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Carbonic anhydrase 3

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https://www.readbyqxmd.com/read/27894244/umbelliferone-decreases-intracellular-ph-and-sensitizes-melanoma-cell-line-a375-to-dacarbazin-comparison-with-acetazolamide
#1
Clémentine Puech, Morgane Chatard, Delphine Felder-Flesch, Nathalie Prevot, Nathalie Perek
The high degree of malignancy of tumour cells is linked to alterations of many physiological parameters like the intracellular pH (pHi). The pHi in cancer cell line is regulated by the anhydrase carbonique IX (CA IX). The main enzymatic function of the CA IX protein is to catalyze the hydration of carbon dioxide into bicarbonate ions and protons. Inhibiton of transmembrane tumor associated isozyme carbonic anhydrase IX (CA IX) with specific inhibitors is a promising and expanding field as CA IX is involved in tumor progression...
November 28, 2016: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/27859585/synthesis-and-carbonic-anhydrase-inhibition-of-novel-2-4-aryl-thiazole-2-yl-3a-4-7-7a-tetrahydro-1h-4-7-methanoisoindole-1-3-2h-dione-derivatives
#2
Umit M Kocyigit, Osman Nuri Aslan, Ilhami Gulcin, Yusuf Temel, Mustafa Ceylan
Carbonic anhydrase (CA, EC 4.2.1.1) is a member of the metalloenzyme family. It catalyzes the rapid conversion of carbon dioxide (CO2 ) and water to bicarbonate (HCO3(-) ) and protons (H(+) ) and also plays an important role in biochemical and physiological processes. In this study, a number of novel 2-(4-(aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives were synthesized and evaluated for their inhibitory characteristics against the human CA isoenzymes I and II (hCA I and hCA II)...
December 2016: Archiv der Pharmazie
https://www.readbyqxmd.com/read/27858178/proteome-analysis-of-hemofilter-adsorbates-to-identify-novel-substances-of-sepsis-a-pilot-study
#3
Tomoaki Hashida, Taka-Aki Nakada, Mamoru Satoh, Keisuke Tomita, Rui Kawaguchi, Fumio Nomura, Shigeto Oda
Blood purification therapy using hemofilters with high adsorbing capabilities has been reported to remove excessive humoral mediators from the blood of patients with sepsis. However, there are insufficient studies of the adsorbates bound to hemofilter membranes. We hypothesized that these adsorbates in acute kidney injury (AKI) patients with sepsis were different from those in patients without sepsis and that proteome analysis of the adsorbates would identify novel substances of sepsis. This study included 20 patients who had AKI upon admission to intensive care units (ICUs) and who received continuous renal replacement therapy using polymethyl methacrylate hemofilters...
November 17, 2016: Journal of Artificial Organs: the Official Journal of the Japanese Society for Artificial Organs
https://www.readbyqxmd.com/read/27852754/ammonia-excretion-in-the-marine-polychaete-eurythoe-complanata-annelida
#4
Daniel Thiel, Maja Hugenschütt, Heiko Meyer, Achim Paululat, Alex R Quijada-Rodriguez, Günter Purschke, Dirk Weihrauch
Ammonia is a toxic waste product from protein metabolism and needs to be either converted into less toxic molecules or, in the case of fish and aquatic invertebrates, excreted directly as is. In contrast to fish, very little is known regarding the ammonia excretion mechanism and the participating excretory organs in marine invertebrates. In the current study ammonia excretion in the marine burrowing polychaete Eurythoe complanata was investigated. As a potential site for excretion the 100-200 micrometer long, 30-50 micrometer wide and up to 25 micrometer thick dentrically branched, well ventilated and vascularized branchiae (gills) were identified...
November 16, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27833999/methyl-%C3%AE-cyclodextrin-treatment-combined-to-incubation-with-interleukin-4-reproduces-major-features-of-atopic-dermatitis-in-a-3d-culture-model
#5
Tatiana do Nascimento Pedrosa, Evelyne De Vuyst, Abdallah Mound, Catherine Lambert de Rouvroit, Silvya Stuchi Maria-Engler, Yves Poumay
Atopic dermatitis (AD) skin is characterized by over-expression of interleukin (IL)-4, IL-13 and IL-25. When methyl-β-cyclodextrin (MβCD) treatment preceded exposure to these interleukins, combination of both treatments was found to mimic hallmarks of AD in vitro, such as barrier weakening, histological alterations and typical signaling responses in a reconstructed human epidermis (RHE). However, the respective role of each IL and whether any of them is critical when combined with MβCD treatment was unknown...
