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Effect of combining phosphodiesterase III inhibitors with St Thomas Hospital's solution used as transplantation preservative solution in isolated rat hearts.

Improved preservation of the harvested heart with attenuation of the reperfusion injury is important for successful outcomes of cardiac transplantations. The most commonly used cardioplegic solution, to prevent ischemic changes has been St Thomas' Hospital cardioplegic solution (STHCS). However, it is neither ideal nor sufficient to prevent myocardial ischemia and reperfusion injury. Phosphodiesterase inhibitors can attenuate the damage due to the injuries of ischemia and reperfusion. In this study we sought to enrich STHCS with a phosphodiesterase inhibitor to improve preservation of cardiac functions. The harvested hearts of 24 rats were divided into four groups. All hearts were mounted on a Langendorff perfusion system. After a stabilization period, cardiac arrest was maintained by STHCS. The hearts were stored in STHCS alone or with milrinone, amrinone, or enoximone for 6 hours. The reperfusion was maintained using a modified Tyrode's solution. All hearts were compared for their preischemic and postischemic left ventricular developed pressure, +dp/dtmax, -dp/dtmax, duration of systole, ejection time, and time to reach peak systolic pressure. Coronary effluent was collected for lactate dehydrogenase (LDH) measurements. The initial values for all metrics were comparable between the groups. During the postreperfusion period, all hearts showed lower peak systolic pressures than the initial values. Although the amrinone group seemed to have higher values, the 25-minute result was at the border of significance and the 30-minute value, significantly higher. All hearts showed far lower results of maximum changes in contractility during the time period (+dp/dtmax) versus the initial values; comparisons between groups were not significant. For the parameter of maximum changes in relaxation during the time period (-dp/dtmax), while other hearts showed lower results, the amrinone group displayed values comparable to the initial ones after 20 minutes. Comparisons between groups were insignificant. While other hearts had comparable values for time of systole, the hearts applied with milrinone reached these values after 15 minutes. Group comparison for time of ejection revealed that the results at 5-minute postreperfusion were higher in the enoximone and the amrinone groups than the milrinone group. Postreperfusion 5-minute results were higher in the enoximone and the amrinone groups than the milrinone group for time to reach peak systolic pressure. LDH levels were lowest in the amrinone group. In conclusion, our study revealed that adding phosphodiesterase inhibitors to STHCS improved peak systolic pressure and maximum changes in relaxation during the time period (-dp/dtmax, mm Hg/s). It also decreased the LDH leakage, which corresponded to the degree of ischemic tissue damage. Amrinone seemed to result in more favorable results, which may be attributed to its additional effects on inflammation, including those on cytokines and leukocyte aggregation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Comparison of a new sulfate-free polyethylene glycol electrolyte lavage solution versus a standard solution for colonoscopy cleansing.

A new sulfate-free polyethylene glycol electrolyte lavage solution (SF-ELS) for colonoscopy was formulated to taste better and have less net water and electrolyte secretion and absorption than a standard polyethylene glycolelectrolyte lavage solution (PEG-ELS). At two centers, 157 patients were prospectively randomized to receive SF-ELS or PEG-ELS to assess adequacy of preparation, patient tolerance, weight changes, and various hematologic and biochemical parameters. Physician assessment of colon cleansing showed no difference between those patients receiving SF-ELS (N = 74) or PEG-ELS (N = 78). Eighty-two percent of all preps were found to be "clinically acceptable." Subjects receiving SF-ELS had significantly less fullness and cramps, while PEG-ELS subjects reported less nausea. There was no difference between groups for vomiting, overall discomfort, or willingness to repeat the preparation received. Eighty percent of all patients would repeat the randomized cleansing methods. There were no clinically significant changes in weight or assessed laboratory parameters, with the exception of potassium where PEG-ELS patients had an mean decrease of 0.22 mEq/liter vs. 0.01 mEq/liter for SF-ELS (p less than or equal to 0.01). Patient taste questionnaires in those patients expressing a preference showed a preference for SF-ELS (76.6%) over PEG-ELS (23.4%) (p less than or equal to 0.001). Thirty-two (22.5%) of total respondents indicated no preference. We conclude that SF-ELS when compared with PEG-ELS is similarly a safe and effective method of colon cleansing for colonoscopy that is well tolerated. Patients prefer the taste of the new solution.

