Addition Of Acetazolamide Research Articles

Acetazolamide and thiamine: An ancillary therapy for chronic mental illness

Twenty-four chronic schizophrenic patients were treated successfully with the addition of acetazolamide and thiamine (A + T) to their unchanged existing therapies in a double-blind, placebo-controlled crossover study. Therapeutic effects were measured by the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Overall, 50% of the patients showed improvement on all assessment scales. No untoward effects occurred in these patients or in patients in previous studies who have been treated continuously with A + T theraoy for as long as 3 years

PH-microclimate at the luminal surface of the intestinal mucosa of guinea pig and rat.

Segments of guinea pig jejunum, proximal and distal colon and of rat jejunum were superfused either in vivo or in vitro with different electrolyte solutions. The pH in the bulk phase solution and at the surface of the epithelium was measured with two different types of glass pH-microelectrodes, a pointed tip (Hinke-type) and a flat membrane electrode (Dubuisson-type); both types of electrodes gave the same results. The existence of a pH-microclimate at the surface of the mucosa was demonstrated under both in vivo and in vitro conditions. In vivo the pH-microclimate was stable and virtually independent of changes in the luminal bulk phase pH. When the bulk phase pH of the guinea pig colon was changed between pH 5 and pH 8.6, the mean pH in the microclimate was 7.08 +/- 0.15 (n = 163) in the proximal colon and 6.91 +/- 0.14 (n = 75) in the distal colon. In the guinea pig jejunum pH in the microclimate was 7.37 +/- 0.21 (n = 10) while the luminal pH was 7.27 +/- 0.10. Under in vitro conditions, the pH in the microclimate was more acidic (guinea pig jejunum delta pH 0.93, rat jejunum delta pH 0.40, guinea pig proximal colon delta pH 0.22). Addition of glucose (10 mM) or short-chain fatty acids (80-90 mM) to the luminal solution or replacement of sodium by lithium did not influence the pH in the microclimate significantly. Also the addition of acetazolamide, amiloride, SITS or sodium deoxycholate to the luminal solution, did not affect the pH in the microclimate in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Chloride transport by rat renal proximal tubule: effects of bicarbonate absorption.

In the early part of the proximal tubule chloride concentration is increased above that in plasma, a change attributed to preferential absorption of bicarbonate with sodium and water. To determine the mechanism(s) of the preferential absorption of HCO3 over chloride, in vivo paired perfusions were done in surface proximal tubules of the rat kidney. Each tubule was perfused with a control bicarbonate solution, similar in ionic composition to the solution normally present in the early part of the proximal tubule, and one of the experimental solutions that were modified by either replacing all of bicarbonate with sulfate, N-2-hydroxyethylpiperazine-N'-ethanesulfonate (HEPES), or all bicarbonate with sulfate and sodium with lithium, or addition of acetazolamide (ATZ), or cyanide (CN). Sufficient mannitol was added to reduce net fluid flux to zero. When sulfate replaced bicarbonate in luminal fluid, net chloride absorption was enhanced, a change associated with low lumen HCO3 and low pH. ATZ inhibited HCO3 absorption, whereas net Cl absorption increased, an effect associated with high HCO3 and low pH. With HEPES-plus-ATZ solutions, chloride absorption also increased but, in contrast to SO4 or ATZ solutions, pH increased. With sulfate and lithium replacement chloride absorption also increased despite net sodium secretion. CN, a metabolic inhibitor, inhibited HCO3 and sodium absorption but stimulated net chloride absorption. The data indicate that HCO3 absorption inhibits chloride absorption, a process independent of luminal HCO3 per se, luminal pH, sodium absorption, and transepithelial volume flux and voltage.

