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Effects of intraperitoneal hyaluronan on peritoneal fluid and solute transport in peritoneal dialysis patients.

BACKGROUND: Hyaluronan (HA) is a glycosaminoglycan found in connective tissues and tissue spaces, including the peritoneal cavity. In vivo studies in a rat model of peritoneal dialysis (PD) have shown that addition of HA to PD solution during an intraperitoneal dwell can alter peritoneal fluid transport and protect the peritoneal membrane from the effects of inflammation and repeated infusions of dialysis solution. The current study sought to evaluate the safety of intraperitoneal HA and its effect on peritoneal fluid and solute transport when administered during a dialysis dwell in humans. METHODS: 13 PD patients were enrolled in a prospective, randomized crossover study involving three dialysis treatments using the following PD solutions: (1) a commercially available PD solution (Dianeal PD-4, 1.36% glucose; Baxter Healthcare Corporation, Alliston, Ontario, Canada); (2) Dianeal PD-4 containing 0.1 g/L HA, and (3) Dianeal PD-4 containing 0.5 g/L HA. Each 6-hour dialysis exchange was separated from the other exchanges by a 2-week washout period. Radioiodinated human serum albumin (RISA) was administered with the dialysis solution to evaluate intraperitoneal volume, net ultrafiltration (UF), and fluid reabsorption. Peritoneal clearances, dialysate/plasma ratios (D/P), and mass transfer area coefficients (MTACs) were determined for sodium, urea, creatinine, albumin, and glucose. Safety was evaluated by monitoring adverse events and changes in serum chemistries. Ten patients completed all three dialysis exchanges and two additional patients completed at least one treatment exchange. RESULTS: There were no reported adverse events related to HA administration and no significant changes in serum chemistries. There were no significant differences in net UF or peritoneal volume profiles among the three treatments. Mean net UF calculated using residual volumes, estimated by RISA dilution, tended to be slightly higher during treatment with solution containing 0.1 g/L HA and 0.5 g/L HA [74 +/- 86 (SE) and 41 +/- 99 mL, respectively] compared to control treatment (-58 +/- 129 mL). Although not statistically significant, there was a trend toward decreased fluid reabsorption during treatment with HA. Solute clearances, D/P ratios, and MTACs were similar for the three treatments. Serum levels of HA were also unaffected by the two treatment solutions. CONCLUSIONS: These data support the acute safety of HA when administered intraperitoneally with the dialysis solution to PD patients. Due to the small sample size and variability in net UF and fluid reabsorption, statistically significant differences were not demonstrated for these parameters. However, a trend toward decreased fluid reabsorption was observed, suggesting that HA may act by a mechanism similar to that observed in animal studies. Further studies are necessary to evaluate whether the beneficial effects of HA observed in animal studies can be shown in humans.

Adjuvants, Immunologic↗

Effect of concentration boundary layers on passive solute flows in a system of two polymeric membranes positioned in vertical planes.

The results of studies of influence of concentration boundary layers on passive diffusive transport in a double-membrane osmo-diffusive cell, containing a series of two (Ml and M(r)) vertically positioned, flat, microporous and symmetric polymer membranes (Nephrophane and Cellulose IMP-1) are presented in this paper. The membranes separated three compartments (l, m, r) containing binary, heterogeneous and non-ionic solutions (aqueous solutions of glucose or ethanol) or ternary non-electrolyte solutions (glucose solutions in 0.75 mol.l-1 solution of ethanol or ethanol solutions in 0.1 mol.l-1 aqueous solution of glucose). Solution concentrations fulfilled the condition C(k)l > C(k)m > C(k)r. The intermembrane compartment (m) was an infinitesimal solution layer. The volume of the m compartment and the volumes of the external (l and r) compartments fulfilled the condition Vl = Vr approximately 170 Vm. The tests were performed for configurations A and B of a double-membrane osmo-diffusive cell. In configuration A, the solution was located behind the M(r) membrane, and water was placed behind the Ml membrane, while in configuration B this sequence was reversed. The results obtained during experiment were interpreted in the categories of convective instability, which increased the value of diffusive permeability coefficient of the system: concentration boundary layer/membrane/concentration boundary layer.

