Comparison of Microplegia Solution and Del Nido Cardioplegia Solution in Coronary Artery Bypass Grafting Surgery: Which One is More Effective?

BACKGROUND: The aim of this study is to compare the efficacy of the microplegia solution and Del Nido cardioplegia solution in coronary artery bypass surgery with clinical, biochemical, and echocardiographic data. METHODS: Three hundred patients, who underwent coronary artery bypass surgery between January 2017 and January 2020, by the same surgical team were included in the study. Preoperative, operative and postoperative data (cardiac biomarker levels, cross-clamp and CPB times, echocardiographic measurements, etc.) of the patients were compared. RESULTS: In the study, cross-clamp time was significantly shorter in the DN cardioplegia group (55.60 ± 13.49 min/75.58 ± 12.43 min, P = 0.024). No significant difference was observed between the two groups in terms of intensive care stay, extubation time, hospital stay, and cardiopulmonary bypass time. In our study, it was shown that both the left and right ventricular ejection fraction was better protected in the Del Nido cardioplegia group (5.34±3.03 vs. 3.40±2.84, P = 0.017 and 3.82±1.19 vs. 2.28±1.87, P = 0.047, respectively), and the need for inotrope support was lower in this group (28% vs. 44%, P < 0.021). There was no significant difference between the groups, in terms of blood transfusion rates, IABP requirement. CONCLUSION: In light of short-term results, we can say that Del Nido cardioplegia provides better myocardial protection than microplegia. In addition, Del Nido cardioplegia can be given as a single dose for 90 minutes of cross-clamp time and therefore can be preferred to increase surgical comfort and reduce cross-clamp times.

Effects of Del Nido and Terminal Warm Blood Cardioplegia on Myocardial Protection and Rhythm in Isolated CABG Patients.

OBJECTIVE: To investigate the effect of using del Nido cardioplegia+terminal hot-shot blood cardioplegia on myocardial protection and rhythm in isolated coronary bypass patients. MATERIAL AND METHODS: A total of 122 patients were given cold (+4-8C') del Nido cardioplegia antegrade and evaluated. Del Nido+terminal warm blood cardioplegia (TWBCP) was applied to 63 patients out of 122 patients, while del Nido cardioplegia alone was applied to the other 59 patients. The preoperative and postoperative data of the patients were recorded and compared. RESULTS: There was a significant statistical difference between the groups, in terms of volume with more cardioplegia in the del Nido+terminal warm blood cardioplegia group. Although there was no significant difference between cardiac arrest times in both groups, a statistically significant difference was found in the del Nido+terminal warm blood cardioplegia group in the starting to work time of the heart. No difference found between the groups regarding myocardial preservation. CONCLUSIONS: We can add a return to spontaneous sinus rhythm to the advantages of terminal warm blood cardioplegia and del Nido cardioplegia in literature. We think it would be a good strategy to extend the safe ischemic time limit of del Nido to 120 minutes with a terminal warm blood cardioplegia. It seems that cardioplegia techniques that will be developed by adding the successful and superior results of crystalloid cardioplegia applications, such as single dose del Nido in various open heart surgery operations and the superior myocardial return effects of terminal warm blood cardioplegia, will be used routinely in the future.

Effect of Concentrated Salts Solutions on the Stability of Immobilized Enzymes: Influence of Inactivation Conditions and Immobilization Protocol.

