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Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man.

AIMS: Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations. METHODS: Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p. l.c. up to 24 h post-dose. RESULTS: Maximum plasma concentrations (Cmax) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25 mg), were higher compared with the unbuffered tablets by about 50-80%. The area under concentration-time data (AUC) was unaffected, and, hence, Cmax/AUC was increased by buffering. Time to Cmax (tmax) and mean residence time (MRT) tended to be or was shortened by buffering. CONCLUSIONS: It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.

Adult↗

Effects of lactate-buffered and lactate-free dialysate in CAVHD patients with and without liver dysfunction.

BACKGROUND: Continuous modalities of renal replacement deplete patients of bicarbonate, which is traditionally replaced indirectly by lactate in dialysate or replacement fluids. We have compared a new lactate-free dialysate (unbuffered dialysate with separate bicarbonate replacement of dialytic bicarbonate loss) with standard lactate-buffered dialysate in terms of acid-base control, lactate accumulation, and hemodynamic stability in patients undergoing continuous renal replacement therapy in an intensive care unit. METHODS: A nonrandomized crossover cohort study involving 54 patients with multi-organ failure (of whom 19 had significant hepatic dysfunction) was performed. All patients completed 24-hour continuous hemodiafiltration against both lactate-buffered and lactate-free dialysate. Arterial pH, blood gases, bicarbonate, and lactate, venous sodium, blood pressure, and inotrope requirements were measured before and at six hourly intervals during the first 24 hours of dialysis against each dialysate. RESULTS: Lactate-free dialysate provided more rapid control of acidosis than lactate buffered with less total administration of buffer than that given during the lactate-buffered period (total mmol bicarbonate vs. total mmol lactate + bicarbonate). Lactate accumulation was slight in both periods, but was higher during lactate-buffered continuous venovenous hemodiafiltration (CVVHD). The mean arterial pressure rose during lactate-free dialysis with decreased inotrope doses and fell during lactate-buffered dialysis with increased inotrope requirement. Results in patients with liver dysfunction were not significantly different from those without it. CONCLUSIONS: Over the time scale of 24 hours, lactate derived from continuous dialysis circuits is efficiently cleared from the blood of most patients with multi-organ failure, but with less effect on systemic acidosis than is produced by equivalent amounts of bicarbonate.

APACHE↗

The spatial relationship between Ca2+ channels and Ca2+-activated channels and the function of Ca2+-buffering in avian sensory neurons.

In order to learn about the endogenous Ca2+-buffering in the cytoplasm of chick dorsal root ganglion (DRG) neurons and the distance separating the ryanodine receptor Ca2+ release channels (RyRs) from the plasma membrane, we monitored the amplitude and time course of Ca2+-activated Cl- currents (I(ClCa)) in protocols that manipulated Ca2+-buffering. I(ClCa)was activated by Ca2+ influx via voltage-gated Ca2+ channels or by Ca2+ release via RyRs activated by 10 mM caffeine. I(ClCa)was measured in neurons at 20 degrees C and 35 degrees C using the amphotericin perforated patch technique that preserves endogenous Ca2+-buffering, or at 20 degrees C in neurons dialyzed with pipette solutions designed to replace the endogenous Ca2+ buffers. The amplitude of I(ClCa)activated by Ca2+ influx or Ca2+ at 20 degrees C was similar in the amphotericin neurons and neurons dialyzed with an 'unbuffered' pipette solution containing 10 mM citrate and 3 mM ATP as the only Ca2+ binding molecules. Thus, endogenous mobile Ca2+ buffers are relatively unimportant in chick DRG neurons. Warming the neurons from 20 degrees C to 35 degrees C increased the amplitude and the rate of deactivation of I(ClCa)consistent with an increased rate of Ca2+ buffering by fixed endogenous Ca2+-buffers. Dialysis with 2 mM EGTA/0.1 microM free Ca2+ reduced the amplitude and increased the rate of deactivation of I(ClCa)activated by Ca2+ influx and abolished I(ClCa)activated by Ca2+ release. Dialysis with 2 mM BAPTA/0.1 microM free Ca2+ abolished I(ClCa)activated by Ca2+ influx or release. Dialysis with 42 mM HEEDTA/0.5 microM free Ca2+ caused the persistent activation of I(ClCa). Calculations using a Ca2+-diffusion model suggest that the voltage-gated Ca2+ channels and the Ca2+-activated Cl- channels are separated by 50-400 nm and that the RyRs are more than 600 nm from the plasma membrane.