Diffusion↗

Peritoneal fluid transport in CAPD patients with different transport rates of small solutes.

BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) patients with high peritoneal solute transport rate often have inadequate peritoneal fluid transport. It is not known whether this inadequate fluid transport is due solely to a too rapid fall of osmotic pressure, or if the decreased effectiveness of fluid transport is also a contributing factor. OBJECTIVE: To analyze fluid transport parameters and the effectiveness of dialysis fluid osmotic pressure in the induction of fluid flow in CAPD patients with different small solute transport rates. PATIENTS: 44 CAPD patients were placed in low (n = 6), low-average (n = 13), high-average (n = 19), and high (n = 6) transport groups according to a modified peritoneal equilibration test (PET). METHODS: The study involved a 6-hour peritoneal dialysis dwell with 2 L 3.86% glucose dialysis fluid for each patient. Radioisotopically labeled serum albumin was added as a volume marker.The fluid transport parameters (osmotic conductance and fluid absorption rate) were estimated using three mathematical models of fluid transport: (1) Pyle model (model P), which describes ultrafiltration rate as an exponential function of time; (2) model OS, which is based on the linear relationship of ultrafiltration rate and overall osmolality gradient between dialysis fluid and blood; and (3) model G, which is based on the linear relationship between ultrafiltration rate and glucose concentration gradient between dialysis fluid and blood. Diffusive mass transport coefficients (K(BD)) for glucose, urea, creatinine, potassium, and sodium were estimated using the modified Babb-Randerson-Farrell model. RESULTS: The high transport group had significantly lower dialysate volume and glucose and osmolality gradients between dialysate and blood, but significantly higher K(BD) for small solutes compared with the other transport groups. Osmotic conductance, fluid absorption rate, and initial ultrafiltration rate did not differ among the transport groups for model OS and model P. Model G yielded unrealistic values of fluid transport parameters that differed from those estimated by models OS and P. The K(BD) values for small solutes were significantly different among the groups, and did not correlate with fluid transport parameters for model OS. CONCLUSION: The difference in fluid transport between the different transport groups was due only to the differences in the rate of disappearance of the overall osmotic pressure of the dialysate, which was a combined result of the transport rate of glucose and other small solutes. Although the glucose gradient is the major factor influencing ultrafiltration rate, other solutes, such as urea, are also of importance. The counteractive effect of plasma small solutes on transcapillary ultrafiltration was found to be especially notable in low transport patients. Thus, glucose gradient alone should not be considered the only force that shapes the ultrafiltration profile during peritoneal dialysis. We did not find any correlations between diffusive mass transport coefficients for small solutes and fluid transport parameters such as osmotic conductance or fluid and volume marker absorption. We may thus conclude that the pathway(s) for fluid transport appears to be partly independent from the pathway(s) for small solute transport, which supports the hypothesis of different pore types for fluid and solute transport.

Algorithms↗

Effectiveness of oral route isosorbide 5-mononitrate on peritoneal solute and fluid transports in CAPD patients.

BACKGROUND: Addition of sodium nitroprusside (NaNTP), a nitric oxide (NO) donor to peritoneal solution could enlarge the effective peritoneal surface area and the peritoneal pore size. This would be leading to increased clearance of all solutes. Generalized clinical usage of NaNTP in CAPD patients however is not practical because it has a very short half-life and needs a specific route of administration. Organic nitrate, another NO donor, has a longer half-life and could be more easily absorbed via many routes. OBJECTIVE: The present study was conducted to determine the effect and mechanism of oral active nitrate (isosorbide 5-mononitrate: ISMN) on solute andfluid transports in stable CAPD patients. MATERIAL AND METHOD: A prospective randomized placebo control with a crossover study was performed in nine stable CAPD patients. In group I (n = 4), the treatment included 1) oral ISMN at the dose of 20 mg bid for 5 days 2) wash out period for 7 days, and 3) placebo for 5 days. In group 2 (n = 5), the treatment regimens were placebo, wash out, and ISMN periods. RESULTS: The MTACs of low molecular weight (LMW) solutes in the ISMN period were greater than the placebo period: median urea, 16.7 vs 13.8 ml/min; creatinine (Cr), 7.9 vs 6.9 ml/min; and urate, 6.1 vs 5.5 ml/min (p < 0.05 for all except MTAC of urea). Administration of ISMN could also enhance the clearances of high molecular weight (HMW) solute with a magnitude of increase as follows: 10% for beta2-microglobulin, 50% for albumin, and 15% for immunoglobulin G (p < 0.05 for all). However, the values of restrictive coefficient of LMW as well as HMW solutes of both groups were not different, indicating that the increased solute transports are not due to alteration in the peritoneal membrane permeability. Despite the increased peritoneal solute clearance, net ultrafiltration (UF) was unchanged after drug administration, 110 (ISMN group) vs 120 ml (placebo group), (NS). CONCLUSION: ISMN has a similar effect as NaNTP in enhancing peritoneal clearances of both LMW and HMW solutes. The effect of ISMN, however, is mediated only via expansion of peritoneal surface area without significant change in pore size. As such, administration of oral ISMN to stable CAPD patients would be practically beneficial in enhancing the achievement of target solute clearances suggested by NKF- DOQI Guidelines.

