RESUMEN
Background: Head injuries are considered as a silent epidemic due to the high incidence rate throughout the world. The main cause of morbidity and mortality in patients with head injury is cerebral edema which is defined as abnormal fluid accumulation in the brain parenchyma. Mannitol is a hyperosmolar solution given to reduce fluid volume in the brain. Increased high intracranial pressure can affect prognosis and can be evaluated by assessing clinical outcomes in patients with severe traumatic brain injury using the Glasgow Outcome Discharge Scale (GODS) instrument. Methods: Observational analytical study with a cross sectional design on 50 patients with severe traumatic brain injury at dr. Zainoel Abidin General Hospital Banda Aceh to determine the effect of mannitol use on the clinical outcomes of severe traumatic brain injury patients which used t test analysis. Results: The mean value of the group that received mannitol had a higher GODS score than the group that did not receive mannitol. The results of the T test between groups obtained a p value of 0.000 which is smaller than 0.05, so it can be concluded that the use of mannitol has an effect on the GODS score in Severe traumatic brain injury patients. The results showed that the mean GODS value in patients who received mannitol was higher than those who did not receive mannitol. Conclusion: This concludes that the administration of mannitol is effective in improving the clinical outcomes of patients with severe traumatic brain injury at dr. Zainoel Abidin General Hospital Banda Aceh.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Manitol , Humanos , Manitol/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Estudios Transversales , Escala de Consecuencias de Glasgow , Adulto JovenRESUMEN
Bacterial cellulose synthesis from defined media and waste products has attracted increasing interest in the circular economy context for sustainable productions. In this study, a glucose dehydrogenase-deficient Δgdh K2G30 strain of Komagataeibacter xylinus was obtained from the parental wild type through homologous recombination. Both strains were grown in defined substrates and cheese whey as an agri-food waste to assess the effect of gene silencing on bacterial cellulose synthesis and carbon source metabolism. Wild type K2G30 boasted higher bacterial cellulose yields when grown in ethanol-based medium and cheese whey, although showing an overall higher D-gluconic acid synthesis. Conversely, the mutant Δgdh strain preferred D-fructose, D-mannitol, and glycerol to boost bacterial cellulose production, while displaying higher substrate consumption rates and a lower D-gluconic acid synthesis. This study provides an in-depth investigation of two K. xylinus strains, unravelling their suitability for scale-up BC production.
Asunto(s)
Carbono , Celulosa , Celulosa/biosíntesis , Celulosa/metabolismo , Carbono/metabolismo , Acetobacteraceae/metabolismo , Acetobacteraceae/genética , Gluconatos/metabolismo , Glicerol/metabolismo , Manitol/metabolismoRESUMEN
Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes.
Asunto(s)
Adenosina , Alopurinol , Antioxidantes , Hígado Graso , Insulina , Hígado , Soluciones Preservantes de Órganos , Procaína , Rafinosa , Ratas Zucker , Daño por Reperfusión , Animales , Soluciones Preservantes de Órganos/farmacología , Ratas , Rafinosa/farmacología , Insulina/metabolismo , Adenosina/metabolismo , Adenosina/farmacología , Hígado Graso/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Antioxidantes/farmacología , Antioxidantes/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Alopurinol/farmacología , Masculino , Procaína/farmacología , Inflamación/metabolismo , Inflamación/patología , Inflamación/tratamiento farmacológico , Glucosa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Manitol/farmacología , Isquemia Fría/efectos adversos , Cloruro de Potasio/farmacología , Preservación de Órganos/métodos , Trasplante de Hígado/métodosRESUMEN
BACKGROUND: Del Nido cardioplegia (DNC) has extensively been used for pediatric population undergoing cardiac surgery. However, its use in adult cardiac surgeries have been limited thus, its benefits are not yet fully known. This analysis was performed to evaluate the impact of DNC versus any other type of cardioplegia in adult patients who are undergoing cardiac surgery. METHODS: We systematically searched PubMed, Cochrane Library, and Scopus from database inception till March 2023, and moderate to high-quality randomized controlled trials were included which compared DNC to other cardioplegia. The primary outcome was postoperative stroke and/or transient ischemic attack (TIA). Secondary outcomes included spontaneous rhythm return, postoperative myocardial infarction, all-cause mortality, postoperative atrial fibrillation, defibrillation after coronary reperfusion, postoperative intra-aortic balloon pump, postoperative kidney injury, postoperative low cardiac output syndrome, inotropic support, cardiopulmonary bypass time, cross-clamp time, blood transfusion, cardioplegia volume, hospital stay, intensive care unit stay, mechanical ventilation