tbuckley/cabot-search huggingface dataset:
Food Restriction Prevents Advanced Glycation End Product Accumulation and Retards Kidney Aging in Lean Rats
Authors: LAURENT TEILLET, PHILIPPE VERBEKE, SABINE GOURAUD, HILAIRE BAKALA, CAROLINE BOROT-LALOI, DIDIER HEUDES, PATRICK BRUNEVAL, BRUNO CORMAN
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Tissue content of advanced glycation end products (AGE) increases with age and contributes to the changes in structure and function of the renal and cardiovascular systems. The effect of chronic food restriction on this AGE accumulation was investigated in lean WAG/Rij rats. A 30% food restriction performed from 10 to 30 mo in female rats reduced their mean body weight from 240 ± 7 to 160 ± 12 g, but did not modify their survival. AGE collagen content increased from 14.3 ± 5.5 to 104.7 ± 13.0 arbitrary units per microgram (AU/μg) of hydroxyproline (OHPro) in kidney between 10 and 30 mo, and from 9.7 ± 1.2 to 310.6 ± 34.6 AU/μg OHPro in the abdominal aorta. Food restriction reduced AGE accumulation to 21.4 ± 3.3 and 74.6 ± 16.5 AU/μg OHPro in kidney and aorta of 30-mo-old animals. Similar results were found for collagen prepared from isolated glomeruli (7.8 ± 1.2, 81.2 ± 16.1, and 10.3 ± 4.3 AU/μg OHPro in 10-mo, 30-mo, and restricted 30-mo-old rats). Reduction of intrarenal and arterial AGE accumulation by food restriction was confirmed by immunostaining in optical microscopy. Age-related changes in arterial and kidney structures as polyuria and proteinuria were mainly prevented by food restriction. These data indicate that chronic food restriction reduces the accumulation of AGE and preserves the structure and function of the renal and cardiovascular systems in learn rats, although it did not affect survival of the animals between 10 and 30 mo.
Limited Value of the Homeostasis Model Assessment to Predict Insulin Resistance in Older Men With Impaired Glucose Tolerance
Authors: Cynthia M. Ferrara, Andrew P. Goldberg
Journal: Diabetes Care (2001)

OBJECTIVE— Insulin resistance (IR) in older individuals is associated with risk factors for coronary artery disease. The glucose clamp measures IR directly, but the homeostasis model assessment (HOMA) of IR,referred to here as HOMA-IR, is based on fasting glucose and insulin and is less invasive and labor intensive. This method requires validation in the elderly. RESEARCH DESIGN AND METHODS— We assessed the validity of HOMA-IR as an index of IR by comparing it to glucose infusion rates (GIRs)measured by a glucose clamp (600 pmol · m-2 ·min-1) in 45 obese men (61 ± 8 years of age, mean ±SD) with normal glucose tolerance (NGT) (n = 21) or impaired glucose tolerance (IGT) (n = 24). We also evaluated relationships between body composition, exercise capacity, and IR. RESULTS— Subjects with NGT had lower BMI (28 ± 3 vs. 31± 3 kg/m2), waist circumference (97 ± 9 vs. 105± 9 cm), waist-to-hip ratio (WHR) (0.93 ± 0.06 vs. 0.97 ±0.05), and percent body fat (25 ± 6 vs. 30 ± 6) than subjects with IGT. Subjects with NGT also had lower areas above basal during the 2-h oral glucose tolerance test for glucose (274 ± 95 vs. 419 ± 124 mmol · min/l) and insulin (38,142 ± 18,206 vs. 58,383 ±34,408 pmol · min/l) and lower HOMA-IR values (2.2 ± 0.8 vs. 4.2± 2.6) than subjects with IGT. GIR (μmol · kg-1FFM · min-1) was higher in subjects with NGT than in subjects with IGT (53 ± 11 vs. 43 ± 14). HOMA-IR correlated with GIR in subjects with NGT (r = -0.59), but not in subjects with IGT(r = -0.13). GIR correlated with Vo2max in subjects with NGT (r = 0.58) and IGT (r = 0.42), but with WHR only in subjects with NGT (r = -0.53). HOMA-IR correlated with Vo2max (r = -0.57) and waist circumference (r =0.54) in subjects with NGT, but with percent body fat in subjects with IGT(r = 0.54). CONCLUSIONS— These findings indicate that HOMA-IR should not be used as an index of IR in older individuals who may be at risk for IGT, and suggest that lifestyle changes that increase Vo2max and decrease body fat may reduce IR in older people.
Treatment of Venous Thromboembolism
Authors: Philip S. Wells, Melissa A. Forgie, Marc A. Rodger
Journal: JAMA (2014)