This paper aims to investigate the effects of some salts (NaCl, (NH4)2SO4 and Na2SO4) at pH 5.0, 7.0 and 9.0 on the stability of 13 different immobilized enzymes: five lipases, three proteases, two glycosidases, and one laccase, penicillin G acylase and catalase. The enzymes were immobilized to prevent their aggregation. Lipases were immobilized via interfacial activation on octyl agarose or on glutaraldehyde-amino agarose beads, proteases on glyoxyl agarose or glutaraldehyde-amino agarose beads. The use of high concentrations of salts usually has some effects on enzyme stability, but the intensity and nature of these effects depends on the inactivation pH, nature and concentration of the salt, enzyme and immobilization protocol. The same salt can be a stabilizing or a destabilizing agent for a specific enzyme depending on its concentration, inactivation pH and immobilization protocol. Using lipases, (NH4)2SO4 generally permits the highest stabilities (although this is not a universal rule), but using the other enzymes this salt is in many instances a destabilizing agent. At pH 9.0, it is more likely to find a salt destabilizing effect than at pH 7.0. Results confirm the difficulty of foreseeing the effect of high concentrations of salts in a specific immobilized enzyme.

Stability of 0.5% Glucose-Containing Balanced Electrolyte Solutions for Patients on Ketogenic Diets: A Laboratory Study.

PURPOSE: Ketogenic diets (KDs) are used to treat epilepsies resistant to pharmacotherapy or some inborn errors of metabolism. For prolonged anesthesia, use of balanced electrolyte solutions (BESs) supplemented with 0.5% glucose has been advocated to maintain ketosis while preventing hypoglycemia. Unfortunately, there is no BES containing 0.5% glucose available from pharmacies. In a laboratory study, we investigated the physical and chemical stability of different BES mixtures containing 0.5% glucose. METHODS: In total, six approaches were chosen to create a BES with 0.5% glucose: three different glucose-free BESs were supplemented with glucose. Additionally, commercially available BES containing 1% glucose was diluted with three different glucose-free BESs to obtain a solution containing 0.5% glucose. Turbidity, pH, electrical conductivity, and macroscopic appearance of these solutions were measured immediately, at 24 hours, and after 7 days, and were compared with the original BES. RESULTS: Turbidity, pH, and electrical conductivity, as well as macroscopic appearance did not exceed the changes of the controls. CONCLUSIONS: No signs of incompatibility reactions could be observed in a 1-week time period. Our study supports the stability of the examined BES containing 0.5% glucose for prolonged anesthesia in patients on KD. Clinical studies are needed to evaluate if BES containing 0.5% glucose is superior in patients on KDs.

An interesting increase in immediate and residual efficacy of a trade mark of alcoholic 2% chlorhexidine gluconate, with and without dye, has been demonstrated by an in vitro study with ATCC micro-organisms and strains isolated from ICU patients.

AIM: ChloraPrep™ (CHP) is a clear solution of 2% (w/v) chlorhexidine (CHG) in 70% (v/v) isopropyl alcohol (IPA) administered with a specially designed sterile single-use applicator in which a tinting agent can be added to the CHP solution upon activation of applicator immediately prior to patient skin preparation (CHP+T). This study investigated whether the immediate and residual efficacy of CHP vs CHP+T and a stock solution of 2% CHG in 70% IPA varied, and whether CHP was compromised by the addition of the dye. METHODS AND RESULTS: We compared the immediate and residual activity (in 1 min) of 70% IPA with that of 2% CHG in 70% IPA stock solution prepared in the laboratory against CHP+T and CHP, against 22 micro-organisms (5 ATCC and 18 clinical isolates) on germ-carriers. CHP and CHP+T demonstrated superior immediate and residual efficacy compared to the 70% IPA plus 2% CHG in 70% IPA stock solutions. Each antiseptic tested showed greater efficacy against the Gram-positive bacteria than against the Gram-negative bacteria. However, their antimicrobial effect on yeasts was even lower. CONCLUSIONS: CHP and CHP+T have superior immediate and residual efficacy compared to stock 70% IPA and 2% CHG in 70% IPA solutions, and CHP+T is not affected by the tinting agent. SIGNIFICANCE AND IMPACT OF THE STUDY: ChloraPrep is a product which can be stained just before use. We have demonstrated that the immediate and residual efficacy of the antimicrobial solution is not compromised by the dye. The efficacy of CHP is greater against bacteria than against yeasts obtained from ICU patients. Interestingly, CHP is more effective against bacteria than a formula made in the laboratory with the same basic components (2% chlorhexidine and 70% IPA). The intermittent heat sterilization process of the commercial preparation might hypothetically have improved the residual activity of the CHP solutions.

