Effect of chronic administration of Boerhaavia diffusa Linn. leaf extract on experimental diabetes in rats

Purpose: The root and aerial parts of Boerhaavia diffusa Linn. (Nyctaginaceae) were used in Ayurveda for the treatment of diabetes. The present study is aimed at evaluating the antidiabetic activity of chloroform extract of Boerhaavia diffusa leaves on chronic administration in streptozotocin-induced non-insulin-dependent diabetes mellitus (NIDDM) model diabetic rats. Methods: The blood glucose lowering activity of the leaf extract was studied in streptozotocin-induced (65 mg/kg, i.v.) NIDDM model diabetic rats after oral administration of the extract at daily doses of 50, 100 and 200 mg/kg body weight for four weeks and compared with glibenclamide. Blood samples were collected from the tail vein before and also at weekly intervals for four weeks from the first dose of drug administration and blood glucose was analyzed by glucose-oxidase method using a visible spectrophotometer. Results: The leaf extract of B. diffusa produced dose-dependent reduction in blood glucose in streptozotocin-induced NIDDM rats comparable to that of glibenclamide. The results indicate that the reduction in blood glucose produced by the extract is probably through rejuvenation of pancreatic b-cells or through extrapancreatic action. Conclusion: The chloroform extract of Boerhaavia diffusa has significant antidiabetic activity and this supports the traditional usage of the plant by Ayurvedic physicians for the control of diabetes. Keywords: Blood glucose, Boerhaavia diffusa, Diabetes mellitus Streptozotocin, Rats> Tropical Journal of Pharmaceutical Research Vol. 3 (1) 2004: pp. 305-30

Curcumin Reduces Tumour Necrosis Factor-Enhanced Annexin V-Positive Microparticle Release in Human Vascular Endothelial Cells

PURPOSE: Circulating microparticles have been highlighted as biomarkers of cardiovascular disease state and progression. The aim of this study was to evaluate the effects of curcumin on microparticle release from endothelial cells undergoing TNF-induced cell activation and apoptosis. METHODS: This study evaluated the effects of curcumin on microparticle release, cytotoxicity, apoptosis, cell adhesion molecule expression and monocyte adhesion in EAhy926 human endothelial cells RESULTS: The results showed that the numbers of microparticles were increased by tumour necrosis factor (TNF) or the combination of TNF and cycloheximide (CHX). Curcumin attenuated microparticle release caused by TNF or TNF plus CHX treatments. The pretreatment by curcumin not only negated the accelerated cell death and apoptosis caused by TNF and CHX, but also diminished TNF-induced cell activation, as assessed by reduced surface expression of intercellular adhesion molecule 1, and adhesion of monocytes to endothelial monolayers CONCLUSION: Curcumin reduced microparticle release from endothelial cells undergoing cell activation and apoptosis, which supports its protective role in TNF-associated endothelial dysfunction, and highlights its potential use as a nutraceutical agent for vascular inflammatory diseases

Numerical analysis of thermal stresses around fasteners in composite metal foils

The process of composite metal foil manufacturing (CMFM) has reduced a number of limitations associated with commercial additive manufacturing (AM) methods. The existing metal AM machines are restricted by their build envelope and there is a growing market for the manufacture of large parts using AM. These parts are subsequently manufactured in fragments and are fastened together. This paper analyses the thermal stresses around cylindrical fasteners for three layered metal composite parts consisting of aluminium foil, brazing paste and copper foil layers. The investigation aims to examine the mechanical integrity of the metallurgically bonded aluminium/copper foils of 100 micron thickness manufactured in a disc shape. A cylindrical fastener set at an elevated temperature of 100 °C is fitted in the middle of the disc which results in a steady-state thermal distribution. Radial and shear stresses are computed using finite element method which shows that non-zero shear stresses developed by the copper layer inhibit the axial slippage of the fastener and thereby establishing the suitability of rivet joints for CMFM parts

Polysaccharide Peptide Extract From <i>Coriolus versicolor</i> Increased T_max of Tamoxifen and Maintained Biochemical Serum Parameters, With No Change in the Metabolism of Tamoxifen in the Rat.

Background: Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Trametes; Polyporaceae) is increasingly used in cancer to support the immune system. However, its interaction with tamoxifen is unknown. Aim of the study: To investigate the effect of a PSP extract on the pharmacokinetics, biochemical parameters, and depletion of tamoxifen. Methods: The pharmacokinetic and biochemical parameters of tamoxifen (20 mg/mL oral single dose and repeated dosing for 12 days) was investigated in female Sprague Dawley rats with or without PSP (340 mg/kg orally for 7 days) (n = 5 per group). Tamoxifen (5 µM) depletion rate with PSP (10–100 μg/mL) was measured in female rat hepatic microsomes in vitro. Results: Compared to tamoxifen alone, the time to reach maximum concentration (Tmax) significantly increased by 228% (4.15 ± 1.15 versus 13.6 ± 2.71 h) in the single tamoxifen dose with PSP and 93% (6 ± 2.17 versus 11.6 ± 0.4 h) in the repeated tamoxifen dosing with PSP (p 0.05). PSP extract did not significantly alter in vitro intrinsic clearance of tamoxifen compared to tamoxifen control. Conclusion: With the increased use of PSP as an adjunct therapy, this study highlights the importance of clinician’s knowledge of its interaction with tamoxifen to avoid compromising clinical actions and enhancing clinical therapy

