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[PMID]: 28438765 [Au] Autor: Codsi E; Garovic VD; Gonzalez-Suarez ML; Milic N; Borowski KS; Rose CH; Davies NP; Kashani KB; Lieske JC; White WM [Ad] Endereço: Department of Maternal Fetal Medicine, Mayo Clinic, Rochester, Minnesota; Codsi.Elisabeth@mayo.edu. [Ti] Título: Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies. [So] Source: Am J Physiol Regul Integr Comp Physiol;312(5):R773-R778, 2017 May 01. [Is] ISSN: 1522-1490 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE ( = 15), gestational hypertension (GH; = 14), and normotensive controls (NC; = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2). [Mh] Termos MeSH primário: alfa-Globulinas/imunologia Complexo de Ataque à Membrana do Sistema Complemento/imunologia Mediadores da Inflamação/imunologia Nefropatias/imunologia Túbulos Renais Proximais/imunologia Pré-Eclâmpsia/imunologia [Mh] Termos MeSH secundário: Adulto alfa-Globulinas/urina Biomarcadores/urina Causalidade Ativação do Complemento/imunologia Complexo de Ataque à Membrana do Sistema Complemento/urina Feminino Seres Humanos Nefropatias/epidemiologia Nefropatias/urina Estudos Longitudinais Minnesota/epidemiologia Pré-Eclâmpsia/epidemiologia Pré-Eclâmpsia/urina Gravidez Prevalência Fatores de Risco [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alpha-Globulins); 0 (Biomarkers); 0 (Complement Membrane Attack Complex); 0 (Inflammation Mediators); 0 (alpha-1-microglobulin) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170825 [Lr] Data última revisão: 170825 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170426 [St] Status: MEDLINE [do] DOI: 10.1152/ajpregu.00509.2016

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[PMID]: 28321043 [Au] Autor: McDuffie JE; Ma JY; Zhang Y; Almy FS; Wu X; Li K; Sonee M; Meng R; Rizzolio M; Snook SS [Ad] Endereço: Discovery Sciences, Preclinical Development & Safety, Janssen Research & Development, LLC, USA. [Ti] Título: Immunolocalization of novel corticomedullary tubule injury markers in Cynomolgus monkeys treated with amphotericin B. [So] Source: J Toxicol Sci;42(2):167-174, 2017. [Is] ISSN: 1880-3989 [Cp] País de publicação: Japan [La] Idioma: eng [Ab] Resumo: Amphotericin B (AmpB) nephrotoxicity was used to assess the utility of drug­induced kidney injury (DIKI) biomarkers in an exploratory study in male cynomolgus monkeys. All animals had quantifiable levels of AmpB in plasma on days 1 and 4. There were no clinical signs of AmpB­induced toxicity in this study. The gold standard method used to confirm AmpB­induced DIKI was anatomic pathology which revealed microscopic lesions with varying grades of severity. Immunolocalization of alpha­1 microglobulin (α­1M), kidney injury molecule 1 (KIM­1), osteopontin (OPN) and neutrophil gelatinase­associated lipocalin (NGAL) proteins was evaluated in formalin­fixed, paraffin­embedded monkey kidney tissue sections. AmpB related immunoreactivities were identified in distinct nephron segments of treated monkeys including α­1M in damaged proximal tubule epithelium, KIM­1 in damaged medullary tubule epithelium, OPN mostly in the infiltrating cells of cortical tubule interstitium, and NGAL in the granular and cellular cast in dilatated cortical tubules. Variations in α­1M, KIM­1, OPN and NGAL immunolocalization appear as promising DIKI protein biomarkers when monitoring for AmpB­induced corticomedullary tubule injury in male cynomolgus monkeys. [Mh] Termos MeSH primário: Anfotericina B/toxicidade Anti-Infecciosos/toxicidade Nefropatias/metabolismo Túbulos Renais/metabolismo [Mh] Termos MeSH secundário: alfa-Globulinas/metabolismo Anfotericina B/sangue Anfotericina B/farmacocinética Animais Anti-Infecciosos/sangue Anti-Infecciosos/farmacocinética Biomarcadores/metabolismo Receptor Celular 1 do Vírus da Hepatite A/metabolismo Imuno-Histoquímica Nefropatias/induzido quimicamente Nefropatias/patologia Túbulos Renais/efeitos dos fármacos Túbulos Renais/patologia Lipocalina-2/metabolismo Macaca fascicularis Masculino Osteopontina/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alpha-Globulins); 0 (Anti-Infective Agents); 0 (Biomarkers); 0 (Hepatitis A Virus Cellular Receptor 1); 0 (Lipocalin-2); 0 (alpha-1-microglobulin); 106441-73-0 (Osteopontin); 7XU7A7DROE (Amphotericin B) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170801 [Lr] Data última revisão: 170801 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170322 [St] Status: MEDLINE [do] DOI: 10.2131/jts.42.167