Decontamination efficacy of sodium hypochlorite solutions for poliovirus.

Effective decontamination procedures are critical to the successful manufacture and control of poliovirus vaccines to minimize the risk to personnel and the environment. Polio viruses have been reported to be more resistant to disinfectants than many other viruses. We assessed the efficacy of sodium hypochlorite-containing disinfectants for decontamination for three poliovirus serotypes to implement decontamination procedures that are fully compliant with the WHO GAP III and Health authorities' requirements. A 10.4 log reduction was observed with a 0.63% sodium hypochlorite solution in a suspension with high protein and high poliovirus concentrations diluted 10-fold compared with a 6 log reduction in an undiluted sample. Treatment efficacy increased with sodium hypochlorite content and decreased with sample protein content. The surface tests showed that two 1-min treatments, 5-min apart, with a 0.63% Chl sodium hypochlorite solution effectively reduced the concentration of all poliovirus serotypes by 10 log10, irrespective of the protein and virus concentration in the sample. Sodium hypochlorite solutions lower than 0.52% were less effective for complete inactivation of poliovirus. In conclusion, we demonstrated that a high level of virus reduction (>10 log10) can be achieved with sodium hypochlorite solutions with poliovirus in suspension and dried on surfaces.

Myocardial Protection by Blood-Based Del Nido versus St. Thomas Cardioplegia in Cardiac Surgery for Adults and Children.

BACKGROUND: St. Thomas (ST) and Del Nido (DN) cardioplegic solutions are widely used for myocardial protection during cardiac surgery. In 2016, our university hospital shifted from modified St. Thomas to Del Nido solution for both adult and pediatric cardiac surgery. This retrospective study was conducted to compare ST and DN solutions regarding surgical workflow and clinical outcome in pediatric and adult patients undergoing cardiac surgery. METHODS: We reviewed 220 patients who underwent cardiac surgery requiring cardioplegic arrest. Patients were categorized in 2 groups: ST (n = 110) and DN (n = 110). Each group included 60 pediatric and 50 adult patients. Demographic, intraoperative, and postoperative variables were collected. RESULTS: In pediatric patients, no significant difference was found between the 2 groups regarding clamping time, bypass time, need for defibrillation, inotropic score, postoperative ejection fraction (EF), period of mechanical ventilation, intensive care unit stay, or postoperative arrhythmias. One patient in the ST group required mechanical support by extracorporeal membrane oxygenation. We had 5 cases of pediatric mortality (3 in DN and 2 in ST, P = .64). In adult patients, significantly fewer patients in the DN group needed defibrillation than in the ST group. No significant difference was found regarding clamping time, inotropic score, or intraaortic balloon pump use. Mortality in adult patients was 6 cases (4 in ST group and 2 in DN group). CONCLUSION: DN cardioplegia solution is as safe as ST solution in pediatric and adult cardiac surgery. It has comparable results of myocardial protection and clinical outcome, with superiority regarding uninterrupted surgery and lower rate of defibrillation.

A Comparison of the Efficacy of Enema Solutions in Pediatric Emergency Department Patients.