November 11, 2016: Archives of Dermatological Research
https://www.readbyqxmd.com/read/27828908/use-of-a-carbonic-anhydrase-inhibitor-in-x-linked-retinoschisis-effect-on-cystic-appearing-macular-lesions-and-visual-acuity
#6
Paola Andreuzzi, Gerald A Fishman, Robert J Anderson
PURPOSE: To evaluate changes in cystic-appearing macular lesions and visual acuity in patients with X-linked retinoschisis while being treated with a carbonic anhydrase inhibitor. METHODS: A retrospective analysis of 68 eyes from 36 patients between the ages of 5 years and 61 years with X-linked retinoschisis were monitored while on a carbonic anhydrase inhibitor. Macular cystic-appearing lesions were monitored with optical coherence tomography. Snellen visual acuity measurements were converted to logarithm of the minimum angle of resolution equivalent Early Treatment Diabetic Retinopathy Study letters for analysis...
November 8, 2016: Retina
https://www.readbyqxmd.com/read/27787547/adjuvant-weekly-girentuximab-following-nephrectomy-for-high-risk-renal-cell-carcinoma-the-ariser-randomized-clinical-trial
#7
Karim Chamie, Nicholas M Donin, Pia Klöpfer, Paul Bevan, Barbara Fall, Olaf Wilhelm, Stephan Störkel, Jonathan Said, Michael Gambla, Robert E Hawkins, Gustavo Jankilevich, Anil Kapoor, Evgeny Kopyltsov, Michael Staehler, Kimmo Taari, Alberto J A Wainstein, Allan J Pantuck, Arie S Belldegrun
Importance: Girentuximab is a chimeric monoclonal antibody that binds carbonic anhydrase IX, a cell surface glycoprotein ubiquitously expressed in clear cell renal cell carcinoma (ccRCC). Its safety and activity in phase 2 studies prompted investigation into its use as adjuvant monotherapy in participants with high-risk ccRCC. Objective: To evaluate the safety and efficacy of adjuvant girentuximab on disease-free survival (DFS) and overall survival (OS) in patients with localized completely resected high-risk ccRCC...
October 27, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27784170/open-saccharin-based-secondary-sulfonamides-as-potent-and-selective-inhibitors-of-cancer-related-carbonic-anhydrase-ix-and-xii-isoforms
#8
Melissa D'Ascenzio, Paolo Guglielmi, Simone Carradori, Daniela Secci, Rosalba Florio, Adriano Mollica, Mariangela Ceruso, Atilla Akdemir, Anatoly P Sobolev, Claudiu T Supuran
A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by reductive ring opening of the newly synthesized N-alkylated saccharin derivatives and were shown to be inactive against the two cytosolic off-target hCA I and II (Kis > 10 µM). Interestingly, these compounds inhibited hCA IX in the low nanomolar range with Kis ranging between 20 and 298 nM and were extremely potent inhibitors of hCA XII isoenzyme (Kis ranging between 4...
October 26, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/27777776/high-dose-interleukin2-a-10-year-single-site-experience-in-the-treatment-of-metastatic-renal-cell-carcinoma-careful-selection-of-patients-gives-an-excellent-outcome
#9
S Chow, V Galvis, M Pillai, R Leach, E Keene, A Spencer-Shaw, A Shablak, J Shanks, T Liptrot, F Thistlethwaite, R E Hawkins
BACKGROUND: VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27777225/wide-bore-columns-of-poly-glycidyl-methacrylate-co-divinylbenzene-based-monolithic-beds-for-reversed-phase-and-anion-exchange-chromatographic-separation-of-biomolecules
#10
Said H Lubbad
Three monoliths based on poly(glycidyl methacrylate-co-divinylbenzene) were prepared in the confines of borosilicate glass columns (100 × 3 mm I.D.). The first monolith was applied for analysis of proteins by reversed-phase high-performance liquid chromatography. It furnished a fast base-line separation for four proteins (ribonuclease A, cytochrome c, α-lactalbumin and myoglobin) in <80 s, with optimum resolution range of 2.11-2.84, and extremely small values of peak width at half height with a range of 1...