Amphotericin B↗

Characteristics of polarographic catalytic waves observed with bovine-serum albumin: effects of type of buffers, pH, ionic strength, calcium, and tetraalkyl salts.

Brdicka currents observed with bovineserum albumin in ammoniacal buffers with Co(III) and Co(II) as catalysts are identical only when the concentrations of ammonia and ammonium chloride are at least 0.5 M and 0.05 M, respectively. When these conditions are not fulfilled, and in all Tris and borate buffers, the pattern of Brdicka currents with Co(III) are quite different from those with Co(II). In such buffers the Co(II) is rapidly reduced at potentials slightly more negative than that at which the Brdicka current attains a peak value. In several such buffers the Brdicka current may then reduced to zero. In buffers of low ionic strength (about 0.02) and with Co(III), small concentrations of alkali salts greatly increase Brdicka currents. When the ionic strength of the buffer is 0.05 M or greater, the effect of alkali salts (up to 0.2 M) is small, but even traces of calcium have a large effect in all buffers with Co(III) as catalyst. Evidence is presented that in the presence of calcium all 17 disulfide groups in bovine-serum albumin are reduced at the dropping mercury electrode. Traces of tetraalkyl salts greatly increase Brdicka currents, but the effects is quite different from that of calcium.

Alkanes↗

Salivary buffer capacity in relation to menarche and progesterone levels in saliva from adolescent girls: a longitudinal study.

The aim of this study was to investigate the relationship between salivary buffer capacity and menarche, and to explore any association with levels of the sex hormone progesterone in stimulated whole saliva in adolescent girls. The material comprised 162 girls, 12 years of age at baseline in the 6th grade, who were followed for 3 years. Every 4th month, a stimulated whole saliva sample was collected, secretion rate and buffer capacity were determined, and information was gathered on menarche, ongoing menses, and caries increment. Once yearly, the salivary concentration of progesterone was determined with an enzyme immunoassay kit. The results showed a significantly impaired salivary buffer capacity over the years (P < 0.05). Low buffer capacity was significantly correlated with low secretion rate (r = 0.42; P< 0.001) and DMFT increment (r=0.20; P<0.05). Pre-menarche buffer capacity did not differ from the postmenarche scores. The concentration of progesterone in saliva increased with age but displayed no significant relationship to buffer capacity, flow rate, or caries increment. In conclusion, the findings of this study suggest that the salivary buffer capacity may be impaired over the adolescent years in females, but the reason remains unclear.

Adolescent↗

Microinjection of strong calcium buffers suppresses the peak of calcium release during depolarization in frog skeletal muscle fibers.

The effects of high intracellular concentrations of various calcium buffers on the myoplasmic calcium transient and on the rate of release of calcium (Rrel) from the sarcoplasmic reticulum (SR) were studied in voltage-clamped frog skeletal muscle fibers. The changes in intracellular calcium concentration (delta[Ca2+]) for 200-ms pulses to 0-20 mV were recorded before and after the injection of the calcium buffer and the underlying Rrel was calculated. If the buffer concentration after the injection was high, the initial rate of rise of the calcium transient was slower after injection than before and was followed by a slow increase of [Ca2+] that resembled a ramp. The increase in myoplasmic [Mg2+] that accompanies the calcium transient in control was suppressed after the injection and a slight decrease was observed instead. After the injection the buffer concentration in the voltage-clamped segment of the fiber decreased as the buffer diffused away toward the open ends. The calculated apparent diffusion coefficient for fura-2 (Dapp = 0.40 +/- 0.03 x 10(-6) cm2/s, mean +/- SEM, n = 6) suggests that approximately 65-70% of the indicator was bound to relatively immobile intracellular constituents. As the concentration of the injected buffer decreased, the above effects were reversed. The changes in delta[Ca2+] were underlined by characteristic modification of Rrel. The early peak component was suppressed or completely eliminated; thus, Rrel rose monotonically to a maintained steady level if corrected for depletion. If Rrel was expressed as percentage of SR calcium content, the steady level after injection did not differ significantly from that before. Control injections of anisidine, to the concentration that eliminated the peak of Rrel when high affinity buffers were used, had only a minor effect on Rrel, the peak was suppressed by 26 +/- 5% (mean +/- SE, n = 6), and the steady level remained unchanged. Thus, the peak component of Rrel is dependent on a rise in myoplasmic [Ca2+], consistent with calcium-induced calcium release, whereas the steady component of Rrel is independent of myoplasmic [Ca2+].

