball, 1993; Dehli, 1996; Gerwitz, Ball, & Bowe, 1995; Kenway, 1993; Robertson, 1995), few have incorporated a critical antiracist framework. As noted by Dehli (1996) the encroachment of market forms, relations, and concepts into educational sites usually results in the marginalization and muting of other dimensions of schooling. Using an integrative antiracist perspective that is informed by the findings of an ongoing study of inclusive schooling in Ontario (Dei et al, 1996), this article critically examines these ongoing reforms in a Canadian context, specifically in relation to the recent reforms in Ontario's educational system. We draw on knowledge about race and difference to argue for serious questioning of these reforms and their impact on socially disadvantaged groups. In doing so, the article asserts that current trends are leading toward the " Marketisation of education" (Ball, 1993; Gerwitz et al., 1995; Kenway, 1993) in Ontario, and that the harmful consequences of this shift will be felt most severely in relation to issues of equity and access in education. Through the rhetoric of cost-effectiveness and bureaucratic efficiency, the "official" agenda for educational change shifts focus away from equity considerations in schooling to those of capital, market forces, and big business. The article interrogates the rhetoric of reform and calls for equity to be placed at the centre of educational change. In conclusion we suggest new ways of examining and addressing genuine educational options in Canadian contexts.La dynamique de marché a commencé à s'inscrire dans les systèmes d'éducation de par le monde. Alors qu'on a beaucoup écrit sur ce phénomène récemment (Bail, 1993; Dehli, 1996; Gerwitz, Bail, & Bowe, 1995; Kenway, 1993; Robertson, 1995), peu d'auteurs ont incorporé un cadre de travail antiraciste dans leur analyse. Comme Dehli (1996) l'a noté, l'empiétement des formes, des relations et des concepts du marché sur les sites éducationnels entraîne habituellement la marginalisation et la mise à l'écart d'autres dimensions de la scolarité. Adoptant une perspective antiraciste integrative reposant sur les résultats d'une étude continue de l'école inclusive en Ontario (Dei et al, 1996), cet article étudie d'un oeil critique les réformes en cours dans un contexte canadien, plus particulièrement par rapport aux réformes récentes dans le système d'éducation en Ontario. Nous puisons dans des connaissances sur la race et les différences pour appuyer nos arguments qui proposent une sérieuse remise en question de ces réformes et leur impact sur les groupes socialement défavorisés. Nous affirmons ainsi que les tendances actuelles mènent à la "Commercialisation de l'éducation" (Bail, 1993; Gerwitz et al, 1995; Kenway, 1993) en Ontario, et que les conséquences néfastes de ce changement se feront surtout sentir dans les questions d'équité et d'accès en matière d'éducation. Par le biais du discours sur la rentabilisation et l'efficacité administrative, les projets "officiels"/l'agenda officiel visant aux cliangements pédagogiques se distancienl des considérations d'équité pour se rapprocher de celles gouvernées par le capital, les forces du marché et les grandes entreprises. Cet article remet en question le discours des réformes et propose que l'équité constitue la base sur laquelle les changements pédagogiques seront formulés. La conclusion présente de nouvelles façons d'aborder et d'étudier les options réelles en matière d'éducation dans divers contextes canadiens

Postdischarge assessment after a heart failure hospitalization: the next step forward.

Heart failure (HF) is the most frequent cause of hospitalization for patients >65 years of age. Mortality during the initial hospitalization ranges from 6% to 7% in Europe to 3% to 4% in the United States, depending on the length of hospital stay. Poor outcomes have universally been shown after discharge, with 60- to 90-day mortality rates of 5% to 15% and hospital readmission rates of 30%. Whereas the prognosis of patients with chronic HF has improved in recent years, there has been no change in the high risk of death or rehospitalization after an HF hospitalization. In addition to the lack of new therapies, incomplete relief from fluid overload, insufficient patient education, lack of implementation of evidence-based therapies, and poor postdischarge follow-up planning are among the main causes of these poor outcomes. A better assessment of the patient at the time of discharge and in the following weeks seems therefore as mandatory. This article outlines the main components of such a program. These include the personnel who should be involved, i.e. HF specialists and cardiologists versus non-specialists, the variables which should be assessed, i.e. those related with congestion and fluid overload, the times when they should be assessed, as the phase at highest risk is immediately after discharge from hospital, and, finally, the aims of such programs. We retain that an improvement of post-discharge follow-up will be able to significantly improve patients’ outcomes with a rate of success comparable, if not greater, to that which can be achieved by new therapies

