SEARCH · Search PubMed

Results for “ACETAZOLAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,783 records · Page 99Linked to original sources

PubMed1999

Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors.

PURPOSE: To evaluate how the oxygen tension of the optic nerve (ONP(O)2) is affected by the administration of the carbonic anhydrase inhibitors dorzolamide and acetazolamide and by alterations in oxygen and carbon dioxide in the breathing mixture. METHODS: Polarographic oxygen electrodes were placed in the vitreous humor immediately over the optic disc in 20 anesthetized pigs. Blood gasses and cardiovascular physiology were monitored. ONP(O)2 was recorded continuously with breathing gasses of 21% O2-79% N2, 100% O2, 20% O2-80% N2, and 5.19% CO2-19.9%, O2-74.9% N2. Acetazolamide (15-1000 mg) and dorzolamide (6-1000 mg) were administered intravenously. RESULTS: The mean (+/- SD) ONP(O)2 was found to be 24.1+/-11.6 mm Hg when the pigs were breathing room air and 50.7+/-29.3 mm Hg when they were breathing 100% O2 (n = 15; P < 0.001). In response to breathing 5.19% CO2, ONP(O)2 changed from 20.8+/-5.6 mm Hg (with 20.0% O2) to 28.9+/-3.6 mm Hg (n = 4; P < 0.001). Intravenous injections of 500 mg dorzolamide increased ONP(O)2 from 16.4+/-6.1 mm Hg to 26.9+/-12.2 mm Hg, or 52.5%+/-21.2% (n = 5; P = 0.017). A dose-dependent effect on ONP(O)2 was seen with intravenous dorzolamide doses of 1000, 500, 250, 125, 63, 27, 15, and 6 mg. Intravenous injections of 500 mg acetazolamide increased ONP(O)2 from 23.6+/-9.5 mm Hg to 30.9+/-10.0 mm Hg (n = 6; P < 0.001), and a dose-dependent effect was seen with doses of 1000, 500, 250, 125, 31, and 15 mg. CONCLUSIONS: ONP(O)2 is significantly increased by the carbonic anhydrase inhibition of dorzolamide and acetazolamide, and the effect is dose dependent. These data demonstrate for the first time a direct effect of carbonic anhydrase inhibitors on ONP(O)2.

Acetazolamide↗

PubMedDate not supplied

[The influence of the arterial pressure in the study of cerebrovascular reactivity in carotid obstructions].

INTRODUCTION: Cerebrovascular reactivity (CVR) is the capacity of the cerebral microcirculation to increase cerebral blood flow on vasodilator stimulation. This is reduced in patients with carotid obstruction. The changes in arterial pressure produced whilst carrying out different tests for estimation of the CVR may affect its measurement by transcranial Doppler. OBJECTIVES: To evaluate the concordance between the different methods for estimation of the CVR by transcranial Doppler in patients with carotid obstruction and to evaluate the importance of monitoring the arterial pressure during CVR tests. PATIENTS AND METHODS: We evaluated 17 patients with internal carotid artery obstruction confirmed on arteriography. The CVR was determined by three different methods: apnea test. Breath-Holding Index (BHI) and intravenous acetazolamide test. RESULTS: During the tests of RCV the arterial pressure was monitored. We found that there was a reduction in the average basal rate of flow and of the pulsatile index on the obstructed side, with a statistically significant association in relation to the contralateral side (p < 0.001). There was good concordance between the different tests of CVR, with reduced CVR seen on the obstructed side as compared to the contralateral side (p < 0.001) for the different tests. However, this correlation was not seen in stenosis < 70%. During the apnea test changes in blood pressure occurred, with a tendency to increase in the systolic pressure. However, there were no significant changes in blood pressure during the acetazolamide test. CONCLUSIONS: There is good concordance in the CVR between the apnea, BHI and acetazolamide tests in carotid obstruction. Changes in arterial pressure occurred during the apnea and BHI tests. However, the acetazolamide test caused no change in arterial pressure.

Acetazolamide↗

PubMed2001

Acute mountain sickness score and hypoxemia.