stay, postoperative left ventricular ejection fraction, and cardiac markers. RESULTS: In this meta-analysis, 13 studies were included with a patient population of 2207. Stroke and/or TIA studies (risk ratio [RR]: 0.54, 95% CI [0.29, 1.00]) and all-cause mortality studies (RR: 1.30, 95% CI [0.66, 2.56]) were insignificant. From the secondary outcomes, spontaneous rhythm return (RR: 1.58, 95% CI [1.02, 2.45]), defibrillation after coronary reperfusion (RR: 0.49, 95% CI [0.30, 0.79]), inotropic support (RR: 0.70, 95% CI [0.57, 0.85]), composite risk of stroke and/or TIA and/or acute kidney injury and mortality (RR: 0.72, 95% CI [0.53, 0.99]), cross-clamp time (mean difference [MD]: -6.01, 95% CI [-11.14, -0.89]), blood transfusion (RR: 0.73, 95% CI [0.60, 0.90]), cardioplegia volume (MD: -537.17, 95% CI [-758.89, -315.45]), troponin T (MD: -1.71, 95% CI [-2.11, -1.32]), creatine phosphokinase-MB (MD: -2.96, 95% CI [-5.84, -0.07]) were significant. Whereas all other secondary outcomes were found to be insignificant. CONCLUSION: No significant difference was observed between patients undergoing Del Nido administration in comparison to other cardioplegia solutions for the primary outcome, stroke or/and TIA.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Paro Cardíaco Inducido , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Paro Cardíaco Inducido/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Adulto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Soluciones Cardiopléjicas/uso terapéutico , Cloruro de Potasio , Manitol , Lidocaína , Soluciones , Electrólitos , Sulfato de Magnesio , Bicarbonato de SodioRESUMEN
The manufacturing of tablets containing biologics exposes the biologics to thermal and shear stresses, which are likely to induce structural changes (e.g., aggregation and denaturation), leading to the loss of their activity. Saccharides often act as stabilizers of proteins in formulations, yet their stabilizing ability throughout solid oral dosage processing, such as tableting, has been barely studied. This work aimed to investigate the effects of formulation and process (tableting and spray-drying) variables on catalase tablets containing dextran, mannitol, and trehalose as potential stabilizers. Non-spray-dried and spray-dried formulations were prepared and tableted (100, 200, and 400 MPa). The enzymatic activity, number of aggregates, reflecting protein aggregation and structure modifications were studied. A principal component analysis was performed to reveal underlying correlations. It was found that tableting and spray-drying had a notable negative effect on the activity and number of aggregates formed in catalase formulations. Overall, dextran and mannitol failed to preserve the catalase activity in any unit operation studied. On the other hand, trehalose was found to preserve the activity during spray-drying but not necessarily during tableting. The study demonstrated that formulation and process variables must be considered and optimized together to preserve the characteristics of catalase throughout processing.
Asunto(s)
Catalasa , Dextranos , Composición de Medicamentos , Excipientes , Manitol , Comprimidos , Trehalosa , Catalasa/química , Trehalosa/química , Manitol/química , Dextranos/química , Excipientes/química , Composición de Medicamentos/métodos , Química Farmacéutica/métodos , Secado por Pulverización , Agregado de ProteínasRESUMEN
INTRODUCTION: Continuous extracorporeal perfusion (ECP), or machine perfusion, holds promise for prolonged skeletal muscle preservation in limb ischemia-reperfusion injury. This study aimed to extend the amputation-to-replantation time window from currently 6 hours to 33 hours using a 24-hour ECP approach. MATERIALS AND METHODS: Six large white pigs underwent surgical forelimb amputation under general anesthesia. After amputation, limbs were kept for 9 hours at room temperature and then perfused by 24-hour ECP with a modified histidine-tryptophan-ketoglutarate (HTK) solution. After ECP, limbs were orthotopically replanted and perfused in vivo for 12 hours. Clinical data, blood, and tissue samples were collected and analyzed. RESULTS: All 6 forelimbs could be successfully replanted and in vivo reperfused for 12 hours after 9 hours of room temperature ischemia followed by 24 hours ECP. Adequate limb perfusion was observed after replantation as shown by thermography and laser Doppler imaging. All pigs survived without severe organ failure, and no significant increase in inflammatory cytokines was found. Macroscopy and histology showed marked interstitial muscular edema of the limbs, whereas myofiber necrosis was not evident, implying the preservation of muscular integrity. CONCLUSIONS: The use of a 24-hour ECP has successfully extended limb preservation to 33 hours. The modified histidine-tryptophan-ketoglutarate perfusate demonstrated its ability for muscle protection. This innovative approach not only facilitates limb replantation after combat injuries, surmounting geographical barriers, but also broadens the prospects for well-matched limb allotransplants across countries and continents.