Secretion of pyruvate and lactate in pancreatic juice induced by acetazolamide or secretin

In vivo studies using pentobarbital sodium-anesthesized dogs were performed to investigate whether a transport pathway for pyruvate and lactate is present in the exocrine pancreas. Concentrations of both acids were measured in peripheral blood and pancreatic juice before and after intravenous 15-min administration of 2.25 mmol/kg DL-lactate, superimposed on continuous intravenous infusion of 3 U X kg-1 X h-1 secretin. The concentration ratio of lactate to pyruvate in pancreatic juice was found to be approximately 1, a lower value than found in other tissues or body fluids. D-lactate, not detected in either blood or juice during basal periods, rapidly appeared in both fluids in parallel with the physiological isomer L-lactate, after the infusion of DL-lactate. Further addition of acetazolamide or a high dose of secretin caused a marked secretory response of pyruvate and lactate with no increase in juice bicarbonate levels. We conclude that these acids can be transported from blood to lumen when the transmembrane pH gradient across the duct cell membranes is augmented by stimulants via a proton pump mechanism involving a CO2-HCO3-buffer system.

Cl- requirement for saliva secretion in the isolated, perfused rat submandibular gland.

Replacement of perfusate Cl- with Br- reduced by 37% the volume of saliva secreted by isolated, perfused rat submandibular glands exposed to 10(-6) M acetylcholine. Replacement of perfusate Cl- with SO4(2-) reduced fluid secretion by 73%, while replacement of bicarbonate with HEPES or addition of acetazolamide had no effect on salivary flows or volumes. Furosemide (10(-3) M) reduced saliva secretion when added to Cl- -(73%) or Br- -containing (56%) perfusates and also to HEPES- (95%) or acetazolamide-containing (82%) perfusates. Perfusion of the glands with furosemide or SO4- containing perfusates resulted in significantly reduced salivary Cl- concentrations and increased residual anion (Na+-K+-Ca2+-Cl-) concentrations, while perfusion with solutions containing acetazolamide or with HCO3- -free (HEPES) perfusates resulted in opposite changes in salivary anions. Addition of furosemide to HEPES- or acetazolamide-containing perfusates reversed these changes and caused a reduction in salivary Cl- concentrations and an increase in residual anion concentrations. It is concluded that 1) extracellular Cl- is required for saliva secretion in the rat submandibular gland, 2) the required external Cl- enters the salivary cells by a furosemide-sensitive transport system, which is likely to be similar to a Na+-K+-Cl- cotransport system described in other epithelia, 3) HCO3- is not normally required for saliva secretion but can sustain it partially when Cl- transport is inhibited by either furosemide or Cl- replacement, and 4) salivary electrolyte changes induced by Cl- or HCO3- replacement or by furosemide probably represent combined effects on acinar secretion and transductal electrolyte transport.

Effects of catecholamines on electrolyte transport in cortical collecting tubule.

We examined the direct effects of isoproterenol (ISO) and L-norepinephrine (NE) on electrolyte transport in isolated rabbit cortical collecting tubules (CCT) perfused in vitro. The addition of either ISO (10(-6) M) or NE (10(-6) M) to the bath decreased transepithelial potential difference (PD), on average by 51 and 25%, respectively. These effects of ISO and NE were abolished by prior addition of the beta-adrenergic blocker, L-propranolol. ISO (10(-5) M) had no effect from lumen. Also, osmotic water permeability was not influenced by ISO. Ouabain and ISO had additive effects on PD. Elimination of chloride from both perfusate and bath, or addition of acetazolamide, abolished the effect of ISO on PD. Although isotopic sodium flux for lumen to bath was not influenced by ISO, chemical net chloride absorption increased from 1.1 +/- 0.4 to 2.7 +/- 0.6 peq . cm-1 . sec-1 (n = 8, p less than 0.005). In conclusion, both ISO and NE and capable of decreasing PD in rabbit CCT perfused in vitro. This effect is mediated by beta-adrenergic receptors and is accompanied by the increase in net chloride absorption. Although the mechanism responsible for this decrease in PD with ISO in unclear, active chloride absorption, active hydrogen secretion, or membrane chloride permeability changes may account for the effects of ISO.

