- Corrigendum to "Acetazolamide-based [18F]-PET tracer: In vivo validation of carbonic anhydrase IX as a sole target for imaging of CA-IX expressing hypoxic solid tumors" [Bioorg. Med. Chem. Lett. 28 (5) (2018) 915-921]. [Published Erratum]
- BMBioorg Med Chem Lett 2018 Jun 18
- Combined treatment with acetazolamide and cisplatin enhances chemosensitivity in laryngeal carcinoma Hep-2 cells. [Journal Article]
- OLOncol Lett 2018; 15(6):9299-9306
- The aim of the present study was to determine whether acetazolamide (Ace) treatment enhances the chemosensitivity of Hep-2 laryngeal cells to cisplatin (Cis). At the logarithmic growth phase, Hep-2 c...
The aim of the present study was to determine whether acetazolamide (Ace) treatment enhances the chemosensitivity of Hep-2 laryngeal cells to cisplatin (Cis). At the logarithmic growth phase, Hep-2 cells were treated with Ace, Cis or both, and cell viability was detected using an MTT assay. The degree of apoptosis was detected using flow cytometry. Expression levels of apoptosis-related proteins, including BCL2 apoptosis regulator (bcl-2), BCL2 associated X (bax) and caspase-3, and of proliferation-related proteins, including proliferating cell nuclear antigen (PCNA) and tumor protein p53 (P53), were detected using western blotting. mRNA expression levels of aquaporin-1 (AQP1) in each group were detected using reverse transcription-polymerase chain reaction. Compared with the drugs used alone, treatment with both Ace and Cis displayed synergistic effects on the growth inhibition and apoptosis induction in Hep-2 cells. The Ace/Cis combination decreased the expression of PCNA but increased the expression of p53. In addition, the combination treatment decreased the ratio of bcl-2/bax and increased the expression of caspase-3, as well as decreased the expression of AQP1. These results demonstrated that the combined use of Ace and Cis enhanced the chemosensitivity of laryngeal carcinoma cells.
- COMPARATIVE ORAL DRUG CLASSIFICATION SYSTEMS: ACETAZOLAMIDE, AZITHROMYCIN, CLOPIDOGREL AND EFAVIRENZ CASE STUDIES. [Journal Article]
- MPMol Pharm 2018 Jun 21
- Biopharmaceutics classification systems based on properties of solubility and permeability or extension of metabolism are very important tools in the early stages of development and regulatory stages...
Biopharmaceutics classification systems based on properties of solubility and permeability or extension of metabolism are very important tools in the early stages of development and regulatory stages of new products. However, until now there is no clear understanding between the interplay among these classification systems. Therefore, the main objective of this work was to make a comparison of concepts of BCS and BDDCS to understand what are the key factors that allowing the integration of these biopharmaceutics classification systems. Also, it was assessed the suitability of an in situ single-pass intestinal perfusion assay in rats (SPIP) development by us to determine the limit between high and low permeability following to what the FDA BCS guidance suggests. An excellent correlation was found between values of permeability obtained by applying SPIP assays and the extensions of the metabolism of the set of compounds studied in this work, with the exception of three compounds that showing disparity between their permeability coefficients (Peff), obtained herein by SPIP, and their metabolism (acetazolamide, azithromycin and efavirenz). Discrepancies allowed us to elucidate the interrelationship between BCS and BDDCS.
- Cystoid Macular Edema due to Accidental Latanoprost Overdose after Uncomplicated Phacoemulsification. [Journal Article]
- CDCurr Drug Saf 2018 Jun 19
- We present an interesting case of accidental overdose of latanoprost eye drops. A 71-year-old patient underwent an uncomplicated cataract surgery in his right eye. During the first postsurgical week ...
