tbuckley/cabot-search huggingface dataset:
P153MicroRNAs involved in cardioprotection by ischemic pre- and postconditioning: ProtectomiRs
Authors: ZV Varga, A Zvara, N Farago, M Pipicz, R Gaspar, A Gorbe, GL Puskas, T Csont, T Thum, P Ferdinandy
Journal: Cardiovascular Research (2014)

Purpose: We aimed to characterize early changes in microRNA expression in acute cardioprotection by ischemic pre- and postconditioning in rat hearts.
Natural products as probes of cell biology: 20 years of didemnin research
Authors: Matthew D. Vera, Madeleine M. Joullié
Journal: Medicinal Research Reviews (2002)

Abstract The discovery of the didemnin family of marine depsipeptides launched an exciting and intriguing chapter in natural product chemistry. The unusual structure of the didemnin congeners has led to several total syntheses by research groups from around the world. The impressive in vitro and in vivo biological activities of the didemnins resulted in the first human clinical trials in the U.S. of a marine natural product against cancer, and additional clinical trials of a second‐generation didemnin, dehydrodidemnin B (aplidine), are underway. As we mark the 20‐year anniversary of the discovery of the didemnins, this class of natural products continues to stimulate active research in fields ranging from synthetic and medicinal chemistry to clinical oncology and cell biology. While some progress was made in dissecting the molecular mechanism of action and in establishing structure‐activity relationships, there are still more questions than answers. This review covers the recent didemnin literature, highlighting the work directed towards understanding how this group of natural products interact with fundamental processes such as cell proliferation, protein biosynthesis, and apoptosis. The didemnin field illustrates how natural product chemistry may be used as a critical tool for the study of cell biology. © 2002 John Wiley &amp; Sons, Inc. Med Res Rev, 22, No. 2, 102–145, 2002; DOI 10.1002/med.10003
EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis
Journal: Journal of Hepatology (2015)

Liver fibrosis is part of the structural and functional alterations in most chronic liver diseases. It is one of the main prognostic factors as the amount of fibrosis is correlated with the risk of developing cirrhosis and liver-related complications in viral and nonviral chronic liver diseases [1,2]. Liver biopsy has traditionally been considered the reference method for evaluation of tissue damage such as hepatic fibrosis in patients with chronic liver disease. Pathologists have proposed robust scoring system for staging liver fibrosis such as the semi-quantitative METAVIR score [3,4]. In addition computer-aided morphometric measurement of collagen proportional area, a partly automated technique, provides an accurate and linear evaluation of the amount of fibrosis [5]. Liver biopsy gives a snapshot and not an insight into the dynamic changes during the process of fibrogenesis (progression, static or regression). However, immunohistochemical evaluation of cellular markers such as smooth muscle actin expression for hepatic stellate cell activation, cytokeratin 7 for labeling ductular proliferation or CD34 for visualization of sinusoidal endothelial capillarization or the use of two-photon and second harmonic generation fluorescence microscopy techniques for spatial assessment of fibrillar collagen, can provide additional ‘‘functional’’ information [6,7]. All these approaches are valid provided that the biopsy is of sufficient size to represent the whole liver [4,8]. Indeed, liver biopsy provides only a very small part of the whole organ and there is a risk that this part might not be representative for the amount of hepatic fibrosis in the whole liver due to heterogeneity in its distribution [9]. Extensive literature has shown that increasing the length of liver biopsy decreases the risk of sampling error. Except for cirrhosis, for which micro-fragments may be sufficient, a 25 mm long biopsy is considered an optimal specimen for accurate evaluation, though 15 mm is considered sufficient in most studies [10]. Not only the length but also the caliber of the biopsy needle is important in order to obtain a piece of liver of adequate size for histological evaluation, with a 16 gauge needle being considered as the most appropriate [11] to use for percutaneous liver biopsy. Interobserver variation
Management of hypertrophic cardiomyopathy
Authors: Paolo Spirito, Camillo Autore
Journal: BMJ (2006)

Hypertrophic cardiomyopathy is the most common familial genetic disease of the heart (1/500 to 1/1000), as well as the most common cause of sudden cardiac death in young people and athletes. Because a timely diagnosis may help to prevent sudden death, it is important for internists and general practitioners to be aware of the clinical features of the disease. The morphological and functional features of hypertrophic cardiomyopathy include marked and asymmetric left ventricular hypertrophy, a non-dilated left ventricular cavity, and preserved systolic function. Left ventricular outflow obstruction at rest is present in about 20% of patients.1–3 The clinical course is heterogeneous. Many patients remain asymptomatic throughout life, others develop severe heart failure or atrial fibrillation, and some die suddenly, often at a young age and in the absence of previous symptoms.1–3 We critically re-examine and place in perspective the most appropriate therapeutic strategies for the management of hypertrophic cardiomyopathy.

