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Double-blind trial of pentigetide ophthalmic solution, 0.5%, compared with cromolyn sodium, 4%, ophthalmic solution for allergic conjunctivitis.

Fifty patients (25 per group) with the signs and symptoms of allergic conjunctivitis confirmed by positive skin test enrolled in this randomized, double-blind, parallel group, 2-week comparison of pentigetide, 0.5%, ophthalmic solution (Pentyde) and cromolyn sodium, 4%, USP ophthalmic solution (Opticrom). The physician and the patient rated the patient's overall ocular condition on days 3, 8, and 15. On day 15 both the physician and the patients rated the pentigetide group as significantly (Chi-square, P less than .05) more improved than the cromolyn sodium group. The physician rated independently conjunctival symptoms and ocular signs at days 1, 3, 8, and 15. Improvement in signs and symptoms favored pentigetide in the majority of comparisons to cromolyn sodium (14 of 18). The pentigetide group showed significantly (ANOVA, P less than .05) greater improvement in hyperemia, edema, lacrimation, and blurred vision/photophobia. Patients completed daily diaries for seven symptoms. At the end of the study, comparisons to baseline between groups favored the pentigetide group for six of the seven symptoms; for itching, improvement favored significantly (ANOVA, P less than .05) the pentigetide group. The mean severity of all symptoms decreased by 64% in the pentigetide group as compared with a decrease of 46% in the cromolyn sodium group. Adverse experiences were minor and comparable in both groups. No clinically abnormal changes were noted for visual acuity, intraocular pressure, or common laboratory tests. This double-blind, active-controlled trial demonstrates that pentigetide, 0.5%, ophthalmic solution is safe and effective in the treatment of allergic conjunctivitis.

Adolescent↗

[Infusion solution with a high concentration of branched-chain amino acids and a high-percentage amino acid solution in an experimental animal model].

Young male rats are randomized into two groups and maintained by total parenteral nutrition with an isocaloric and isonitrogenous regimen for 6 days. Group I receives a 15% amino acid solution containing 17% branched chain amino acids while group II is given a 10% amino acid solution containing 26.6% branched chain amino acids. By this regimen group I receives 1.02 g and group II 1.77 g branched chain amino acids/kg B.W./day. No significant differences are observed in weight gain, nitrogen balance, amino acid excretion and amino acid concentrations in muscle. The higher supply with branched chain amino acids is simply reflected in significant augmented plasma concentrations of these amino acids. Simultaneously there is a significant increase of glycine and threonine in plasma. The infusion of the concentrated amino acid solution is well tolerated by the animals and results in a decreased urinary volume.

Amino Acids↗

[Determination of diffusion coefficients in a solution by the transport of a solute through porous membranes].

The possibility of determining the coefficients of diffusion in solution by the transport of solutes through porous polymeric membrane was studied. Reliable and reproducible results can be obtained by using nucleoporous filters with cylindrical pores. The method enables the selective determining of the diffusion coefficients of solutes being in complex mixtures, which is of special interest for biochemical research. The possibilities of the method are illustrated on the pattern of some globular proteins, polyethylene glycols and proteolytic enzymes.

Diffusion↗

[Conformation of nucleotides, oligonucleotides and their analogues in aqueous solution. II. Syn-anti-equilibrium in solutions of adenosine, 5'-AMP, 3'-AMP, 5'-CMP and 3'-CMP].

A method for determining the equilibrium constant of sin-anti-states in the aqueous solution of purine and pyrimidine nucleotides and nucleosides has been proposed. This method is based on the measurement of the spin-lattice relaxation rate of H(1') atom of purine nucleotides before and after exchange of H(8) deuterium in the case of purine nucleotides or H(1') and H(5) atoms of pyrimidine nucleotides. The results obtained were interpreted by the two-state dynamic model. The method applied for investigation of the conformation situation in solutions of Ado, 5'-AMP, 3'-AMP, 5'-CMP and 3'-CMP. 5'-AMP and 5'-CMP were shown to exist predominantly in the anti-state (90%). In the case of 3'-nucleotides the enhancement of the relativity weight of sin-populations to 0.2 and 0.85 for 3'-CMP and 3'-AMP, respectively, was found. In the solution Ado both anti- and sin-state were equiprobable. Experimentally measured relaxation rates of H(8) of adenine or H (6) of cytosine nucleotides were used for determination of the time average orientation of nucleic bases towards the ribose ring in the anti-state. For all compounds investigated with the exception of 3'-AMP the "normal" anti-conformation was confirmed. The 3'-AMP was found to be characterized by high anti-conformation. The probable causes of the conformational situation organization and correlation between the N/S and sin/anti rations are discussed.