BACKGROUND: Hypoxemia is the immediate consequence of hyobaric hypoxia, which is the crucial starting mechanism of acute mountain sickness (AMS). The AMS is generally a benign and self-limiting condition which can be prevented by gradual ascent. However, ascent rates recommended for prophylaxis of AMS are far slower than those attempted during military operations and by climbers. OBJECTIVE: The current study was carried out to quantify the relationship between AMS and hypoxemia alongwith evaluating the benefits of acetazolamide-dexamethasone chemoprophylaxis during acute ascent. SUBJECTS AND METHODS: Twenty-four low lander male adults (age mean +/- SE 27.8 +/- 1.24 years) were selected. They were grouped in a double-blind fashion into four groups and each group (n = 6) received placebo (multivitamin) or acetazolamide (250 mg) or dexamethasone (4 mg) or a combined regimen of the two drugs twice daily for 5 days, commencing 24 hours before ascent. The volunteers reached the altitude of 4578 meters within a span of one day. Their AMS symptoms were recorded on modified environmental symptoms questionnaire (ESQ), after 24 and 72 hours of ascent. Arterial PO2, SO2 and PCO2 were measured by GEMSTAT blood-gas analyzer (Mallincrodt-USA). RESULTS: The ESQ, AMS-C (cerebral) and AMS-R (respiratory) scores of combined therapy group were significantly lower as compared to the other groups on the symptom rating scale. The significant finding amongst the volunteers taking acetazolamide was mild to moderate diuresis whereas severity of headache was markedly less in dexamethasone group. The commonest feature of combined therapy was that none of the volunteers complained of headache, dysponea, irritability and more than mild disturbance of sleep. The ESQ scores of volunteers were inversely correlated to PaO2 and SaO2 after 24 hours of ascent to 4578 meters. CONCLUSION: The study concludes that severity of AMS is closely related to hypoxemia and combination therapy of acetazolamide-dexamethasone may be effective in preventing AMS.

Acetazolamide↗

PubMed2004

Reduced blood flow and preserved vasoreactivity characterize oxygen hypometabolism due to incomplete infarction in occlusive carotid artery diseases.

UNLABELLED: Recent studies have clarified that hemodynamically compromised patients are at high risk for subsequent stroke. The acetazolamide test is widely used to detect the patients with hemodynamic compromise due to occlusive carotid artery disease. Previous studies have suggested that patients with impaired reactivity to acetazolamide had an increased oxygen extraction fraction (OEF) on PET. However, the underlying pathophysiology has not been defined in patients with reduced blood flow and preserved reactivity to acetazolamide due to carotid occlusive diseases regardless of a normal appearance on MRI. This study aimed to clarify hemodynamic and metabolic parameters in such patients, using (15)O gas and (11)C-flumazenil (FMZ) PET. METHODS: Our study included 15 patients who had reduced cerebral blood flow (CBF) and preserved cerebrovascular reactivity (CVR) to acetazolamide in the ipsilateral middle cerebral artery territory due to occlusive carotid diseases on N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) SPECT. We determined the CBF, cerebral metabolic rate for oxygen (CMRO(2)), cerebral blood volume (CBV), and OEF using (15)O gas PET. The binding potential for (11)C-FMZ was also measured in 5 patients. All patients were medically treated and followed-up during a mean period of 2.7 y. RESULTS: (15)O gas PET scans revealed that the ipsilateral CBF and CMRO(2) were reduced to 80% +/- 11% (P < 0.0001) and 78% +/- 8% (P < 0.0001) of the contralateral side, respectively. However, there was no significant side-to-side difference in the CBV and OEF. The ipsilateral binding potential for (11)C-FMZ was also significantly reduced to 82% +/- 2% of the contralateral side (P < 0.05), being very similar to the asymmetry of the CBF and CMRO(2). No patients suffered further ischemic stroke in the ipsilateral hemisphere during the follow-up period. CONCLUSION: Our results strongly suggest that a reduced CBF and a normal CVR characterize oxygen hypometabolism probably due to ischemia-related neuronal loss-namely, incomplete infarction. Such an ischemic lesion is not hemodynamically compromised and is at very low risk for a subsequent ischemic stroke even if the patient is medically treated.

Acetazolamide↗

PubMed2006

[Effect of inhibiting aquaporin-1 on proliferation and apoptosis of the Hep-2 cell].

