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Carbonic anhydrase 3

Jason An, Branko Braam
Rationale: We hope to increase awareness that hypokalemic paralysis may be the first presentation of Sjögren syndrome, for which potassium-sparing diuretics can be an effective adjunct to potassium replenishment. Presenting concerns: A 73-year-old female presented to a peripheral hospital with quadriparesis and a critically low serum potassium of 1.6 mmol/L with U waves on the electrocardiogram (ECG). The initial arterial blood gas showed a pH of 7.19, bicarbonate of 13 mEq/L, and a CO2 of 35 mm Hg...
2018: Canadian Journal of Kidney Health and Disease
Tanvi V Wani, Silvia Bua, Pravin S Khude, Abdul H Chowdhary, Claudiu T Supuran, Mrunmayee P Toraskar
A series of novel sulphonamide derivatives was obtained from sulphanilamide which was N4-alkylated with ethyl bromoacetate followed by reaction with hydrazine hydrate. The hydrazide obtained was further reacted with various aromatic aldehydes. The novel sulphonamides were characterised by infrared, mass spectrometry, 1 H- and 13 C-NMR and purity was determined by high-performance liquid chromatography (HPLC). Human (h) carbonic anhydrase (CA, EC isoforms hCA I and II and Mycobacterium tuberculosis β-CA encoded by the gene Rv3273 (mtCA 3) inhibition activity was investigated with the synthesised compounds which showed promising inhibition...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Fredric Cohen
Single-and multiple-dose pharmacokinetics and safety were investigated in this phase 1 study of dichlorphenamide, a carbonic anhydrase inhibitor approved in the United States for treatment of primary periodic paralysis. Dichlorphenamide was administered to 6 cohorts (n = 6 each) of healthy adults. Cohorts A through E received single doses of 25-400 mg followed by 50-800 mg/day in divided doses for 10 total doses. Cohort F (safety analysis only) received up to 28 titrated doses from 100-800 mg/day. Plasma for pharmacokinetics sampling was obtained predose and up to 48 hours postdose...
May 15, 2018: Clinical Pharmacology in Drug Development
Yichao Wan, Shengzhuo He, Wei Li, Zilong Tang
Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new anti-tumor agents to make up for the deficiency. Indazoles is an important class of heterocyclic compounds possessing a variety of biological activities, such as anti-tumor, anti-bacterial, anti-inflammatory, anti-depressant and anti-hypertensive...
May 9, 2018: Anti-cancer Agents in Medicinal Chemistry
Mutaz Dana, Eitan Fibach
The major hemoglobin (Hb) during fetal life is fetal Hb (Hb F). It is mostly replaced by adult Hbs before birth and during the first year of life. In adults, where Hb F comprises <2.0% of the total Hb, it is not homogenously distributed among the red blood cells (RBCs) but is concentrated in a few RBCs, termed F-cells. Interestingly, for reasons that are unclear, Hb F increases in the maternal circulation during pregnancy. This increased Hb F could have two potential origins that are not mutually exclusive: A) maternal origin, due to inducing environment of Hb F in the maternal erythroid precursors; B) fetal origin, due to fetal cells crossing the placenta and entering the maternal circulation...
May 10, 2018: Hemoglobin
Bani Kaur Suri, Navin Kumar Verma, Artur Schmidtchen
Carbonic anhydrases are ubiquitously expressed enzymes that reversibly hydrate carbon dioxide to bicarbonate and protons. While the main function of carbonic anhydrases is to regulate pH and osmotic balance, their involvement in other physiological processes remains to be explored. This study analysed changes in mRNA and protein levels of carbonic anhydrase II in human primary keratinocytes treated with various toll-like receptor agonists and cytokines. A significant upregulation of carbonic anhydrase II at the mRNA and protein levels was observed upon treatment with polyinosinic-polycytidylic acid, a toll-like receptor 3 agonist...
May 8, 2018: Acta Dermato-venereologica
Dimitrios Tsikas, Erik Hanff, Alexander Bollenbach, Ruan Kruger, Vu Vi Pham, Kristine Chobanyan-Jürgens, Dirk Wedekind, Tanja Arndt, Anne Jörns, Jimmy F P Berbée, Hans M G Princen, Thomas Lücke, François Mariotti, Jean-François Huneau, Stefan Ückert, Jürgen C Frölich, Sigurd Lenzen
We recently found that renal carbonic anhydrase (CA) is involved in the reabsorption of inorganic nitrite (NO2 - ), an abundant reservoir of nitric oxide (NO) in tissues and cells. Impaired NO synthesis in the endothelium and decreased NO bioavailability in the circulation are considered major contributors to the development and progression of renal and cardiovascular diseases in different conditions including diabetes. Isolated human and bovine erythrocytic CAII and CAIV can convert nitrite to nitrous acid (HONO) and its anhydride N2 O3 which, in the presence of thiols (RSH), are further converted to S-nitrosothiols (RSNO) and NO...