Adenosine Monophosphate↗

[Further improvement of the ACD-AG protective solution for blood. III. Improvement of the oxygen transport function of erythrocytes in sorbitol xylitol pyruvate solutions with elevated Ph].

If the pH value in the ACD or in the ACD-AG storage solution is enhanced, the glucose in the autoclaving with undergo a caramelizing process. For this reason glucose was replaced by sorbite in the storage solutions with a pH value of 6.0 and additions of xylitol and pyruvate. The initial pH value in the blood amounted to 7.3. The content of 2.3 DPG of the erythrocytes remained fully preserved in the blood with sorbitol and additions of xylitol and pyruvate during the first 2 weeks of storage and decreased to 30% only in the third week. There were only slight amounts of 2.3 DPG in the ACD-AG blood at that time of storage. Up to the third week of storage the ATP content of erythrocytes as well as the haemoglobin level in the plasma revealed no essential differences between stored blood with sorbitol and xylitol as a substrate or glucose + xylitol respectively. The quick decrease of the ATP level to zero and the simultaneous strong increase of haemolysis in the sorbitol blood within the fourth week of storage is discussed in connection with a lowering of the NAD/NADH2 quotient. For the purpose of keeping the 2.3 DPG level of erythrocytes a storage solution with sorbite and xylitol (ASCX-AG-Pyr 10mM) seems to be well suited for a storing time of 2---3 weeks at first.

Adenosine Triphosphate↗

Physical-chemical compatibility of cromolyn sodium nebulizer solution--bronchodilator inhalant solution admixtures.

Cromolyn sodium nebulizer solution, 1%, is physically and chemically compatible (stable) for up to 60 minutes when mixed in vitro with metaproterenol, isoproterenol, isoetharine, epinephrine, terbutaline, and acetylcysteine inhalant solutions, respectively. Similarly, cromolyn does not adversely affect the stability of the individual bronchodilator/mucolytic drugs in the admixtures. Adding a bronchodilator/mucolytic agent to a cromolyn nebulizer solution should not negatively influence the in vivo efficacy or safety of either active ingredient.

Aerosols↗

[The postoperative protein and energy metabolism during infusion therapy with high-calorie carbohydrate solutions, compared with low-calorie amino acid solutions].

In a comparative study two infusion regimens applicable via the peripheral veins were examined with regard to their efficacy for the protein and energy metabolism. 20 male metabolically normal patients having undergone gastric resections were divided into 2 groups: Group I received a combined 17.2% carbohydrate solution containing no amino acids, group II received a combined 5% carbohydrate solution together with a 2.5% amino acid solution. In group I an optimal protein sparing was observed with significantly lower serum urea levels than preoperatively and in group II. The serum urea levels of group II showed a significant increase without exceeding the upper normal range and thus indicated partial utilization of amino acids for gluconeogenesis. Nevertheless, the nitrogen balances of the postoperative days 1-4 in group II were significantly improved in comparison with group I. The amino acid utilization in group II was therefore considerable despite increased gluconeogenesis. The concentration of free fatty acids in the serum of group II which was significantly increased during the postoperative days 1-5 suggested an enhanced endogenous production of energy by way of lipolysis. In group II the low-dosed supply of carbohydrates produced a correspondingly lower insulin secretion which on the one hand enabled increased lipolysis and on the other hand resulted in the utilization of carbohydrates in insulin-independent organs essential for glucose utilization. In contrast to group II there was found to be a significantly lower concentration of free fatty acids in the serum of group I because of insulin-induced reesterification rates and impaired lipolysis.