OBJECTIVE: To explore the effect of inhibiting aquaporin-1 (AQP-1) on proliferation and apoptosis of the Hep-2 cell. METHOD: The expression of AQP-1 in Hep-2 cell was identified through immunohistochemistry. After using acetazolamide, an antagonist of AQP-1, the assay of cell proliferation, apoptosis and the expression of AQP-1 were performed by microculture tetrazolium salt(MTT) and flow cytometry, TUNEL respectively. RESULT: The expression of AQP-1 is mainly found on membrane of Hep-2 cell and the expression is significantly reduced when the concentration of acetazolamide is 5 x 10(-5) mol/L. Noteworthily, inhibiting AQP-1 by acetazolamide, the rate of cell growth and cell apoptosis significantly increases with the time prolong. It showed time-dependent phenomena. There is positive relationship obviously between cell apoptosis rate and inhibition rate of the AQP-1 protein expression. CONCLUSION: The inhibiting AQP-1 with acetazolamide may significantly induce apoptosis of Hep-2 cell. It suggest that AQP-1 may be as new target of therapy of laryngeal cancer.

Acetazolamide↗

PubMed1983

Effects of competitive red blood cell binding and reduced hematocrit on the blood and plasma levels of [14C]Indapamide in the rat.

The effects of chlorthalidone and acetazolamide on the red blood cell binding of indapamide were investigated. Both drugs caused a substantial decrease in the amount of indapamide bound to the erythrocytes in vitro. This effect was demonstrated by a change in the indapamide blood/plasma ratio from approximately 6 in control samples, to a value of 1 when either of the displacing agents was added. Coadministration of acetazolamide with 14C-labeled indapamide to rats, resulted in a 5-fold drop in the blood levels of total radioactivity, relative to rats dosed with [14C]indapamide alone. Concomitantly, there was a 2-fold increase in the plasma levels of total radioactivity after acetazolamide coadministration. In rats whose hematocrits had been reduced by extensive bleeding, there were only minor alterations in the blood/plasma partitioning of [14C]indapamide. Thus, chlorthalidone and acetazolamide were able to displace indapamide from erythrocytes in vitro and in vivo, possibly by competition at a carbonic anhydrase binding site. The pharmacokinetics of drugs which are extensively bound to erythrocytes may be significantly altered by the presence of other agents capable of competitive binding.

Acetazolamide↗

PubMed1994

Pharmacological inhibition of brain carbonic anhydrase protects against 4-aminopyridine seizures.

The effects of the inhibition of carbonic anhydrase on the manifestation of tonic-clonic seizures were investigated in freely-moving rats. 4-Aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult male rats with 20 or 40 mg/kg acetazolamide, 3, 5, 7 or 9 mg/kg 4-aminopyridine was injected intraperitoneally and the latencies of the symptoms were measured. Pharmacological inhibition of brain carbonic anhydrase significantly increased the latency of onset of seizures. Bolus administration of acetazolamide decreased the incidence of generalized convulsions and protected against status epilepticus. Chronic acetazolamide treatment for 2 days affected only the generalized convulsions. The results suggested that alterations of the extracellular and intracellular pH by acetazolamide decreased the efficacy of synaptic transmission in several areas of the brain. The possible effects of the HCO3- ions on the sensitivity of synaptic and nonsynaptic neuronal receptors are discussed.

4-Aminopyridine↗

PubMedDate not supplied

Further electrophysiological characterization of the alpha- and beta-intercalated cells along the rabbit distal nephron segments: effects of inhibitors.

To further characterize the alpha- and beta-intercalated cells (alpha-IC, beta-IC) in the isolated and perfused connecting tubule (CNT), cortical collecting duct (CCD) and outer medullary collecting duct in the inner stripe (OMCDi) of rabbit kidneys, we studied the effects of various transport inhibitors on electrical parameters. They included inhibitors of Cl-/HCO3- exchanger (4-acetamino-4'-isothiocyanostilbene-2,2'-disulfonic acid, SITS), carbonic anhydrase (acetazolamide) and Na(+)-K(+)-ATPase (ouabain). Upon addition of 10(-3) M SITS to the bath, the basolateral membrane voltage (VB) of alpha-IC in the OMCDi and CCD was significantly hyperpolarized by 20.8 +/- 4.6 (n = 5) and 29.8 +/- 5.6 mV (n = 11), respectively. On the other hand, luminal addition of SITS had no effects on VB of alpha-IC in the OMCDi and CCD. Neither bath nor lumen SITS affected VB of beta-IC in the CCD and CNT. When 10(-4) M acetazolamide was added to the bath, VB of alpha-IC in the OMCDi and CCD was significantly hyperpolarized by 20.0 +/- 4.1 (n = 4) and 18.6 +/- 1.7 mV (n = 3), respectively. Similarly, 10(-4) M acetazolamide in the bath caused the basolateral membrane of beta-IC in the CCD and CNT to hyperpolarize significantly by 34.3 +/- 7.9 (n = 6) and 21.6 +/- 2.9 mV (n = 3), respectively. Luminal addition of acetazolamide had no effect on VB of alpha-IC in the CCD and OMCDi and beta-IC in the CCD and CNT.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

PubMed1975

[Prevention of altitude sickness].