Colonoscopy↗

Three-dimensional solution structure of the oxidized high potential iron-sulfur protein from Chromatium vinosum through NMR. Comparative analysis with the solution structure of the reduced species.

The NMR solution structure of the oxidized HiPIP from Chromatium vinosum has been solved. Despite the fact that the protein is paramagnetic, 85% of the 1H and 80% of the 15N signals have been assigned. Through 1537 NOEs, out of which 1142 were found to be relevant for the structure determination, a family of structures has been obtained by distance geometry calculations. These structures have then been subjected to restrained energy minimization (REM) and restrained molecular dynamics (RMD) calculations in vacuum. Finally, the mean structure of the RMD family has been treated through RMD in water. The RMSD values for the backbone and heavy atoms within the RMD family are 0.57 +/- 0.14 and 1.08 +/- 0.16 A, respectively. These values together with other parameters indicate that the structure is of good quality and as good as the structure of the reduced protein. The RMDw structures of the reduced and oxidized proteins are different beyond the experimental indetermination. The set of constraints for the reduced and oxidized forms have been used to treat the available X-ray structure by RMD in water. The two structures generated in this way are quite similar to their respective solution structures, thus confirming that the experimental constraints are capable of yielding two different structures from the same starting structural model. This is the first time that independently determined solution structures of two redox states of a paramagnetic protein are available. Differences between them and the X-ray structure are discussed.

Amino Acid Sequence↗

Protein-conjugated nanoparticles from rapid expansion of supercritical fluid solution into aqueous solution.

The method of rapid expansion of a supercritical solution into a liquid solvent (RESOLV) was applied to the preparation of bovine serum albumin protein-conjugated silver sulfide nanoparticles. The conjugate samples were characterized by using a series of instrumental techniques. The results show that the monodispersed nanoparticles in the conjugates are well-coated directly with the protein. Because the protein undergoes solution pH-dependent association and dissociation, the protein-nanoparticle conjugates also assemble and disassemble with changes in solution pH in a reversible fashion.

Hydrogen-Ion Concentration↗

NMR solution structure and dynamics of motilin in isotropic phospholipid bicellar solution.

The structure and dynamics of the gastrointestinal peptide hormone motilin, consisting of 22 amino acid residues, have been studied in the presence of isotropic q = 0.5 phospholipid bicelles. The NMR solution structure of the peptide in acidic bicelle solution was determined from 203 NOE-derived distance constraints and six backbone torsion angle constraints. Dynamic properties for the 13Calpha-1H vector in Leu10 were determined for motilin specifically labeled with 13C at this position by analysis of multiple-field relaxation data. The structure reveals an ordered alpha-helical conformation between Glu9 and Lys20. The N-terminus is also well structured with a turn resembling that of a classical beta-turn. The 13C dynamics clearly show that motilin tumbles slowly in solution, with a correlation time characteristic of a large object. It was also found that motilin has a large degree of local flexibility as compared with what has previously been reported in SDS micelles. The results show that motilin interacts with the bicelle, displaying motional properties of a peptide bound to a membrane. In comparison, motilin in neutral bicelles seems less structured and more flexible. This study shows that the small isotropic bicelles are well suited for use as membrane-mimetic for structural as well as dynamical investigations of membrane-bound peptides by high-resolution NMR.

Electron Spin Resonance Spectroscopy↗

[Is epidural injection treatment with hypertonic saline solution in intervertebral disk displacement useful? (The effect of NaCl solution on intervertebral disk tissue)].

The effect of sodium chloride solution on disc tissue was investigated in vitro. Tissue material was obtained from 19 discectomies. The specimens were incubated in aqua ad injectionem and in different sodium chloride solutions and weighted regularly during a maximum of 24 hours. Following the incubation periods the specimens were examined histologically. After one hour the surgical specimens showed a weight increase of 290% for aqua bidest., 170% for 0.9% NaCl and 100% for 5.85% NaCl and 10% NaCl. Disc tissue obtained from six autopsies was also examined under the same conditions. The weight increase in nucleus pulposus and anulus fibrosus tissue was less than in the disc tissue obtained from surgery. The weight increase in anulus fibrosus tissue was less than in nucleus pulposus tissue. In vitro incubation of disc tissue in a hypermolar sodium chloride solution always resulted in a weight increase. Successful therapy could not be explained by shrinkage of disc tissue treated with hypermolar sodium chloride.