Administration, Oral↗

Stability of ceftazidime and amino acids in parenteral nutrient solutions.

The stability of ceftazidime was studied under conditions simulating administration via a Y-injection site into a primary infusion of parenteral nutrient (PN) solution; the stabilities of ceftazidime and amino acids when the drug was added directly to PN solutions were also studied. Three PN solutions containing 25% dextrose were used; the amino acid contents were 0, 2.5%, and 5%. Ceftazidime with sodium carbonate was used to prepare stock solutions of ceftazidime 40 mg/mL in both 0.9% sodium chloride injection and 5% dextrose injection; to simulate Y-site injection, samples were added to the three PN solutions to achieve ceftazidime concentrations of 10 and 20 mg/mL, or 1:1 and 1:3 ratios of drug solution to PN solution. Samples of these admixtures were assayed by high-performance liquid chromatography (HPLC) initially and after room-temperature (22 degrees C) storage for one and two hours. Additional solutions were prepared by adding sterile water for injection to ceftazidime with sodium carbonate; drug solutions were added to each PN solution in polyvinyl chloride bags to achieve ceftazidime concentrations of 1 and 6 mg/mL. The samples were assayed by HPLC for ceftazidime concentration after storage at 22 degrees C for 3, 6, 12, 24, and 36 hours and at 4 degrees C for 1, 3, 7, and 14 days. Amino acid stability was analyzed in admixtures containing 5% amino acids and ceftazidime 6 mg/mL after 24 and 48 hours at 22 degrees C and after 7 and 10 days at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Small-volume resuscitation with hypertonic saline solution in hypovolemic cats.

We evaluated the hemodynamic effects of IV and intraaortic (aortic root) administration of 7.5% NaCl solution on hemodynamics in anesthetized cats with severe hypovolemia. Hypovolemic shock was induced by exsanguinating cats to a mean arterial blood pressure of 50 mm of Hg, which was maintained for 30 minutes prior to treatment. Shed blood volume was 38.4 +/- 2.1 ml/kg of body weight. The cats were treated with a small volume (4 ml/kg) of 0.9% NaCl solution IV, 7.5% NaCl solution IV, or 7.5% NaCl solution administered into the aortic root. The IV administration of 0.9% NaCl solution did not improve hemodynamics. The IV administration of 7.5% NaCl solution induced rapid restoration of arterial blood pressure, aortic blood flow, and cardiac contractility. Total peripheral vascular resistance decreased. The administration of 7.5% NaCl solution into the aortic root induced a further deterioration in hemodynamics resulting in death in 3 cats and a marked improvement in hemodynamics similar to that observed after IV administration of 7.5% NaCl solution in 2 cats. The duration of the beneficial hemodynamic effects after IV or intra-aortic administration of 7.5% NaCl solution did not exceed 60 minutes. Results of these studies suggested that either the IV or intra-aortic administration of 7.5% NaCl solution in cats can induce beneficial hemodynamic effects that may be of value in the field resuscitation of hypovolemic patients.

Animals↗

Effects of hypertonic solutions on conjunctival epithelium and mucinlike glycoprotein discharge.