In experimental and clinical studies the effect of Acetazolamide (Diamox) on acute mountain sickness was investigated. It could be established that Acetazolamide does influence the symptoms, the man effect seems to be a reduction of the respiratory alkalosis, which is found in control persons in high altitudes. Observations made with a group of 25 tourists mountaineering in the Cordilleras (South America) over 24 days in altitudes between 3200 and 6000 m are described. In accordance with other published data the favorable influence of Acetazolamide on acute mountain sickness could be confirmed. Persons taking Acetazolamide were more efficient and better prepared to cope with the extreme situations in high altitude. They also showed to be more resistent to other diseases, which are following the stress in high altitude and are caused by the different climate and food.

Acclimatization↗

PubMedDate not supplied

A carbonic anhydrase inhibitor as a potential modulator of cancer therapies.

Since several anticancer drugs are known to become more cytotoxic to cells in an acidic milieu, we have attempted to utilize the carbonic anhydrase inhibitor, Acetazolamide, to acidify the blood and tumor of C3H mice bearing the FSaIIC fibrosarcoma in order to sensitize tumor cells in vivo to CDDP, Melphalan, BCNU, SR4233 or PtCl4 (Fast Black)2 +/- hyperthermia. The direct cytotoxic interactions between the anticancer drugs and Acetazolamide were tested in FSaIIC cells in vitro with the monacidifying diuretic Chlorothrozide as a control. When cells were exposed to CDDP both diuretics protected against cytotoxicity in a dose dependent fashion. In contrast, cells exposed to Melphalan were minimally sensitized and those exposed to BCNU, SR4233, or PtCl4 (Fast Black)2 were essentially unaffected by the presence of the diuretic agents. Both diuretics were essentially non-toxic to cells in vitro, and, interestingly, both drugs markedly protected cells against hyperthermia under low pH conditions. In vitro, however, Acetzolamide produced a tumor growth delay of 2.3 days alone when given at 10 mg/kg i.p. once (the most effective dose) and produced additive growth delays with CDDP and Melphalan, but probably greater than additive delays with SR4233 and PtCl4 (Fast Black)2. When Acetazolamide was given daily for 5 days starting on the day the anticancer drugs were given once (day 7) essentially no further increase in tumor growth delay of nearly 16 days was observed versus only 4,6 days for the drug alone. When hyperthermia (43 degrees C min.) was delivered locally to the tumor after i.p. injection of the drugs, further growth delays were produced for every drug combination which probably were additive in extent. Blood and urine pH determinations revealed that a pH drop of 1 units occurred in the blood and a pH elevation of 1 to 21 units occurred in the urine 1 hr. after i.p. injection of Acetazolamide. These results indicate that this carbonic anhydrase inhibitor can add to the anticancer activity of the drugs tested. The mechanism may involve its ability to acidify the intratumoral environment, but other mechanisms can not be excluded.

Acetazolamide↗

PubMedDate not supplied

Retention of carbon dioxide in tissue following carbonic anhydrase inhibition in dogs.

To evaluate the retention of carbon dioxide in tissue during the reduction of carbonic anhydrase activity following the administration of 5, 10, 20, or 30 mg/kg of acetazolamide in dogs, we measured carbon dioxide pressure (PCO2) in arterial blood, mixed venous blood, alveoli, and tissue. Respiration was maintained at a constant level. In the control (noninjected) group, PCO2 in tissue did not change for 3 hours under controlled respiration. Following the injection of 5 to 30 mg/kg of acetazolamide, PCO2 increased in arterial blood, mixed venous blood, and tissue in a dose-related manner, and decreased in the alveoli. The (a-et)PCO2 widened to 21.9 +/- 1.0 mmHg from 0.6 +/- 1.0 mmHg, and the (t-v)PCO2 to 16.1 +/- 2.0 mmHg from 5.1 +/- 0.6 mmHg, in response to acetazolamide. It is suggested that carbon dioxide is retained in tissue when carbonic anhydrase activity is inhibited by acetazolamide.