Possible mechanisms of hypotension produced 70% alcoholic extract of Terminalia arjuna (L.) in anaesthetized dogs

BACKGROUND: The bark of Terminalia arjuna L. (Combretaceae) is used in Ayurveda since ancient times for the treatment of cardiac disorders. Previous laboratory investigations have demonstrated the use of the bark in cardiovascular complications. The present study was aimed to find the effect of 70% alcoholic extract of Terminalia arjuna on anaesthetized dog blood pressure and probable site of action. METHODS: Six dogs were anaesthetized with intraperitoneal injection of thiopental sodium and the blood pressure of each dog (n = 6) was measured from the left common carotid artery connected to a mercury manometer on kymograph. The femoral vein was cannulated for administration of drug solutions. The extract of T. arjuna (dissolved in propylene glycol) in the dose range of 5 to 15 mg/kg were administered intravenously in a pilot study and the dose (6 mg/kg) which produced appreciable hypotension was selected for further studies. RESULTS: Intravenous administration of T. arjuna produced dose-dependent hypotension in anaesthetized dogs. The hypotension produced by 6 mg/kg dose of the extract was blocked by propranolol but not by atropine or mepyramine maleate. This indicates that muscarinic or histaminergic mechanisms are not likely to be involved in the hypotension produced by the extract. The blockade by propranolol of the hypotension produced by T. arjuna indicates that the extract might contain active compound(s) possessing adrenergic ß(2)-receptor agonist action and/or that act directly on the heart muscle. CONCLUSION: The results indicated the likely involvement of peripheral mechanism for hypotension produced by the 70% alcoholic extract of Terminalia arjuna and lends support for the claims of its traditional usage in cardiovascular disorders

Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update

Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients

Attenuation of Cigarette-Smoke-Induced Oxidative Stress, Senescence, and Inflammation by Berberine-Loaded Liquid Crystalline Nanoparticles: In Vitro Study in 16HBE and RAW264.7 Cells

Cigarette smoke is considered a primary risk factor for chronic obstructive pulmonary disease. Numerous toxicants present in cigarette smoke are known to induce oxidative stress and airway inflammation that further exacerbate disease progression. Generally, the broncho-epithelial cells and alveolar macrophages exposed to cigarette smoke release massive amounts of oxidative stress and inflammation mediators. Chronic exposure of cigarette smoke leads to premature senescence of airway epithelial cells. This impairs cellular function and ultimately leads to the progression of chronic lung diseases. Therefore, an ideal therapeutic candidate should prevent disease progression by controlling oxidative stress, inflammation, and senescence during the initial stage of damage. In our study, we explored if berberine (an alkaloid)-loaded liquid crystalline nanoparticles (berberine-LCNs)-based treatment to human broncho-epithelial cells and macrophage inhibits oxidative stress, inflammation, and senescence induced by cigarette-smoke extract. The developed berberine-LCNs were found to have favourable physiochemical parameters, such as high entrapment efficiency and sustained in vitro release. The cellular-assay observations revealed that berberine-LCNs showed potent antioxidant activity by suppressing the generation of reactive oxygen species in both broncho-epithelial cells (16HBE) and macrophages (RAW264.7), and modulating the genes involved in inflammation and oxidative stress. Similarly, in 16HBE cells, berberine-LCNs inhibited the cigarette smoke-induced senescence as revealed by X-gal staining, gene expression of CDKN1A (p21), and immunofluorescent staining of p21. Further in-depth mechanistic investigations into antioxidative, anti-inflammatory, and antisenescence research will diversify the current findings of berberine as a promising therapeutic approach for inflammatory lung diseases caused by cigarette smoking.</jats:p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Pharmacological Evaluation of the Recuperative Effect of Morusin Against Aluminium Trichloride (AlCl3)-Induced Memory Impairment in Rats.

BACKGROUND: Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action. METHODS: Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acid-reactive species (TBARS) and glutathione (GSH) levels. RESULTS: AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also produced a significant deterioration in brain AChE action and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Treatment with morusin (5.0 and 10.0 mg/kg, dose orally) significantly overturned AlCl3- induced learning and memory shortages along with diminution of AlCl3-induced rise in brain AChE activity and brain oxidative stress levels. CONCLUSION: It may be concluded that morusin exerts a memory-preservative outcome in mental discrepancies of rats feasibly through its various activities