Animals↗

Comparison of ischaemic preconditioning in blood perfused and buffer perfused isolated heart models.

OBJECTIVE: The aim was to compare the effects of ischaemic preconditioning in the buffer perfused and parabiotic blood perfused Langendorff rabbit heart models. METHODS: Isolated hearts were perfused with either Krebs-Henseleit buffer solution or blood from a support rabbit. Hearts were subjected to an initial 30 min stabilisation period followed by 30 min of global ischaemia and 60 min of reperfusion. Ischaemic preconditioned (IP) hearts were also subjected to one cycle of 5 min global ischaemia and 10 min of reperfusion before the 30 min ischaemia. For each experiment, left ventricular function and necrosis were measured. RESULTS: Necrosis, as measured by tetrazolium staining and expressed as a percentage of the left ventricular area, was significantly different between the buffer perfused control [42.5% (SEM 6.9), n = 7] and buffer perfused IP group [22.2% (5.4), n = 7, p < 0.01]. In the blood perfused experiments, the IP group also had less necrosis [9.3% (3.1), n = 9] as compared to controls [22.9%(4.2), n = 9, p < 0.01]. The percentage reduction in necrosis produced by ischaemic preconditioning was not significantly different between the buffer perfused and blood perfused models. Peak left ventricular systolic pressure was not different between the control and IP hearts in either model at any time during the 60 min reperfusion period. In buffer perfused hearts, left ventricular end diastolic pressure at 60 min reperfusion was not significantly different between the IP and the control groups, at 34.3(5.5) mm Hg v 37.8(4.9) mm Hg, respectively. Similarly, there was no statistically significant difference in left ventricular end diastolic pressure in the blood perfused groups at this time: 13.3(2.8) in the IP group v 24.0(6.5) in controls. CONCLUSIONS: In isolated heart models of global ischaemia and reperfusion, in which both recovery of function and necrosis were assessed together, ischaemic preconditioning was highly effective in reducing necrosis in both blood perfused and buffer perfused models. However, ischaemic preconditioning did not significantly improve postischaemic recovery of function in either of the two preparations.

Animals↗

Hemodynamic effects of epinephrine in combination with different alkaline buffers during experimental, open-chest, cardiopulmonary resuscitation.

OBJECTIVE: To evaluate the hemodynamic actions of epinephrine combined with different alkaline buffers during experimental, open-chest, cardiopulmonary resuscitation (CPR). DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental animal laboratory in a university hospital. SUBJECTS: A total of 28 anesthetized piglets. INTERVENTIONS: After catheterization and application of a pulmonary artery flow probe (transit-time ultrasound flowmetry), the animals were stabilized. Induction of ventricular fibrillation was followed by a 15-min period of CPR, including manual heart compressions and mechanical ventilation with pure oxygen. On commencement of CPR, a 4-min alkaline buffer infusion began, with 50 mmol of sodium bicarbonate (n = 7), tris buffer mixture (n = 7), or tris buffer (n = 7), or, as a control (n = 7), the same volume of normal saline. After 8 mins of CPR, 0.5 mg of epinephrine was given intravenously; after 15 mins, direct current shocks were used to revert the heart to sinus rhythm. MEASUREMENTS AND MAIN RESULTS: Blood flow measured in the pulmonary artery during open-chest CPR was approximately 20% of normal cardiac output. Administration of epinephrine reduced pulmonary artery flow irrespective of buffer. Sodium bicarbonate alone resulted in higher systemic blood pressure than pure tris: tris buffer mixture and normal saline were intermediate. Sodium bicarbonate combined with epinephrine tended to produce lower systemic blood pressure than other combinations. CONCLUSIONS: Experimental open-chest CPR generates pulmonary artery blood flows (20% of normal cardiac output) that are at best at the lower level of those blood flow rates previously reported (25% to 40% of normal cardiac output) from studies of closed-chest CPR. Different alkaline buffers influence circulatory and acid-base parameters differently before and after administration of epinephrine.

