bluuebunny/crossref_metadata_2025_split huggingface dataset:
The quality of commercially available nutraceutical supplements and food sources
Authors: Lockwood G Brian 
Published: October 2010

Abstract

Objectives
Nutraceuticals are components of dietary origin, with claimed beneficial therapeutic activities. The quality of nutraceuticals is paramount for efficacy and safety, and it includes quality of raw materials, different available chemical forms, complex products, lack of substitution of inappropriate materials, and the absence of contaminants. The aim of this review is to investigate the extent of substandard formulated and raw material nutraceuticals, and to highlight any consequent health concern.

Key findings
Reports of the quality of raw materials have revealed wide variations, often as a result of lack of clear regulatory definitions with respect to size of polymeric entities and also presence of glycosidic and salt forms. Published evaluations of over 70 formulations of 25 different nutraceuticals revealed variable quality; no nutraceutical showed consistent high quality, but a number revealed consistent low quality, thereby making the case for closer regulation of manufacturers. Whole food sources have also been shown to be widely variable in constituent levels. The effect of different formulations requires consideration, as the different types have been shown to have marked effects on bioavailability.

Summary
The poor quality of commercially available nutraceuticals has been highlighted. In addition, incidences of side effects and drug interactions are increasing, as consumption of nutraceuticals rises. Pharmacists and health practitioners need to be aware of the scientific literature to advise accordingly.
In-vitro permeability screening of melt extrudate formulations containing poorly water-soluble drug compounds using the phospholipid vesicle-based barrier
Authors: Kanzer Johanna , Tho Ingunn , Flaten Gøril Eide , Mägerlein Markus , Hölig Peter , Fricker Gert , Brandl Martin 
Published: October 2010

Abstract

Objectives
The phospholipid vesicle-based barrier has recently been introduced as an in-vitro permeation model mimicking gastro-epithelial barriers in terms of passive diffusion of drugs. The aim of this study was to investigate whether the phospholipid vesicle-based barrier was suitable for permeability screening of complex formulations such as solid dispersions.

Methods
Solid dispersions containing the poorly water-soluble drugs HIV-PI 1 (log P = 6.2, molar mass = 628.80 g/mol) and HIV-PI 2 (log P = 5.3, molar mass = 720.95 g/mol), a hydrophilic polymer and different surfactants were tested with respect to their influence on integrity of the barrier in terms of electrical resistance and permeability for calcein. Furthermore, utilisation of a more biologically relevant medium, Hank's balanced salt solution supplemented with Mg2+- and Ca2+-ions (HBSS (Mg2+, Ca2+)), has been tested.

Key findings
Except for the polyoxyl 40 hydrogenated castor oil-containing solid dispersion, no influence on the phospholipid vesicle-based barrier could be observed from the tested samples. Presence of active pharmaceutical ingredients (APIs) in the solid dispersions led to the same results as the corresponding placebo results. First experiments analysing the passive diffusion of both APIs in HBSS (Mg2+, Ca2+), evaluated as suitable transport medium, have shown promising results regarding the suitability of the phospholipid vesicle-based barrier for investigation of solid dispersions.

Conclusions
The study indicated that the phospholipid vesicle-based barrier was compatible with selected melt extrudate formulations. The model seemed capable to reveal different transport routes in comparison with Caco-2 cell permeability tests.
Factors affecting crystallization of hydrates
Authors: Tian Fang , Qu Haiyan , Zimmermann Anne , Munk Tommy , Jørgensen Anna C , Rantanen Jukka 
Published: October 2010

Abstract

Objectives
To provide a comprehensive understanding of the competing thermodynamic and kinetic factors governing the crystallization of various hydrate systems. The ultimate goal is to utilize this understanding to improve the control over the unit operations involving hydrate formation, as well as to optimize the bioavailability of a given drug product.

Key findings
The thermodynamic and kinetic factors that govern hydrate crystallization are introduced and the current status of the endeavour to gain a mechanistic understanding of the phenomena that occur during the crystallization of different hydrate systems is discussed. The importance of hydrate investigation in the pharmaceutical field is exemplified by examining two specific hydrate systems: the polymorphic hydrate system and hydrates of pharmaceutical salts.