A simple, semiquantitative, histochemical method using periodic acid-Schiff (PAS) staining was developed to measure the mucinlike glycoprotein content of bathing solutions exposed to rabbit conjunctiva. Rabbit eyes were bathed in vivo in solutions of various tonicity (160, 260, 300, 330, and 363 mOsm/L). Eyes bathed in hypotonic or isotonic solutions (160, 260, and 300 mOsm/L) exhibited a steady-state glycoprotein secretion (50-100 micrograms/h). In hypertonic solutions (330 and 363 mOsm/L), glycoprotein discharge increased to 150-360 micrograms/h when the solutions were exchanged hourly for 6 h, but glycoprotein discharge increased to a much lower rate (100-167 micrograms/h) after prolonged bathing for 6 h without solution exchange. Periodic acid-Schiff--positive glycoprotein aggregates were noted more frequently on the filters of hypertonic solutions than on those of other tonicity. After eyes were bathed in hypertonic solutions, increased disruption of the surface epithelium, increased abnormal discharge of mucin granules, and decreased goblet cell density were noted in the biopsied conjunctiva. These data suggest that mucinlike glycoprotein secretion from the conjunctival goblet cells can be enhanced by the tonicity of the bathing solution, and that nonphysiological hypertonic solutions can also affect the conjunctival epithelium.

Animals↗

Canine kidney preservation: comparison of "intracellular", "extracellular," and high molecular weight dextran flushing solutions.

The effects of modified Collins-2 solution, adjusted lactated Ringer's solution, and a solution containing dextran 70 on kidney preservation and red blood cell (RBC) washout in dogs were evaluated. Excised kidneys were stored on ice for 24 hours and then reimplanted, at which time the contralateral kidney was removed. RBC washout from the preserved kidneys was measured at the time of initial cold flush. For 20 days after transplantation, serial measurements were made of serum creatinine, blood urea nitrogen, creatinine clearance, serum and urine osmolality, blood pH, and dog weight. No one solution cleared RBCs from the kidneys better than the other solutions. Renal function was significantly better in transplanted kidneys flushed and preserved with the Collins-2 solution than that in kidneys flushed and preserved with the other two solutions. There was generally no significant difference in function between kidneys preserved with dextran and those preserved with lactated Ringer's solution. Our findings suggest that the electrolyte composition of the flush solution may be more important than maintaining a high osmolality in the flush solution in the preservation of renal function during 24 hours' cold storage.

Animals↗

Cell volumes and water contents of frog muscles in solutions of permeant sugars and sugar alcohols.

1. Previous work has suggested that living cells may acquire and then maintain different water contents and hence volume, in solutions containing different concentrations of solutes that are permeant to the cell membrane. Toward better understanding of this phenomenon, two hypotheses were introduced: one hypothesis is based on the membrane-pump theory; another represents an extension of the polarized multilayer theory of cell water, a part of the association-induction (AI) hypothesis. To test the different predictions of these hypotheses, the water contents of frog muscle equilibrated at 25 degrees C in solutions of different concentrations of seven pentoses, seven hexoses, seven dissacharides, two trisaccharides, and six sugar alcohols were determined. 2. The earlier finding of sustained shrinkage of muscle cells in concentrated solutions of permeant solutes was confirmed once more. 3. In equimolal solutions of sugars and sugar alcohols with different steric conformations but the same or closely similar molecular weight(s), muscles had the same or closely similar water content(s). 4. In equimolal solutions of different sugars and sugar alcohols, the equilibrium water contents of the muscles increased with decreasing molecular weights of these solutes. 5. The water contents of muscles, equilibrated in 0.4 M solutions of different sugars and sugar alcohols, are positively correlated with the equilibrium distribution coefficients (or q-values) of the sugar and sugar alcohols in the muscle cell water with a linear correlation coefficient of +0.973. 6. The relationships between the equilibrium water contents of muscles (in solutions containing different concentrations of different sugars and sugar alcohols) and the concentrations of these sugars and sugar alcohols agree in general contours with that predicted by an equation derived on the basis of the polarized multilayer theory of cell water. 7. The experimental findings described above do not agree with the prediction based on the membrane-pump hypothesis; they do agree with all four predictions of the hypothesis based on the polarized multilayer theory of cell water.