Asunto(s)
Amputación Traumática , Reimplantación , Animales , Reimplantación/métodos , Porcinos , Amputación Traumática/cirugía , Factores de Tiempo , Perfusión/métodos , Procaína/farmacología , Procaína/uso terapéutico , Cloruro de Potasio/farmacología , Cloruro de Potasio/uso terapéutico , Daño por Reperfusión , Miembro Anterior/fisiopatología , Glucosa , ManitolRESUMEN
OBJECTIVE: Postoperative delirium (POD), especially after cardiac surgery with cardiopulmonary bypass (CPB), is a relatively common and severe complication increasing side effects, length of hospital stay, mortality and healthcare resource costs. This study aimed to determine the impact of using mannitol serum in the prime of CPB for preventing the occurrence of delirium in patients undergoing coronary artery bypass surgery. METHODS: This study is a single-centre, double-blinded, randomised, controlled trial that was conducted from December 2022 to May 2023. Patients in the age range of 18-70 who underwent elective coronary artery bypass surgery were included in the study. In the control group (n=45), the prime solution included Ringer's lactate serum. In the intervention group (n=45), the prime solution consisted of 200 mL mannitol serum and Ringer's lactate serum. The primary outcome of the study was the incidence of POD. Secondary outcomes included the duration of mechanical ventilation, length of stay in the intensive care unit (ICU) and 30-day in-hospital mortality. RESULTS: There were no statistically significant differences in demographic characteristics and risk factors between the control and intervention groups (p<0.05). However, the incidence of POD was significantly lower in the intervention group compared with the control group (22.25% vs 42.2%, p=0.035). There were no significant differences between the two groups regarding CPB time, aortic cross-clamp time, duration of mechanical ventilation and length of stay in ICU (p<0.05). Additionally, mortality rates and rates of return to the operating room did not differ significantly between the two groups (p<0.05). CONCLUSIONS: This study concluded that adding mannitol to the prime of CPB pump can help reduce the incidence of delirium after cardiac surgery. TRIAL REGISTRATION NUMBER: IRCT20221129056660N1.
Asunto(s)
Puente de Arteria Coronaria , Delirio , Manitol , Complicaciones Posoperatorias , Humanos , Manitol/administración & dosificación , Manitol/uso terapéutico , Manitol/efectos adversos , Masculino , Femenino , Puente de Arteria Coronaria/efectos adversos , Persona de Mediana Edad , Método Doble Ciego , Anciano , Delirio/prevención & control , Delirio/epidemiología , Delirio/etiología , Incidencia , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Adulto , Resultado del Tratamiento , Factores de Riesgo , Adolescente , Adulto Joven , Enfermedad de la Arteria Coronaria/cirugía , Mortalidad Hospitalaria , Factores de Tiempo , Tiempo de Internación , Estudios de SeguimientoRESUMEN
Introduction: Understanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions. This evaluation should be compared to established probes like lactulose, a non-digestible disaccharide indicative of paracellular permeability, and mannitol, reflecting transcellular permeability. Methods: Fifteen participants underwent simultaneous ingestion of standardized doses of gluten (10 g), lactulose (10 g), and mannitol (1 g) under fasting conditions for at least 8 hours pre-ingestion and during 6 hours post-ingestion period. Urine samples were collected over specified time intervals. Excretion patterns were analyzed, and correlations between the lactulose-to-mannitol ratio (LMR) and u-GIP parameters were assessed. Results: The majority of u-GIP were detected within the first 12 hours post-ingestion. Analysis of the variability in cumulative excretion across two sample collection ranges demonstrated that lactulose and u-GIP exhibited similar onset and excretion dynamics, although GIP reached its maximum peak earlier than either lactulose or mannitol. Additionally, a moderate correlation was observed between the LMR and u-GIP parameters within the longest urine collection interval, indicating potential shared characteristics among permeability pathways. These findings suggest that extending urine collection beyond 6 hours may enhance data reliability. Discussion: This study sheds light on the temporal dynamics of u-GIP in comparison to lactulose and mannitol, established probes for assessing intestinal permeability. The resemblance between u-GIP and lactulose excretion patterns aligns with the anticipated paracellular permeability pathway. The capacity to detect antigenic food protein fragments in urine opens novel avenues for studying protein metabolism and monitoring pathologies related to the digestive and intestinal systems.