Postcapillary pH disequilibrium after gas exchange in isolated perfused liver.

pH equilibration after gas exchange in a systemic vascular bed was investigated using an isolated guinea pig liver preparation perfused with a blood-free Krebs-Ringer-bicarbonate solution. Effluent perfusate was withdrawn into a stopped-flow apparatus in which pH and temperature were continuously monitored. A decrease in pH of the perfusate after exit from the liver was observed. Addition of acetazolamide to inflowing perfusate had little effect on this fall in effluent fluid pH, while the addition of carbonic anhydrase completely abolished the decrease in pH. These results suggest that: 1) after the addition of metabolically produced CO2, the reaction CO2 leads to H2CO3 leads to H+ + HCO3- in the perfusate did not reach equilibrium during passage through the liver; 2) acetazolamide had little effect on the magnitude of the pH disequilibrium; and 3) carbonic anhydrase accelerated the reaction to equilibrium. We conclude that little or no catalysis of the conversion of perfusate CO2 to H2CO3 takes place within the hepatic circulation and that the presence of slow postcapillary blood pH changes in vivo may be dependent on the specific species and organ vascular bed from which the blood exited after participating in gas exchange.

Renal Excretion of Calcium and Magnesium during Acetazolamide or Parathyroid Hormone Administration in Dogs with Distal Blockade

Renal absorption of calcium and magnesium occurs in the proximal tubule, and at unknown site(s) beyond this segment. In the presence of blockade of Henle’s loop by ethacrynic acid, the excretion of calcium, magnesium and sodium in response to acetazolamide as compared to that with parathyroid hormone (PTH) was examined. Addition of acetazolamide to ethacrynic acid increased calcium and sodium excretion, but did not change magnesium excretion. In contrast, PTH added to ethacrynic acid did not change the excretion of any of the ions under investigation. Analysis of calcium and magnesium excretion as a function of sodium excretion, however, suggests that ethacrynic acid inhibited the effect of PTH to augment calcium absorption, but did not alter magnesium absorption, implying that the nephron site of PTH action to augment calcium absorption is the ascending limb of Henle’s loop and that to augment magnesium absorption resides beyond Henle’s loop.

CANINE ILEAL CHLORIDE ABSORPTION: EFFECT OF CARBONIC ANHYDRASE INHIBITOR ON TRANSPORT.

The rates of movement of chloride and water from ileal loops into blood (insorption) and from blood into ileal contents (exsorption) were determined in dogs by the use of radiochloride and deuterium. The transmural electrical potential was measured. The appropriate values then were applied to Ussing's equation. The data indicated that chloride is actively transported by the ileum of the dog. The addition of acetazolamide (Diamox) decreased the observed transport flux ratio of chloride to a value which was similar to the calculated value for passive transport. It was concluded that acetazolamide inhibited active transport of chloride. When acetazolamide was present, the insorption of chloride was decreased while the exsorption of chloride was not affected. Water transport was decreased in parallel with chloride transport. Determinations of carbon dioxide content of the luminal fluid during the tests suggested that the effect of acetazolamide on chloride and water insorption is not related to its carbonic anhydraseinhibiting action.

EFFECTS OF ACID-BASE ALTERATIONS ON CEREBROSPINAL FLUID PRODUCTION.

Cerebrospinal (CSF) fluid formation rates were measured by ventriculocisternal perfusion with an inulin containing buffer during metabolic acidosis and alkalosis and respiratory acidosis and alkalosis in dogs. Some of the animals also received acetazolamide, 50 mg/kg, intravenously during the acid-base alteration. It was found that metabolic and respiratory acidosis had no constant effect on CSF production rates. Metabolic alkalosis reduced CSF production 23% and respiratory alkalosis reduced it 46%. The addition of acetazolamide during metabolic acidosis and alkalosis as well as during respiratory alkalosis caused a significant decrease in CSF production rates as compared to production during the periods of acid-base alterations alone.