Animals↗

Gastric tonometry: precision and reliability are improved by a phosphate buffered solution.

OBJECTIVE: To compare a phosphate buffered solution with normal saline as tonometric fluid in intramucosal PCO2 measurement in humans. DESIGN: Prospective, unblinded comparison. SETTING: Postsurgical critical care unit of a university hospital. PATIENTS: Six septic patients. INTERVENTIONS: Two tonometric probes were positioned in the gastric lumen in each patient. One tube was used for conventional tonometry (saline-filled balloon), while phosphate buffered solution was instilled into the second tube. MEASUREMENTS AND MAIN RESULTS: PCO2 was determined with three blood gas analyzers (ABL 2 [Radiometer, Copenhagen, Denmark], Corning 288 [Ciba Corning Diagnostics GmbH, Neuss, Germany], and StatProfile 9 Plus [Nova Biomedical, Waltham, MA]). Eight parallel PCO2 measurements per patient were evaluated, yielding a total of 48 measurements with each tonometric solution. Intrainstrumental comparison of the PCO2 determinations demonstrated an increase of 12.3 +/- 9.9% for ABL 2, 3.10 +/- 12.9% for Ciba Corning 288, and 101.2 +/- 31.5% for StatProfile 9 Plus with the phosphate buffered solution. The PCO2 values were decreased by the following amounts when the three instruments were compared, using the saline method: 14.2 +/- 8.2% (Ciba Corning 288 vs. ABL 2); 40.7 +/- 9.9% (StatProfile 9 Plus vs. ABL 2); and 30.9 +/- 9.35% (StatProfile 9 Plus vs. Ciba Corning 288). The difference in PCO2 determination, resulting from the different instrument designs, were significant between the three blood gas analyzers (p<.001). In addition, the variance of the intramucosal PCO2 values was significant between blood gas analyzers (p<.001) with normal saline as tonometric solution, but not with phosphate buffered solution. The coefficients of determination between PCO2 values in saline and phosphate buffered solution were r2=.85 for ABL 2, r2=.81 for Ciba Corning 288, and r2=.74 for StatProfile 9 Plus. When all 48 PCO2 values were analyzed, the interinstrumental coefficients of determination within a method for saline (and for phosphate buffered solution in parenthesis) were:r2=.83 (.92) between ABL 2 and Ciba Corning 288, r2=.72 (.92) between ABL 2 and StatProfile 9 Plus, and r2=.81 (.98) between Ciba Corning 288 and StatProfile 9 Plus. CONCLUSIONS: A considerable instrumental bias in PCO2 analysis is observed when saline is used as tonometric fluid in gastric tonometry, thus preventing a reliable determination of intramucosal pH. The present in vivo data show that the accuracy and reliability of intramucosal pH measurement can be improved by the use of phosphate buffered solution as tonometric fluid.

Adult↗

Effect of tris buffer on free cytosolic calcium in myocardial cells.

OBJECTIVE: To study the effect of tris buffer on free cytosolic calcium in vitro. DESIGN: Open, randomized, control trial of dispersed rat myocardial cells. SETTING: Experimental laboratory in a large university hospital. SUBJECTS: Dispersed myocardial cells from Sprague-Dawley rats. INTERVENTIONS: The influences of pure trometamol (tris) and a tris butter mixture, as well as conventional sodium bicarbonate on free cytosolic calcium in suspended rat myocardial cells were studied with the fluorescent intracellular probe fura-2. MEASUREMENTS AND MAIN RESULTS: Addition of pure trometamol (tris) resulted in a significant increase of free cytosolic calcium in myocardial cells suspended in a buffer containing 1.25 mM of ionized calcium. The actions of trometamol display a dose-dependency in relation to the concentration of external ionized calcium since the ionized calcium response was reduced in a buffer with 0.5 mM of extracellular ionized calcium. Furthermore, removal of external ionized calcium totally prevented trometamol induced increases of ionized calcium, indicating that this increase is dependent on transmembrane ionized calcium fluxes. When tris buffer mixture was investigated in 1.25 mM of calcium, as well as 0.5 mM of external ionized calcium, a decrease of ionized calcium was noted initially, followed by an increase during the observation period. Addition of sodium bicarbonate to the two experimental settings resulted in a more prominent initial decrease of ionized calcium, followed by a slower increase which did not reach the initial values during the 20-min observation period. Extracellular pH was also included as a variable. When the cells were suspended in a buffer containing 1.25 mM of ionized calcium with a pH of 6.80 instead of 7.40 (as above), addition of pure trometamol also resulted in an increase of ionized calcium; however, after 20 mins this increase was smaller as compared with the results above. When tris buffer mixture as well as sodium bicarbonate was added, initial decreases of ionized calcium were recorded, followed by smaller increases during the observation period, compared with the increase in buffers with a pH of 7.40. CONCLUSIONS: Pure trometamol (tris) induces an increase in free cytosolic calcium in suspended myocardial cells.