Acetazolamide↗

PubMed1991

Combined photic and nonphotic electro-oculographic responses in the clinical evaluation of the retinal pigment epithelium.

In an attempt to simplify the recording technique in electrophysiologic evaluation of the retinal pigment epithelium, we combined the electro-oculographic light rise, hyperosmolarity and acetazolamide responses in a single recording session. Recordings were performed in six normal subjects and in seven patients with diabetic retinopathy or retinitis pigmentosa. In the patients with background diabetic retinopathy, the hyperosmolarity responses were slightly reduced, while the acetazolamide response and the light rise was normal. In the patients with proliferative diabetic retinopathy, the hyperosmolarity response and light rise were remarkably reduced, while the acetazolamide response was normal. In the patients with retinitis pigmentosa, the hyperosmolarity response and light rise were decreased, while the acetazolamide response was normal. Despite a small study population, we concluded that the clinical results from our combined recording protocol were essentially the same as those reported for each response separately. Because this recording technique simplifies electrophysiologic evaluation of the retinal pigment epithelium, it may help clarify the mechanisms or localization of retinochoroidal and pigment epithelial diseases.

Adolescent↗

PubMed2004

Assessment of cerebral hemodynamics in childhood moyamoya disease using a quantitative and a semiquantitative IMP-SPECT study.

BACKGROUND: We evaluated the cerebral hemodynamics in childhood moyamoya disease patients before and after surgery to assess both surgical indication and the effect of revascularization using single photon emission computed tomography (SPECT) study with N-isopropyl-p-123I-iodoamphetamine (IMP). We compared results of quantitative and semi-quantitative SPECT studies to determine parameters by the semi-quantitative method to define severe hemodynamic ischemia. METHODS: There were 14 pediatric patients with moyamoya disease who suffered transient ischemic attacks (TIAs) in the anterior circulation. Before and after surgical revascularization by STA-MCA bypass and encephalomyosynangiosis (EMS), quantitative IMP-SPECT studies using the autoradiographic method (IMP-ARG method) were performed. Resting regional cerebral blood flow (rCBF) and regional vascular reserve (rVR) were measured in bilateral cortical territories (ROI) and cerebellum. Semi-quantitative parameters were calculated from the ratio of ROI counts to the dominant cerebellar counts (ROI/Ce ratio) at resting and acetazolamide-activated conditions. RESULTS: Before surgery, the mean resting rCBF and rVR in bilateral ACA and MCA territories were less than 40 ml/100 g/min and less than 10%, respectively, indicating severe hemodynamic ischemia. Except for the ACA territories, both the mean resting rCBF and mean rVR values in the entire cortex increased significantly after surgery (p < 0.05). By semi-quantitative studies, before surgery, the mean resting and acetazolamide-activated ROI/Ce ratios in bilateral ACA and MCA territories were less than 0.90 and 0.80, respectively. The mean resting and acetazolamide-activated ROI/Ce ratios increased significantly in the MCA territory after surgery. Severe hemodynamic ischemia, which categorized by the quantitative thresholds (resting rCBF < 40 ml/100 g/min and rVR < 10%) was diagnosed by the semi-quantitative thresholds (resting ROI/ Ce ratio < 0.90 and acetazolamide-activated ROI/Ce ratio < 0.85), the sensitivity and specificity of which were 87.5% and 90.9%, respectively. CONCLUSIONS: The cerebral hemodynamics in childhood moyamoya disease was improved entirely after surgery. Severe hemodynamic cerebral ischemia was diagnosed by not only quantitative but also semi-quantitative IMP-SPECT studies.

Adolescent↗

PubMed2005

Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides.