Animals↗

[Gastric emptying in children. V. Effect of the replacement of glucose by sucrose in a solution for oral rehydration].

A study was carried out on 18 children of both sexes aged 3 to 32 months (median 8 months) and weighing 3440 to 9520 grams (median 5120 grams). Each child was submitted to three consecutive gastric emptying tests at 24 hour intervals, using three solutions of different composition. The children were divided into two groups: Group I: twelve children submitted to the gastric emptying test 10 minutes after the administration of the test meal; Group II: six children submitted to the gastric emptying test 30 minutes after the administration of the test meal. The hydrating solutions used in the study consisted of the basic electrolyte composition recommended by the World Health Organization, and only differed in terms of the amount of sugar added. Solution A contained 20 grams of glucose per liter, solution B, 20 grams of sucrose per liter, and solution C, 40 grams of sucrose per liter. Gastric retention, expressed as a percentage of the volume of the test meal, was similar for solutions A and C and significantly higher than for solution B in Group I. In Group II, gastric retention of solution B also tended to be lower than for solutions A and C, although no statistically significant differences were observed between the three solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Oral rehydration therapy for acute diarrhea in ambulatory children in the United States: a double-blind comparison of four different solutions.

Oral rehydration solutions containing 50 to 90 mmol/L of sodium have recently been recommended for the treatment of diarrhea in both hospitalized and ambulatory children in the United States. Few data are available, however, from ambulatory US children. Therefore, we conducted a randomized double-blind study comparing the use of four different oral rehydration solutions with differing concentrations of sodium, glucose, and base. Ambulatory children less than 2 years of age with acute diarrhea (N = 140) were randomly chosen to receive solutions containing sodium at 90 (solution A), 50 (solution B), and 30 mmol/L (solutions C and D). All oral rehydration solutions contained 20 g/L of glucose except solution D which contained 50 g/L of glucose. Solution A contained bicarbonate as its base source whereas the other three contained citrate. All but three (98%) children were treated uneventfully according to the study protocol, and there were no differences among groups in measurements of clinical outcome. It was concluded that in ambulatory US children, oral rehydration solutions containing 90, 50, or 30 mmol/L of sodium can be used safely for the treatment of mild acute diarrhea and that citrate is as efficacious as bicarbonate in the correction of acidosis.

Ambulatory Care↗

[Demonstration of three protonated forms of poly(A): potentiometric and conductometric study of isoionic solutions].

It is shown that there are three parts on the potentiometric titration curves of isoionic solutions of poly(A) ascribed to the three protonated structures. Double-helical protonated structures are especially stable in isoionic solution. These parts on potentiometric curves are attributed to the single-stranded poly(A), to the completely protonated double-stranded poly(A+).poly(A+), and to the semiprotonated poly(A+).poly(A) structures: D, A, B forms of poly(A), respectively. pK0 values of these forms are calculated. The D form portion is found to be about 18% in isoionic solution, 40% in KCl solution (from 0.01 to 1.0 M), 40% in solution, containing 1.2 X 10(-3) M MgCl2 and 70% in 8 X 10(-4) M MgCl2 solution. The increase of MgCl2 concentration up to 8 X 10(-4) M leads to complete degradation of the double-helical structure. Only single-stranded D form exists in 5 X 10(-3) M MgCl2 solution. About 5-7% of all protons become inaccessible for titration in all solutions containing KCl and in the presence of small amounts of MgCl2. This phenomenon can not be explained by aggregation of poly(A), because all protons become accessible for titration in more concentrated MgCl2 solution when aggregation of poly(A) is significant and accompanied by the precipitation of sediment insoluble in NaOH. The supposition is made, that unprotonated double-stranded poly(A) can exist in salt-free solution at neutral pH. It is this form that is protonated with decrease of pH.

Chemical Phenomena↗

Questionable role of glucose-insulin in cardioplegic solution.