This review is based on the main studies on hypertrophic cardiomyopathy published in recent years, as well as on the clinical experience of doctors and investigators with particular knowledge of this disease. The treatment strategies reported in the expert consensus document on hypertrophic cardiomyopathy from the American College of Cardiology and the European Society of Cardiology are also incorporated in this article.

Hypertrophic cardiomyopathy is usually suspected after marked electrocardiographic abnormalities or a heart murmur have been identified during routine clinical evaluation, or because of recent development of dyspnoea or palpitations.1–3 The diagnosis is established by the echocardiographic identification of a hypertrophied and non-dilated left ventricle in the absence of other cardiovascular diseases capable of producing a similar magnitude of hypertrophy1–4 (fig 1). In a minority of patients with electrocardiographic abnormalities suggestive of hypertrophic cardiomyopathy, the echocardiogram may fail …
Characterisation of the size and composition of circulating immune complexes in patients with rheumatoid arthritis.
Authors: R A Mageed, J R Kirwan, P W Thompson, D A McCarthy, E J Holborow
Journal: Annals of the Rheumatic Diseases (1991)

The size and composition of circulating immune complexes in the sera of patients with rheumatoid arthritis (RA) were studied in relation to different manifestations of the disease. Circulating immune complexes from the sera of 94 patients (50 with extra-articular disease) and 10 matched controls were fractionated by sucrose density gradient ultracentrifugation. The composition, immunoglobulin and rheumatoid factor (RF) concentrations within each of the fractions were determined by a sensitive enzyme linked immunosorbent assay (ELISA). Intermediate size (14S-21S) IgG complexes containing RF activity and 22S IgG-IgM RF complexes were found in the sera of 40 patients with RA, while intermediate size complexes of self associated IgG RF and larger size complexes (greater than 22S) of IgG RF and IgM RF were associated with extra-articular features of RA (50% of extra-articular disease). Complexes containing IgA were found in the sera of many patients with RA, and dimeric IgA RF mainly in patients with extra-articular disease. These results support the view that whereas small size circulating immune complexes are of no primary pathogenic importance in synovitis, large size (greater than 22S) circulating immune complexes may play a role in extra-articular disease in RA. Current understanding of the formation of large complexes provides a biological explanation for their occurrence and effects.
Influence of Respiratory Acidosis on Circulatory Effect of Epinephrine in Dogs
Authors: HENRIK H. BENDIXEN, MYRON B. LAVER, WERNER E. FLACKE
Journal: Circulation Research (1963)

The circulatory depressant effects of respiratory acidosis and the relation between acidosis and the circulatory effects of epinephrine were studied in anesthetized intact dogs after sympathetic and parasympathetic block. Respiratory acidosis invariably depressed myocardial contractile force, cardiac rate, and mean arterial pressure, but only the fall, in contractile force showed a relation with the degree of acidosis. The effect of epinephrine on myocardial contractile force decreased with decreasing arterial pH, but no correlation was found between pH and the effect of epinephrine on arterial blood pressure and on cardiac rate. During continuous infusion of epinephrine, arterial pressure continued to rise after the contractile force had reached its maximum. With repeated periods of epinephrine infusion in the same animal, the response of the myocardial contractile force declined, while the response of the arterial blood pressure was unchanged. Such "differential tachyphylaxis" may occur under clinical conditions with prolonged infusions of vasopressor agents.
Preferential Inhibition of Akt and Killing of Akt-Dependent Cancer Cells by Rationally Designed Phosphatidylinositol Ether Lipid Analogues
Authors: S. Sianna Castillo, John Brognard, Pavel A. Petukhov, Chunyu Zhang, Junji Tsurutani, Courtney A. Granville, Min Li, Michael Jung, Kip A. West, Joell G. Gills, Alan P. Kozikowski, Phillip A. Dennis
Journal: Cancer Research (2004)

Activation of the PI3k/Akt pathway controls key cellular processes and contributes to tumorigenesis in vivo, but investigation of the PI3k/Akt pathway has been limited by the lack of specific inhibitors directed against Akt. To develop Akt inhibitors, we used molecular modeling of the pleckstrin homology (PH) domain of Akt to guide synthesis of structurally modified phosphatidylinositol ether lipid analogues (PIAs). Here, we characterize the biochemical and cellular effects of PIAs. Of 24 compounds tested, five PIAs with modifications at two sites on the inositol ring inhibited Akt with IC(50)s < 5 micro M. Molecular modeling identified putative interactions of PIAs with the phosphoinositide-binding site in the PH domain of Akt, and growth factor-induced translocation of Akt to the plasma membrane was inhibited by PIA administration. Inhibition of Akt occurred rapidly and was maintained for hours. PIAs decreased phosphorylation of many downstream targets of Akt without affecting upstream kinases, such as PI3k or phosphoinositide-dependent kinase-1, or members of other kinase pathways such as extracellular signal-regulated kinase. Importantly, PIAs increased apoptosis 20-30-fold in cancer cell lines with high levels of endogenous Akt activity but only 4-5-fold in cancer cell lines with low levels of Akt activity. These studies identify PIAs as effective Akt inhibitors, and provide proof of principle for targeting the PH domain of Akt.
Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery
Authors: Richard O. Cannon, Alan N. Schechter, Julio A. Panza, Frederick P. Ognibene, Margaret E. Pease-Fye, Myron A. Waclawiw, James H. Shelhamer, Mark T. Gladwin
Journal: Journal of Clinical Investigation (2001)

Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood. Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation. While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress. L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation. With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise. S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation. Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood. S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients. These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function. This effect may have application for the treatment of diseases characterized by endothelial dysfunction.
Chondroitin for Osteoarthritis of the Knee or Hip
Authors: Michael D. Levin
Journal: Annals of Internal Medicine (2007)

Letters18 December 2007Chondroitin for Osteoarthritis of the Knee or HipMichael D. Levin, BAMichael D. Levin, BAFrom Health Business Strategies, Clackamas, OR 97015.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-12-200712180-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their meta-analysis of the literature on chondroitin for osteoarthritis of the knee or hip, Reichenbach and colleagues (1) correctly observed that their study is “limited by the quality of [the] included trials.” They further disclosed that “several relevant variables were poorly reported” and that “most trials had poor methodological quality or inadequate reporting.”One critically important, poorly controlled relevant variable in the review (and in others involving therapeutic uses of dietary ingredients) deserves comment. As an expert who reviews analytical results for a variety of dietary ingredients and dietary supplements, I have found that the authenticity, ...References1. Reichenbach S, Sterchi R, Scherer M, Trelle S, Bürgi E, Bürgi U, et al. Meta-analysis: chondroitin for osteoarthritis of the knee or hip. Ann Intern Med. 2007;146:580-90. [PMID: 17438317] LinkGoogle Scholar2. ConsumerLab.com. Product review: joint supplements (glucosamine, chondroitin, and MSM). 11 April 2007. Accessed at www.consumerlab.com/news/news_041107_jointsupplements.asp on 22 October 2007. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Health Business Strategies, Clackamas, OR 97015.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeta-analysis: Chondroitin for Osteoarthritis of the Knee or Hip Stephan Reichenbach , Rebekka Sterchi , Martin Scherer , Sven Trelle , Elizabeth Bürgi , Ulrich Bürgi , Paul A. Dieppe , and Peter Jüni Chondroitin for Osteoarthritis of the Knee or Hip Sven Trelle , Stephan Reichenbach , and Peter Jüni Chondroitin for Osteoarthritis of the Knee or Hip Harley Goldberg , Andrew Avins , and Stephen Bent Chondroitin for Osteoarthritis of the Knee or Hip Jean-Pierre Pelletier Metrics 18 December 2007Volume 147, Issue 12Page: 884KeywordsChondroitinChromatographyClinical trialsConflicts of interestForecastingHipKneesOsteoarthritis ePublished: 18 December 2007 Issue Published: 18 December 2007 CopyrightCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
The Effect of Caffeine on Renal Epithelial Cells from Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: Franck A. Belibi, Darren P. Wallace, Tamio Yamaguchi, Marcy Christensen, Gail Reif, Jared J. Grantham
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder characterized by the progressive enlargement of cysts derived from tubules. Tubule cell proliferation and chloride-dependent fluid accumulation, mechanisms underlying cyst expansion, are accelerated by adenosine 3′:5′-cyclic monophosphate (cAMP). This study examined the extent to which caffeine may stimulate the production of cAMP by cyst epithelial cells, thereby adversely increasing proliferation and fluid secretion. Mural epithelial cells from ADPKD cysts and normal human kidney cortex cells (HKC) were cultured, and cAMP levels were determined in response to caffeine and receptor-mediated agonists linked to adenylyl cyclase. Caffeine, a methylxanthine, slightly increased basal levels of cAMP, as did other nonselective phosphodiesterase (PDE) inhibitors, 1-methyl-3- isobutyl xanthine and theophylline and rolipram, a specific PDE IV inhibitor. More importantly, clinically relevant concentrations of caffeine (10 to 50 μM) potentiated the effects of desmopressin (DDAVP), prostaglandin E2 (PGE2), and isoproterenol to increase cAMP levels in both ADPKD and HKC cells. By contrast, at concentrations that augmented the DDAVP response, caffeine attenuated cAMP accumulation by adenosine, implicating an action apart from the inhibition of PDE. Caffeine enhanced the effect of DDAVP to stimulate transepithelial short-circuit current of polarized ADPKD monolayers, reflecting an increase in chloride secretion. Caffeine potentiated the effect of DDAVP and PGE2 to increase the levels of phosphorylated extracellular signal-regulated kinase (P-ERK). By contrast, P-ERK levels in HKC cells were not raised by increased intracellular concentrations of cAMP. It is concluded that PDE inhibition by caffeine increases the accumulation of cAMP, and through this mechanism activates the ERK pathway to cellular proliferation and increases transepithelial fluid secretion in ADPKD cystic epithelium. Caffeine is, therefore, a risk factor for the promotion of cyst enlargement in patients with ADPKD.
Effect of chronic airflow limitation on resting oxygen consumption.
Authors: C Lanigan, J Moxham, J Ponte
Journal: Thorax (1990)