May 4, 2018: Amino Acids
Marlène C Hekman, Mark Rijpkema, Constantijn H Muselaers, Egbert Oosterwijk, Christina A Hulsbergen-Van de Kaa, Otto C Boerman, Wim J Oyen, Johan F Langenhuijsen, Peter F Mulders
Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue. In this study, we demonstrate the feasibility and safety of intraoperative dual-modality imaging with the carbonic anhydrase IX (CAIX)-targeting antibody 111 In-DOTA-girentuximab-IRDye800CW in clear cell renal cell carcinoma (ccRCC) patients. Methods: A phase I protein dose escalation study was performed in patients with a primary renal mass who were scheduled for surgery...
2018: Theranostics
Alexander Chamessian, Michael Young, Yawar Qadri, Temugin Berta, Ru-Rong Ji, Thomas Van de Ven
The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying the transcriptomic profile of SST neurons could elucidate the unique genetic features of this population and enable selective analgesic targeting. To that end, we combined the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) method and Fluorescence Activated Nuclei Sorting (FANS) to capture tagged SST nuclei in the SDH of adult male mice...
May 1, 2018: Scientific Reports
Verônica da Silva Cardoso, Alane Beatriz Vermelho, Eduardo Ricci Junior, Igor Almeida Rodrigues, Ana Maria Mazotto, Claudiu T Supuran
The β-carbonic anhydrase (CA, EC from Leishmania spp. (LdcCA) is effectively inhibited by aromatic/heterocyclic sulphonamides, in the low nanomolar range, but no in vitro antileishmanial activity was detected for such compounds. We formulated some of these sulphonamides as nanoemulsions (NEs) in clove oil, and tested them in vitro against Leishmania infantum MHOM/BR/1974/PP75 and Leishmania amazonensis IFLA/BR/1967/PH8 strains. Interesting inhibitory concentrations IC50 were observed for some of the sulphonamides NEs, with IC50 as low as 3...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Gabriela Tonini Peterle, Lucas Lima Maia, Leonardo Oliveira Trivilin, Mayara Mota de Oliveira, Joaquim Gasparini Dos Santos, Suzanny Oliveira Mendes, Elaine Stur, Lidiane Pignaton Agostini, Lília Alves Rocha, Raquel Ajub Moysés, Patrícia Maluf Cury, Fábio Daumas Nunes, Iúri Drumond Louro, Marcelo Dos Santos, Adriana Madeira Álvares da Silva
BACKGROUND: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX) and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. MATERIALS AND METHODS: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery...
April 25, 2018: Journal of Oral Pathology & Medicine
Shuwen Zhang, Yangzi Zhang, Xiang Zhou, Xing Fu, Jennifer J Michal, Guoli Ji, Min Du, Jon F Davis, Zhihua Jiang
Currently available mouse knockout (KO) lines remain largely uncharacterized for genome-to-phenome (G2P) information flows. Here we test our hypothesis that altered myogenesis seen in AMPKα1- and AMPKα2-KO mice is caused by use of alternative polyadenylation sites (APSs). AMPKα1 and AMPKα2 are two α subunits of adenosine monophosphate-activated protein kinase (AMPK), which serves as a cellular sensor in regulation of many biological events. A total of 56,483 APSs were derived from gastrocnemius muscles...
April 24, 2018: Scientific Reports
Mariela Arias-Hidalgo, Qinggong Yuan, Fabrizio Carta, Claudiu T Supuran, Gerolf Gros, Volker Endeward
BACKGROUND/AIMS: It has been described that cells in culture with very low oxidative metabolism possess a low CO2 membrane permeability, PCO2, of ∼ 0.01 cm/s. On the other hand, cardiomyocytes and mitochondria with extremely high rates of O2 consumption exhibit very high CO2 membrane permeabilities of 0.1 and 0.3 cm/s, repectively. To ascertain that this represents a systematic relationship, we determine here PCO2 of hepatocytes, which exhibit an intermediate rate of O2 consumption...