Adult↗

Injury and recovery of the liver from preservation assessed by 31P NMR spectroscopy: the contrast between preservation with Collins' solution and Ringer's lactate solution.

The biochemistry of hepatic injury and recovery from preservation for transplantation was studied in rat liver perfused in vitro with erythrocytes. ATP and its metabolites, inorganic phosphate (Pi) and pH were quantitated as often as every 2.5 min by 31P NMR spectroscopy during preservation and recovery. Release of the hepatocellular enzymes, lactate dehydrogenase V (LDV) and aspartate aminotransferase (AST) were also measured. The duration of preservation with Collins' solution, the standard clinical preservative, affected the rate of recovery of ATP and monophosphate esters (MP), which include AMP + IMP, and the final recovery of Pi, but not of ATP. The difference between Collins' and Ringer's lactate solution, a poor preservative, became more apparent as preservation time increased. The differences included (1) pH at the end of preservative infusion; (2) pH between 0 and 2.5 min of reperfusion; (3) the MP increase (AMP + IMP) at the end of 13 h of preservation; (4) rate of recovery of ATP after preservation; (5) final ATP recovery during reperfusion; (6) LDV after 13h of preservation. These biochemical differences between good and poor preservation form a rational basis for prediction of liver failure after transplantation and for tests of the quality of new preservatives.

Animals↗

[Safety and tolerance of a new dipeptide-containing amino acid solution DP-Gln 20 versus a conventional amino acid solution Vamin 18EF in patients after elective colon surgery].

OBJECTIVE AND METHODS: Recent studies have demonstrated the important role of glutamine in postoperative metabolism. Using dipeptide-containing amino acid solutions it is possible to enhance glutamine supply. Safety and tolerance of DP-Gln 20 (gly-gln, gly-tyr) and Vamin 18EF were investigated in an open, prospective, randomised study. 16 patients received isonitrogenous parenteral nutrition over 4 days. RESULTS: There was no difference in clinical and biochemical patterns between both groups. Complications and adverse events due to the infused amino acid solutions were not observed.

Adolescent↗

Enteral resuscitation of burn shock using World Health Organization oral rehydration solution: a potential solution for mass casualty care.

Enteral resuscitation could provide a means to resuscitate burn shock when intravenous (IV) therapy is unavailable, such as in mass disasters. We evaluated the extent of intestinal absorption and resuscitative effects of World Health Organization Oral Rehydration Solution after a 40% TBSA burn in anesthetized swine compared with the IV infusion of lactated Ringer's infused by Parkland formula. Plasma volume (PV) was measured using indocyanine green dye dilution. Intestinal absorption was assessed using phenol red as a nonabsorbable marker. Changes in hematocrit, hemodynamics, and measured PV showed equivalent resuscitative effects of enteral and IV resuscitation. The duodenal fluid absorption rate started at 77 +/- 32 ml/hr per meter of intestine during the first hour and increased to 296 +/- 40 ml/hr during the fourth hour of resuscitation, with a total of 93 +/- 2% of World Health Organization Oral Rehydration Solution infused into the intestine being absorbed. Intestinal absorption rates after burn injury are sufficient to resuscitate a 40% TBSA burn.

Animals↗

Half-strength citrate CPD and new additive solutions for improved blood preservation. I. Studies of six experimental solutions.

Poor stability of plasma factor VIII in whole blood and loss of erythrocyte 2,3-bis-phosphoglycerate (BPG) during red cell storage are limitations with systems for blood component preparation in current use. This study presents attempts to improve post-collection storage conditions in both these respects using half-strength citrate CPD solution (0.5CPD) for blood collection, which has been shown by others to improve the stability of factor VIII, and some compositions of hypotonic additive solutions for red cell storage containing citrate, adenine, mannitol, and phosphate. Guanosine was also included in some of the media. The erythrocyte BPG concentration was maintained at a normal level for 3-4 weeks with the best of the tested compositions. Total adenine nucleotide concentration was maintained at the original level for 49 days and adenosine triphosphate for 28 days. Spontaneous storage haemolysis was low, 0.31% (mean) +/- 0.08-0.10% (SD) after 49 days in the two best compositions. The intracellular pH was 0.2-0.3 pH units higher than the extracellular pH at the beginning of storage, but this difference gradually diminished and disappeared after 4-5 weeks. We suggest two likely explanations of the effects: the maintenance of intracellular pH at a level sufficiently high not to impair BPG synthesis until after several weeks of storage, and a sufficient supply of phosphate needed in the synthesis of organic phosphate compounds. The content of citrate was selected such that the total amount supplied to a patient in a massive transfusion, when using a combination of 0.5CPD plasma and red cell suspension, would be smaller than that provided by a transfusion of CPD whole blood.