Summary
This review identifies the factors that are of critical importance in the investigation of anhydrate/hydrate systems. This knowledge can be used to control the phase transformation during pharmaceutical processing and storage, as well as in building a desired functionality for the final formulation.
Microwave induced solubility enhancement of poorly water soluble atorvastatin calcium
Authors: Maurya Durgaprasad , Belgamwar Veena , Tekade Avinash 
Published: October 2010

Abstract

Objectives
The objective of the present investigation was to enhance the solubility and dissolution rate of atorvastatin calcium (ATR) by a solid dispersion technique using poly(ethylene glycol) 6000 (PEG 6000).

Methods
Microwave energy was used to prepare an enhanced release dosage form of the poorly water soluble drug ATR with PEG 6000 as a hydrophilic carrier. After the microwave treatment, the drug and hydrophilic polymer get fused together to form a solid dispersion. An in-vivo study was performed to determine the lipid-lowering efficacy (cholesterol, high density lipoprotein and triglyceride) of the solid dispersions using a Triton-induced hypercholesterolemia model in rats.

Key findings
An increase in the solubility of ATR was observed with increasing concentration of PEG 6000. The optimized ratio for preparation of solid dispersions of ATR with PEG 6000 was 1 : 12 w/w by conventional fusion and the microwave induced fusion method. Differential scanning calorimetry and powder X-ray diffraction studies of the solid dispersions confirmed the conversion of some crystalline ATR into the amorphous form. Scanning electron microscopy images also showed conversion of some crystalline ATR into the amorphous form. The in-vitro study showed that solid dispersions increased the solubility and dissolution rate of ATR, and thus may improve its bioavailability compared with plain ATR. The solid dispersion formulation prepared by the microwave induced fusion method significantly (P &lt; 0.05) reduced serum lipid levels in phases I and II (18 h and 24 h) of the Triton test compared with plain ATR.

Conclusions
The microwave induced fusion method could be considered as a simple, efficient method to prepare solid dispersions of ATR with significant enhancement of the in-vitro dissolution rate as well as in-vivo activity.
Peripartum cardiomyopathy: current understanding, comprehensive management review and new developments
Authors: Pyatt Jason R , Dubey Gopal 
Published: October 2010

ABSTRACT
Peripartum cardiomyopathy (PPCM) is a rare and potentially fatal disease which presents with symptoms of heart failure primarily due to left ventricular (LV) systolic dysfunction in the last month of pregnancy and up to 5–6 months after delivery. PPCM is still regarded as a disease of unknown aetiology, although recent evidence suggests a role for a 16 kDa prolactin derivative produced by proteolytic cleavage of prolactin secondary to unbalanced oxidative stress present during late pregnancy and early puerperium. The medical management of PPCM is similar to other forms of non-ischaemic dilated cardiomyopathy, but with the management tailored to choose safe drugs in pregnancy and lactation to minimise maternal and fetal morbidity. There is an increased risk of venous thromboembolism, and anticoagulation is recommended. About 30–50% of the patients recover without complications, with their baseline LV systolic function at rest returning to normal. The risk of recurrence of PPCM is high, especially if the LV systolic function has not fully recovered. However, for those women who have normal LV systolic function as demonstrated on echocardiography and dobutamine stress test, the risk of severe cardiomyopathy including death is relatively low in a subsequent pregnancy.
Spectrum of hypokalaemic periodic paralysis in a tertiary care centre in India
Authors: Maurya Pradeep Kumar , Kalita Jayantee , Misra Usha Kant 
Published: October 2010

Abstract

Background
Acute flaccid paralysis is a common neurological emergency with diverse causes and variable outcome. There is a paucity of reports documenting the spectrum of hypokalaemic paralysis in neurological practice.

Objective
To report the clinical features, aetiology, and outcome of patients with hypokalaemic paralysis in a tertiary care teaching hospital in India.

Methods
Consecutive patients with acute flaccid paralysis with hypokalaemia from 2008 to 2010 were included in the study. Patients with Guillain–Barré syndrome, porphyria, polio and non-polio enterovirus infection and myositis were excluded. Detailed clinical examination, urinalysis, renal function tests, arterial blood gas analysis, thyroid hormones, and electrocardiogram were carried out. Patients received intravenous or oral potassium supplementation and their underlying causes were treated.

