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- Acetazolamide promotes decreased consumption of carbonated drinks and weight loss. [Journal Article]
- OMOxf Med Case Reports 2018; 2018(11):omy081
- Excessive consumption of carbonated drinks contributes to the dietary surplus of carbohydrates, and is a main driver of the obesity epidemic in the USA. From a public health standpoint, it is therefo...
Excessive consumption of carbonated drinks contributes to the dietary surplus of carbohydrates, and is a main driver of the obesity epidemic in the USA. From a public health standpoint, it is therefore crucial to develop strategies that enable individuals to regulate this calorie-rich, but nutrient-poor food intake. However, conservative medical approaches to this end have met with limited success. Using a pharmacological strategy to eliminate the effervescent aspect of carbonated drinks, we report significant weight loss in a patient with long-standing obesity. Administration of low-dose acetazolamide, a carbonic anhydrase inhibitor, resulted in altered taste of carbonation, and in turn a marked reduction in the patient's carbonated drink intake and the loss of almost 1 kg of body weight per week. The pharmacological intervention also resulted in appetite suppression, which might synergistically contribute to weight loss. These findings point to the use of low-dose acetazolamide as a novel weight reduction strategy.
- Cerebral MR oximetry during acetazolamide augmentation: Beyond cerebrovascular reactivity in hemodynamic failure. [Journal Article]
- JMJ Magn Reson Imaging 2018 Nov 03
- CONCLUSIONS: These results suggest QSM is sensitive to dynamic OEF modulation during hemodynamic augmentation.
- Intracerebral steal phenomenon in symptomatic carotid artery disease. [Journal Article]
- JNJ Neuroradiol 2018 Oct 30
- CONCLUSIONS: Intracerebral steal occurs in patients with obstructive ICA disease and can be assesses at brain tissue level with ASL perfusion MRI. Its presence is related to more severely declined CVR in the surrounding brain tissue area and the volume is associated with impaired primary collateral blood flow through the CoW.
- A thylakoid-located carbonic anhydrase regulates CO2 uptake in the cyanobacterium Synechocystis sp. PCC 6803. [Journal Article]
- NPNew Phytol 2018 Nov 01
- Carbonic anhydrases (CAs) are involved in CO2 uptake and conversion, a fundamental process in photosynthetic organisms. Nevertheless, the mechanism underlying the regulation of CO2 uptake and intrace...
Carbonic anhydrases (CAs) are involved in CO2 uptake and conversion, a fundamental process in photosynthetic organisms. Nevertheless, the mechanism underlying the regulation of CO2 uptake and intracellular conversion in cyanobacteria is largely unknown. We report the characterization of a previously unrecognized thylakoid-located CA Slr0051 (EcaB) from the cyanobacterium Synechocystis sp. PCC 6803, which possesses CA activity to regulate CO2 uptake. Inactivation of ecaB stimulated CO2 hydration in the thylakoids, suppressed by the classical CA inhibitor acetazolamide. Absence of ecaB increased the reduced state of the photosynthetic electron transport system, lowered the rate of photosynthetic O2 evolution at high light (HL) and pH and decreased the cellular affinity for extracellular inorganic carbon. Furthermore, EcaB was upregulated in cells grown at limiting CO2 level or HL in tandem with CupA. EcaB is mainly located in the thylakoid membranes where it interacts with CupA and CupB involved in CO2 uptake by converting it to bicarbonate. We propose that modulation of the EcaB level and activity in response to CO2 changes, illumination or pH reversibly regulates its conversion to HCO3 by the two CO2 uptake systems (CupA, CupB), dissipating the excess HCO3- , alleviating photoinhibition and thereby optimizes photosynthesis especially under HL and alkaline conditions. This article is protected by copyright. All rights reserved.
- GeneReviews® [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- Episodic ataxia type 1 (EA1) is a potassium channelopathy characterized by constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with los...
Episodic ataxia type 1 (EA1) is a potassium channelopathy characterized by constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks individuals may experience a number of variable symptoms including vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing, among others. EA1 may be associated with epilepsy. Other possible associations include delayed motor development, cognitive disability, choreoathetosis, and carpal spasm. Usually, onset is in childhood or early adolescence.
- FTIR and TG analyses coupled with factor analysis in a compatibility study of acetazolamide with excipients. [Journal Article]
- SASpectrochim Acta A Mol Biomol Spectrosc 2019 Feb 05; 208:285-293
- A compatibility study of drug substance with excipients is a crucial step in the drug development process in order to generate potent final drug formulations for efficient and safe therapy for variou...
A compatibility study of drug substance with excipients is a crucial step in the drug development process in order to generate potent final drug formulations for efficient and safe therapy for various diseases. Thus, the development of new methods for compatibility studies is a great challenge. For this reason, a new approach based on improvement of FTIR spectra and TG curves interpretation using factor analysis (FA) was developed as a screening technique for assessing the compatibility of acetazolamide with selected excipients. This multivariate method demonstrates that in some cases acetazolamide and mixtures with high acetazolamide content formed one cluster, while a second cluster consisted of excipient and mixtures with high excipient content. Such clustering of the analyzed samples (drug substance, excipient and their mixtures) demonstrates the compatibility between ingredients. This in turn means that the FTIR spectra and TG curves of mixtures are the sum of absorption bands or of the thermal profiles of ingredients. In the case of incompatibility, the FTIR spectra and TG curves of mixtures differ from those of ingredients. The FA score scatter plot shows that clusters consist of mixtures which differ with respect to ingredient content. In conclusion, FA proved the incompatibility of acetazolamide mixtures with β-cyclodextrin, chitosan, lactose, mannitol, meglumine and starch. This was also confirmed by complementary techniques such as DSC and PXRD. Hence, the application of FA can be helpful for better comprehension of data obtained from FTIR spectra and TG curves.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Acetazolamide is a diuretic and carbonic anhydrase inhibitor medication that is used to treat several illnesses.