2,3-Diphosphoglycerate↗

Intravenous administration of hypertonic sodium chloride solution with dextran or isotonic sodium chloride solution for treatment of septic shock secondary to pyometra in dogs.

OBJECTIVE: To determine effects of i.v. administration of hypertonic saline (7.5% NaCl) solution with 6% dextran 70 (HSSD) or isotonic saline (0.9% NaCl) solution (ISS) to dogs with septic shock secondary to pyometra. DESIGN: Prospective, randomized, clinical study. ANIMALS: 14 client-owned dogs with septic shock secondary to pyometra. PROCEDURE: Prior to emergency ovariohysterectomy, catheters were placed in pulmonary and femoral arteries of each dog to evaluate hemodynamic and oxygenation status. Immediately prior to surgery, 7 dogs received HSSD (4 ml/kg [1.82 ml/lb] of body weight, i.v.) and 7 dogs received ISS (32 ml/kg [14.54 ml/lb], i.v.) during a 5-minute period. Measurements of hemodynamic and oxygenation variables were obtained before and 5 and 20 minutes after administration of fluids. RESULTS: Mean arterial pressure (MAP) increased significantly 5 and 20 minutes after administration of HSSD, whereas ISS did not affect MAP. However, cardiac output, cardiac index, and oxygen delivery increased and hematocrit decreased after both treatments. Oxygen consumption and extraction rate and degree of acidosis did not improve after either treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of small volumes of HSSD to dogs with septic shock secondary to pyometra resulted in improvement of hemodynamic and oxygenation status. Although cardiac output, cardiac index, and oxygen delivery improved after administration of a volume of ISS equal to 8 times that of HSSD, MAP increased to > 80 mm Hg only after treatment with HSSD. Administration of HSSD may be an effective treatment for septic shock in dogs.

Animals↗

Structure of protein solutions. Part 2. Solutions of total protein of yeast Saccharomyces cerevisiae.

Water systems formed by total protein of yeast Saccharomyces cerevisiae and model systems on the basis of unfractionated casein were studied by viscosimetry and electron microscopy. Methodologically, both methods offered a possibility of distinguishing several quantitatively different concentration intervals in protein solutions under different conditions. Viscosimetry gave the most informative results at the concentration intervals where the solutions approached the true ones, while electron microscopy did so when supermolecular formations prevailed. In comparing the data obtained by these two methods the following conclusions were drawn: At low temperatures (4-10 degrees C) yeast protein was in molecular-dissociated condition. Association in the system starts at 10 degrees C, and becomes enhanced with a rise in temperature. A temperature rise to 25-30 degrees C promotes a more compact packing of polypeptide chains; further heating leads to high-temperature denaturation. Lipids induce covering of polypeptide chains and prevent associations, thus leading to an increase in the system's thermostability.

Caseins↗

The 13C chemical shifts of amino acids in aqueous solution containing organic solvents: application to the secondary structure characterization of peptides in aqueous trifluoroethanol solution.