Animals↗

Selection of pH buffers for use in conductimetric microbiological assays.

Many metabolic activities of micro-organisms lead to changes in the pH value of cultures and consequently pH buffer compounds are potentially a major source of conductivity changes in cultures. To maximize changes in conductivity associated with microbial growth the pH buffer-associated changes should occur in a direction that reinforces those due to other metabolic activities. In agreement with this, studies with Escherichia coli showed that fermentation of glucose and aerobic growth on L-alanine yielded greater changes in the conductivity of media containing Tris(hydroxymethyl)aminomethane or L-histidine buffers than in a medium containing phosphate buffer, whereas aerobic growth on glucose or succinate yielded greater changes with phosphate buffer than with Tris(hydroxymethyl)aminomethane or L-histidine buffers. Criteria for the selection of appropriate pH buffer compounds are presented.

Aerobiosis↗

Base excess or buffer base (strong ion difference) as measure of a non-respiratory acid-base disturbance.

Stewart in 1983 (Can J Physiol Pharmacol 1983: 61: 1444) reintroduced plasma buffer base under the name "strong ion difference" (SID). Buffer base was originally introduced by Singer and Hastings in 1948 (Medicine (Baltimore) 1948: 27: 223). Plasma buffer base, which is practically equal to the sum of bicarbonate and albuminate anions, may be increased due to an excess of base or due to an increased albumin concentration. Singer and Hastings did not consider changes in albumin as acid-base disorders and therefore used the base excess, i.e., the actual buffer base minus the buffer base at normal pH and pCO2, as measure of a non-respiratory acid-base disturbance. Stewart and followers, however, consider changes in albumin concentration to be acid-base disturbances: a patient with normal pH, pCO2, and base excess but with increased plasma buffer base due to increased plasma albumin concentration get the diagnoses metabolic (strong ion) alkalosis (because plasma buffer base is increased) combined with metabolic hyperalbuminaemic acidosis. Extrapolating to whole blood, anaemia and polycytaemia should represent types of metabolic alkalosis and acidosis, respectively. This reveals that the Stewart approach is absurd and anachronistic in the sense that an increase or decrease in any anion is interpreted as indicating an excess or deficit of a specific acid. In other words, a return to the archaic definitions of acids and bases as being the same as anions and cations. We conclude that the acid-base status (the hydrogen ion status) of blood and extracellular fluid is described in terms of the arterial pH, the arterial pCO2, and the extracellular base excess. It is measured with a modern pH-blood gas analyser. The electrolyte status of the plasma is a description of the most important electrolytes, usually measured in venous blood with a dedicated electrolyte analyser, i.e., Na+, Cl-, HCO3-, and K+. Albumin anions contribute significantly to the anions, but calculation requires measurement of pH in addition to albumin and is usually irrelevant. The bicarbonate concentration may be used as a screening parameter of a nonrespiratory acid-base disturbance when respiratory disturbances are taken into account. A disturbance in the hydrogen ion status automatically involves a disturbance in the electrolyte status, whereas the opposite need not be the case.

Acid-Base Equilibrium↗

Effect of carbamination on the buffering power of purified human hemoglobin A solutions at two temperatures.