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[PMID]: 28249709 [Au] Autor: Nakamura M; Takeuchi T; Kawahara T; Hirose J; Nakayama K; Hosaka Y; Furusako S [Ad] Endereço: Discovery Research, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan. Electronic address: mnakamur@mochida.co.jp. [Ti] Título: Simultaneous targeting of CD14 and factor XIa by a fusion protein consisting of an anti-CD14 antibody and the modified second domain of bikunin improves survival in rabbit sepsis models. [So] Source: Eur J Pharmacol;802:60-68, 2017 May 05. [Is] ISSN: 1879-0712 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Severe sepsis is a complex, multifactorial, and rapidly progressing disease characterized by excessive inflammation and coagulation following bacterial infection. To simultaneously suppress pro-inflammatory and pro-coagulant responses, we genetically engineered a novel fusion protein (MR1007) consisting of an anti-CD14 antibody and the modified second domain of bikunin, and evaluated the potential of MR1007 as an anti-sepsis agent. Suppressive effects of MR1007 on lipopolysaccharide (LPS)-induced inflammatory responses were assessed using peripheral blood mononuclear cells or endothelial cells. Its inhibitory activity against the coagulation factor XIa was assessed using a purified enzyme and a chromogenic substrate. Anticoagulant activity was assessed using human or rabbit plasma. Anti-inflammatory and anti-coagulant effects and/or survival benefits were evaluated in an endotoxemia model and a cecal ligation and puncture model. MR1007 inhibited LPS-induced cytokine production in peripheral blood mononuclear cells and endothelial cells, inhibited factor XIa, and exhibited anticoagulant activity. In an endotoxemia model, 0.3-3mg/kg MR1007 suppressed pro-inflammatory and pro-coagulant responses in a dose-dependent manner; at a dose of 3mg/kg, the protein improved survival even when administered 8h after the LPS injection. In addition, 10mg/kg MR1007 administered 2h post cecal ligation and puncture improved survival. However, MR1007 administered at doses up to 30mg/kg did not increase ear bleeding time or bacterial counts in the cecal ligation and puncture model. Thus, simultaneous targeting of CD14 and factor XIa improves survival in the rabbit endotoxemia and sepsis models and represents a promising approach for the treatment of severe sepsis. [Mh] Termos MeSH primário: alfa-Globulinas/química Anticorpos Monoclonais/farmacologia Endotoxemia/tratamento farmacológico Fator XIa/antagonistas & inibidores Receptores de Lipopolissacarídeos/imunologia Terapia de Alvo Molecular Proteínas Recombinantes de Fusão/farmacologia [Mh] Termos MeSH secundário: Animais Anticorpos Monoclonais/imunologia Anticorpos Monoclonais/uso terapêutico Anticoagulantes/imunologia Anticoagulantes/farmacologia Anticoagulantes/uso terapêutico Tempo de Sangramento Modelos Animais de Doenças Selectina E/metabolismo Endotoxemia/metabolismo Regulação da Expressão Gênica/efeitos dos fármacos Seres Humanos Interleucina-6/biossíntese Domínios Proteicos Coelhos Proteínas Recombinantes de Fusão/imunologia Proteínas Recombinantes de Fusão/uso terapêutico Análise de Sobrevida [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alpha-Globulins); 0 (Antibodies, Monoclonal); 0 (Anticoagulants); 0 (E-Selectin); 0 (Interleukin-6); 0 (Lipopolysaccharide Receptors); 0 (Recombinant Fusion Proteins); 0 (alpha-1-microglobulin); EC 3.4.21.27 (Factor XIa) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170303 [St] Status: MEDLINE