2018: Cellular Physiology and Biochemistry
Ismini C Mainta, Thomas Zilli, Jean-Christophe Tille, Thomas De Perrot, Jean-Paul Vallée, Franz Buchegger, Valentina Garibotto, Raymond Miralbell
PURPOSE: Tumor hypoxia is associated with radioresistance and poor prognosis after radiation therapy for prostate cancer (PCa). In this prospective pilot study, we assessed the ability of 18 F-misonidazole (18 F-MISO) positron emission tomography (PET)-magnetic resonance imaging (MRI) to detect hypoxia in high-grade PCa patients who were candidates for curative radiation therapy, and we evaluated 18 F-MISO PET-MRI modulation after 3 months of neoadjuvant androgen deprivation therapy (nADT)...
March 8, 2018: International Journal of Radiation Oncology, Biology, Physics
Philipp A Pickerodt, Sebastian Kronfeldt, Martin Russ, Adrian Gonzalez-Lopez, Philipp Lother, Elvira Steiner, Katja Vorbrodt, Thilo Busch, Willehad Boemke, Roland C E Francis, Erik R Swenson
The carbonic anhydrase (CA) inhibitors, acetazolamide and its structurally similar analogue, methazolamide prevent or reduce hypoxic pulmonary vasoconstriction (HPV) in dogs and humans in vivo, by a mechanism unrelated to CA inhibition. In rodent blood and isolated blood vessels, Aamand et al. (2009) reported that inhibition of CA led to increased generation of nitric oxide (NO) from nitrite and vascular relaxation in vitro. We tested the physiological relevance of augmented NO generation by CA from nitrite with acetazolamide in anaesthetized pigs during alveolar hypoxia in vivo...
April 16, 2018: Journal of Physiology
Shohei Kitahata, Yasuhiko Hirami, Seiji Takagi, Cody Kime, Masashi Fujihara, Yasuo Kurimoto, Masayo Takahashi
Objective: We investigated the efficacy of additional topical betamethasone in persistent cystoid macular oedema (CMO) after carbonic anhydrase inhibitors (CAIs) therapy. Methods and analysis: This retrospective cohort study included 16 eyes of 10 patients with retinitis pigmentosa (RP). All patients were previously administered CAI for at least 3 months to treat CMO secondary to RP and lacking an effective reduction (≥11%) of central foveal thickness (CFT)...
2018: BMJ Open Ophthalmology
Müslüm Kuzu, Veysel Çomaklı, Ebru Akkemik, Mehmet Çiftci, Ömer İrfan Küfrevioğlu
In this study, CA I and II isoenzymes were purified from Van Lake fish gills by using Sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography and to determine the effects of some metals on the enzyme activities. For purified CA I isoenzyme, yield, specific activity, and purification fold were obtained as 42.07%, 4948.12 EU/mg protein, and 116.61 and for CA II isoenzyme, 7%, 1798.56 EU/mg protein, and 42.38 respectively. Activity of CA was determined by measuring "CO2 -hydratase activity". Purity control was checked by SDS-PAGE...
April 8, 2018: Fish Physiology and Biochemistry
Shanti N Dessai
Laboratory friendly, cryopreservation procedures with respect to cryopreservation formulations and cryopreservation temperatures were attempted, in the present study to ensure perennial availability of cultured mantle cells of bivalve (Paphia malabarica). Screening of cryopreservative formulations with different concentrations of DMSO, Propylene glycol and Glycerol was carried out for cryopreservation of freshly dissociated cells of Paphia malabarica. Out of these cryopreservative formulations, 10% DMSO, 10% Propylene glycol and 15% Glycerol were selected for cryopreservation of the mantle cells pooled from 1-day old primary culture and cell line after 3 passages at the end of different cryopreservation periods...
April 4, 2018: Cryobiology
Halise Inci Gul, Cem Yamali, Merve Bulbuller, Petek Ballar Kirmizibayrak, Mustafa Gul, Andrea Angeli, Silvia Bua, Claudiu T Supuran
In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5-aryl-3,4-dihydro-1'H,H-[3,4'-bipyrazole]-1',2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by1 H NMR,13 C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4...
March 30, 2018: Bioorganic Chemistry
Muhammad Ovais, Ali Talha Khalil, Abida Raza, Nazar Ul Islam, Muhammad Ayaz, Muthupandian Saravanan, Muhammad Ali, Irshad Ahmad, Muhammad Shahid, Zabta Khan Shinwari
Phytochemicals offer immense promise for sustainable development and production of nanotechnology-enabled products. In the present study, Olax nana Wall. ex Benth. (family: Olacaceae) aqueous extract was used as an effective stabilizing agent to produce biogenic silver (ON-AgNPs) and gold nanoparticles (ON-AuNPs), which were investigated for biocompatibility and prospective biomedical applications (antibacterial, anticancer, antileishmanial, enzyme inhibition, antinociceptive, and anti-inflammatory activities)...
March 29, 2018: Applied Microbiology and Biotechnology
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