Adult↗

A successful maintenance approach in inflammatory acne with adapalene gel 0.1% after an initial treatment in combination with clindamycin topical solution 1% or after monotherapy with clindamycin topical solution 1%.

BACKGROUND METHODS: A total of 300 acne subjects entered this multicentre, randomized, investigator-blinded study comparing the efficacy and safety of adapalene gel 0.1% plus clindamycin topical solution 1% versus clindamycin topical solution 1% alone. In the second part of the study (weeks 12-24), completed by 241 subjects, the efficacy and safety of adapalene gel 0.1% alone as a maintenance therapy was investigated. RESULTS: A statistically significant greater reduction was observed from week 4 until week 12 in total lesion counts and from week 8 on for inflammatory and non-inflammatory lesion counts during the initial treatment for combination therapy compared with monotherapy. Results at week 24 for the reduction in all lesion counts during the maintenance phase were statistically significant in favour of adapalene (41.6%) compared with an increase for all lesion counts in the control group (92.1%). Adapalene alone or in combination with clindamycin topical solution was well tolerated. Few adverse events occurred, all of them during the initial treatment phase. Most of these local events were mild or moderate. CONCLUSION: The present study confirmed the importance of a maintenance therapy after a successful initial treatment and underlined the benefit of a combination therapy with a topical retinoid such as adapalene and a topical antibiotic in the treatment of inflammatory acne.

Acne Vulgaris↗

Randomized, controlled trial on the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury.

OBJECTIVE: The aim of this pilot study was to compare the effects of equimolar doses of hypertonic saline and dextran solution (HSD, Rescueflow) with 20% mannitol solution for reduction of increased intracranial pressure. DESIGN: Prospective, randomized, controlled, crossover trial in the intensive care unit of a large teaching hospital. SETTING: Academic hospital and tertiary referral center for neuroscience. PATIENTS: Nine patients with an intracranial pressure of >20 mm Hg were recruited and received two treatments of each, HSD and 20% mannitol, in a randomized order. INTERVENTION: Equimolar, rapid intravenous infusions of either 200 mL of 20% mannitol or 100 mL of 7.5% saline and 6% dextran-70 solution (HSD) over 5 mins. MEASUREMENTS: Intracranial pressure, blood pressure, serum and urine sodium and osmolality, and urine output. MAIN RESULTS: Treatments reduced intracranial pressure with both mannitol (median decrease, 7.5 mm Hg, 95% confidence interval, 5.8-11.8) and HSD (median decrease, 13 mm Hg; 95% confidence interval, 11.5-17.3). HSD caused a significantly greater decrease in intracranial pressure than mannitol (p = .044). HSD had a longer duration of effect than mannitol (p = .044). CONCLUSION: When given in an equimolar, rapid, intravenous infusion, HSD reduces intracranial pressure more effectively than mannitol.

Adolescent↗

Comparison of histidine-tryptophan ketoglutarate solution and University of Wisconsin solution in prolonged cold preservation of kidney allografts.

Although University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation, Histidine-Tryptophan Ketogluatarate (HTK) solution has been increasingly used. This study compared HTK or UW for cold static storage of kidney allografts. In all, 149 renal transplants were performed with cold ischemic times (CI) greater than 16 hr (UW 87, HTK 62) and a subset analysis was performed with CI over 24 hr (HTK 31, UW 38). Data from receiving renal transplant centers focused on delayed graft function (DGF), patient and allograft survival. In CI greater than 16 hr, graft and patient survival were comparable. HTK cohort had lower DGF. In CI greater than 24 hr, there was no difference in patient survival, a trend towards improved graft survival in HTK, and decreased rate of DGF in HTK. This data suggests that UW and HTK have at least similar efficacy in kidney preservation at longer ischemic times.

Adenosine↗

Improvements in the equation for calculating the contribution to osmotic potential of the separate solutes of water solutions.