Asunto(s)
Ayuno , Glútenes , Voluntarios Sanos , Lactulosa , Manitol , Humanos , Glútenes/orina , Glútenes/inmunología , Masculino , Adulto , Femenino , Ayuno/orina , Lactulosa/orina , Manitol/orina , Adulto Joven , Péptidos/orina , Péptidos/inmunología , Permeabilidad , Biomarcadores/orina , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Persona de Mediana EdadRESUMEN
D-mannitol is a six-carbon sugar alcohol and one of the most abundant polyols in the nature. With antioxidant and osmotic pressure-regulating effects and non-metabolism by the human body, D-mannitol has been widely used in functional food and pharmaceutical industries. At present, a major way for industrial production of D-mannitol is chemical hydrogenation. In addition, D-Mannitol can be produced by microbial metabolism or catalysis. Compared with the chemical hydrogenation, the microbial methods for synthesizing mannitol do not produce sorbitol as a by-product and have the advantages of mild reaction conditions, strong specificity, and high conversion rate. Microbial fermentation is praised for easy access of strains and raw materials and simple separation of the product. Microbial catalysis usually adopts a multi-enzyme coupling strategy, which uses enzymes produced by engineered bacteria for whole-cell catalysis, and the cofactor recycling pathway is introduced to replenish expensive cofactor. This method can achieve high yields with cheap substrates under mild conditions without the formation of by-products. However, the application of microbial methods in the industrial production of D-mannitol is limited by the high costs of fermentation media and substrates and the long reaction time. This article reviews the reported microbial methods for producing D-mannitol, including the use of high-yielding strains and their fermentation processes, the utilization of low-cost substrates, whole-cell catalytic strategies, and the process control for high productivity. The biosynthesis of mannitol is not only of great significance for promoting industrial upgrading and realizing green manufacturing, but also provides strong support for the development of new bio-based products to meet the growing market demand. With the continuous improvement of technological innovation and industrial chain, it is expected to become one of the main ways of mannitol production in the future.
Asunto(s)
Fermentación , Microbiología Industrial , Manitol , Manitol/metabolismo , Microbiología Industrial/métodos , Bacterias/metabolismo , Bacterias/genética , Ingeniería Metabólica/métodosRESUMEN
Biochemistry of carbon assimilation in aerobic methylotrophs growing on reduced C1 compounds has been intensively studied due to the vital role of these microorganisms in nature. The biochemical pathways of carbon assimilation in methylotrophs growing on multi-carbon substrates are insufficiently explored. Here we elucidated the metabolic route of mannitol assimilation in the alphaproteobacterial facultative methylotroph Methylobrevis pamukkalensis PK2. Two key enzymes of mannitol metabolism, mannitol-2-dehydrogenase (MTD) and fructokinase (FruK), were obtained as His-tagged proteins by cloning and expression of mtd and fruK genes in Escherichia coli and characterized. Genomic analysis revealed that further transformation of fructose-6-phosphate proceeds via the Entner-Doudoroff pathway. During growth on mannitol + methanol mixture, the strain PK2 consumed both substrates simultaneously demonstrating independence of C1 and C6 metabolic pathways. Genome screening showed that genes for mannitol utilization enzymes are present in other alphaproteobacterial methylotrophs predominantly capable of living in association with plants. The capability to utilize a variety of carbohydrates (sorbitol, glucose, fructose, arabinose and xylose) suggests a broad adaptability of the strain PK2 to live in environments where availability of carbon substrate dynamically changes.