An inhibition study of the human and bovine membrane-associated isozymes of carbonic anhydrase (CA, EC 4.2.1.1), hCA IV and bCA IV, with a series of sulfonamides and sulfamates, some of which are widely clinically used, such as acetazolamide, methazolamide, ethoxzolamide, topiramate, dorzolamide, dichlorophenamide, celecoxib, and valdecoxib among others, is reported. In contrast to bCA IV, which is generally strongly inhibited by most of these derivatives, hCA IV has a rather different inhibition profile. Several of these compounds such as acetazolamide, ethoxzolamide, and bromosulfanilamide are potent hCA IV inhibitors (K(i)'s of 74-93 nM), others, such as celecoxib and some halogenated sulfanilamides are medium potency inhibitors (K(i)'s of 450-880 nM) whereas most of them are weak hCA IV inhibitors (methazolamide: 6.2 microM; dorzolamide 8.5 microM; topiramate 4.9 microM; dichlorophenamide: 15.3 microM). The hCA IV/bCA IV inhibition ratios for all the investigated compounds ranged between 1.05 (for acetazolamide) and 198.37 (for dorzolamide). Based on these results, we doubt that hCA IV is indeed one of the main contributors to the intraocular pressure (IOP) lowering effects of sulfonamide CA inhibitors, in addition to hCA II, as hypothesized earlier by Maren et al. (Mol. Pharmacol.1993, 44, 901-906). Indeed, both the very good hCA IV inhibitors (acetazolamide and ethoxzolamide) as well as the quite weak hCA IV inhibitors (methazolamide, dorzolamide, or dichlorophanamide) are effective in lowering IOP when administered either systemically or topically. The membrane-associated isozyme which probably is critical for aqueous humor secretion is hCA XII and not hCA IV.

Animals↗

PubMed2005

Carbonic anhydrase metabolism is a key factor in the toxicity of CO2 and COS but not CS2 toward the flour beetle Tribolium castaneum [Coleoptera: Tenebrionidae].

The analogues carbon dioxide (CO(2)), carbonyl sulfide (COS) and carbon disulfide (CS(2)) have been useful as substrate probes for enzyme activities. Here we explored the affinity of the enzyme carbonic anhydrase for its natural substrate CO(2), as well as COS and CS(2) (1) by in vitro kinetic metabolism studies using pure enzyme and (2) through mortality bioassay of insects exposed to toxic levels of each of the gases during carbonic anhydrase inhibition. Hydrolysis of COS to form hydrogen sulfide was catalysed rapidly showing parameters K(m) 1.86 mM and K(cat) 41 s(-1) at 25 degrees C; however, the specificity constant (K(cat)/K(m)) was 4000-fold lower than the reported value for carbonic anhydrase-catalysed hydration of CO(2). Carbonic anhydrase-mediated CS(2) metabolism was a further 65,000-fold lower than COS. Both results demonstrate the deactivating effect toward the enzyme of sulfur substitution for oxygen in the molecule. We also investigated the role of carbonic anhydrases in CO(2), COS and CS(2) toxicity using a specific inhibitor, acetazolamide, administered to Tribolium castaneum (Herbst) larvae via the diet. CO(2) toxicity was greatly enhanced by up to seven-fold in acetazolamide-treated larvae indicating that carbonic anhydrases are a key protective enzyme in elevated CO(2) concentrations. Conversely, mortality was reduced by up to 12-fold in acetazolamide-treated larvae exposed to COS due to reduced formation of toxic hydrogen sulfide. CS(2) toxicity was unaffected by acetazolamide. These results show that carbonic anhydrase has a key role in toxicity of the substrates CO(2) and COS but not CS(2), despite minor differences in chemical formulae.

Animals↗

PubMed1996

Selective effect of thiazides on the human osteoblast-like cell line MG-63.