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[PMID]: 28161704 [Au] Autor: Yamaguchi Y; Noda H; Okaniwa N; Adachi K; Shinmura T; Nakagawa S; Ebi M; Ogasawara N; Funaki Y; Zhuo L; Kimata K; Sasaki M; Kasugai K [Ad] Endereço: Department of Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Japan. [Ti] Título: Serum-Derived Hyaluronan-Associated Protein Is a Novel Biomarker for Inflammatory Bowel Diseases. [So] Source: Digestion;95(2):146-155, 2017. [Is] ISSN: 1421-9867 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: BACKGROUND/AIMS: We evaluated the role of serum-derived hyaluronan-associated protein (SHAP) in inflammatory bowel disease (IBD) pathogenesis and its potential as a novel IBD biomarker. METHODS: We studied the SHAP expression in a mouse model of colitis and in human intestinal samples of IBD and compared serum concentrations with normal controls. RESULTS: SHAP was expressed in the connective tissue derived from inflamed regions of the intestine. In mice, serum levels of SHAP-hyaluronic acid (SHAP-HA) were positively correlated with the histological damage of the colon (r = 0.566, p < 0.001). Serum concentration of SHAP-HA complex was significantly higher in patients with active ulcerative colitis than in those in remission, and this value was positively correlated with the erythrocyte sedimentation rate, serum level of tumor necrosis factor (TNF)-α, and endoscopic damage (r = 0.568, p < 0.001; r = 0.521, p < 0.001, and r = 0.641, p < 0.001). In patients with Crohn's disease, the serum SHAP-HA level correlated only with TNF-α (r = 0.630, p = 0.002). CONCLUSION: SHAP is a novel IBD biomarker that is related to disease activity in certain types of colitis, and it may affect disease pathogenesis. Future studies are needed to evaluate the therapeutic potential of this complex. [Mh] Termos MeSH primário: alfa-Globulinas/análise Doenças Inflamatórias Intestinais/sangue Mucosa Intestinal/metabolismo [Mh] Termos MeSH secundário: alfa-Globulinas/metabolismo Animais Biomarcadores/sangue Biomarcadores/metabolismo Colo/metabolismo Colo/patologia Sulfato de Dextrana/toxicidade Modelos Animais de Doenças Seres Humanos Doenças Inflamatórias Intestinais/induzido quimicamente Doenças Inflamatórias Intestinais/patologia Mucosa Intestinal/patologia Masculino Camundongos Camundongos Endogâmicos C57BL Fator de Necrose Tumoral alfa/sangue [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alpha-Globulins); 0 (Biomarkers); 0 (Tumor Necrosis Factor-alpha); 39346-44-6 (inter-alpha-inhibitor); 9042-14-2 (Dextran Sulfate) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170606 [Lr] Data última revisão: 170606 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170206 [St] Status: MEDLINE [do] DOI: 10.1159/000456071

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[PMID]: 27759575 [Au] Autor: Baxi SM; Scherzer R; Jotwani V; Estrella MM; Abraham AG; Parikh CR; Bennett MR; Cohen MH; Nowicki MJ; Gustafson DR; Sharma A; Young MA; Shlipak MG; Womenʼs Interagency HIV Study (WIHS) [Ad] Endereço: *Department of Medicine, University of California San Francisco (UCSF), San Francisco, CA; †Division is Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA; ‡Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Hospital, San Francisco, CA; §Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD; ‖Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; ¶Section of Nephrology, Department of Medicine, Program of Applied Translational Research, Yale University, New Haven, CT; #Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; **Department of Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, IL; ††Department of Medicine, University of Southern California, Los Angeles, CA; ‡‡Department of Neurology, State University of New York, Downstate Medical Center, Brooklyn, NY; §§Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; and ‖‖Department of Medicine, Division of Infectious Diseases and Travel Medicine, Georgetown University Medical Center, Washington, DC. [Ti] Título: Changes in Urinary Biomarkers Over 10 Years Is Associated With Viral Suppression in a Prospective Cohort of Women Living With HIV. [So] Source: J Acquir Immune Defic Syndr;74(5):e138-e145, 2017 Apr 15. [Is] ISSN: 1944-7884 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Urine biomarkers have helped identify persons at risk for progressing to kidney disease