Asunto(s)
Fructoquinasas , Manitol , Manitol/metabolismo , Fructoquinasas/metabolismo , Fructoquinasas/genética , Manitol Deshidrogenasas/metabolismo , Manitol Deshidrogenasas/genética , Fructosafosfatos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Redes y Vías Metabólicas/genética , Metanol/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/crecimiento & desarrolloRESUMEN
The aim of this study was to provide insight into high-energy phosphate compound concentration dynamics under realistic clinical cold-storage conditions using the Celsior solution in seven heart grafts discarded from transplantation. The hearts of seven local donors (three males, four females, age 37 ± 17 years, height 175 ± 5 cm, weight 75 ± 9 kg) initially considered for transplantation and eventually discarded were submitted to a Magnetic Resonance Spectroscopy observation in a clinical Magnetic Resonance Imaging scanner over at least 9 h. The grafts remained in their sterile container at 4°C during the entire examination. Hence, Phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH were recorded non-destructively at a 30-minute interval. With the ischemic time Ti, the concentration ratios decreased at PCr/ATP = 1.68-0.0028·Tis, Pi/ATP = 1.38 + 0.0029·Tis, and intracellular pH at 7.43-0.0012·Tis. ATP concentration remained stable for at least 9 h and did not decrease as long as phosphocreatine was detectable. Acidosis remained moderate. In addition to the standard parameters assessed at the time of retrieval, Magnetic Resonance Spectroscopy can provide an assesment of the metabolic status of heart grafts before transplantation. These results show how HEPC metabolites deplete during cold storage. Although many parameters determine graft quality during cold storage, the dynamics of HEPC and intracellular pH may be helpful in the development of strategies aiming at extending the ischemic time.
Asunto(s)
Adenosina Trifosfato , Disacáridos , Electrólitos , Glutamatos , Glutatión , Trasplante de Corazón , Histidina , Manitol , Soluciones Preservantes de Órganos , Preservación de Órganos , Fosfatos , Humanos , Femenino , Masculino , Adenosina Trifosfato/metabolismo , Adulto , Persona de Mediana Edad , Preservación de Órganos/métodos , Espectroscopía de Resonancia Magnética , Concentración de Iones de Hidrógeno , Fosfocreatina/metabolismo , Adulto Joven , Criopreservación , Imagen por Resonancia MagnéticaRESUMEN
Dry powder inhalers (DPIs) are the first choice for inhalation drug development. However, some conventional DPI formulation processes require heating, which may damage high molecular weight drugs such as proteins and nucleic acids. In this study, we propose a novel DPI preparation process that avoids the use of heat. Dry powders were prepared by cryomilling nanofiber mats composed of polyvinyl alcohol, D(-)-mannitol (Man), and α-chymotrypsin (α-Chy) as the model drug using the electrospinning method. The addition of Man conferred high dispersibility and excellent in vitro aerosol performance to the nanofiber mat powder in a very short milling time (less than 0.5 min) as assessed using the Andersen cascade impactor. Powders were classified according to the degree of friability, and among these, nanofiber mats containing 15 % Man and milled for 0.25 min exhibited the highest aerosol performance. Nanofiber mats containing Man milled for less than 0.5 min also exhibited greater α-Chy enzymatic activity than a nebulized α-Chy solution. Furthermore, single inhalation induced no significant lung tissue damage as evidenced by lactate dehydrogenase activity assays of mouse bronchoalveolar lavage fluid. This novel DPI formulation process may facilitate the safe and efficient inhalational delivery of therapeutic proteins.