Thiazide diuretics have been shown to decrease bone-loss rate and to improve bone mineral density in patients using this medication. However, the exact role of thiazides on bone cells is still debated. In the present work, we studied whether thiazides could affect the normal features of osteoblasts using the human model cell line MG-63. Hydrochlorothiazide (HCTZ) did not affect cell growth nor DNA synthesis in these cells, yet slightly increased alkaline phosphatase activity in these cells at pharmacologically relevant concentrations. Under similar conditions, HCTZ dose-dependently inhibited 1,25(OH)2D3-induced osteocalcin secretion by these cells (maximal effect, -40 to 50%, P < 0.005). However, HCTZ did not inhibit the basal production of osteocalcin in MG-63 cells (without 1,25(OH)2D3 induction), which was very low to undectable. Two different thiazide derivatives, chlorothiazide and cyclothiazide, and two structurally related sulfonamides with selective inhibition of carbonic anhydrase (Acetazolamide) or hyperglycemic effects (Diazoxide) were also tested. Chlorothiazide (1000 microM) inhibited osteocalcin secretion (-42 +/- 12.7%) at doses 10-fold higher than HCTZ (100 microM) while cyclothiazide was effective at doses of 1 microM (-27 +/- 3.6%), and hence 100-fold lower than HCTZ, compatible with the relative natriuretic effect in vivo of these compounds. Acetazolamide (10 microM) poorly affected osteocalcin secretion at doses 100-fold higher than those needed in vivo to inhibit carbonic anhydrase. Likewise, Diazoxide (100 microM) poorly affected osteocalcin secretion at doses known to promote its biological effect. Higher doses of acetazolamide and diazoxide induced cell death. Neither Acetazolamide nor Diazoxide affected alkaline phosphatase, whereas chlorothiazide had a weak positive effect on this enzymatic activity. The production of macrophage colony-stimulating factor (M-CSF) was stimulated in the presence of 1,25(OH)2D3 (50 nM), TNF-alpha (2 ng/ml) or both in MG-63 cells. HCTZ (25 microM, 24 hr of preincubation) did not modify basal M-CSF production and did not reduce the response to 1,25(OH)2D3 alone. In contrast, HCTZ inhibited the response to TNF-alpha alone (P < 0.05), and also reduced the response to a combination of 1,25(OH)2D3 and TNF-alpha (P < 0.01). In conclusion, these results indicate that thiazide diuretics show a selective inhibition of osteocalcin secretion and M-CSF production by MG-63 cells unlike structurally related drugs. Therefore, these features may explain, in part, the positive effect of thiazides on bone mineral density.

Alkaline Phosphatase↗

PubMed1995

Haemodynamic evaluation of paraparetic transient ischaemic attacks in childhood moyamoya disease.

The haemodynamic mechanisms responsible for the appearance of paraparetic transient ischaemic attacks in ten patients with childhood moyamoya disease who subsequently underwent bifrontal omental transplantation were investigated. Cerebral perfusion (CP) was measured with 99mTc-hexamethylene-propyleneamine oxime single photon computed tomography prior to and after administration of acetazolamide. Cerebral perfusion was obtained by dividing radioisotope uptake per pixel in regions of interest by that in cerebellum. Haemodynamic reserve was defined as [CP after acetazolamide--CP before acetazolamide]/CP before acetazolamide x 100. Amounts of CP in the anterior portion of the frontal lobe and in the paracentral lobule were 0.70 +/- 0.04 and 0.74 +/- 0.03, respectively, before appearance of the transient ischaemic attacks. The latter was significantly higher than the former (p < 0.0001). Haemodynamic reserves were -11.1 +/- 2.8 and -9.6 +/- 3.0, respectively, at that time. These two parameters were significantly decreased just after paraparetic transient ischaemic attacks and two parameters in the paracentral lobule were more decreased than those in the anterior portion of the frontal lobe. But these increased again after bifrontal omental transplantation in these two regions. In summary, the watershed region was located anterior to the paracentral lobule before appearance of the transient ischaemic attacks, and widened and moved backward to include the paracentral lobule just before their appearance.

Cerebral Angiography↗

PubMed2003

The in vitro and in vivo inhibitory effects of some sulfonamide derivatives on rainbow trout (Oncorhynchus mykiss) erythrocyte carbonic anhydrase activity.

The in vitro and in vivo inhibitory effects of 5-(3alpha, 12alpha-dihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (1), 5-(3alpha, 7alpha, 12alpha-trihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (2), 5-(3alpha, 7alpha, 12alpha-triacetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (3) and acetazolamide on rainbow trout (Oncorhynchus mykiss) (RT) erythrocyte carbonic anhydrase (CA) were investigated. The RT erythrocyte CA was obtained by affinity chromatography with a yield of 20.9%, a specific activity of 422.5EU/mg protein and a purification of 222.4-fold. The purity of the enzyme was confirmed by SDS-PAGE. Inhibitory effects of the sulfonamides and acetazolamide on the RT erythrocyte CA were determined using the CO2-Hydratase method in vitro and in vivo studies. From in vitro studies, it was found that all the compounds inhibited CA. The obtained I50 value for the sulfonamides (1), (2) and (3) and acetazolamide were 0.83, 0.049, 0.82 and 0.052 microM, respectively. From in vivo studies, it was observed that CA was inhibited by the sulfonamides (1), (2) and (3) and acetazolamide.

Animals↗