Results
Thirty patients aged 17–52 years, including three females, were included. Secondary causes of hypokalaemic paralysis were present in 13 patients and included thyrotoxic paralysis in five and renal tubular acidosis (RTA) and Gitelman syndrome in four each. All the patients had quadriparesis and 10 had severe weakness (MRC grade &lt;2). Tendon reflexes were reduced in eight and brisk in four patients. Respiratory paralysis was present in six patients and one needed artificial ventilation. Fifteen patients had severe hypokalaemia (&lt;2 mmol/l), four had acidosis, and six had alkalosis. The secondary group had more severe hypokalaemia and needed longer time to recover.

Conclusion
43.3% of patients with hypokalaemic paralysis had a secondary cause for their condition. Patients with severe hypokalaemia with acidosis or alkalosis should be investigated for secondary causes as their management differ.
Curcumin Enhances the Effect of Cisplatin in Suppression of Head and Neck Squamous Cell Carcinoma via Inhibition of IKKβ Protein of the NFκB Pathway
Authors: Duarte Victor M. , Han Eugene , Veena Mysore S. , Salvado Amanda , Suh Jeffrey D. , Liang Li-Jung , Faull Kym F. , Srivatsan Eri S. , Wang Marilene B. 
Published: October 2010

AbstractPrevious experiments have shown that curcumin or cisplatin treatment suppresses growth of head and neck squamous cell carcinoma (HNSCC). To study the potential cooperative effect of both agents, two HNSCC cell lines were treated with curcumin or cisplatin alone or in combination. In vivo studies consisted of intravenous tail vein injection of liposomal curcumin, with intraperitoneal cisplatin, into nude mice growing xenograft HNSCC tumors. Introduction of curcumin and suboptimal concentrations of cisplatin showed a significant suppressive effect compared with treatment with either agent alone. Reduced expression of cyclin D1, IκBα, phospho-IκBα, and IKKβ occurred in cisplatin- and curcumin-treated cell lines. Confocal microscopy showed expression of IKKβ in the nucleus of the cell lines. Chromatin immunoprecipitation assay on DNA isolated from IKKβ immunoprecipitated samples showed PCR amplification of interleukin-8 promoter sequences, a binding site of NFκB, indicating an interaction between IKKβ and NFκB. Curcumin inhibited IKKβ in the cytoplasm and nucleus, leading to reduced NFκB activity, with no effect on phospho-AKT. In vivo studies showed significant growth inhibition of xenograft tumors treated with a combination of liposomal curcumin and cisplatin. The suppressive effect of curcumin was mediated through inhibition of cytoplasmic and nuclear IKKβ, resulting in inhibition of NFκB activity. Cisplatin treatment led to cellular senescence, indicating an effect mediated by p53 activation. The mechanisms of the two agents through different growth signaling pathways suggest potential for the clinical use of subtherapeutic doses of cisplatin in combination with curcumin, which will allow effective suppression of tumor growth while minimizing the toxic side effects of cisplatin. Mol Cancer Ther; 9(10); 2665–75. ©2010 AACR.
Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody
Authors: Coxon Angela , Bready James , Min Hosung , Kaufman Stephen , Leal Juan , Yu Dongyin , Lee Tani Ann , Sun Ji-Rong , Estrada Juan , Bolon Brad , McCabe James , Wang Ling , Rex Karen , Caenepeel Sean , Hughes Paul , Cordover David , Kim Haejin , Han Seog Joon , Michaels Mark L. , Hsu Eric , Shimamoto Grant , Cattley Russell , Hurh Eunju , Nguyen Linh , Wang Shao Xiong , Ndifor Anthony , Hayward Isaac J. , Falcón Beverly L. , McDonald Donald M. , Li Luke , Boone Tom , Kendall Richard , Radinsky Robert , Oliner Jonathan D. 
Published: October 2010