Acetazolamide is a diuretic and carbonic anhydrase inhibitor medication that is used to treat several illnesses.
- The Effects of Acetazolamide on Exercise Performance at Sea Level and in Hypoxic Environments: A Review. [Review]
- WEWilderness Environ Med 2018 Oct 09
- Lowlanders rapidly ascending to high altitude (>2500 m) often develop acute mountain sickness (AMS). While acclimatization is the most effective method of reducing symptoms of AMS (ie, headache, fati...
Lowlanders rapidly ascending to high altitude (>2500 m) often develop acute mountain sickness (AMS). While acclimatization is the most effective method of reducing symptoms of AMS (ie, headache, fatigue, nausea, gastrointestinal distress, etc.), it may take several days to become fully acclimated. Prophylactic use of acetazolamide (AZ), a carbonic anhydrase inhibitor, has become a popular alternative to staged acclimatization because it can be a less time-consuming method of reducing symptoms of AMS. While numerous studies have shown the effectiveness of AZ in mitigating the symptoms of AMS, a review of the existing literature regarding the effects of AZ on submaximal and maximal exercise performance at sea level and at altitude has not been performed.Literature search identified 17 peer reviewed articles examining the effects of AZ on exercise performance both at sea level and at altitude, as well as the associated side effects of prophylactic AZ use for the attenuation of AMS. This review finds that AZ treated cohorts experience a reduction in time to exhaustion during both submaximal and maximal exercise performance at sea level. At altitude, AZ treated cohorts' recorded widely variable submaximal and maximal exercise performance. At sea level, AZ impairs submaximal and maximal exercise performance. Due to the wide variation of findings of previously published studies, the effects of AZ on submaximal and maximal exercise performance at altitude remain unknown.
- Whole-Exome Sequencing Implicates SCN2A in Episodic Ataxia, but Multiple Ion Channel Variants May Contribute to Phenotypic Complexity. [Case Reports]
- IJInt J Mol Sci 2018 Oct 11; 19(10)
- Although the clinical use of targeted gene sequencing-based diagnostics is valuable, whole-exome sequencing has also emerged as a successful diagnostic tool in molecular genetics laboratories worldwi...
Although the clinical use of targeted gene sequencing-based diagnostics is valuable, whole-exome sequencing has also emerged as a successful diagnostic tool in molecular genetics laboratories worldwide. Molecular genetic tests for episodic ataxia type 2 (EA2) usually target only the specific calcium channel gene (CACNA1A) that is known to cause EA2. In cases where no mutations are identified in the CACNA1A gene, it is important to identify the causal gene so that more effective treatment can be prioritized for patients. Here we present a case of a proband with a complex episodic ataxias (EA)/seizure phenotype with an EA-affected father; and an unaffected mother, all negative for CACNA1A gene mutations. The trio was studied by whole-exome sequencing to identify candidate genes responsible for causing the complex EA/seizure phenotype. Three rare or novel variants in Sodium channel α2-subunit; SCN2A (c.3973G>T: p.Val1325Phe), Potassium channel, Kv3.2; KCNC2 (c.1006T>C: p.Ser336Pro) and Sodium channel Nav1.6; SCN8A (c.3421C>A: p.Pro1141Thr) genes were found in the proband. While the SCN2A variant is likely to be causal for episodic ataxia, each variant may potentially contribute to the phenotypes observed in this family. This study highlights that a major challenge of using whole-exome/genome sequencing is the identification of the unique causative mutation that is associated with complex disease.
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- 1,2,4-Trisubstituted imidazolinones with dual carbonic anhydrase and p38 mitogen-activated protein kinase inhibitory activity. [Journal Article]
- BCBioorg Chem 2018 Oct 01; 82:109-116
- Various 1,2,4 trisubstituted imidazolin-5-one derivatives were synthesized and evaluated for their inhibitory activity against p38 mitogen-activated protein kinase (p38MAPK) and carbonic anhydrase (C...
Various 1,2,4 trisubstituted imidazolin-5-one derivatives were synthesized and evaluated for their inhibitory activity against p38 mitogen-activated protein kinase (p38MAPK) and carbonic anhydrase (CA) enzymes aiming to explore potential dual inhibitors. Results revealed that compounds 3c, 3g, 3h, 4a, 6c and 6d were the most effective derivatives against p38αMAPK (IC50 = 0.14, 0.14, 0.056, 0.14, 0.13 and 0.14 μM, respectively) compared to sorafenib (IC50 = 1.58 μM) as standard drug. On the other hand, compound 4a revealed the best inhibitory activity against all the tested carbonic anhydrase isoforms CA I, II, IV and IX with Ki values of 95.0, 0.83, 6.90 and 12.4 nM, respectively compared to acetazolamide with Ki values 250, 12.1, 74 and 12.8 nM, respectively. Therefore, compound 4a can be considered as a potent dual p38αMAPK/CA inhibitor.