Hepatoprotective potential of Tecomella undulata stem bark is partially due to the presence of betulinic acid

Ethnopharmacological relevance

Tecomella undulata (TU;` Family Bignoniaceae) is used in Indian Ayurvedic system of medicine for treating various diseases including hepatic ailments. It is also incorporated in various marketed hepatoprotective polyherbal formulations.

Aim

The present study was aimed at evaluating possible hepatoprotective role of isolated compounds from TU stem bark (TSB) using in vitro and in vivo experimental models.

Methods

In vitro cytotoxicity and hepatoprotective potential of various extract, fractions and isolated compounds from TU stem bark were evaluated using HepG2 cells. Rats were pre-treated with TU methanolic extract (TSB-7) or betulinic acid (MS-2) or silymarin for 7 days followed by a single dose of CCl₄ (0.5 ml/kg, i.p.). Plasma markers of hepatic damage, hepatic antioxidants and indices of lipid peroxidation along with microscopic evaluation of liver were assessed in control and treatment groups.

Results

TSB-2 and MS-1 accounted for significant cell death whereas; TSB-1, TBS-7, TSB-9, TSB-10 and, MS-2 did not register significant cytotoxicity. Further, non-cytotoxic components exhibited ascending grade of hepatoprotection in vitro (TSB-10<TSB-1<TSB-7<TSB-9<MS-2). Pre-treatment of TSB-7 or MS-2 to CCl₄ treated rats prevented hepatocyte damage as evidenced by biochemical and histopathological observations.

Conclusion

It can be concluded that, hepatoprotective potential of Tecomella undulata stem bark is partially due to the presence of betulinic acid.     

Hepatitis C Management Simplification From Test to Cure: A Framework for Primary Care Providers

This article proposes a strategy for primary care providers to begin treating patients with hepatitis C virus (HCV). We are motivated by the need to expand HCV treatment and by developments that have simplified treatment for most patients. This article presents 5 steps to achieving quality HCV treatment in the primary care setting: (1) accurate diagnosis via reflex testing; (2) risk stratification and identifying comorbidities via pretreatment evaluation; (3) simple, once-daily, pan-genotypic HCV treatment regimens; (4) minimized on-treatment monitoring: and (5) posttreatment monitoring and high-quality care for comorbidities such as cirrhosis and injection drug use. We provide indications for referral to specialists: notably children, patients with genotype 3 and cirrhosis, advanced liver or kidney disease, previous treatment failures, drug interactions with recommended regimens, and hepatitis B co-infection. Finally, potential barriers for providers are discussed, as well as further research findings and policy interventions that can promote HCV treatment in the primary care setting. We believe that a substantial portion of patients with HCV can be treated safely and effectively by nonspecialists and that the engagement of primary care providers is critical to efforts to end the HCV epidemic.     

Long-term sequelae of herpes simplex virus encephalitis–related white matter injury: correlation of neuropsychological outcome and diffusion tensor imaging

Journal of NeuroVirology - The pathophysiology of the memory impairment following Herpes Simplex virus encephalitis is not yet established and understood. This study attempts to elucidate the role...     

Elevated circulating levels of serum tumor necrosis factor-alpha in patients with hemodynamically significant pressure and volume overload