AYURVEDIC MANAGEMENT OF PRIMARY INFERTILITY DUE TO POLYCYSTIC OVARIAN SYNDROME ASSOCIATED WITH MULTIPLE UTERINE FIBROIDS: A CASE REPORT

Infertility is a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. As one of the leading causes of anovulatory infertility, it is believed that 5-10% of the reproductive-aged female population is living with polycystic ovary syndrome. Ayurveda considers the excellence of 4 factors- Ritu (ovulatory phase), Kshetra (garbhasaya), Ambu (proper nourishment to embryo), and Bija (healthy sperm and ovum) for a successful pregnancy. Impairment to any of these factors leads to Vandhytva or pregnancy failure. This case study helps to plan a treatment protocol for the patient with PCOS having infertility. A 25 yr old female having regular cycles came to OPD of Streeroga of IPGT & RA, having the complaints of weight gain and failure to conceive since 2 year of active married life. On presentation she was a medium sized woman with android body habits and had mild hirsute and acanthosis nigricans over nape of neck. Gynaecological examination revealed a normal sized uterus with no other abnormalities. Sonography revealed bulky ovaries with multiple small follicles with no evidence of ovulation along with small fibroids on anterior wall (1.8cm×1.5cm) and posterior wall (2.7cm×2.8cm). Her husbands semen analysis was normal. Based on clinical findings and investigation, anovulatory factor infertility due to PCOS was diagnosed along with fibroid. Virechana and Samana were decided due to both of these factors and Sthanyasodhana gana kashaya was selected as Samana drug. Treatment was done for 3 months, during treatment itself ovulation occured and the patient conceived after 3 months. This case being a Krichrasadhya vyadhi, proper care was taken including correction of the lifestyle and food habits. This case will help to understand the importance of Sodhana in gynecological disorders and explore the probable mode of action of Sthanyasodhana gana kashaya which helped in menstrual regulation

Integrated smart system for energy audit: methodology and application

Abstract The article describes the design and the application stage of a smart energy audit system, integrated within building, and the methodologies adopted for the detection of malfunctions of the plant. The system is set up as a "black box" consisting of a hardware aimed at logging both energy and environmental parameters and a software for the assessment of building behavior and the management of energy flows. The Energy Signature was chosen as the reference method for the evaluation of the energy performance of building. The system was tested in an existing public office building

Bacterial community analysis on the Mediaeval stained glass window "Natività" in the Florence Cathedral

Microbial corrosion of glass causes problems on delicates antique glass samples. Until now, the effect of microbial activity on corrosion phenomena has not been well documented. Only a few studies have been published concerning the microflora growing on glass surfaces. The present study deals with the characterization of cultivable aerobic bacteria isolated from the historical glass window "Natività" in the Florence Cathedral, designed by Paolo Uccello and realized by Angelo Lippi between 1443 and 1444. Microbial strains were sampled from four of the 25 panels of the "Natività" in the occasion of a recent conservation treatment, due to the presence of various kinds of crusts. One hundred microorganisms were isolated, about 50% bacteria and 50% fungi. Bacteria were submitted to morphological characterization and classified in the Gram group. For twenty strains, from different glass panels, the 16S rDNA gene was amplified and sequenced. Sequence analysis showed genus Bacillus, Arthrobacter and Paenibacillus as the most representative. In particular Bacillus and Paenibacillus are crusts associated. Phylogenetic relationship among isolates was determined. Chemical analysis of the glass and crusts completed the study

Nontuberculous mycobacteria in hospital water systems: Application of HPLC for identification of environmental mycobacteria

Nontuberculous mycobacteria (NTM), ubiquitous in water environments, are increasingly recognized as nosocomial pathogens. Our study reports a one-year survey of the water system of two hospitals, A and B, in a small town near Florence, Italy. NTM were found throughout the study period in both settings, but B showed a significantly higher mycobacterial load. Mycobacterium gordonae and Mycobacterium fortuitum were the most frequent species isolated. Identification was carried out by conventional techniques and by high performance liquid chromatography (HPLC) analysis of cell wall mycolic acids. HPLC profiling could be used as a first-choice method for identification of environmental mycobacteria