in the setting of HIV infection. We explored factors associated with changes in 3 urine biomarkers over 10 years among women living with HIV. METHODS: Prospective cohort of 294 HIV-infected women from the multicenter Women's Interagency HIV Study. Predictors included HIV viral and immunological parameters, comorbid conditions, and health-related behaviors. Outcomes were patterns of changes of urine interleukin-18 (IL-18), albumin-to-creatinine ratio (ACR), and alpha-1-microglobulin (α1m) over 10 years. We used quantile regression to examine patterns of change in each urine biomarker during follow-up and multivariable analysis of variance regression to identify predictors of biomarker changes. RESULTS: Over 10 years, the median concentrations of IL-18 declined from 120 to 64 pg/mL, α1m rose from 0.7 to 1.5 ng/mL, and ACR remained stable (9-8 mg/g). In multivariate analyses, the strongest predictors of increases in IL-18 were higher baseline body mass index, increase in waist circumference, higher follow-up HIV viral load, lower follow-up CD4 cell count, hepatitis C virus (HCV) coinfection, and higher follow-up high density lipoprotein cholesterol. Predictors of increasing concentration of α1m were lower CD4 cell counts, higher diastolic blood pressure, HCV coinfection, and smoking. Finally, determinants of ACR increases during follow-up were higher follow-up diastolic blood pressure, HCV coinfection, higher follow-up HIV viral load, and triglyceride concentration. CONCLUSIONS: Over 10 years, HIV disease status had different associations with each urine biomarker under study. Overall, the associations with changes in each biomarker support research into their use for longitudinal monitoring of kidney health. [Mh] Termos MeSH primário: Antirretrovirais/efeitos adversos Antirretrovirais/uso terapêutico Biomarcadores/urina Infecções por HIV/complicações Infecções por HIV/tratamento farmacológico Insuficiência Renal/induzido quimicamente Resposta Viral Sustentada [Mh] Termos MeSH secundário: Adulto Albuminúria alfa-Globulinas/urina Creatinina/urina Feminino Seres Humanos Interleucina-18/urina Meia-Idade Estudos Prospectivos Insuficiência Renal/epidemiologia Insuficiência Renal/patologia [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY [Nm] Nome de substância: 0 (Alpha-Globulins); 0 (Anti-Retroviral Agents); 0 (Biomarkers); 0 (Interleukin-18); 0 (alpha-1-microglobulin); AYI8EX34EU (Creatinine) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170714 [Lr] Data última revisão: 170714 [Sb] Subgrupo de revista: IM; X [Da] Data de entrada para processamento: 161021 [St] Status: MEDLINE [do] DOI: 10.1097/QAI.0000000000001200

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[PMID]: 27745748 [Au] Autor: Shah BA; Migliori A; Kurihara I; Sharma S; Lim YP; Padbury J [Ad] Endereço: Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Department of Pediatrics, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, RI. Electronic address: Birju-Shah@ouhsc.edu. [Ti] Título: Blood Level of Inter-Alpha Inhibitor Proteins Distinguishes Necrotizing Enterocolitis From Spontaneous Intestinal Perforation. [So] Source: J Pediatr;180:135-140.e1, 2017 Jan. [Is] ISSN: 1097-6833 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To examine circulating levels of inter-alpha inhibitor protein (IaIp) in infants with necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), and matched controls to assess the diagnostic accuracy of IaIp to differentiate NEC from SIP and to compare receiver operating characteristics of IaIp for NEC with C-reactive protein (CRP). STUDY DESIGN: A prospective, nested case-control study of infants with feeding intolerance was carried out. Blood and clinical data were collected from 27 infants diagnosed with NEC or SIP and from 26 matched controls admitted to our unit. Infants with modified Bell criteria stage 2 or greater were included as NEC. Clinical, radiologic, and/or surgical findings were used to identify infants with SIP. Controls were matched for gestational age, postnatal age, sex, and birth weight. RESULTS: Mean ± SD IaIp blood levels were 147 ± 38 mg/L, 276 ± 67 mg/L, and 