OBJECTIVES: We sought to determine whether serum tumor necrosis factor-alpha (TNF-alpha) levels are elevated in patients with hemodynamically significant pressure and volume overload. BACKGROUND: It has been previously shown that TNF-alpha messenger ribonucleic acid (mRNA) and protein are rapidly expressed in the hearts of animal models subjected to abrupt hemodynamic overloading. The clinical significance of these experimental findings has not been tested in pathophysiologically relevant clinical models in human subjects. METHODS: We prospectively measured serum TNF-alpha levels and serum TNF receptor 1 and 2 levels in 21 patients with severe aortic stenosis (AS), in 26 patients with 3+ to 4+ mitral regurgitation (MR) and in normal age- and gender-matched control subjects. Patients with AS and MR were either in New York Heart Association (NYHA) functional class I or II and had no significant coronary disease. We compared the cytokine levels among the groups using analysis of variance. We related cytokine levels to the severity of AS using simple regression analysis. RESULTS: Serum TNF-alpha levels in patients with AS (2.1 +/- 1.6 pg/ml, n = 21) and MR (1.3 +/-0.7 pg/ml, n = 26) were significantly higher than those in the control subjects (0.7 +/-0.2 pg/ml, n = 28). Serum TNF receptor 1 and 2 levels were also higher in patients with AS and MR than in control subjects. Cytokine levels were higher in patients in NYHA class II than in those in class I. In patients with a normal ejection fraction (>50%, n = 16), there was a mild positive correlation (r = 0.56, p = 0.025) between serum TNF-alpha levels and the mean gradient across the aortic valve. CONCLUSIONS: This study demonstrates that serum TNF-alpha is elevated in patients with chronic hemodynamic overloading and early cardiac decompensation. Furthermore, these findings suggest not only that peripheral TNF-alpha levels correlate with the severity of the hemodynamic pressure overload, but also that peripheral TNF-alpha and TNF receptor levels increase in direct relation to deteriorating NYHA functional class.     

A prolonged observational study of tracheal tube displacements: Benchmarking an incidence <0.5-1% in a medical-surgical adult intensive care unit

Background and Aims:

Tracheal tubes are commonly used in intensive care unit (ICU) and lead to complications like displacements. The primary aim of the study was to evaluate if the rate of tracheal tube displacement benchmarked at <1% per patient and <0.5% per tracheal tube day, could be sustained over a prolonged period. The secondary aim was to document the patterns of all forms airway accident and to evaluate their consequences.

Subjects and Methods:

This was a prospective observational study of Intubated and ventilated patients in a General Medical-Surgical Adult ICU. The incidence of accidental extubation, self extubation, partial displacement and blockages of tracheal tubes were recorded.

Results:

The overall tracheal tube displacement rate was 61/10,112 (0.6%) per patient and 61/28,464 (0.22%) per tracheal tube day. There were 30 additional incidents of blockage, kinking or biting of the tracheal tube. Physiological consequences-69 were mild, 10 moderate, 12 major and one death. Of the 91 accidents, 30 were partly and 30 were completely preventable. 76 incidents involved an endotracheal tube (54 displaced, 12 blocked and 10 bitten-kinked) and 15 a tracheostomy tube (seven displaced and eight blocked). Accidents were more common in medical than surgical patients (medical = 48, cardiac surgical = 17 and other surgical/trauma = 26).

Conclusion:

Tracheal tube displacement rate in a mixed medical-surgical adult ICU was maintained below the pre-set benchmark of <1% per patient and <0.5% per intubated day over nearly a decade.     