A minor conceptual improvement, the elimination of an approximation and its revision in relativistic terms, has resulted in a twofold increase in the predictability of the equation for calculating the contribution to osmotic potential of the separate solutes of water solutions. The molecular model inherent to its formulation would provide unifying principles for visualizing water movements associated with solute concentration gradients in tissues.

Mathematics↗

Comparison of topical treatment with desoxymethasone solution 0.25% with salicylic acid 1% and betamethasone valerate solution 0.1% in patients with psoriasis of the scalp.

A new preparation for treatment of psoriasis of the scalp, containing desoxymethasone 0.25%, salicylic acid 1% and polyol-fatty esters in ethanolic solution (Ibaril) was tested in patients with psoriasis of the scalp. In a double-blind study comprising forty patients there was a significant difference in favour of this solution in comparison with betamethasone valerate solution, 0.1% (Betnovat) after 2 weeks of treatment.

Administration, Topical↗

Comparative study of rice-based oral rehydration salt solution versus glucose-based oral rehydration salt solution (WHO) in children with acute dehydrating diarrhoea.

One hundred children with acute dehydrating diarrhoea were studied. They were divided into two groups: Group A (n = 50) were given rice-based oral rehydration salt (ORS) solution and group B (n = 50) were given glucose-based ORS solution (WHO). There was no significant decrease in mean stool output and percentage weight gain with rice-based ORS. Both the groups were comparable for volume of ORS solution consumed, time taken for initial rehydration, mean stool output and for correcting biochemical abnormalities.

Acute Disease↗

Sonolysis of concentrated aqueous solutions of nonvolatile solutes: spin-trapping evidence for free radicals formed by pyrolysis.

The sonolysis of argon-saturated aqueous solutions of sodium acetate, sodium propionate, amino acids, and sugars was investigated by ESR and spin trapping over a large range of concentrations. The spin trap 3,5-dibromo-2,6-dideutero-4-nitrosobenzene sulfonate was used to examine the possibility of detecting new radicals specifically generated in the high temperature zones surrounding the collapsing cavitation bubbles. At lower concentrations of these solutes, no evidence for specific new radicals formed in the high temperature regions induced by cavitation could be found, and only radicals formed by hydroxyl radical and hydrogen atom abstraction reactions could be detected. These were identified by comparison with the radicals produced by uv photolysis in the presence of hydrogen peroxide. However, at higher concentrations, new radicals (typically methyl radicals) formed in the high temperature interfacial regions induced by cavitation were found for sodium acetate, sodium propionate, amino acids, and sugars (D-mannose, D-glucose, 2-deoxy-D-ribose). These results indicate that pyrolysis radicals can be detected when the nonvolatile solutes are present at high concentrations in the interfacial regions of the cavitation bubbles.

Acetates↗

[Kidney function parameters following ischemia stress using the Euro-Collins solution or the Bretschneider cardioplegic HTK solution].

Protection-methods, for an improvement of ischemic tolerance of the kidney, can be investigated by intraischemic analysis of metabolism and structure. A definite proof for the effectiveness of a protection method is only postischemic function in combination with postischemic structure-regeneration. For this reason postischemic function was chosen for examination of the protective ability of the Euro-Collins-solution and the HTK-solution during a two-hour reperfusion period. We perfused 57 dog kidneys either with the Euro-Collins- or with the HTK-solution prior to ischemia. Ischemia was 7, 60, 90 and 120 min after Euro-Collins-perfusion and 7, 120, 150 and 180 min after HTK-protection. The protected and ischemic kidneys were left in-situ; the mean ischemic temperature was therefore 20-25 degrees C for the shorter ischemic times and 30-34 degrees C for the longer ischemic times. We compared the protected and ischemic kidneys with 14 untreated kidneys (control). Postischemic renal blood flow (RBF) was measured by an electromagnetic flow probe; renal oxygen consumption (V02/min) was calculated by arterio-venous oxygen content difference and the renal blood flow. If urine could be collected, the glomerular filtration rate (GFR) was measured by an endogenous creatinine clearance. In Euro-Collins-protected kidneys after 60-120 min ischemia the RBF was after 15 min of reperfusion between 20 and 100 ml/min/100 g. After 30 min we got values of 100-200 ml/min/100 g. The V02/min, which was in the control kidneys between 5-6 ml/min/100 g, was about 2 ml/min/100 g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A compact form of DNA in solution. 2. Peculiarities of acidic titration of double-stranded DNA in PEG-containing water-salt solutions].