The work of breathing in patients with severe chronic airflow limitation is increased even at rest but little is known about the magnitude of this increase. Resting oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ) were measured in 13 patients with severe chronic airflow limitation (mean FEV1 0.78 1, vital capacity 2.1 1) and compared with those of 13 age, weight, and height matched control subjects. Whereas mean RQ was the same in the two groups (0.82), mean VO2 and VCO2 were higher in the patients (+ 18 ml min-1 and + 15 ml min-1 respectively). When VO2 was standardised for body surface area it was 10.9% higher in the patients (p less than 0.05). If the increased resting VO2 in these patients were solely due to increased activity of the respiratory muscles, it would represent a fourfold increase in the oxygen cost of breathing.
Evidence of <i>Trypanosoma cruzi</i> Infection (Chagas’ Disease) Among Patients Undergoing Cardiac Surgery
Authors: David A. Leiby, Francisco J. Rentas, Kenrad E. Nelson, Veronica A. Stambolis, Paul M. Ness, Cheryl Parnis, Hugh A. McAllister, David H. Yawn, Robert J. Stumpf, Louis V. Kirchhoff
Journal: Circulation (2000)

Background — Trypanosoma cruzi , the agent of Chagas’ heart disease, is transmitted by triatomine insects and by blood transfusion. The emigration of several million people from T cruzi –endemic countries to the United States has raised concerns regarding a possible increase in cases of Chagas’ heart disease here, as well as an increased risk of transfusion-transmitted T cruzi . To investigate these 2 possible outcomes, we tested a repository of blood specimens from multiply transfused cardiac surgery patients for antibodies to T cruzi . Methods and Results —Postoperative blood specimens from 11 430 cardiac surgery patients were tested by enzyme immunoassay, and if repeat-reactive, were confirmed by radioimmunoprecipitation. Six postoperative specimens (0.05%) were confirmed positive. Corresponding preoperative specimens, available for 4 of these patients, were also positive. The other 2 patients had undergone heart transplantations. Tissue samples from their excised hearts were tested for T cruzi by polymerase chain reaction and were positive. Despite the fact that several of these 6 patients had histories and clinical findings suggestive of Chagas’ disease, none of them were diagnosed with or tested for it. Patient demographics showed that 5 of 6 positive patients were Hispanic, and overall, 2.7% of Hispanic patients in the repository were positive. Conclusions —No evidence for transfusion-transmitted T cruzi was found. All 6 seropositive patients apparently were infected with T cruzi before surgery; however, a diagnosis of Chagas’ disease was not known or even considered in any of these patients. Indeed, Chagas’ disease may be an underdiagnosed cause of cardiac disease in the United States, particularly among patients born in countries in which T cruzi is endemic.
Influence of Glycemic Index/Load on Glycemic Response, Appetite, and Food Intake in Healthy Humans
Authors: Rita C.G. Alfenas, Richard D. Mattes
Journal: Diabetes Care (2005)

OBJECTIVE—High glycemic index (GI)/load (GL) diets reportedly enhance appetite and promote positive energy balance. Support for this hypothesis stems largely from acute feeding trials and longer-term studies lacking control over the macronutrient composition and palatability of test foods. This study evaluated the effects of consuming high- and low-GI/GL meals, matched on macronutrient composition and palatability, plasma glucose and insulin, appetite, and food intake. RESEARCH DESIGN AND METHODS—Thirty-nine healthy adults consumed only low- or only high-GI foods ad libitum in the laboratory for 8 days in either high (three foods per meal)- or low (one food per meal)-variety conditions. Glucose and insulin concentrations as well as appetitive sensations were determined before and for 2 h following breakfast and lunch on days 1 and 8. Energy intake was monitored daily. RESULTS—There were no significant differences in plasma glucose or insulin responses, appetitive ratings, or food intake between treatments. CONCLUSIONS—These data indicate that the differential glycemic response of foods tested in isolation under fixed time are not preserved under conditions of chronic ad libitum consumption of mixed meals.