Size and complexity in model financial systems

The global financial crisis has precipitated an increasing appreciation of the need for a systemic perspective toward financial stability. For example: What role do large banks play in systemic risk? How should capital adequacy standards recognize this role? How is stability shaped by concentration and diversification in the financial system? We explore these questions using a deliberately simplified, dynamic model of a banking system that combines three different channels for direct transmission of contagion from one bank to another: liquidity hoarding, asset price contagion, and the propagation of defaults via counterparty credit risk. Importantly, we also introduce a mechanism for capturing how swings in “confidence” in the system may contribute to instability. Our results highlight that the importance of relatively large, well-connected banks in system stability scales more than proportionately with their size: the impact of their collapse arises not only from their connectivity, but also from their effect on confidence in the system. Imposing tougher capital requirements on larger banks than smaller ones can thus enhance the resilience of the system. Moreover, these effects are more pronounced in more concentrated systems, and continue to apply, even when allowing for potential diversification benefits that may be realized by larger banks. We discuss some tentative implications for policy, as well as conceptual analogies in ecosystem stability and in the control of infectious diseases.Although global financial systems have seen considerable growth in size, concentration, and complexity over the past few decades (1), our understanding of the dynamic behavior of such systems has not necessarily kept pace. Indeed, the current financial crisis has presented a stark demonstration of the potential for modern financial systems to amplify and disseminate financial distress on a global scale. From a regulatory perspective, these events have prompted fresh interest in understanding financial stability from a system level. In particular, although precrisis regulation (as typified by the Basel II accords) sought to minimize the risk of failure of individual banks irrespective of systemic importance, new regulation will seek to target the systemic consequences of bank collapse as well. To quote Haldane and May (2), “What matters is not a bank’s closeness to the edge of the cliff; it is the extent of the fall.”In this context, a clear feature of interest is the presence of large, highly connected banks. These banks have conceptual parallels in biology: simple models have been influential in underlining the importance of “superspreaders” in the spread and control of infectious diseases (3, 4), and “keystone” species are thought to serve a valuable role in ecosystem stability (5, 6). Here we develop dynamic models to apply and extend these lessons to financial systems. Our approach is theoretical, and our models necessarily oversimplified. Nonetheless, by considering transmission mechanisms specific to modern financial systems, our approach recognizes some important differences between these and other complex systems. We show how, even with such distinctions, the basic insights deriving from our model allow us to draw certain parallels with other situations where size and complexity are important.If financial crises may be compared with forest fires, causes for the initiating sparks pose important questions in their own right: for example, the role of excessive leverage and credit growth (7) or the pricing for complex financial instruments (8, 9). Here, however, our focus is on the role of large banks in the “flammability” of the system, or its capacity for amplification and propagation of an initiating shock. We ask the following questions: How does the impact of a bank’s collapse scale with its size? How might capital adequacy standards seek to mitigate this impact? More broadly, what is the effect of concentration and diversification on system stability?Network approaches (10–14) are well-suited for such questions, particularly in modeling contagion that is transmitted through linkages in the financial system. Here we adopt such an approach to bring together three important transmission channels into a unified framework: (i) liquidity hoarding, where banks cut lending to each other as a defensive measure (1, 15); (ii) asset price contagion linked to market illiquidity (16–18); and (iii) the propagation of defaults via counterparty credit risk (19–21).Although the network effects listed above act on defined webs of connectivity, confidence effects can operate more broadly, with the overall state of the system potentially influencing an individual bank’s actions, and vice versa. This motivates a special feature of our model, which explicitly integrates network dynamics with confidence effects.The interaction of such network and confidence effects arguably played a major role in the collapse of the interbank market (a network of lending exposures among banks) and global liquidity “freeze” that occurred during the crisis (22). Interbank loans have a range of maturities, from overnight to a matter of years, and may often be renewed, or rolled over, at the point of maturity. A pronounced feature of the 2007/2008 crisis was that, as the system deteriorated, banks stopped lending to each other at all but the shortest maturities (7, 29). The bankruptcy of Lehman Brothers in September 2008 transmitted distress further across the financial network, and signaled that there was no guarantee of government support for institutions in distress. The effects extended well beyond those institutions directly exposed to Lehman Brothers, with banks throughout the system withdrawing interbank lending outright and propagating distress to the real economy by sharply contracting household and corporate lending (23). At the time of writing, ongoing events illustrate the potential for similar dynamics in the context of sovereign and banking sector distress in some Eurozone countries.Several specific motivating factors have been proposed to explain “liquidity hoarding” (the maturity-shortening and ultimate withdrawal of interbank lending): precautionary measures by lending banks in anticipation of future liquidity shortfalls, counterparty concerns over specific borrowing banks, or collapses in overall system confidence (24, 25). Our framework parsimoniously incorporates all of these mechanisms, but also captures the idea that a bank’s distress may affect not just those directly exposed or linked to it, but also confidence in the market at large.In what follows we summarize essential features of the model structure, with details provided in Materials and Methods, and a summary of model parameters and their default values given in Table S1. We use this model to explore the impact of an initiating shock, with particular reference to the nonlinearities arising from each of the contagion channels modeled, the effects of size disparity among banks and system concentration, and the effects of diversification. We then outline tentative implications for regulatory capital requirements before discussing important caveats to our work. Throughout the paper, we abstract from extraordinary policy intervention in crisis, so that liquidity cannot be obtained more easily from the central bank than from the market, and failing institutions are not bailed out.