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common, potentially lethal condition with acute morbidity.To review the etiology of VTE and the 3 phases of VTE treatment: acute (first 5-10 days), long-term (from end of acute treatment to 3-6 months), and extended (beyond 3-6 months).Cochrane reviews, meta-analyses, and randomized controlled trials, as well as other clinical trials for topics not covered by the former, were reviewed. Literature searches using broad terms were used to find meta-analyses published in the last 15 years. The ninth edition of the American College of Chest Physicians Antithrombotic Therapy Guidelines was used to supplement the literature search. Guidelines from specialty organizations were consulted when relevant. The Canadian Agency for Drugs and Technologies in Health was searched for relevant cost-effectiveness studies. We also searched our own literature database of 8386 articles for relevant research.Low-molecular-weight heparin (LMWH) along with with vitamin K antagonists and the benefits and proven safety of ambulation have allowed for outpatient management of most cases of DVT in the acute phase. Development of new oral anticoagulants further simplifies acute-phase treatment and 2 oral agents can be used as monotherapy, avoiding the need for LMWH. Patients with PE can also be treated in the acute phase as outpatients, a decision dependent on prognosis and severity of PE. Thrombolysis is best reserved for severe VTE; inferior vena cava filters, ideally the retrievable variety, should be used when anticoagulation is contraindicated. In general, DVT and PE patients require 3 months of treatment with anticoagulants, with options including LMWH, vitamin K antagonists, or direct factor Xa or direct factor IIa inhibitors. After this time, decisions for further treatment are based on balancing the risk of VTE recurrence, determined by etiology of the VTE (transient risk factors, unprovoked or malignancy associated), against the risk of major hemorrhage from treatment. Better prediction tools for major hemorrhage are needed. Experience with new oral anticoagulants as acute, long-term, and extended therapy options is limited as yet, but as a class they appear to be safe and effective for all phases of treatment.The mainstay of VTE treatment is anticoagulation, while interventions such as thrombolysis and inferior vena cava filters are reserved for limited circumstances. Multiple therapeutic modes and options exist for VTE treatment with small but nonetheless important differential effects to consider. Anticoagulants will probably always increase bleeding risk, necessitating tailored treatment strategies that must incorporate etiology, risk, benefit, cost, and patient preference. Although great progress has been made, further study to understand individual patient risks is needed to make ideal treatment decisions.
Impaired Acetylcholine-Induced Release of Nitric Oxide in the Aorta of Male Aromatase-Knockout Mice
Authors: Masahiko Kimura, Krishnankutty Sudhir, Margaret Jones, Evan Simpson, Ann-Maree Jefferis, Jaye P.F. Chin-Dusting
Journal: Circulation Research (2003)

The consequences of estrogen deficiency on the cardiovascular system have been widely examined in females. The effects of endogenous estrogen deficiency in males are less clear. The aromatase-knockout (ArKO) mouse lacks a functional Cyp19 gene, which encodes aromatase, and is thus incapable of synthesizing endogenous estrogen. In the present study, we examined the effect of lack of endogenous estrogens on vascular function in aortic rings isolated from male ArKO mice and compared these effects to rings from wild-type (WT) littermates. Full concentration-response curves to norepinephrine, acetylcholine, isoprenaline, and sodium nitroprusside were obtained in the absence and presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine in aortic segments set up in isometric myographs. Responses to noradrenaline were not different in aorta from ArKO compared with WT mice. Both Nomega-nitro-L-arginine and endothelium denudation significantly shifted the noradrenaline concentration-response curve to the left; however, this shift was not different in ArKO compared with WT. Responses to the endothelium-dependent vasodilator acetylcholine were significantly blunted in aortic rings from ArKO mice (Emax, 58.2+/-0.9% and 34.0+/-0.5% in wild-type and ArKO, respectively; P<0.05), whereas responses to the endothelium-independent agonist sodium nitroprusside and to the partial endothelium-dependent agonist isoprenaline were not affected. These findings suggest that endogenous estrogen facilitate vasorelaxation in males. This may be via modulating endothelial function rather than vascular smooth muscle cell responsiveness.
Regulation of Aromatase Expression in Estrogen-Responsive Breast and Uterine Disease: From Bench to Treatment
Authors: Serdar E. Bulun, Zhihong Lin, Gonca Imir, Sanober Amin, Masashi Demura, Bertan Yilmaz, Regina Martin, Hiroki Utsunomiya, Steven Thung, Bilgin Gurates, Mitsutoshi Tamura, David Langoi, Santanu Deb
Journal: Pharmacological Reviews (2005)