October 24, 2016: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/27774818/synthesis-carbonic-anhydrase-i-and-ii-inhibition-studies-of-the-1-3-5-trisubstituted-pyrazolines
#11
Halise Inci Gul, Ebru Mete, Parham Taslimi, Ilhami Gulcin, Claudiu T Supuran
4-(3-(4-Substituted-phenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamides (9-16) were successfully synthesized and their chemical structures were confirmed by (1)H NMR, (13)C NMR, and HRMS spectra. Carbonic anhydrase I and II inhibitory effects of the compounds were investigated. Ki values of the compounds were in the range of 316.7 ± 9.6-533.1 ± 187.8 nM towards hCA I and 412.5 ± 115.4-624.6 ± 168.2 nM towards hCA II isoenzymes. While Ki values of the reference compound Acetazolamide were 278...
October 24, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/27774817/designing-synthesis-and-bioactivities-of-4-3-4-hydroxyphenyl-5-aryl-4-5-dihydro-pyrazol-1-yl-benzenesulfonamides
#12
Halise Inci Gul, Ebru Mete, Sakip Emre Eren, Hiroshi Sakagami, Cem Yamali, Claudiu T Supuran
In this study, 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]benzenesulfonamide (1-9) types compounds were synthesized and their chemical structures were confirmed by (1)H NMR, (13)C NMR and HRMS spectra. Cytotoxic and carbonic anhydrase (CA) inhibitory effects of the compounds were investigated. Cytotoxicity experiments pointed out that compound 4, (4-[5-(4-chlorophenyl)-3-(4-hydroxyphenyl)-4,5-dihydro-pyrazol-1-yl]benzenesulfonamide), exerting the highest tumor selectivity (TS) and potency selectivity expression (PSE) values, can be considered as a lead compound of this study in terms of development of novel anticancer agents...
October 23, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/27743401/bile-acids-and-their-oxo-derivatives-potential-inhibitors-of-carbonic-anhydrase-i-and-ii-androgen-receptor-antagonists-and-cyp3a4-substrates
#13
Jovana Trifunović, Vladan Borčić, Momir Mikov
Some biological properties of bile acids and their oxo derivatives have not been sufficiently investigated, although the interest for bile acids as signaling molecules is rising. The aim of this work was to evaluate physico-chemical parametar b (slope) that represents lipophilicity of the examined molecules and to investigate interactions of bile acids with carbonic anhydrase I, II, androgen receptor and CYP450s. 13 candidates were investigated using normal phase thin layer chromatography in two solvent systems...
October 14, 2016: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/27731352/methazolamide-improves-neurological-behavior-by-inhibition-of-neuron-apoptosis-in-subarachnoid-hemorrhage-mice
#14
Mingchang Li, Wei Wang, Haojian Mai, Xinmu Zhang, Jian Wang, Yufeng Gao, Yuefei Wang, Gang Deng, Ling Gao, Shuanhu Zhou, Qianxue Chen, Xin Wang
Subarachnoid hemorrhage (SAH) results in significant nerve dysfunction, such as hemiplegia, mood disorders, cognitive and memory impairment. Currently, no clear measures can reduce brain nerve damage. The study of brain nerve protection after SAH is of great significance. We aim to evaluate the protective effects and the possible mechanism of methazolamide in C57BL/6J SAH animal model in vivo and in blood-induced primary cortical neuron (PCNs) cellular model of SAH in vitro. We demonstrate that methazolamide accelerates the recovery of neurological damage, effectively relieves cerebral edema, and improves cognitive function in SAH mice as well as offers neuroprotection in blood- or hemoglobin-treated PCNs and partially restores normal neuronal morphology...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27717855/isothermal-titration-calorimetry-for-drug-design-precision-of-the-enthalpy-and-binding-constant-measurements-and-comparison-of-the-instruments
#15
Vaida Linkuvienė, Georg Krainer, Wen-Yih Chen, Daumantas Matulis
Isothermal titration calorimetry (ITC) is one of the most robust label- and immobilization-free techniques used to measure protein - small molecule interactions in drug design for the simultaneous determination of the binding affinity (ΔG) and the enthalpy (ΔH), both of which are important parameters for structure-thermodynamics correlations. It is important to evaluate the precision of the method and of various ITC instrument models by performing a single well-characterized reaction. The binding between carbonic anhydrase II and acetazolamide was measured by four ITC instruments - PEAQ-ITC, iTC200, VP-ITC, and MCS-ITC and the standard deviation of ΔG and ΔH was determined...