To evaluate the myocardial protective effect of glucose-insulin (GI) in a cold cardioplegic solution, we compared the effect of a solution not containing GI (solution I) with that of an identical solution containing GI (solution II) under cardiopulmonary bypass in mongrel dogs. After 120 minutes of ischemic arrest, defibrillation was necessary to restore cardiac activity in 12.5% of the solution I group and 42.8% of the solution II group, respectively. No distinct intergroup differences were noted in recovery of left ventricular function, oxygen and lactate extraction of the myocardium during the post-arrest period, the myocardial ultrastructure, and myocardial ATP levels. Although creatine phosphate was less well preserved, glucose-6-phosphate and lactate were more accumulated in the solution II group than in the solution I group. Thus, significant advantages of substrate enhancement by addition of GI to cold cardioplegic solution were not found in spite of multidose cardioplegia and presence of noncoronary collateral blood flow.

Adenosine Triphosphate↗

Gastric-emptying characteristics of two glucose polymer-electrolyte solutions.

Inadequate carbohydrate and fluids can limit physical performance; optimal delivery of both should be the goal of any beverage designed especially for the athlete. In this study, the gastric-emptying characteristics of two carbohydrate-electrolyte solutions were compared with water. The 5% carbohydrate solution contained 3% Polycose glucose polymers and 2% fructose, whereas the 7% solution contained 5% Polycose glucose polymers and 2% fructose. Both solutions contained similar amounts of sodium, potassium, calcium, magnesium, and chloride in the range suggested by the American College of Sports Medicine for rehydration solutions. Four hundred milliliters of each solution were administered to six male subjects and the amount of fluid emptied at 30 and 60 min by each subject was calculated. A non-absorbable dye, phenol red, was used to correct for gastric secretion. The gastric emptying of the 7% solution in healthy adult male subjects was not significantly different from the 5% solution or cold water. Inclusion of a polymerized form of glucose in a 7% glucose polymer-fructose solution can supply 70 g of carbohydrate per liter and also maximizes rehydration. This solution may be particularly useful in those activities where fluid and energy loss are particularly important.

Body Water↗

The potential hazard of particulate contamination of cardioplegic solutions.

The potential hazard of particulate debris in unfiltered cardioplegic solutions was assessed using the isolated rat heart preparation. Five intravenous solutions were evaluated: These were manufactured by three pharmaceutical firms (two United States and one British) and are commonly used as bases for preparing clinical cardioplegic solutions. Particles were counted in each solution, and each fell well within the limits for particle contamination defined by both the United States and the British Pharmacopoeias. Intracoronary continuous infusion of each solution over 20 minutes at constant temperature and pressure (20 degrees C, 60 cm H2O) resulted in a progressive reduction in coronary flow (mean reduction 55.7% +/- 6.6%) due to a rise in coronary vascular resistance; filtration of these same solutions through a 0.8 micron filter just prior to their entry into the heart largely prevented these coronary vascular changes. The filter was examined by scanning electron microscopy and showed amorphous and crystalline debris. Nifedipine (0.1 mumol/L) added to the cardioplegic solution reduced by almost 50% the impairment in coronary flow seen in the unfiltered group. In more clinically relevant studies of 180 minutes of hypothermic (20 degrees C) ischemia using multidose cardioplegia (3 minutes every 30 minutes), hearts infused with filtered solution recovered almost 90% of their preischemic functional capacity. Hearts receiving identical but unfiltered solution, however, essentially failed to recover (p less than 0.001) and had significantly higher levels of creatine kinase leakage. These results suggest that commercially produced solutions conforming to limits of particulate contamination acceptable for intravenous administration may prove harmful if given unfiltered directly into coronary arteries, with the likely mechanism of action being particle-induced coronary vasoconstriction.

Animals↗

Irrigating solutions for arthroscopy. A metabolic study.

UNLABELLED: In an effort to determine the optimum solution for irrigation during arthroscopic procedures, an in vitro metabolic experiment was performed in which cartilage slices were incubated with 35SO4 in various commercially available solutions, harvested at regular intervals, and assayed for incorporated radioactivity. The solutions were compared with Ham F12 medium, a complex, ionically balanced salt and amino-acid solution that is used for tissue culture. The data show that neither normal saline or phosphate-buffered saline supports metabolic activity as well as Ringer lactate or acetate, both of which approximate the values for the control, Ham F12 solution. CLINICAL RELEVANCE: Arthroscopy and arthroscopic surgical procedures have become commonplace in orthopaedic practice. Normal saline solution, commonly used in large quantities as an irrigating solution, is in fact not physiological, and we showed that it inhibits normal synthesis of proteoglycan by the chondrocytes. Ringer lactate seemed to support cartilage metabolism as well as an "ideal" tissue-culture medium (Ham F12 solution). Since Ringer solution and normal saline cost the same in our hospital, we strongly recommend that this more physiological solution be used for arthroscopic procedures.