We present an interesting case of accidental overdose of latanoprost eye drops. A 71-year-old patient underwent an uncomplicated cataract surgery in his right eye. During the first postsurgical week he mistakenly used latanoprost eye drops six times daily instead of the prescribed tobramycin/dexamethasone eye drops. The patient experienced gradually decreasing visual acuity and was diagnosed with cystoid macular edema seven weeks after surgery. The cystoid macular edema resolved 4 weeks later after treatment with nepafenac 0.3% eye drops and oral acetazolamide. The cystoid macular edema recurred 2 weeks after rechallenge with latanoprost. The rechallenge-induced cystoid macular edema once again resolved after cessation of latanoprost and retreatment with nepafenac eye drops. A Naranjo assessment score of 7 was obtained, indicating a probable relationship between the patient's symptoms and the suspect drug.
- Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans. [Journal Article]
- HHypertension 2018 Jun 18
- Greater aortic stiffness and pulse pressure are associated with cerebrovascular remodeling, reduced white matter microstructure, and cognitive performance with aging in humans. However, it is unclear...
Greater aortic stiffness and pulse pressure are associated with cerebrovascular remodeling, reduced white matter microstructure, and cognitive performance with aging in humans. However, it is unclear whether aortic stiffness and pulse pressure are associated with reduced basal global cerebral blood flow (CBF) and cerebrovascular reserve among older adults. Global CBF was quantified in 205 adults (range, 19-87 years; mean±SE: 30.6±1.3 years) using quantitative [15O]water brain positron emission tomography imaging. In a subset of older adults (n=24; 70.0±2.0 years), aortic stiffness (carotid femoral pulse wave velocity) and cerebrovascular reserve (change in global CBF after intravenous infusion of acetazolamide) were assessed. In the entire cohort, global CBF was lower in older compared with young adults (36.5±1.1 versus 50.5±0.7 mL/min per 100 mL; P<0.001). Global CBF was higher in young women compared with young men (51.0±0.30 versus 47.4±0.03 mL/min per 100 mL; P<0.001) but did not differ between older women and men (P=0.63). In older adults, greater carotid femoral pulse wave velocity was associated with lower cerebrovascular reserve (r=-0.68; P=0.001 adjusted for age, sex, and mean arterial pressure) but not global CBF (r=0.13; P=0.60). Brachial pulse pressure was not associated with lower cerebrovascular reserve (r=-0.37; P=0.159) when adjusted for age and sex. These data indicate that the age-related increases in aortic stiffness may contribute, in part, to the brain's impaired ability to augment blood flow in response to a stimulus with aging in humans.
- Design and synthesis of novel benzenesulfonamide containing 1,2,3-triazoles as potent human carbonic anhydrase isoforms I, II, IV and IX inhibitors. [Journal Article]
- EJEur J Med Chem 2018 Jun 08; 155:545-551
- In a quest to discover new biologically active compounds, a series of twenty novel heterocyclic derivatives substituted at position 5 with -H (7a-7j) or -CF3 (8a-8j), bearing benzenesulfonamide at N-...
In a quest to discover new biologically active compounds, a series of twenty novel heterocyclic derivatives substituted at position 5 with -H (7a-7j) or -CF3 (8a-8j), bearing benzenesulfonamide at N-1 position and various aroyl groups at position 4 of the 1,2,3-triazole ring was synthesized and screened for their carbonic anhydrase (CA, EC 184.108.40.206) inhibition potential against four human (h) isoforms hCA I, II, IV and IX. All the compounds (7a-7j and 8a-8j) were synthesized via [3+2] cycloaddition reaction from 4-azidobenzenesulfonamide. Interestingly, compounds 7a-7j were prepared in one pot manner via enaminone intermediate using novel methodology. All the newly synthesized compounds (7a-7j &8a-8j) were found to be excellent inhibitors of edema related isoform hCA I with their inhibition constant (Ki) ranging from 30.1 to 86.8 nM as compared to standard drug acetazolamide (AAZ) with Ki = 250 nM. Further it was found that most of tested compounds were weaker inhibitors of isoform, hCA II although compounds 7b, 7d-7e, 8a, 8d-8f, 8i (mostly with electron withdrawing substituents) have shown better inhibition potential (Ki < 50 nM). Against glaucoma associated hCA IV, compound 7d was found to be better inhibitor (Ki = 52.4 nM) than AAZ (Ki = 74 nM) while against tumor associated hCA IX, all the compounds have shown moderate inhibition potential. Present study have added one more step in exploring the 1,2,3-triazlole moiety in the medicinal field.