Abstract
AMG 386 is an investigational first-in-class peptide-Fc fusion protein (peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 (Ang1) and Ang2 with their receptor, Tie2. Although the therapeutic value of blocking Ang2 has been shown in several models of tumorigenesis and angiogenesis, the potential benefit of Ang1 antagonism is less clear. To investigate the consequences of Ang1 neutralization, we have developed potent and selective peptibodies that inhibit the interaction between Ang1 and its receptor, Tie2. Although selective Ang1 antagonism has no independent effect in models of angiogenesis-associated diseases (cancer and diabetic retinopathy), it induces ovarian atrophy in normal juvenile rats and inhibits ovarian follicular angiogenesis in a hormone-induced ovulation model. Surprisingly, the activity of Ang1 inhibitors seems to be unmasked in some disease models when combined with Ang2 inhibitors, even in the context of concurrent vascular endothelial growth factor inhibition. Dual inhibition of Ang1 and Ang2 using AMG 386 or a combination of Ang1- and Ang2-selective peptibodies cooperatively suppresses tumor xenograft growth and ovarian follicular angiogenesis; however, Ang1 inhibition fails to augment the suppressive effect of Ang2 inhibition on tumor endothelial cell proliferation, corneal angiogenesis, and oxygen-induced retinal angiogenesis. In no case was Ang1 inhibition shown to (a) confer superior activity to Ang2 inhibition or dual Ang1/2 inhibition or (b) antagonize the efficacy of Ang2 inhibition. These results imply that Ang1 plays a context-dependent role in promoting postnatal angiogenesis and that dual Ang1/2 inhibition is superior to selective Ang2 inhibition for suppression of angiogenesis in some postnatal settings. Mol Cancer Ther; 9(10); 2641–51. ©2010 AACR.
Maytansine and Cellular Metabolites of Antibody-Maytansinoid Conjugates Strongly Suppress Microtubule Dynamics by Binding to Microtubules
Authors: Lopus Manu , Oroudjev Emin , Wilson Leslie , Wilhelm Sharon , Widdison Wayne , Chari Ravi , Jordan Mary Ann 
Published: October 2010

AbstractMaytansine is a potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at subnanomolar concentrations. However, its side effects and lack of tumor specificity have prevented successful clinical use. Recently, antibody-conjugated maytansine derivatives have been developed to overcome these drawbacks. Several conjugates show promising early clinical results. We evaluated the effects on microtubule polymerization and dynamic instability of maytansine and two cellular metabolites (S-methyl-DM1 and S-methyl-DM4) of antibody-maytansinoid conjugates that are potent in cells at picomolar levels and that are active in tumor-bearing mice. Although S-methyl-DM1 and S-methyl-DM4 inhibited polymerization more weakly than maytansine, at 100 nmol/L they suppressed dynamic instability more strongly than maytansine (by 84% and 73%, respectively, compared with 45% for maytansine). However, unlike maytansine, S-methyl-DM1 and S-methyl-DM4 induced tubulin aggregates detectable by electron microscopy at concentrations ≥2 μmol/L, with S-methyl-DM4 showing more extensive aggregate formation than S-methyl-DM1. Both maytansine and S-methyl-DM1 bound to tubulin with similar KD values (0.86 ± 0.2 and 0.93 ± 0.2 μmol/L, respectively). Tritiated S-methyl-DM1 bound to 37 high-affinity sites per microtubule (KD, 0.1 ± 0.05 μmol/L). Thus, S-methyl-DM1 binds to high-affinity sites on microtubules 20-fold more strongly than vinblastine. The high-affinity binding is likely at microtubule ends and is responsible for suppression of microtubule dynamic instability. Also, at higher concentrations, S-methyl-DM1 showed low-affinity binding either to a larger number of sites on microtubules or to sedimentable tubulin aggregates. Overall, the maytansine derivatives that result from cellular metabolism of the antibody conjugates are themselves potent microtubule poisons, interacting with microtubules as effectively as or more effectively than the parent molecule. Mol Cancer Ther; 9(10); 2689–99. ©2010 AACR.
Maytansinoid-Antibody Conjugates Induce Mitotic Arrest by Suppressing Microtubule Dynamic Instability
Authors: Oroudjev Emin , Lopus Manu , Wilson Leslie , Audette Charlene , Provenzano Carmela , Erickson Hans , Kovtun Yelena , Chari Ravi , Jordan Mary Ann 
Published: October 2010

Abstract
Maytansine and its analogues (maytansinoids) are potent microtubule-targeted compounds that inhibit proliferation of cells at mitosis. Antibody-maytansinoid conjugates consisting of maytansinoids (DM1 and DM4) attached to tumor-specific antibodies have shown promising clinical results. To determine the mechanism by which the antibody-DM1 conjugates inhibit cell proliferation, we examined the effects of the cleavable anti-EpCAM-SPP-DM1 and uncleavable anti-EpCAM-SMCC-DM1 conjugates on MCF7 human breast tumor cells. We also examined the effects of the free maytansinoids, maytansine and S-methyl DM1 (a version of DM1 that is stable in cell culture medium), for comparison. Both the conjugates and free maytansinoids potently inhibited MCF7 cell proliferation at nanomolar and subnanomolar concentrations, respectively, by arresting the cells in mitotic prometaphase/metaphase. Arrest occurred in concert with the internalization and intracellular processing of both conjugates under conditions that induced abnormal spindle organization and suppressed microtubule dynamic instability. Microtubule depolymerization occurred only at significantly higher drug concentrations. The results indicate that free maytansinoids, antibody-maytansinoid conjugates, and their metabolites exert their potent antimitotic effects through a common mechanism involving suppression of microtubule dynamic instability. Mol Cancer Ther; 9(10); 2700–13. ©2010 AACR.
The Beginning of Literati Poetry: Four Poems from First-century BCE China
Authors: Raft Zeb 
Published: October 2010