Animals↗

Loss of bactericidal activity from contact lens storage solutions.

PURPOSE: The purpose of this study was to evaluate the effect of lens storage on the bactericidal activities of disinfecting solutions. METHODS: HYDROCURVEII (55% water content) soft contact lenses were soaked in OPTI-FREE Rinsing, Disinfecting, and Storage Solution (preserved with polyquaternium-1 [PQ-1]) or ReNu Multi-Purpose Solution (polyaminopropyl biguanide [PHMB]). After the lenses were removed, solutions were challenged with Pseudomonas aeruginosa and Staphylococcus aureus. Uptake of the antimicrobial agents by the lenses was evaluated by placing the lenses on plates seeded with S. aureus and observing for zones of growth inhibition. RESULTS: The bactericidal activity of the PHMB preserved solution decreased after 4 hours of storage time and showed no activity after storage for 3 days. Lenses soaked in the PHMB preserved solution produced zones of inhibition. The results suggest that the PHMB in the solution accumulates in the lens. This decreases the levels of preservative in the solution that is no longer available during lens storage. Neither decrease in bactericidal activity nor accumulation of the PQ-1 preservative in the lens occurred during storage with the PQ-1 solution. CONCLUSION: These results demonstrate that PQ-1 preserved solutions maintain bactericidal activity overnight and during prolonged storage without detectable uptake by lenses.

Biguanides↗

Effect of bicarbonate-based dialysis solutions on intracellular pH (pHi) and TNFalpha production by peritoneal macrophages.

OBJECTIVE: To compare the effect of Dianeal and two newly-formulated bicarbonate-based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-alpha (TNFalpha) mRNA level, and TNFalpha secretion by peritoneal macrophages (PMphi). DESIGN AND MEASUREMENTS: Peritoneal macrophages were isolated from dialysates collected after overnight dwells in peritonitis-free continuous ambulatory peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25% dextrose. HCO3 concentrations of bicarbonate-(TB) and bicarbonate/lactate-buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg, respectively. In all experiments pCO2 was carefully maintained at a stable level. The pHi was measured by spectrofluorometry in BCECF-loaded PMphi exposed to different dialysis solutions or Hank's balanced salt solution. TNFalpha levels were measured by ELISA in the supernatant of lipopolysaccharide- (LPS) stimulated PMphi after their incubation in different solutions for 15 and 30 minutes. TNFalpha mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR) of total RNA extracted from LPS-stimulated PMphi after their incubation in different solutions for 30 minutes. beta-actin mRNA was used as the control. RESULTS: Dianeal caused a profound drop in pHi to below 6.2. Following an initial drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation in TB and TBL, respectively. In comparison to the control solution, a fall of 11% and 21% in TNFalpha secretion was seen after incubation in TB for 15 and 30 minutes, respectively, and 15% and 26% after incubation in TBL. Under identical conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95% suppression of TNFalpha secretion. Accordingly, TNFalpha mRNA level in PMphi was severely depressed by Dianeal but no detectable inhibition was observed following incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and TBL was increased from 1.5% to 4.25%, TNFalpha secretion by PMphi was not suppressed by more than 49%, even after 30 minutes incubation. Moreover, suppression of TNFalpha mRNA levels could not be detected with TB or TBL even at high dextrose concentrations. CONCLUSIONS: In contrast to Dianeal, both bicarbonate-based solutions caused only a mild drop in pHi of PMphi. We postulate this effect to be responsible for the improved capacity of PMphi to secrete TNFalpha when incubated in bicarbonate-based solutions compared to Dianeal. Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the protective effect of TB and TBL on immune function of PMphi. TBL is as effective as TB in preventing the deleterious effect of Dianeal on PMphi function.

Bicarbonates↗