The 13C chemical shifts for all of the protonated carbons of the 20 common amino acid residues in the protected linear pentapeptide Gly-Gly-X-Gly-Gly have been obtained in water at low pH as well as in aqueous solution containing 10, 20 and 30% acetonitrile or trifluoroethanol. Dioxane was used as an internal reference and its carbon chemical shift value was found to be 66.6 ppm relative to external TMS in water. Comparison of the different referencing methods for 13C chemical shifts in organic cosolvent mixtures showed that an external standard (either TMS or TSP capillary) was the most appropriate. In the present study, external TSP was chosen to define the 0 ppm of the 13C chemical shift scale. When the difference in referencing the dioxane carbon resonance is taken into account, the carbon chemical shift values of the amino acids in aqueous solution are similar to those previously reported (Richarz and Wüthrich (1978) Biopolymers, 17, 2133-2141; Howarth and Lilley (1979) Prog. NMR Spectrose., 12, 1-40). The pentapeptides studied were assumed to be in a random coil conformation and the measured 13C chemical shifts were used as reference values to correlate carbon chemical shifts with the secondary structure of two well-characterized peptides, bombesin and the 1-29 amino acid fragment of Nle27 human growth hormone-releasing factor. In both cases, the C alpha chemical shifts exhibited a characteristic positive deviation from the random coil values, which indicates the presence of alpha-helices.

Amino Acid Sequence↗

Localization of bound water in the solution structure of the immunoglobulin binding domain of streptococcal protein G. Evidence for solvent-induced helical distortion in solution.

The presence of bound water in the solution structure of the IgG binding domain of streptococcal protein G has been investigated by nuclear magnetic resonance using three-dimensional 1H rotating frame Overhauser 1H-15N multiple quantum coherence spectroscopy. The backbone amide protons of three residues, Ala20, Gln32 and Tyr33, are found to be in close proximity to bound water. Examination of the three-dimensional structure of the IgG binding domain indicates that in the vicinity of these three residues there are no backbone groups that do not already participate in hydrogen bonding and there are no suitably placed side-chain groups available for hydrogen bonding with water. As the lifetime of the bound water detected in this nuclear magnetic resonance experiment is greater than about one nanosecond, it is likely that the two bound water molecules participate in a bifurcating hydrogen bonding network comprising a CO-NH hydrogen bonded pair, such that the water molecule accepts a hydrogen bond from the NH proton and donates one to the carbonyl oxygen with the result that the amide proton is involved in a three center hydrogen bond. On the basis of the structure, one water molecule participates in such an interaction with the Ala20(NH)-Met1(CO) hydrogen bonded pair at the beginning of an anti-parallel beta-sheet, and the other with the Tyr33(NH)-Val29(CO) hydrogen bonded pair in the single alpha-helix. The latter, which is external and solvent accessible, is associated with a distortion in the alpha-helix centered around Tyr33 which consists of a significant increase in the CO(i-4)-N(i) and CO(i-4)-NH(i) distances relative to those in the rest of the helix, as well as a significant departure in the phi, psi angles of Tyr33 relative to regular helical geometry. Such solvent induced distortions in alpha-helices have been previously noticed in crystal structures and were postulated as possible folding intermediates for helical structures. The present observation of this phenomenon in solution indicates, however, that these water molecules are tightly bound and represent an integral part of the protein framework.

Bacterial Proteins↗

An analytical solution to solute transport in continuous arterio-venous hemodiafiltration (CAVHD).

In conventional intermittent hemodialysis, the overall mass transfer coefficient (Kd) of a dialyser is mostly calculated at zero ultrafiltration and at relatively high dialysate flow rates. In continuous arterio-venous hemodiafiltration (CAVHD), the dialysate flow rates are low as comparable to the rates of ultrafiltration flows, making the dialysis treatment as slow as possible. Therefore the overall mass transfer coefficient (Kd) of a CAVHD hemofilter has to be calculated in the presence of ultrafiltration. A mathematical model of CAVHD is presented in order to calculate the diffusive mass transfer coefficient (Kd) for a solute when blood, filtrate and dialysate flow rates and solute concentrations are known. The ultrafiltration volume flux (Jv) is assumed to vary linearly along the axial direction of the hemofilter. The calculated mass transfer coefficient Kd shows that at high values of dialysate flow and low values of ultrafiltration, the overall mass transfer coefficient (Kd) of a CAVHD hemofilter equals mass transfer coefficient (Kd) of a dialyser in conventional intermittent hemodialysis. Also, the calculated mass transfer coefficient Kd shows no significant differences when the ultrafiltration volume flux is assumed to be constant along the length of the hemofilter if no backfiltration occurs in the hemofilter.