- 22q11.2 microduplication syndrome and juvenile glaucoma. [Journal Article]
- OGOphthalmic Genet 2018 Jun 14; :1-7
- CONCLUSIONS: 22q11.2 microduplication syndrome can be associated with juvenile glaucoma. Trabeculectomy may be complicated by persistent hypotony. Deep sclerectomy appears to be a better surgical option, although the presence of a thin sclera may result in conversion to trabeculectomy.
- Topiramate is more effective than acetazolamide at lowering intracranial pressure. [Journal Article]
- CCephalalgia 2018 Jan 01; :333102418776455
- Background The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of som...
Background The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats. Methods We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate. Results At clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% (p = 0.0009) and 21% (p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% (p = 0.018), compared to 5% reduction with acetazolamide (p = >0.999). Conclusion Our in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.
- Editor's Choice-Diuretic resistance in acute heart failure. [Journal Article]
- EHEur Heart J Acute Cardiovasc Care 2018; 7(4):379-389
- Diuretic resistance is a powerful predictor of adverse outcome in acute heart failure (AHF), irrespectively of underlying glomerular filtration rate. Metrics of diuretic efficacy such as natriuresis,...
Diuretic resistance is a powerful predictor of adverse outcome in acute heart failure (AHF), irrespectively of underlying glomerular filtration rate. Metrics of diuretic efficacy such as natriuresis, urine output, weight loss, net fluid balance, or fractional sodium excretion, differ in their risk for measurement error, convenience, and biological plausibility, which should be taken into account when interpreting their results. Loop diuretic resistance in AHF has multiple causes including altered drug pharmacokinetics, impaired renal perfusion and effective circulatory volume, neurohumoral activation, post-diuretic sodium retention, the braking phenomenon and functional as well as structural adaptations in the nephron. Ideally, these mechanisms should guide specific treatment decisions with the goal of achieving complete decongestion. Therefore, volume overload needs to be identified correctly to avoid poor diuretic response due to electrolyte depletion or dehydration. Next, renal perfusion should be optimised if possible and loop diuretics should be prescribed above their threshold dose. Addition of thiazide-type diuretics should be considered when a progressive decrease in loop diuretic efficacy is observed with prolonged use (i.e., the braking phenomenon). Furthermore, thiazide-type diuretics are a useful addition in patients with low glomerular filtration rate. However, they limit free water excretion and are relatively contraindicated in cases of hypotonic hyponatremia, where acetazolamide is the better option. Finally, ultrafiltration should be considered in patients with refractory diuretic resistance as persistent volume overload after decongestive treatment is associated with worse outcomes. Whether more upfront use of any of these individually tailored decongestion strategies is superior to monotherapy with loop diuretics remains to be shown by adequately powered randomised clinical trials.
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- Raised intracranial pressure with bilateral anterior uveitis. [Journal Article]
- BCBMJ Case Rep 2018 Jun 10; 2018
- We report the rare case of a 5-year-old boy with an infective cause of papilloedema and bilateral uveitis secondary to Mycoplasma pneumoniae The patient presented with generalised headache and malais...
We report the rare case of a 5-year-old boy with an infective cause of papilloedema and bilateral uveitis secondary to Mycoplasma pneumoniae The patient presented with generalised headache and malaise. MRI showed signs of raised intracranial pressure and lumbar puncture opening pressure was 43 cmH2O.Lumbar puncture did not reveal any infective organisms. Blood tests showed raised inflammatory markers. The patient was started on prednisolone, acetazolamide and intravenous cefotaxime. Following an improvement, the patient was discharged.However, the patient re-presented 2 weeks later with bilateral anterior uveitis. With the combination of papilloedema and bilateral uveitis, M. pneumoniae infection was suspected. Tests confirmed recent mycoplasma infection. Topical dexamethasone and oral azithromycin were given and symptoms improved.Vision remained normal throughout. At 1-year follow-up, the patient remains well. The authors would like to highlight a rare infectious cause of papilloedema in young children.