330 ± 100 mg/L in infants with NEC, SIP, and matched controls, respectively (P < .004 and P < .01). Receiver operating characteristics analysis to establish the predictive value of NEC demonstrated areas under curve of 0.98 and 0.63 for IaIp and CRP, respectively. CONCLUSIONS: IaIp levels were significantly decreased in infants with NEC compared with SIP and matched controls. The diagnostic accuracy of IaIp for NEC was superior to that of CRP. [Mh] Termos MeSH primário: alfa-Globulinas/análise Enterocolite Necrosante/sangue Enterocolite Necrosante/diagnóstico Perfuração Intestinal/sangue Perfuração Intestinal/diagnóstico [Mh] Termos MeSH secundário: Proteína C-Reativa/análise Estudos de Casos e Controles Diagnóstico Diferencial Feminino Seres Humanos Recém-Nascido Masculino Estudos Prospectivos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alpha-Globulins); 39346-44-6 (inter-alpha-inhibitor); 9007-41-4 (C-Reactive Protein) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170615 [Lr] Data última revisão: 170615 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 161018 [St] Status: MEDLINE

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[PMID]: 27685836 [Au] Autor: Ohyama K; Yoshimi H; Aibara N; Nakamura Y; Miyata Y; Sakai H; Fujita F; Imaizumi Y; Chauhan AK; Kishikawa N; Kuroda N [Ad] Endereço: Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. [Ti] Título: Immune complexome analysis reveals the specific and frequent presence of immune complex antigens in lung cancer patients: A pilot study. [So] Source: Int J Cancer;140(2):370-380, 2017 Jan 15. [Is] ISSN: 1097-0215 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Cancer immunotherapies such as antibodies targeting T cell checkpoints, or adaptive tumor-infiltrating lymphocyte (TIL) transfer, have been developed to boost the endogenous immune response against human malignancies. However, activation of T cells by such antibodies can lead to the risk of autoimmune diseases. Also, the selection of tumor-reactive T cells for TIL relies on information regarding mutated antigens in tumors and does not reflect other factors involved in protein antigenicity. It is therefore essential to engineer therapeutic interventions by which T cell reactivity against tumor cells is selectively enhanced (i.e., "focused cancer immunotherapy") based on tumor antigens that are specifically expressed in the tumor of a certain cancer and in many patients with this cancer. Immune complexes (ICs) are the direct and stable products of immunological recognition by humoral immunity. Here, we searched for tumor-specific IC antigens in each of five cancers (lung (n = 28), colon (n = 20), bladder (n = 20), renal cell (n = 15) and malignant lymphoma (n = 9)), by using immune complexome analysis that comprehensively identifies and profiles the constituent antigens in ICs. This analysis indicated that gelsolin and inter-alpha-trypsin inhibitor heavy chains were specifically and frequently detected (at a frequency higher than 80%), and that phosphoproteins (VENTX, VCIP135) were also specifically present in the ICs of lung cancer patients. Immune complexome analysis successfully identified several tumor-specific IC antigens with high detection frequency in lung cancer patients. These specific antigens are required to validate the clinical benefit by further analysis using a large number of patients. [Mh] Termos MeSH primário: Complexo Antígeno-Anticorpo/imunologia Neoplasias Pulmonares/imunologia [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais alfa-Globulinas/imunologia Antígenos de Neoplasias/imunologia Doenças Autoimunes/imunologia Feminino Gelsolina/imunologia Seres Humanos Imunoterapia/métodos Linfócitos do Interstício Tumoral/imunologia Masculino Meia-Idade Fosfoproteínas/imunologia Projetos Piloto Linfócitos T/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alpha-Globulins); 0 (Antigen-Antibody Complex); 0 (Antigens, Neoplasm); 0 (Gelsolin); 0 (Phosphoproteins); 39346-44-6 (inter-alpha-inhibitor) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170501 [Lr] Data última revisão: 170501 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160930 [St] Status: MEDLINE [do] DOI: 10.1002/ijc.30455