BACKGROUND: Children presenting to pediatric emergency departments (EDs) are frequently given enemas for relief of constipation symptoms; there is very little literature guiding solution selection. OBJECTIVE: Our aim was to assess and compare the efficacy of the various enema solutions used in a pediatric ED, including the "pink lady," a previously unreported compounded combination of docusate, magnesium citrate, mineral oil, and sodium phosphate. METHODS: We identified all children who received any enema over a 5-year period in an urban, quaternary care pediatric ED for inclusion in the study via electronic record review. Physician investigators retrospectively reviewed routine visit documentation to confirm the type and dosage of enema and assess comorbidities, indications, efficacy, and side effects. Subjective descriptions of output were classified as none, small, medium, or large by reviewer consensus. RESULTS: There were 768 records included. Median age was 6.2 years (interquartile range 3.3-10.3 years). Solutions used were sodium phosphate (n = 396), pink lady (n = 198), soap suds (n = 160), and other (n = 14). There was no significant difference in output by solution type (p = 0.88). Volume delivered was highest for pink lady, with no significant association between volume delivered and output (p = 0.48). Four percent of patients had side effects. Soap suds had a significantly higher rate of side effects (10.6%; p = 0.0003), primarily abdominal pain. CONCLUSIONS: There was no significant difference in reported stool output produced by sodium phosphate, soap suds, and pink lady enemas in children treated in an ED. Further study via randomized controlled trials would be beneficial in guiding selection of enema solution.

Self-Organization of Recombinant Membrane Porin OmpF from Yersinia pseudotuberculosis in Aqueous Environments.

Recombinant porin OmpF (an integral protein of bacterial outer membrane) from Yersinia pseudotuberculosis was synthesized in Escherichia coli cells as inclusion bodies. By combining the methods of anion-exchange and gel filtration chromatographies, recombinant OmpF (rOmpF) was isolated as an individual protein in its denatured state, and its characteristic properties (molecular mass, N-terminal amino acid sequence, and hydrodynamic radius of the protein in 8 M urea solution) were determined. According to the data of gel filtration, dynamic light scattering, optical spectroscopy, and binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, the rOmpF is fully unfolded in 8 M urea and exists in random coil conformation. In aqueous solutions, rOmpF undergoes conformational changes, reversible self-association, and aggregation. When transferred from 8 M urea into water, PBS (containing 0.15 M NaCl, pH 7.4), or buffer containing 0.8 M urea (pH 8.0), fully unfolded rOmpF forms relatively compact monomeric intermediates prone to self-association with formation of multimers. The oligomeric intermediates have high content of native protein-like secondary structure and pronounced tertiary structure. In acidic media (pH 5.0, close to the protein isoelectric point), rOmpF undergoes rapid irreversible aggregation. Therefore, we found that medium composition significantly affects both porin folding and processes of its self-association and aggregation.

Effect of electro-activated aqueous solutions, nisin and moderate heat treatment on the inactivation of Clostridium sporogenes PA 3679 spores in green beans puree and whole green beans.

In this work, the synergistic effect of electro-activated solutions (EAS) of potassium acetate and potassium citrate, nisin and moderate heat treatment to inactivate C. sporogenes PA 3679 spores was evaluated in green beans puree and whole green beans. Electro-activated solutions (EAS) of potassium acetate and potassium citrate were generated under 400 mA during 60 min. They were characterized by an oxidation-reduction potential (ORP) and pH values ranged from +300 to +1090 mV and 2.8 to 3.67, respectively. Moreover, the EAS were combined with a bacteriocin nisin at concentrations of 250, 500, 750 and 1000 IU/mL and the targeted sporicidal effect was evaluated under moderate heat treatment. The inoculated mixtures were subjected to temperatures of 95, 105 and 115 °C for exposure times of 5, 15 and 30 min. After plate counting, the synergistic effect of the hurdle principle composed of electro-activated solutions, nisin and moderate temperatures was demonstrated. The obtained results showed that the synergistic effect of the used hurdle was able to achieve an inactivation efficacy of 5.9-6.1 log CFU/mL. Furthermore, experiments carried out with whole green beans showed that spore inactivation level was significantly higher and reach 6.5 log CFU/mL. Moreover, spore morphology was examined by transmission electron microscopy and the obtained micrographs showed important damages in all of the treated spores.

[Comparative study of three different decalcifying solutions in bone metastasis specimens with breast cancer].