A single gene encodes the key enzyme for estrogen biosynthesis termed aromatase, inhibition of which effectively eliminates estrogen production. Aromatase inhibitors successfully treat breast cancer and endometriosis, whereas their roles in endometrial cancer, uterine fibroids, and aromatase excess syndrome are less clear. Ovary, testis, adipose tissue, skin, hypothalamus, and placenta express aromatase normally, whereas breast and endometrial cancers, endometriosis, and uterine fibroids overexpress aromatase and produce local estrogen that exerts paracrine and intracrine effects. Tissue-specific promoters distributed over a 93-kilobase regulatory region upstream of a common coding region alternatively control aromatase expression. A distinct set of transcription factors regulates each promoter in a signaling pathway- and tissue-specific manner. Three mechanisms are responsible for aromatase overexpression in a pathologic tissue versus its normal counterpart. First, cellular composition is altered to increase aromatase-expressing cell types that use distinct promoters (breast cancer). Second, molecular alterations in stromal cells favor binding of transcriptional enhancers versus inhibitors to a normally quiescent aromatase promoter and initiate transcription (breast/endometrial cancer, endometriosis, and uterine fibroids). Third, heterozygous mutations, which cause the aromatase coding region to lie adjacent to constitutively active cryptic promoters that normally transcribe other genes, result in excessive estrogen formation owing to the overexpression of aromatase in many tissues.
PREVENTION OF ROTAVIRUS INFECTION BY COW COLOSTRUM CONTAINING ANTIBODY AGAINST HUMAN ROTAVIRUS
Authors: T. Ebina, K. Umezu, S. Ohyama, K. Aikawa, N. Katsushima, S. Kitaoka, A. Sato, N. Ishida, A. Ohizumi, S. Katagiri, A. Imai, H. Suzuki, T. Konno
Journal: The Lancet (1983)
Plasma Lipoproteins in Familial Lecithin:Cholesterol Acyltransferase Deficiency FURTHER STUDIES OF VERY LOW AND LOW DENSITY LIPOPROTEIN ABNORMALITIES
Authors: John A. Glomset, Alex V. Nichols, Kaare R. Norum, Weiling King, Trudy Forte
Journal: Journal of Clinical Investigation (1973)

Plasma lipoproteins of d<1.006 g/ml, d 1.006-1.019 g/ml, and d 1.019-1.063 g/ml from patients with familial lecithin:cholesterol acyltransferase deficiency yielded abnormal subfractions upon being separately filtered through 2% agarose gel. A subfraction that emerged with the void volume and contained unusually large amounts of unesterified cholesterol and phosphatidylcholine was present in each lipoprotein group, and in each group this subfraction was less prominent in the nonlipemic plasma of one patient than in the lipemic plasma of other patients. A subfraction containing smaller lipoproteins also was present in each lipoprotein group. These lipoproteins were of the same size as normal lipoproteins of the corresponding density, but contained abnormally small amounts of cholesteryl ester. The lipoproteins of 1.019-1.063 g/ml contained abnormal components of intermediate molecular weight as well as large and small abnormal components similar to those described previously. The intermediate components were more prominent in the nonlipemic plasma but were easily recognized in the hyperlipemic plasma as a peak of S(f) 20-30 in the analytical ultracentrifuge. Also they could be recognized, upon electron microscopy of the lipoproteins of d 1.019-1.063 g/ml, as particles 340-1000 A in diameter. The data suggest that related large, abnormal particles pervade the patients' very low and low density lipoproteins, and that the large particles are affected by, but are not dependent on, the lipemia that frequently accompanies the disease. The smaller very low and low density lipoproteins appear to be counterparts of lipoproteins present in normal plasma. Their abnormal composition is compatible with the possibility that lecithin:cholesterol acyltransferase normally decreases the triglyceride and phosphatidylcholine and increases the cholesteryl ester of very low density and low density plasma lipoproteins in vivo.
cAMP-Independent Dilation of Coronary Arterioles to Adenosine
Authors: Travis W. Hein, Lih Kuo
Journal: Circulation Research (1999)

