- Functional Involvement of Carbonic Anhydrase in the Lysosomal Response to Cadmium Exposure in Mytilus galloprovincialis Digestive Gland. [Journal Article]
- FPFront Physiol 2018; 9:319
- Carbonic anhydrase (CA) is a ubiquitous metalloenzyme, whose functions in animals span from respiration to pH homeostasis, electrolyte transport, calcification, and biosynthetic reactions. CA is sens...
Carbonic anhydrase (CA) is a ubiquitous metalloenzyme, whose functions in animals span from respiration to pH homeostasis, electrolyte transport, calcification, and biosynthetic reactions. CA is sensitive to trace metals in a number of species. In mussels, a previous study demonstrated CA activity and protein expression to be enhanced in digestive gland by cadmium exposure. The aim of the present work was to investigate the functional meaning, if any, of this response. To this end the study addressed the possible involvement of CA in the lysosomal system response of digestive gland cells to metal exposure. The in vivo exposure to acetazolamide, specific CA inhibitor, significantly inhibited the acidification of the lysosomal compartment in the digestive gland cells charged with the acidotropic probe LysoSensor Green D-189, demonstrating in vivo the physiological contribution of CA to the acidification of the lysosomes. Under CdCl2 exposure, CA activity significantly increased in parallel to the increase of the fluorescence of LysoSensor Green charged cells, which is in turn indicative of proliferation and/or increase in size of lysosomes. Acetazolamide exposure was able to completely inhibit the cadmium induced Lysosensor fluorescence increase in digestive gland cells. In conclusion, our results demonstrated the functional role of CA in the lysosomal acidification of Mytilus galloprovincialis digestive gland and its involvement in the lysosomal activation following cadmium exposure. CA induction could physiologically respond to a prolonged increased requirement of H+ for supporting lysosomal acidification during lysosomal activation.
- Idiopathic basal ganglia calcification associated with cerebral micro-infarcts: a case report. [Journal Article]
- BNBMC Neurol 2018 Apr 17; 18(1):42
- CONCLUSIONS: Cerebrovascular insufficiency due to the lack of elasticity caused by microvascular calcification might have been one of the pathophysiological features of IBGC in this case. Thus, vascular calcification may cause cerebrovascular disturbance and could lead to ischemic stroke in patients with IBGC.
- Carbonic anhydrase is not a relevant nitrite reductase or nitrous anhydrase in the lung. [Journal Article]
- JPJ Physiol 2018 Apr 16
- 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 ...
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. We found that acetazolamide prevents HPV in anaesthetized pigs as in other mammalian species. A single nebulization of sodium nitrite reduces HPV, but this action wanes in the succeeding 3 h of hypoxia as nitrite is metabolized and excreted. Pulmonary artery pressure reduction, as well as NO formation as measured by exhaled gas concentration from inhaled sodium nitrite, were not increased by acetazolamide during alveolar hypoxia. Thus, our data argue against a physiological role of carbonic anhydrase as a nitrous anhydrase or nitrite reductase in the lung and blood in vivo as a mechanism for its inhibition of HPV. This article is protected by copyright. All rights reserved.
- Side-to-Side and End-to-Side Double Anastomosis Using the Parietal-Branch of the Superficial Temporal Artery-A Novel Technique for Extracranial to Intracranial Bypass Surgery: 3-Dimensional Operative Video. [Journal Article]
- ONOper Neurosurg (Hagerstown) 2018 Apr 12
- In this 3-dimensional video, we perform a side-to-side and end-to-side double anastomosis using the parietal-branch of the superficial temporal artery (STA) to provide flow augmentation in a symptoma...
In this 3-dimensional video, we perform a side-to-side and end-to-side double anastomosis using the parietal-branch of the superficial temporal artery (STA) to provide flow augmentation in a symptomatic 59-yr-old male with bilateral internal carotid artery occlusion at the origin, and left M1 segment occlusion. The patient suffered multiple left hemispheric strokes despite maximal medical therapy and was found to have poor hemodynamic reserve in the left hemisphere during evaluation with regional and global blood oxygenation level-dependent functional magnetic resonance imaging with CO2-challenge as well as quantitative magnetic resonance angiography and noninvasive optimal vessel analysis pre- and post-acetazolamide challenge. Postoperatively, the patient did very well and his hemodynamic studies improved significantly. The importance of this technique relies on the fact that we are using a single donor vessel to perform 2 anastomoses, and carries the following advantages: (1) the frontal STA branch remains intact and therefore can still be used at a later time if further revascularization is needed; (2) wound complications related to devascularizing the scalp from harvesting both STA branches are reduced; (3) 2 vascular territories are augmented (frontal and temporal) while using a single donor; (4) we are maximizing donor potential and optimizing cut flow index (CFI; total bypass flow postanastomosis divided by bypass cut flow) by flow augmenting 2 separate vascular beds therefore increasing demand. To explain that fourth point further: if the STA donor is able to carry a maximum 100 mL/min when cut, and after performing the first anastomosis bypass flow is only 37 mL/min, CFI will be 37/100 = 0.37, reflecting low demand, a poor indicator of graft patency, as previously published.1,2 By adding a second anastomosis which demands an additional 60 mL/min from the same STA donor, CFI (60 + 37)/100 improves to 1. Institutional Review Board approval was obtained for the review of patient chart and video files. Informed consent was obtained directly from the patient via telephone regarding use of media for educational and publication purposes.