Objective: To investigate the optimal strategy for immunohistochemical (IHC) staining in bone metastasis specimens from breast cancer. Methods: Twenty-eight bone metastases specimens from breast cancers were divided into three groups and subjected to different decalcifying agents (group A-10% nitrate, group B-EDTA decalcification, and group C-imported decalcifying solution RapidCal). The effects of those on HE and IHC staining for Ki-67, ER, PR, GATA3, RANK, RANKL, HER2 and HER2 FISH results were assessed. Results: There were no significant differences among three groups in HE morphology and IHC staining. Antigen content in the RapidCal group were all intact; the EDTA group showed a similar staining rate, which was better than the nitrate group (P<0.05). Nitrate group showed marked reduction in nuclear Ki-67 staining, but the loss of cytoplasmic antigens (RANK, RANKL) was less than cell membrane antigen (HER2). For FISH, the RapidCal group and EDTA group showed same results, concordant with IHC staining results. The expression of HER2 protein in the nitric acid group was significantly decreased and chromosome 17 labelling was lost (P<0.05). Conclusions: RapidCal treated bone metastases specimens from breast cancer show excellent sample quality in morphological, IHC and FISH results compared with traditional decalcifying agents. Owing to the longer time of EDTA decalcification, the new decalcifying agent RapidCal plays an important role in quality control and clinical application.

A cell transportation solution that preserves live circulating tumor cells in patient blood samples.

BACKGROUND: Circulating tumor cells (CTCs) are typically collected into CellSave fixative tubes, which kills the cells, but preserves their morphology. Currently, the clinical utility of CTCs is mostly limited to their enumeration. More detailed investigation of CTC biology can be performed on live cells, but obtaining live CTCs is technically challenging, requiring blood collection into biocompatible solutions and rapid isolation which limits transportation options. To overcome the instability of CTCs, we formulated a sugar based cell transportation solution (SBTS) that stabilizes cell viability at ambient temperature. In this study we examined the long term viability of human cancer cell lines, primary cells and CTCs in human blood samples in the SBTS for transportation purposes. METHODS: Four cell lines, 5 primary human cells and purified human PBMCs were tested to determine the viability of cells stored in the transportation solution at ambient temperature for up to 7 days. We then demonstrated viability of MCF-7 cells spiked into normal blood with SBTS and stored for up to 7 days. A pilot study was then run on blood samples from 3 patients with metastatic malignancies stored with or without SBTS for 6 days. CTCs were then purified by Ficoll separation/microfilter isolation and identified using CTC markers. Cell viability was assessed using trypan blue or CellTracker™ live cell stain. RESULTS: Our results suggest that primary/immortalized cell lines stored in SBTS remain ~90% viable for > 72 h. Further, MCF-7 cells spiked into whole blood remain viable when stored with SBTS for up to 7 days. Finally, live CTCs were isolated from cancer patient blood samples kept in SBTS at ambient temperature for 6 days. No CTCs were isolated from blood samples stored without SBTS. CONCLUSIONS: In this proof of principle pilot study we show that viability of cell lines is preserved for days using SBTS. Further, this solution can be used to store patient derived blood samples for eventual isolation of viable CTCs after days of storage. Therefore, we suggest an effective and economical transportation of cancer patient blood samples containing live CTCs can be achieved.

Storage of platelets at 4°C in platelet additive solutions prevents aggregate formation and preserves platelet functional responses.