Abstract —Adenosine is known to play an important role in the regulation of coronary blood flow during metabolic stress. However, there is sparse information on the mechanism of adenosine-induced dilation at the microcirculatory levels. In the present study, we examined the role of endothelial nitric oxide (NO), G proteins, cyclic nucleotides, and potassium channels in coronary arteriolar dilation to adenosine. Pig subepicardial coronary arterioles (50 to 100 μm in diameter) were isolated, cannulated, and pressurized to 60 cm H 2 O without flow for in vitro study. The arterioles developed basal tone and dilated dose dependently to adenosine. Disruption of endothelium, blocking of endothelial ATP-sensitive potassium (K ATP ) channels by glibenclamide, and inhibition of NO synthase by N G -nitro- l -arginine methyl ester and of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one produced identical attenuation of vasodilation to adenosine. Combined administration of these inhibitors did not further attenuate the vasodilatory response. Production of NO from coronary arterioles was significantly increased by adenosine. Pertussis toxin, but not cholera toxin, significantly inhibited vasodilation to adenosine, and this inhibitory effect was only evident in vessels with an intact endothelium. Tetraethylammonium, glibenclamide, and a high concentration of extraluminal KCl abolished vasodilation of denuded vessels to adenosine; however, inhibition of calcium-activated potassium channels by iberiotoxin had no effect on this dilation. Rp-8-Br-cAMPS, a cAMP antagonist, inhibited vasodilation to cAMP analog 8-Br-cAMP but failed to block adenosine-induced dilation. Furthermore, vasodilations to 8-Br-cAMP and sodium nitroprusside were not inhibited by glibenclamide, indicating that cAMP- and cGMP-induced dilations are not mediated by the activation of K ATP channels. These results suggest that adenosine activates both endothelial and smooth muscle pathways to exert its vasodilatory function. On one hand, adenosine opens endothelial K ATP channels through activation of pertussis toxin–sensitive G proteins. This signaling leads to the production and release of NO, which subsequently activates smooth muscle soluble guanylyl cyclase for vasodilation. On the other hand, adenosine activates smooth muscle K ATP channels and leads to vasodilation through hyperpolarization. It appears that the latter vasodilatory process is independent of G proteins and of cAMP/cGMP pathways.
Type 2 Diabetes Prevalence in Asian Americans
Authors: Marguerite J. McNeely, Edward J. Boyko
Journal: Diabetes Care (2004)

Asians are thought to be at high risk for diabetes, yet there is little population-based information about diabetes in Asian Americans. The purpose of this study was to directly compare the prevalence of type 2 diabetes in Asian Americans with other racial and ethnic groups in the U.S. using data from the 2001 Behavioral Risk Factor Surveillance System (BRFSS).The BRFSS is a population-based telephone survey of the health status and health behaviors of Americans in all 50 states, Guam, Puerto Rico, and the U.S. Virgin Islands. Subjects included 3,071 Asians, 12,561 blacks, 12,153 Hispanics, 2,299 Native Americans, 626 Pacific Islanders, and 129,116 non-Hispanic whites aged >/=30 years. Subjects who reported a physician-diagnosis of diabetes were considered to have type 2 diabetes unless they were diagnosed before age 30.Compared with whites, odds ratios (95% CIs) for diabetes, adjusted for age and sex, were 1.0 (0.7-1.4) for Asians, 2.3 (2.1-2.6) for blacks, 2.0 (1.8-2.3) for Hispanics, 2.2 (1.6-2.9) for Native Americans, and 3.1 (1.4-6.8) for Pacific Islanders. Results adjusted for BMI, age, and sex were 1.6 (1.2-2.3) for Asians, 1.9 (1.7-2.2) for blacks, 1.9 (1.6-2.1) for Hispanics, 1.8 (1.3-2.5) for Native Americans, and 3.0 (1.4-6.7) for Pacific Islanders.Similar proportions of Asian and non-Hispanic white Americans report having diabetes, but after accounting for the lower BMI of Asians, the adjusted prevalence of diabetes is 60% higher in Asian Americans.
Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs
Authors: Ingrid G. Winkler, Natalie A. Sims, Allison R. Pettit, Valérie Barbier, Bianca Nowlan, Falak Helwani, Ingrid J. Poulton, Nico van Rooijen, Kylie A. Alexander, Liza J. Raggatt, Jean-Pierre Lévesque
Journal: Blood (2010)
International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding
Authors: Alan N. Barkun
Journal: Annals of Internal Medicine (2010)