- Pseudotumor cerebri in kaposiform lymphangiomatosis: a case report and pathogenetic hypothesis. [Journal Article]
- CNChilds Nerv Syst 2018 Apr 13
- CONCLUSIONS: A network of intracranial lymphatics is presently being investigated. Neuroimaging excluded KLA infiltration of the skull and/or meninges, leaving as the most plausible explanation for the child's pseudotumor cerebri the existence of an increase in intracranial venous pressure by venous compression at the thorax. To our knowledge, our case constitutes the first report of pseudotumor cerebri occurring in the context of KLA.
- Comparative cost evaluation of brand name and generic ophthalmology medications in Ontario. [Review]
- CJCan J Ophthalmol 2018; 53(2):173-187
- Medication cost for the same indication can vary considerably and can affect patient compliance. In this comparative cost analysis of commonly prescribed ophthalmology medications, the differences in...
Medication cost for the same indication can vary considerably and can affect patient compliance. In this comparative cost analysis of commonly prescribed ophthalmology medications, the differences in cost between generic and brand name medications as well as different medications within an individual drug class were evaluated. Eye preparations from the Ontario Drug Benefit Formulary were identified, and further agents commonly prescribed by ophthalmologists were included. The standardized prescription drug cost, which includes the cost of the medication, mark-up, and dispensing cost, was provided by Ontario Shoppers Drug Mart stores in July 2016 for 103 common medications using typical dosages and durations. Based on medication class, the highest and lowest cost medications were antiallergy agents (Zaditor [ketotifen], Vasocon [naphazoline]), antibiotic ophthalmic solutions (Vigamox [moxifloxacin], generic ciprofloxacin), oral antibiotics (Cipro [ciprofloxacin], generic cephalexin), antibiotic ophthalmic ointments (generic erythromycin, Tobrex [tobramycin]), antiviral treatment (Valtrex [oral valacyclovir], Viroptic [topical trifluridine]), blepharitis treatment (Zithromax [oral azithromycin], generic oral tetracycline), beta-adrenergic inhibitors (Timoptic [topical timolol], generic topical timolol), topical prostaglandin analogues (Xalatan [latanoprost], generic travoprost), oral carbonic anhydrase inhibitors (methazolamide, acetazolamide), topical carbonic anhydrase solutions (Trusopt preservative-free [dorzolamide], Azopt [brinzolamide]), topical alpha-adrenergic agonists (Alphagan [brimonidine], generic brimonidine), topical muscarinic agonists (Isopto carpine [pilocarpine], Diocarpine [pilocarpine]), topical combination glaucoma agents (Cosopt [dorzolamide-timolol], generic dorzolamide-timolol), topical lubricants (Lacri-lube, Isopto tears), topical nonsteroidal anti-inflammatory drugs (Acuvail [ketorolac], Ilevro [nepafenac]), and steroids (Durezol [difluprednate], Pred mild [prednisolone]). Substantial cost differences exist between ophthalmology medications of the same class. We encourage ophthalmologists to be aware of the associated costs of the medications they prescribe and to use this information in their decision making.
- Evaluating off-label uses of acetazolamide. [Review]
- AJAm J Health Syst Pharm 2018 Apr 15; 75(8):524-531
- CONCLUSIONS: Acetazolamide is a carbonic anhydrase inhibitor typically used for indications including epilepsy, glaucoma, edema, and altitude sickness but it may be prescribed in hospitalized patients for off-label indications. It inhibits carbonic anhydrase, which leads to reduced hydrogen ion secretion in the proximal renal tubule, resulting in increased bicarbonate and cation excretion and causing urinary alkalization and diuresis. In addition, acetazolamide decreases the production of cerebrospinal fluid (CSF) and aqueous humor, reducing intracranial pressure (ICP) and intraocular pressure. This allows acetazolamide to be used for treatment of idiopathic intracranial hypertension and elevated ICP due to CSF leaks to avoid invasive procedures. It is a sulfonamide derivative, with dosages ranging from 250 to 4,000 mg daily divided every 6-12 hours. The plasma half-life is 4-8 hours, though the pharmacologic effects of acetazolamide last longer. Acetazolamide is highly protein bound and primarily eliminated by the kidneys, so administration should not be more frequent than every 12 hours if creatinine clearance is less than 50 mL/min. Limited literature exists describing the optimal patients to receive acetazolamide therapy.The potential benefits of acetazolamide include ventilator weaning for chronic obstructive pulmonary disease patients, avoidance of invasive procedures in patients with a CSF leak or elevated ICP, and prevention of high-dose methotrexate toxicity and contrast-induced nephropathy. Uncertainty remains regarding the selection of patients who would best benefit from acetazolamide use.
- Coronary artery bypass surgery in patients with chronic brain hypoperfusion. [Journal Article]
- JCJ Cardiovasc Surg (Torino) 2018 Apr 03
- CONCLUSIONS: CABG can be performed at an acceptable risk in patients with brain hypoperfusion. However, these patients suffered high stroke incidence during the follow-up. It is therefore, important to identify those patients preoperatively to plan and implement an appropriate treatment regime.
- Characterizing the glymphatic influx by utilizing intracisternal infusion of fluorescently conjugated cadaverine. [Journal Article]
- LSLife Sci 2018 Mar 29
- CONCLUSIONS: Subarachnoid CSF could flow into the brain parenchyma via the glymphatic influx, in which the transcellular pathway was faithfully traced by intracisternal infusion with fluorescently conjugated cadaverine. These observations extend our comprehension on the glymphatic influx pathway.
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- Interstitial Pulmonary Edema and Acetazolamide in High-Performance Sport: A Case Report. [Journal Article]
- ABArch Bronconeumol 2018 Mar 27