BACKGROUND: Platelet (PLT) storage has been limited to 5 days at room temperature due to metabolic decline and risk for bacterial contamination. Refrigeration preserves PLT metabolism and function as well as limits bacterial growth; however, cold storage of PLTs also leads to aggregate formation. We hypothesized that storage of PLT concentrates at 4°C leads to glycoprotein (GP)IIb-IIIa activation and thus aggregate formation through fibrinogen binding and that this could be prevented by storing PLTs in PLT additive solution (PAS) without compromising PLT function. STUDY DESIGN AND METHODS: Apheresis PLTs in plasma (AP) or apheresis PLTs in PAS were stored at 22 or 4°C for up to 15 days. Measurements include PLT counts, blood gases, aggregation response, flow cytometry analysis of integrin levels, activation markers, and microparticle formation. RESULTS: Storage of AP 4°C led to a gradual decline in PLT count and an increase in aggregate formation that was mediated by intracellular calcium leak and fibrinogen receptor activation. Storage of PAS at 4°C prevented aggregate formation due to dilution of plasma fibrinogen. PAS stored at 4°C maintained aggregation responses to multiple agonists better than 22°C controls. CONCLUSION: Storage of AP at 4°C leads to low level GPIIb-IIIa activation and results in aggregate formation over time. Separating the PLTs from the plasma component and storing them in PAS at 4°C resolves aggregate formation and preserves the metabolic and functional responses of these stored PLTs.

Pharmaceutical Perspective on Opalescence and Liquid-Liquid Phase Separation in Protein Solutions.

Opalescence in protein solutions reduces aesthetic appeal of a formulation and can be an indicator of the presence of aggregates or precursor to phase separation in solution signifying reduced product stability. Liquid-liquid phase separation of a protein solution into a protein-rich and a protein-poor phase has been well-documented for globular proteins and recently observed for monoclonal antibody solutions, resulting in physical instability of the formulation. The present review discusses opalescence and liquid-liquid phase separation (LLPS) for therapeutic protein formulations. A brief discussion on theoretical concepts based on thermodynamics, kinetics, and light scattering is presented. This review also discusses theoretical concepts behind intense light scattering in the vicinity of the critical point termed as "critical opalescence". Both opalescence and LLPS are affected by the formulation factors including pH, ionic strength, protein concentration, temperature, and excipients. Literature reports for the effect of these formulation factors on attractive protein-protein interactions in solution as assessed by the second virial coefficient (B2) and the cloud-point temperature (Tcloud) measurements are also presented. The review also highlights pharmaceutical implications of LLPS in protein solutions.

Adding Biotin to Parenteral Nutrition Solutions Without Lipid Accelerates the Growth of Candida albicans.

BACKGROUND: We have previously demonstrated that Candida albicans requires multivitamins (MVs) or lipid to increase rapidly in parenteral nutrition (PN) solutions. In this study, in detail, the effects of vitamins on the growth of C. albicans in PN solutions without lipid were investigated. METHODS: In the 1st experiment, a commercial PN solution without lipid was supplemented with water-soluble vitamins (SVs: vitamins B1, B2, B6, B12 and C, folic acid, nicotinamide, biotin and panthenol), water-insoluble vitamins (IVs: vitamins A, D, E and K) or both (MVs). In the 2nd experiment, the test solutions were prepared by supplementing the PN solution with one of each or all of the SVs. In the 3rd experiment, another commercial peripheral PN (PPN) solution without lipid was supplemented with SVs, nicotinic acid, biotin or both nicotinic acid and biotin. In each of the experiments, a specified number of C. albicans organisms was added to each test solution, and all of the test solutions were allowed to stand at room temperature (23-26ºC). The number of C. albicans was counted at 0, 24, 48 and 72 hours after the addition of the organism. RESULTS: In the 1st experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs, but increased slowly without the SVs, regardless of the addition of the IVs. In the 2nd experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs or biotin, but increased slowly with each of the other water-soluble vitamins. In the 3rd experiment, the C. albicans increased rapidly in the PPN solution supplemented with the SVs or biotin, but increased slowly with the addition of nicotinic acid. CONCLUSIONS: These results suggested that adding MVs or SVs to PN solutions without lipid promotes the growth of C. albicans, and that this effect is mostly attributable to biotin.

Accumulation of oxidized peroxiredoxin 2 in red blood cells and its prevention.