A multidisciplinary group of 34 experts from 15 countries developed this update and expansion of the recommendations on the management of acute nonvariceal upper gastrointestinal bleeding (UGIB) from 2003. The Appraisal of Guidelines for Research and Evaluation (AGREE) process and independent ethics protocols were used. Sources of data included original and published systematic reviews; randomized, controlled trials; and abstracts up to October 2008. Quality of evidence and strength of recommendations have been rated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Recommendations emphasize early risk stratification, by using validated prognostic scales, and early endoscopy (within 24 hours). Endoscopic hemostasis remains indicated for high-risk lesions, whereas data support attempts to dislodge clots with hemostatic, pharmacologic, or combination treatment of the underlying stigmata. Clips or thermocoagulation, alone or with epinephrine injection, are effective methods; epinephrine injection alone is not recommended. Second-look endoscopy may be useful in selected high-risk patients but is not routinely recommended. Preendoscopy proton-pump inhibitor (PPI) therapy may downstage the lesion; intravenous high-dose PPI therapy after successful endoscopic hemostasis decreases both rebleeding and mortality in patients with high-risk stigmata. Although selected patients can be discharged promptly after endoscopy, high-risk patients should be hospitalized for at least 72 hours after endoscopic hemostasis. For patients with UGIB who require a nonsteroidal anti-inflammatory drug, a PPI with a cyclooxygenase-2 inhibitor is preferred to reduce rebleeding. Patients with UGIB who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid (ASA) again as soon as cardiovascular risks outweigh gastrointestinal risks (usually within 7 days); ASA plus PPI therapy is preferred over clopidogrel alone to reduce rebleeding.
Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion
Authors: H TADA, Y KAGAYA, M TAKEDA, J OHTA, Y ASAUMI, K SATOH, K ITO, A KARIBE, K SHIRATO, N MINEGISHI
Journal: Cardiovascular Research (2006)

Recent studies suggested that erythropoietin (Epo) receptors (EpoR) are expressed not only in the hematopoietic lineage cells but also in the heart and that the administration of recombinant human Epo elicits protective effects in myocardial ischemia and reperfusion (I/R). We tested our hypothesis that endogenous Epo signals mediated by EpoR expressed in the non-hematopoietic lineage cells play a protective role against myocardial I/R injury.Transgene-rescued EpoR null mutant mice (RES), which express EpoR exclusively in the hematopoietic lineage cells, were subjected to 30 min left coronary artery occlusion followed by reperfusion.Hematocrit, heart rate, blood pressure, heart weight, and echocardiographic parameters were comparable between wild-type mice (WT) and RES under the baseline condition. After 24 h of reperfusion, the infarct size in RES with I/R (RES/MI) was larger than that in WT/MI. Caspase-3 activity and number of TUNEL-positive cardiomyocytes in the ischemic area were increased in RES/MI compared with WT/MI. The extents of p38 and JNK phosphorylations in the ischemic area were significantly increased in WT/MI, but not in RES/MI as compared with corresponding sham-operated mice. Plasma Epo concentration in RES/MI did not differ from that in sham-operated RES, while that in WT/MI was peaked at 24 h post I/R. Additionally, left ventricular (LV) end-diastolic diameter was increased and LV fractional shortening tended to be reduced in the RES/MI compared with WT/MI at 21 days after I/R.These results suggest that the endogenous Epo-EpoR system in the non-hematopoietic lineage cells plays an important protective role against myocardial I/R injury.
Flavokawain A, a Novel Chalcone from Kava Extract, Induces Apoptosis in Bladder Cancer Cells by Involvement of Bax Protein-Dependent and Mitochondria-Dependent Apoptotic Pathway and Suppresses Tumor Growth in Mice
Authors: Xiaolin Zi, Anne R. Simoneau
Journal: Cancer Research (2005)

Abstract Consumption of the traditional kava preparation was reported to correlate with low and uncustomary gender ratios (more cancer in women than men) of cancer incidences in three kava-drinking countries: Fiji, Vanuatu, and Western Samoa. We have identified flavokawain A, B, and C but not the major kavalactone, kawain, in kava extracts as causing strong antiproliferative and apoptotic effect in human bladder cancer cells. Flavokawain A results in a significant loss of mitochondrial membrane potential and release of cytochrome c into the cytosol in an invasive bladder cancer cell line T24. These effects of flavokawain A are accompanied by a time-dependent decrease in Bcl-xL, a decrease in the association of Bcl-xL to Bax, and an increase in the active form of Bax protein. Using the primary mouse embryo fibroblasts Bax knockout and wild-type cells as well as a Bax inhibitor peptide derived from the Bax-binding domain of Ku70, we showed that Bax protein was, at least in part, required for the apoptotic effect of flavokawain A. In addition, flavokawain A down-regulates the expression of X-linked inhibitor of apoptosis and survivin. Because both X-linked inhibitor of apoptosis and survivin are main factors for apoptosis resistance and are overexpressed in bladder tumors, our data suggest that flavokawain A may have a dual efficacy in induction of apoptosis preferentially in bladder tumors. Finally, the anticarcinogenic effect of flavokawain A was evident in its inhibitory growth of bladder tumor cells in a nude mice model (57% of inhibition) and in soft agar.