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[PMID]: 27615121 [Au] Autor: van den Berg CB; Duvekot JJ; Güzel C; Hansson SR; de Leeuw TG; Steegers EA; Versendaal J; Luider TM; Stoop MP [Ad] Endereço: Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands. [Ti] Título: Elevated levels of protein AMBP in cerebrospinal fluid of women with preeclampsia compared to normotensive pregnant women. [So] Source: Proteomics Clin Appl;11(1-2), 2017 Jan. [Is] ISSN: 1862-8354 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: PURPOSE: To investigate the cerebrospinal fluid (CSF) proteome of patients with preeclampsia (PE) and normotensive pregnant women, in order to provide a better understanding of brain involvement in PE. EXPERIMENTAL DESIGN: Ninety-eight CSF samples (43 women with PE and 55 normotensive controls) were analyzed by LC-MS/MS proteome profiling. CSF was obtained during the spinal puncture before caesarean delivery. RESULTS: Eight proteins were higher abundant and 17 proteins were lower abundant in patients with PE. The most significantly differentially abundant protein was protein AMBP (alpha-1-microglobulin/bikunin precursor). This finding was validated by performing an ELISA experiment (p = 0.002). CONCLUSIONS AND CLINICAL RELEVANCE: The current study showed a clear difference between the protein profiles of CSF from patients with PE and normotensive pregnant women. Protein AMBP is a precursor of a heme-binding protein that counteracts the damaging effects of free hemoglobin, which may be related to the presence of free hemoglobin in CSF. Protein levels showed correlations with clinical symptoms during pregnancy and postpartum. To our knowledge, this is the first LC-MS/MS proteome profiling study on a unique set of CSF samples from (severe) preeclamptic patients and normotensive pregnant women. [Mh] Termos MeSH primário: alfa-Globulinas/líquido cefalorraquidiano Pré-Eclâmpsia/patologia [Mh] Termos MeSH secundário: Adulto Estudos de Casos e Controles Cromatografia Líquida de Alta Pressão Ensaio de Imunoadsorção Enzimática Feminino Seres Humanos Pré-Eclâmpsia/metabolismo Gravidez Proteoma/análise Espectrometria de Massas em Tandem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alpha-Globulins); 0 (Proteome); 0 (alpha-1-microglobulin) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170920 [Lr] Data última revisão: 170920 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160913 [St] Status: MEDLINE [do] DOI: 10.1002/prca.201600082

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[PMID]: 27587605 [Au] Autor: Kirsch AH; Lyko R; Nilsson LG; Beck W; Amdahl M; Lechner P; Schneider A; Wanner C; Rosenkranz AR; Krieter DH [Ad] Endereço: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Ti] Título: Performance of hemodialysis with novel medium cut-off dialyzers. [So] Source: Nephrol Dial Transplant;32(1):165-172, 2017 01 01. [Is] ISSN: 1460-2385 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Background: Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules. Methods: In two prospective, open-label, controlled, randomized, crossover pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF). Primary outcome was lambda free light chain (λFLC) overall clearance. Secondary outcomes included overall clearances and pre-to-post-reduction ratios of middle and small molecules, and safety of MCO HD treatments. Results: MCO HD provided greater λFLC overall clearance [least square mean (standard error)] as follows: study 1: MCO AA 8.5 (0.54), MCO BB 11.3 (0.51), MCO CC 15.0 (0.53) versus high-flux HD 3.6 (0.51) mL/min; study 2: MCO AA 10.0 (0.58), MCO BB 12.5 (0.57) versus high-flux HD 4.4 (0.57) and HDF 6.2 (0.58) mL/min. Differences between MCO and high-flux dialyzers were consistently significant in mixed model analysis (each P < 0.001). Reduction ratios of λFLC were greater for MCO. Clearances of α1-microglobulin, complement factor D, kappa FLC (κFLC) and myoglobin were generally greater with MCO than with high-flux HD and similar to or greater than clearances with HDF. Albumin loss was moderate