The formation of compact double-stranded DNA molecules in PEG-containing watersalt solutions (0.3 M NaCl) may be observed within the pH-range 3-10; i.e. under conditions at which parameters of double-stranded DNA helices are not strongly different from those of B-form. At pH less than 3, when regularity of double helices is significantly changed, the formation of the specific compact particles of DNA in PEG-containing solutions does not take place. Denaturation of the compact form of DNA in PEG-containing solution is accompanied by disappearance of the negative band in CD spectrum. Hyperchromic effect of denaturation of DNA compact form is uninformative because of the influence of the light-scattering by compact DNA molecules.

Circular Dichroism↗

Osmolality electrolyte and carbohydrate type and oral rehydration solutions: a controlled study to compare the efficacy of two commercially available solutions (osmolalities 240 mmol/L and 340 mmol/L).

An open-label, inpatient study was undertaken to compare the efficacy of two oral rehydration solutions (ORS) given randomly to children aged 1-10 years who had acute gastroenteritis with mild or moderate dehydration (n = 45). One solution contained 60 mmol/l sodium and 1.8% glucose, total osmolality 240 mosm/l (Gastrolyte, Rhone-poulenc, Rorer) and the other contained 26 mmol/l sodium, 2.7% glucose and 3.6% sucrose, total osmolality 340 mOsm/l (Glucolyte, Gilseal). Analysis of data indicated that Gastrolyte therapy resulted in significantly fewer episodes and volume of vomiting over all time periods in comparison to Glucolyte and significantly less stool volume during the first 8 h and in the 0-24 h period. The differences between treatments in degree of dehydration at each follow-up period, duration of diarrhoea, and duration of hospital stay were not significant. No adverse drug reactions occurred. Six patients received intravenous rehydration treatment and were considered treatment failures. We conclude that oral rehydration therapy is safe and efficacious in the management of dehydration in acute diarrhoea and that the lower osmolar rehydration solution has clinically marginal advantages.

Acute Disease↗

[Anaphylactoid reactions to an injectable solution of a cremophor-containing solution of multivitamins].

We report four anaphylactoid reactions after intravenous administration of a cremophor-containing multivitamin hydrosol (Hydrosol Polyvitaminé Roche), observed over an 8-month period in a small region of France. The reactions occurred immediately following intravenous infusion of either ionic solutions or parenteral nutrition mixture containing the multivitamin solution. In three cases, erythema and dyspnoea appeared within minutes. The infusion was rapidly stopped and corticosteroids were given to two patients. The fourth patient had erythema and swelling of the face within 30 min of infusion, and severe bronchoconstriction and hypotension within 60 min, before infusion was stopped. In-vivo histamine release from mast cell was proved. These reactions are highly suggestive of an anaphylactoid mechanism, due to the multivitamin solution, as all the other drugs were continued without subsequent reactions. The responsible agent is thought to be polyethoxylated castor oil (Cremophor EL), as it is known to produce such effects. Medical practitioners should evaluate the risk/benefit ratio each time they give this drug.

Adult↗

Flame photometric and atomic absorption determination of calcium, potassium, and sodium in Ringer's solution and injection and in lactated Ringer's solution.

Authentic and commerical counterparts of Ringer's solution and lactated Ringer's solution were analyzed by 14 collaborators. Calcium, potassium, and sodium were to be determined by any flame emission or atomic absorption instrument operated at prescribed performance levels, and basic procedures for comparing samples and standards were also given. Recoveries of the cations from authentic and commercial solutions were as follows: calcium 95.6-102.1 and 95.6-103.6%, respectively; potassium 97.9-101.7 and 98.7-102.4%; sodium 98.2-103.1 and 97.3-103.7%. The results indicate that the method yields acceptable precision for the determination of the 3 cations in fluid and electrolyte replenishers. The method has been adopted as official first action.

Calcium↗