December 15, 2016: Analytical Biochemistry
https://www.readbyqxmd.com/read/27688658/carbonic-anhydrase-enzymes-ii-vii-ix-and-xii-in-colorectal-carcinomas
#16
Pia Viikilä, Antti J Kivelä, Harri Mustonen, Selja Koskensalo, Abdul Waheed, William S Sly, Jaromir Pastorek, Silvia Pastorekova, Seppo Parkkila, Caj Haglund
AIM: To investigate expression of four alpha-carbonic anhydrases (CAs) in colorectal carcinomas (CRC) and compare the results with patients' survival. METHODS: Colorectal carcinoma samples from 539 CRC patients and control tissues were arranged as tissue microarrays and analyzed with antibodies against CA II, CA VII, CA IX, and CA XII. Intensity and extent of staining were both scored from 0 to 3 in each sample. These enzyme expression levels were then correlated to patients' survival and clinicopathological parameters, which were tumor differentiation grade and stage, site of tumor, patients' age, and gender...
September 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27664622/protein-markers-for-discrimination-of-meat-species-in-raw-beef-pork-and-poultry-and-their-mixtures
#17
Gap-Don Kim, Jin-Kyu Seo, Hyeon-Woong Yum, Jin-Yeon Jeong, Han-Sul Yang
The purpose of this study was to find discrimination markers for four major meat species such as beef, pork, chicken and duck. Myofibrillar and sarcoplasmic proteins isolated from each meat type were analyzed by one-dimensional gel electrophoresis and some proteins were identified through LC-MS/MS analysis. We confirmed that troponin I (TnI), enolase 3, l-lactate dehydrogenase (LDH) and triose-phosphate isomerase (TPI) could be useful markers for discrimination of mammals from poultry due to their different electrophoretic mobility...
February 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27643502/anti-inflammatory-anti-osteoclastogenic-and-antioxidant-effects-of-malva-sylvestris-extract-and-fractions-in-vitro-and-in-vivo-studies
#18
Bruna Benso, Marcelo Franchin, Adna Prado Massarioli, Jonas Augusto Rizzato Paschoal, Severino Matias Alencar, Gilson Cesar Nobre Franco, Pedro Luiz Rosalen
Given their medical importance, natural products represent a tremendous source of drug discovery. The aim of this study was to investigate Malva sylvestris L. extract and fractions and their pharmacological activities followed by chemical identification. The aqueous fraction (AF) was identified as the bioactive fraction in the in vitro and in vivo assays. The AF controlled the neutrophil migration to the peritoneal cavity by 66%, inhibited the antiedematogenic activity by 58.8%, and controlled IL-1β cytokine expression by 54%...
2016: PloS One
https://www.readbyqxmd.com/read/27636377/cytomorphology-of-clear-cell-papillary-renal-cell-carcinoma
#19
Xiaoqi Lin
BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) shares some morphologic and immunohistochemical markers with clear cell RCC and papillary RCC. To the author's knowledge, its cytomorphology on fine-needle aspiration (FNA) or touch preparations (TPs) of core needle biopsy specimens has not been well delineated in the English language literature. METHODS: The FNA/TP cytomorphology of 7 retrieved cases was studied. RESULTS: The tumor cells were arranged in small nests (100%), 3-dimensional clusters (71%), papillary/tubular/acinar arrays (43%), and as single cells (57%)...
September 16, 2016: Cancer Cytopathology
https://www.readbyqxmd.com/read/27634011/lactobacillus-acidophilus-counteracts-inhibition-of-nhe3-and-dra-expression-and-alleviates-diarrheal-phenotype-in-mice-infected-with-citrobacter-rodentium
#20
Anoop Kumar, Arivarasu N Anbazhagan, Hayley Coffing, Ishita Chatterjee, Shubha Priyamvada, Tarunmeet Gujral, Seema Saksena, Ravinder K Gill, Waddah A Alrefai, Alip Borthakur, Pradeep K Dudeja
Impaired absorption of electrolytes is a hallmark of diarrhea associated with inflammation or enteric infections. Intestinal epithelial luminal membrane NHE3 (Na(+)/H(+) exchanger 3) and DRA (Down-Regulated in Adenoma; Cl(-)/HCO3(-) exchanger) play key roles in mediating electroneutral NaCl absorption. We have previously shown decreased NHE3 and DRA function in response to short-term infection with enteropathogenic E coli (EPEC), a diarrheal pathogen. Recent studies have also shown substantial downregulation of DRA expression in a diarrheal model of infection with Citrobacter rodentium, the mouse counterpart of EPEC...
November 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
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