The effect of CO2 on hemoglobin buffering power was studied in purified human hemoglobin A solutions, native and specifically carbamoylated on N-terminal valines, at 26 degrees C and 42 degrees C, in the oxy and deoxy states. Titrations were performed by varying Pco2 and by strong acid or base in the absence of CO2. The participation of N-terminal valines to the total buffering power was estimated by subtracting the buffering value measured on carbamoylated hemoglobin solutions from that measured on native hemoglobin solutions. In the absence of CO2 the buffering value of native and modified hemoglobin increased slightly (less than 10%) (a) on going from the deoxy to the oxy state, and (b) on raising the temperature from 26 degrees C to 42 degrees C. In the presence of CO2 the buffering value of Hb increased from 9.1 to 16.6 mol mol Hb4-1 pH-1 and that of HbO2 from 10.1 to 19.6 mol mol Hb4-1 pH-1 when the temperature was raised from 26 degrees C to 42 degrees C. These figures correspond to a rise in the fraction of the total buffering value attributable to N-terminal valines from 11% to 25% for Hb and from 3% to 33% for HbO2. The present results point to a non-specific effect of CO2 within the hemoglobin molecule independent of that of N-terminal valines. This effect nearly doubles the buffering value for CO2 when the temperature is raised, and contributes to pH regulation and CO2 removal in tissues with a high metabolic rate.

Buffers↗

Effect of sperm preparation with TEST yolk buffer on sperm-binding capacity under hemizona assay conditions.

The study was conducted to evaluate the diverse effect and clinical significance of TEST yolk buffer treatment on sperm samples of 128 infertile men. Sperm samples were incubated with TEST yolk buffer and control medium (Ham's F-10) at room temperature for 2 h. The hemizona indices (mean +/- SE) of the TEST yolk buffer and medium-treated sperm samples were 29 +/- 2.3% and 22 +/- 1.6%, respectively. Inspection of the individual response of each sperm sample to TEST yolk buffer revealed that 63 samples (49%) improved (double the interassay variation = 28%) their binding to zona pellucida, 36 (28%) remained unchanged, whereas the binding capacity of 29 samples (23%) decreased. Furthermore, TEST yolk buffer treatment of 24 samples (19%) resulted in an increased binding beyond the hemizona index threshold set up at 23%. This level was previously shown to be the cut-off point between fertile and infertile sperm samples. It was concluded that when applied to an unselected group of infertile men, TEST yolk buffer significantly increased sperm binding capacity to the zona pellucida. However, only 19% of the sperm samples showed improvement with clinical significance. The other sperm samples may have improved, remained unchanged or even deteriorated independently on basic sperm variables. Thus, the effect of TEST yolk buffer treatment on sperm binding should be tested prior to its clinical use to avoid possible damage to certain sperm samples.

Buffers↗

Adverse effects of artificial buffers on contractile responses of arterial and venous smooth muscle.

1 In vitro studies were undertaken on rat aortic strips and portal vein segments in order to determine whether or not several commonly used artificial buffers, i.e., tris(hydroxymethyl) aminomethane (Tris), N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid (HEPES), morpholine propanesulphonic acid (MOPS), N,N bis(2-hydroxyethyl) glycine (BICINE) and 1,4-piperazinediethanesulphonic acid (PIPES), can exert direct actions on vascular smooth muscle. 2 All artificial buffers used in 5 mM concentrations were found to inhibit development of spontaneous mechanical activity. 3 Tris, HEPES, MOPS, BICINE and PIPES markedly attenuated contractions induced by adrenaline, angiotensin and KCl. The fast phase components of the agonist-induced contractions were either obliterated or reduced in the presence of the artificial buffers. The sustained slow phase components were greatly reduced and retarded by the artificial buffers. 4 The relative order of artificial buffer potency (i.e., from 100% to 14% inhibition) seems to depend upon the agonist and type of smooth muscle. 5 All of these inhibitory effects were reversible, since normal contractile responses and spontaneous mechanical activity could be obtained by simply reincubating the smooth muscles in Krebs-Ringer bicarbonate buffer. 6 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects of Tris, HEPES, MOPS, PIPES and BICINE. 7 These data show that five of the most commonly used artificial buffers, to study muscles in vitro, exert adverse effects on contractility of arterial and venous smooth muscle.