Biological Transport, Active↗

A comparison of the clinical efficacy of pheniramine maleate/naphazoline hydrochloride ophthalmic solution and olopatadine hydrochloride ophthalmic solution in the conjunctival allergen challenge model.

BACKGROUND: The signs and symptoms of allergic conjunctivitis include ocular redness and itching. Two treatment options currently indicated for acute ocular allergic reaction are pheniramine maleate 0.3%/naphazoline hydrochloride 0.025% ophthalmic solution, an over-the-counter antihistamine/vasoconstrictor combination; and olopatadine hydrochloride 0.1% ophthalmic solution, a prescription antihistamine/mast cell stabilizer. OBJECTIVE: This study was designed to compare, at onset of action, the relative effectiveness of pheniramine/naphazoline and olopatadine, when administered before conjunctival allergen challenge (CAC), using the ocular allergy index (OAI) as the primary end point. METHODS: This was a prospective, randomized, double-masked, contralateral, active- and placebo-controlled, single-center study of the CAC model. The first 2 study visits established and confirmed the subjects' ocular allergic reaction (no medication administered). At visit 3, the subjects were randomly assigned to 1 of 3 contralateral (right eye vs left eye) treatment combinations: pheniramine/naphazoline + olopatadine, pheniramine/naphazoline + placebo, or olopatadine + placebo. Medication was given 10 minutes before CAC. The subjects' erythema in the ciliary, conjunctival, and episcleral vessel beds; eyelid swelling; chemosis; and itching were evaluated at 7, 12, and 20 minutes after CAC. The OAI was calculated as a composite score of 6 signs and symptoms of allergic conjunctivitis to assess global severity. Between-treatment differences in OAI scores were used to evaluate efficacy. Subjects were asked their eye drop preference at the conclusion of visit 3. RESULTS: Subjects (n = 83) ranged in age from 20 to 70 years (mean, 42.5 years), 61.4% (n = 51) were female, and 94.0% (n = 78) were white. Both pheniramine/naphazoline and olopatadine were associated with significantly lower OAI scores than placebo at all 3 time points (all, P < 0.001). OAI scores were significantly lower with pheniramine/naphazoline than with olopatadine at 12 and 20 minutes (P = 0.005 and P = 0.001, respectively). CONCLUSION: In this patient sample, studied in a CAC model of onset of action, prophylactic pheniramine/naphazoline was more effective than olopatadine and placebo in alleviating the signs and symptoms of the acute ocular allergic reaction, as measured by the OAI.

Administration, Topical↗

University of Wisconsin solution versus Celsior solution in clinical pancreas transplantation.

INTRODUCTION: This study compared the safety and efficacy of University of Wisconsin solution (UW) and Celsior solution (C) in pancreas transplantation (PTx). METHODS: A retrospective review of 154 PTx performed over a 61-month period included 77 grafts preserved with UW and 77 with C. The two groups were comparable for both donor and recipient characteristics. RESULTS: After a mean cold ischemia time of 624 minutes (range 360 to 945 minutes) for UW versus 672 minutes (range 415 to 1005 minutes) for C (P = NS), no primary endocrine nonfunction occurred. Delayed endocrine function was diagnosed in two grafts in the UW group (2.6%) versus none in the C group (P = NS). After a minimum follow-up of 4 months (mean 26.5 +/- 15.2 months), 22 recipients (UW = 11 vs C = 11; P = NS) required relaparotomy. Overall, 18 pancreata were lost due to either patient death with functioning graft (UW = 4 vs C = 1; P = NS) or graft loss due to other reasons (UW = 8 vs C = 5; P = NS). Actuarial 1- and 5-year patient survival rates were 93.5% and 86.8% for UW compared with 98.7% and 98.7% for C (P = .04). Actuarial graft survival rates at the same times were 88.3% and 75.0% for UW compared with 90.4% and 90.4% for C (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and C show similar safety and efficacy profiles for PTx.

Adenosine↗