BACKGROUND: The thiol protein peroxiredoxin 2 (Prx2) is a major red blood cell (RBC) antioxidant that breaks down hydroperoxides and in the process is converted to an oxidized disulfide. Our objective was to determine whether Prx2 becomes oxidized during storage of RBCs, to understand the underlying mechanism, and to find ways of preventing the accumulation of the oxidized form. STUDY DESIGN AND METHODS: RBCs were stored for up to 6 weeks under simulated blood banking conditions and Prx2 oxidation was monitored by nonreducing gel electrophoresis. The ability of the cells to reverse Prx2 oxidation after storage and to respond to added hydrogen peroxide was also evaluated. RESULTS: Prx2 remained predominantly reduced during the first 3 weeks of storage, and then the oxidized form accumulated progressively. In contrast to fresh cells, oxidation was not reversed by incubation with glucose. Storage of RBCs in a high-pH, low-chloride, and high-phosphate/bicarbonate buffer (EAS-76v6) largely prevented accumulation of oxidized Prx for at least 6 weeks, and dihydrolipoic acid (DHLA), but not Rejuvesol, N-acetylcysteine, or α-lipoic acid, was able to reverse or protect against Prx2 oxidation. Additional, Prx2 oxidation occurred when hydrogen peroxide was added. However, this was reversible, suggesting that the reductive capacity was compromised in some but not in all cells. CONCLUSION: Prx2 remains mostly reduced in a high-pH storage solution with buffering capacity. Addition of DHLA to stored RBCs might be advantageous. Prx2 redox status could be used as a biomarker for the quality of stored RBCs.

Hormetic effects of extremely diluted solutions on gene expression.

This paper summarizes the results of investigations showing how molecular biological tools, such as DNA-microarrays, can provide useful suggestions about the behaviour of human organisms treated with microamounts of drugs or homeopathic medicines. The results reviewed here suggest firstly that the action of drugs is not quenched by ultra-high dilution and proceeds through modulation of gene expressions. The efficacy of drug solutions seems to be maintained in ultra-highly diluted preparations, a fact which constitutes a challenge to the dogma of quantization of matter. The second and more important result is that the different gene expression profiles of cell systems treated with the same drugs at different dilutions suggest the existence of hormetic mechanisms. The gene expression profiles of cells treated with copper(II) sulfate, Gelsemium sempervirens and Apis mellifica, are characterized by the same common denominator of the concentration-dependent inversion of gene expression, which can justify at a molecular level the concept of simile adopted in homeopathy. The main conclusion we draw from these results is that these procedures provide new kinds of information and a tool for disclosing the mechanisms involved in hormetic effects. The application of these effects to modern medicine may allow researchers to conceive unprecedented therapeutic applications or to optimize the currently used ones in the framework of a low-dose pharmacology based on a reliable experimental platform.

Automated preparation of whole blood-derived platelets suspended in two different platelet additive solutions and stored for 7 days.

BACKGROUND: The Atreus system (Terumo BCT) automates the preparation of blood components from whole blood donations. Intermediate platelet (PLT) products can be pooled manually or with the OrbiSac (Terumo BCT) and suspended in different PLT additive solutions (PASs) to obtain PLT concentrates (PCs). The aim of our study was to compare the in vitro PLT quality of PCs obtained with either the Atreus 2C+ and the OrbiSac or the Atreus 3C and suspended in PAS-II or PAS-IIIM during storage for up to 7 days. STUDY DESIGN AND METHODS: We prepared eight PCs from buffy coats obtained with Atreus 2C+, pooled with the OrbiSac, and suspended in PAS-II and eight PCs from interim PLT units obtained with the Atreus 3C and suspended either in PAS-II or in PAS-IIIM. We measured volume, PLT content, and mean PLT component and performed metabolic assays (pH, glucose, lactate, pO2, and pCO2) and flow cytometry analyses (GPIb, GPIIbIIIa, GPIV, CD62P, CD63, von Willebrand factor [vWF], fibrinogen, Factor V, and annexin V). RESULTS: PCs prepared with the Atreus 3C showed lower volume and higher PLT concentration when compared with PCs prepared with the Atreus 2C+ and the OrbiSac (p < 0.05). Glucose consumption rate and the expression of CD62P, CD63, and vWF were lower in PCs suspended in PAS-IIIM when compared with PCs suspended in PAS-II (p < 0.05). CONCLUSION: PCs prepared with the Atreus 3C and suspended in PAS-IIIM preserve satisfactorily the in vitro PLT quality during 7-day storage. PLT activation during a 7-day storage period was lower when the storage solution was PAS-IIIM in comparison with PAS-II.