with MCO, but greater than with high-flux HD and HDF. Conclusions: MCO HD removes a wide range of middle molecules more effectively than high-flux HD and even exceeds the performance of high-volume HDF for large solutes, particularly λFLC. [Mh] Termos MeSH primário: Hemodiafiltração/métodos Diálise Renal/métodos [Mh] Termos MeSH secundário: Idoso Albuminas/análise alfa-Globulinas/análise Estudos Cross-Over Feminino Seres Humanos Cadeias lambda de Imunoglobulina/análise Masculino Membranas Artificiais Meia-Idade Permeabilidade Projetos Piloto Estudos Prospectivos [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Albumins); 0 (Alpha-Globulins); 0 (Immunoglobulin lambda-Chains); 0 (Membranes, Artificial); 0 (alpha-1-microglobulin) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170926 [Lr] Data última revisão: 170926 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160903 [St] Status: MEDLINE [do] DOI: 10.1093/ndt/gfw310

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[PMID]: 27809794 [Au] Autor: Head BM; Rubinstein E; Meyers AF [Ad] Endereço: Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada. umheadb@outlook.com. [Ti] Título: Alternative pre-approved and novel therapies for the treatment of anthrax. [So] Source: BMC Infect Dis;16(1):621, 2016 Nov 03. [Is] ISSN: 1471-2334 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient's chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies. METHODS: A literature search was conducted using the University of Manitoba search engine. Using this search engine allowed access to a greater variety of journals/articles that would have otherwise been restricted for general use. In order to be considered for discussion for this review, all articles must have been published later than 2009. RESULTS: The alternative pre-approved antibiotics demonstrated high efficacy against B. anthracis both in vitro and in vivo. In addition, the safety profile and clinical pharmacology of these drugs were already known. Compounds that targeted underexploited bacterial processes (DNA replication, RNA synthesis, and cell division) were also very effective in combatting B. anthracis. In addition, these novel compounds prevented bacterial resistance. Targeting B. anthracis virulence, more specifically the anthrax toxins, increased the length of which treatment could be administered. CONCLUSIONS: Several novel and pre-existing antibiotics, as well as toxin inhibitors, have shown increasing promise. A combination treatment that targets both bacterial growth and toxin production would be ideal and probably necessary for effectively combatting this armed bacterium. [Mh] Termos MeSH primário: Antraz/tratamento farmacológico Antibacterianos/uso terapêutico Antitoxinas/uso terapêutico [Mh] Termos MeSH secundário: alfa-Globulinas/uso terapêutico Antibióticos Antineoplásicos/uso terapêutico Anticorpos Monoclonais/uso terapêutico Antígenos de Bactérias Bacillus anthracis Toxinas Bacterianas DNA Helicases/antagonistas & inibidores Daunorrubicina/análogos & derivados Daunorrubicina/uso terapêutico Doxorrubicina/uso terapêutico Descoberta de Drogas Fluoroquinolonas Seres Humanos Indutores de Interferon/uso terapêutico Levofloxacino Linezolida Ofloxacino Policetídeos/uso terapêutico Inibidores de Serino Proteinase/uso terapêutico Tilorona/uso terapêutico Virulência [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Alpha-Globulins); 0 (Anti-Bacterial Agents); 0 (Antibiotics, Antineoplastic); 0 (Antibodies, Monoclonal); 0 (Antigens, Bacterial); 0 (Antitoxins); 0 (Bacterial Toxins); 0 (Fluoroquinolones); 0 (Interferon Inducers); 0 (Polyketides); 0 (Serine Proteinase Inhibitors); 0 (anthracimycin); 0 (anthrax toxin); 29Z5DNL48C (obiltoxaximab); 39346-44-6 (inter-alpha-inhibitor); 64314-28-9 (baumycins); 6GNT3Y5LMF (Levofloxacin); 794PGL549S (raxibacumab); 80168379AG (Doxorubicin); A4P49JAZ9H (Ofloxacin); EC 3.6.4.- (DNA Helicases); ISQ9I6J12J (Linezolid); O6W7VEW6KS (Tilorone); U188XYD42P (moxifloxacin); ZS7284E0ZP (Daunorubicin) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161105 [St] Status: MEDLINE

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