AbstractThis article examines a set of four tetrasyllabic poems from the first century BCE, situating them between the ancient poetry of the Shijing and the medieval poetry that would appear two centuries later. The author outlines the emergence of a learned elite in the latter half of the Western Han and shows how the intellectual and socio-political background of this group is instantiated in the poems. As statements of a classicist mentality ascendant in the late Western Han, the poems stand firmly in their age, but as products of this newly emerging group they bear definite connection to the literati poetry of medieval China. Thus, the poems offer a viewpoint onto both the scholarly culture of the first century BCE and the poetic culture of early medieval China.
Emerging from Anonymity: The First Generation of Writers of Songs and Drama in Mid-Ming Nanjing
Authors: Tan Tian Yuan 
Published: October 2010

AbstractThis article traces the first generation of writers of songs and drama in Nanjing who emerged from the anonymous context of early Ming court entertainment and established their name and reputation in the second half of the fifteenth century. These writers—Shi Zhong (1437-after 1516), Chen Duo (1454?-1507?), and Xu Lin (1462-1538)—represented a different mode of writing songs and drama. For them it was no longer a professional occupation, as in the case of the court performers, but became part of their cultural and social life. The extent to which our knowledge of these first-generation qu writers depends on local sources and on acts of remembrance by later Nanjing authors is also examined.
Royal Hospitality and Geopolitical Constitution of the Western Zhou Polity
Authors: Khayutina Maria 
Published: October 2010

AbstractThe present article examines how political communication and administration were effected in the Western Zhou polity (1046/5-771 BC) and investigates the significance of the royal residences as political and administrative centers. Bronze inscriptions referring to royal receptions that were offered to Zhou regional rulers, rulers of non-Zhou polities, royal officers and other subjects provide the basis for this study. It is argued that the form of "royal hospitality" described in these inscriptions was a political and, partially, administrative institution of the Zhou kings, and that its territorial localization both reflected and defined the geopolitical constitution of the polity. The article concludes by arguing that in the "larger Zhou polity" embracing the regional states of the zhuhou, political communication was decentralized, and that none of the royal residences held the status as political "capital" throughout the entire period. It is further found that a process of territorial centralization was underway in the territories under the direct control of the king, and that the oldest royal residence Zhou-under-Qi was gradually established as political and administrative capital.
Recurrent Supersynoptic Evolution of the Great Plains Low-Level Jet
Authors: Weaver Scott J. , Nigam Sumant 
Published: October 2010

Abstract
The evolution of supersynoptic (i.e., pentad) Great Plains low-level jet (GPLLJ) variability, its precipitation impacts, and large-scale circulation context are analyzed in the North American Regional Reanalysis (NARR)—a high-resolution precipitation-assimilating dataset—and the NCEP–NCAR reanalysis. The analysis strategy leans on the extended EOF technique, which targets both spatial and temporal recurrence of a variability episode.
Pentad GPLLJ variability structures are found to be spatially similar to those in the monthly analysis. The temporal evolution of the supersynoptic GPLLJ-induced precipitation anomalies reveal interesting lead and lag relationships highlighted by GPLLJ variability-leading precipitation anomalies. Interestingly, similar temporal phasing of the GPLLJ and precipitation anomalies were operative during the 1993 (1988) floods (drought) over the Great Plains, indicating the importance of these submonthly GPLLJ variability modes in the instigation of extreme hydroclimatic episodes. The northward-shifted (dry) GPLLJ variability mode is linked to large-scale circulation variations emanating from remote regions that are modified by interaction with the Rocky Mountains, suggesting that the supersynoptic GPLLJ fluctuations may have their origin in orographic modulation of baroclinic development.