The heritability of metabolite concentrations in stored human red blood cells.

BACKGROUND: The degeneration of red blood cells (RBCs) during storage is a major issue in transfusion medicine. Family studies in the 1960s established the heritability of the RBC storage lesion based on poststorage adenosine triphosphate (ATP) concentrations. However, this critical discovery has not been further explored. In a classic twin study we confirmed the heritability of poststorage ATP concentrations and established the heritability of many other RBC metabolites. STUDY DESIGN AND METHODS: ATP concentrations and metabolomic profiles were analyzed in RBC samples from 18 twin pairs. On samples stored for 28 days, the heritability of poststorage ATP concentrations were 64 and 53% in CP2D- and AS-3-stored RBCs, respectively. RESULTS: Metabolomic analyses identified 87 metabolites with an estimated heritability of 20% or greater. Thirty-six metabolites were significantly correlated with ATP concentrations (p ≤ 0.05) and 16 correlated with borderline significance (0.05 ≤ p ≤ 0.10). Of the 52 metabolites that correlated significantly with ATP, 24 demonstrated 20% or more heritability. Pathways represented by heritable metabolites included glycolysis, membrane remodeling, redox homeostasis, and synthetic and degradation pathways. CONCLUSION: We conclude that many RBC metabolite concentrations are genetically influenced during storage. Future studies of key metabolic pathways and genetic modifiers of RBC storage could lead to major advances in RBC storage and transfusion therapy.

Coinfusion of dextrose-containing fluids and red blood cells does not adversely affect in vitro red blood cell quality.

BACKGROUND: Transfusion guidelines advise against coinfusing red blood cells (RBCs) with solutions other than 0.9% saline. We evaluated the impact of coinfusion with dextrose-containing fluids (DW) on markers of RBC quality. STUDY DESIGN AND METHODS: A pool-and-split design was used to allow conditions to be tested on each pool within 2 hours of irradiation. Three pools at each storage age (5, 14, and 21 days) were created for each phase. In Phase 1, samples were infused through a neonatal transfusion apparatus alone or with treatment solutions: D5W, D10W, D5W/0.2% saline, and 0.9% saline. In Phase 2, samples were incubated alone or in a 1:1 ratio with treatment solutions and tested after 5, 30, and 180 minutes. Hemolysis, supernatant potassium, RBC indices, morphology, and deformability were measured on all samples. RESULTS: In Phase 1, RBCs transfused alone through the apparatus had higher (p<0.01) hematocrit, total hemoglobin, and supernatant potassium compared to all other groups. No statistical differences were identified between groups for other measured variables. In Phase 2, mean corpuscular volume of all samples containing DW increased with incubation length and were higher (p<0.01) than RBCs incubated alone or with 0.9% saline after 30 and 180 minutes. RBCs incubated with D5W and D5W/0.2% saline had greater (p<0.05) hemolysis than RBCs alone after 180 minutes. CONCLUSION: In vitro characteristics of RBCs coinfused with 0.9% saline or D10W were not adversely impacted. When developing clinical studies in neonates, we recommend use of D10W and a transfusion apparatus that minimizes the contact volume of the coinfusate with the RBC.