Alkanesulfonates↗

Infiltration pain and local anesthetic effects of buffered vs plain 1% diphenhydramine.

OBJECTIVE: To compare the levels of infiltration pain and local anesthetic effects of plain and buffered 1% diphenhydramine. METHODS: A prospective, randomized, double-blind, paired study was performed using 30 adult volunteers. Intradermal injections (0.5 mL) of plain and buffered 1% diphenhydramine were made in the subjects' forearms, one in the left and the other in the right. The pain of infiltration was recorded on a previously validated 10-cm visual analog scale (VAS). The volunteers also were asked which injection was less painful. Sequential measurements of the diameter of anesthesia to pinprick were made at 1, 2, 5, 10, 15, 20, 25, and 30 minutes. The VAS scores and anesthetic diameters were compared for plain and buffered diphenhydramine using a paired Wilcoxon rank sum test. RESULTS: There was no statistically significant difference between buffered diphenhydramine and plain diphenhydramine for pain of injection (23.5 +/- 19.2 mm vs 28.2 +/- 18.7 mm, p = 0.24). Repeated-measures analysis of variance for anesthetic diameters demonstrated no significant difference between buffered diphenhydramine and plain diphenhydramine (p = 0.87). At no single measurement period were the anesthetic diameters different. CONCLUSIONS: In a study with a sample size large enough to detect an 11-mm difference in VAS scores (power = 80%), no difference was found in pain of infiltration and anesthetic effects when plain 1% diphenhydramine was compared with buffered 1% diphenhydramine. Buffering of diphenhydramine does not appear to result in a clinically significant reduction in the pain of infiltration.

Adult↗

Effect of buffers on testing of Candida species susceptibility to flucytosine.

Synthetic amino acid medium for fungi (SAAMF) is a totally defined, nutritionally adequate, macromolecule-free culture medium for fungi that is buffered with an organic weak acid-weak base pair: 2-(N-morpholino)-propanesulfonic acid (MOPS) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris). In 1984, it was reported that MOPS-Tris in SAAMF antagonized the activity of flucytosine against Candida albicans (D. L. Calhoun and J. N. Galgiani, Antimicrob. Agents Chemother. 26:364-367, 1984). Accordingly, we evaluated the buffering capacity of seven synthetic organic buffers and monobasic potassium phosphate, both singly and in pairs, over the pH range 7.4 to 6.0. Of these buffers, MOPS, BES [N,N-bis(2-hydroxyethyl)-2-aminomethanesulfonic acid], a BES-MOPS combination, and KH2PO4 provided the best buffering. Growth of C. albicans, in unbuffered SAAMF was equivalent overall to that in SAAMF containing buffers, singly or in pairs. Twelve strains of C. albicans and five strains of Candida lusitaniae were tested for susceptibility to flucytosine in SAAMF, with and without buffers. In the presence of Tris, the geometric mean MICs were 6.5- and 3.6-fold higher, respectively, for C. albicans and C. lusitaniae. We recommend replacing Tris with the nonantagonistic MOPS.

Buffers↗

Effect of pH on sporicidal and microbicidal activity of buffered mixtures of alcohol and sodium hypochlorite.

The effect of pH on the activity of buffered sodium hypochlorite solution, and a buffered methanol/sodium hypochlorite mixture, against Bacillus subtilis spores was investigated. The best results, considering both sporicidal activity and stability, were achieved in the pH range 7.6--8.1. The sporicidal activity and stability of five alcohol/hypochlorite mixtures, each containing a different alcohol and buffered to pH 7.6 and of hypochlorite alone buffered to pH 7.6, were compared. The mixtures were marginally more sporicidal than hypochlorite alone when fresh but were much less stable. An unbuffered methanol/hypochlorite mixture, a methanol/hypochlorite mixture buffered to pH 7.6, and hypochlorite alond buffered to pH 7.6 were all found to be effective against six vegetative organisms and spores of B. subtilis and Clostridium sporogenes. By buffering alcohol/hypochlorite mixtures or hypochlorite solution alone in the pH range 7.6--8.1, high sporicidal activity can be achieved with low concentrations of alcohol and hypochlorite. Such formulations show promise for the disinfection of heat-sensitive medical equipment.

Bacillus subtilis↗