Asunto(s)
Aerosoles , Quimotripsina , Manitol , Nanofibras , Nanofibras/química , Nanofibras/administración & dosificación , Animales , Administración por Inhalación , Manitol/química , Quimotripsina/química , Ratones , Inhaladores de Polvo Seco , Alcohol Polivinílico/química , Polvos , Sistemas de Liberación de Medicamentos , Pulmón/metabolismo , Líquido del Lavado Bronquioalveolar/química , MasculinoRESUMEN
Red blood cell (RBC) storage solutions have evolved significantly over the past decades to optimize the preservation of cell viability and functionality during hypothermic storage. This comprehensive review provides an in-depth analysis of the effects of various storage solutions and conditions on critical RBC parameters during refrigerated preservation. A wide range of solutions, from basic formulations such as phosphate-buffered saline (PBS), to advanced additive solutions (ASs), like AS-7 and phosphate, adenine, glucose, guanosine, saline, and mannitol (PAGGSM), are systematically compared in terms of their ability to maintain key indicators of RBC integrity, including adenosine triphosphate (ATP) levels, morphology, and hemolysis. Optimal RBC storage requires a delicate balance of pH buffering, metabolic support, oxidative damage prevention, and osmotic regulation. While the latest alkaline solutions enable up to 8 weeks of storage, some degree of metabolic and morphological deterioration remains inevitable. The impacts of critical storage conditions, such as the holding temperature, oxygenation, anticoagulants, irradiation, and processing methods, on the accumulation of storage lesions are also thoroughly investigated. Personalized RBC storage solutions, tailored to individual donor characteristics, represent a promising avenue for minimizing storage lesions and enhancing transfusion outcomes. Further research integrating omics profiling with customized preservation media is necessary to maximize post-transfusion RBC survival and functions. The continued optimization of RBC storage practices will not only enhance transfusion efficacy but also enable blood banking to better meet evolving clinical needs.
Asunto(s)
Conservación de la Sangre , Supervivencia Celular , Eritrocitos , Eritrocitos/metabolismo , Eritrocitos/citología , Humanos , Conservación de la Sangre/métodos , Supervivencia Celular/efectos de los fármacos , Hemólisis/efectos de los fármacos , Glucosa/metabolismo , Adenosina Trifosfato/metabolismo , Manitol/farmacologíaRESUMEN
The rise of gene therapy has solved many diseases that cannot be effectively treated by conventional methods. Gene vectors is very important to protect and deliver the therapeutic genes to the target site. Polyethyleneimine (PEI) modified with mannitol could enhance the gene transfection efficiency reported by our group previously. In order to further control and improve the effective gene release to action site, disulfide bonds were introduced into mannitol-modified PEI to construct new non-viral gene vectors PeiSM. The degrees of mannitol linking with disulfide bonds were screened. Among them, moderate mannitol-modified PEI with disulfide bonds showed the best transfection efficiency, and significantly enhanced long-term systemic transgene expression for 72 hin vivoeven at a single dose administration, and could promote caveolae-mediated uptake through up-regulating the phosphorylation of caveolin-1 and increase the loaded gene release from the nanocomplexes in high glutathione intracellular environment. This functionalized gene delivery system can be used as an potential and safe non-viral nanovector for further gene therapy.
Asunto(s)
Vectores Genéticos , Glutatión , Polietileneimina , Transfección , Polietileneimina/química , Transfección/métodos , Glutatión/metabolismo , Glutatión/química , Animales , Humanos , Vectores Genéticos/química , Vectores Genéticos/genética , Manitol/química , Ratones , Caveolina 1/metabolismo , Caveolina 1/genética , Terapia Genética/métodos , Técnicas de Transferencia de Gen , Disulfuros/químicaRESUMEN
Riboflavin overproduction byCorynebacterium glutamicumwas achieved by screening synthetic operons, enabling fine-tuned expression of the riboflavin biosynthetic genesribGCAH.The synthetic operons were designed by means of predicted translational initiation rates of each open reading frame, with the best-performing selection enabling riboflavin overproduction without negatively affecting cell growth. Overexpression of the fructose-1,6-bisphosphatase (fbp) and 5-phosphoribosyl 1-pyrophosphate aminotransferase (purF) encoding genes was then done to redirect the metabolic flux towards the riboflavin precursors. The resulting strain produced 8.3 g l-1of riboflavin in glucose-based fed-batch fermentations, which is the highest reported riboflavin titer withC. glutamicum. Further genetic engineering enabled both xylose and mannitol utilization byC. glutamicum, and we demonstrated riboflavin overproduction with the xylose-rich feedstocks rice husk hydrolysate and spent sulfite liquor, and the mannitol-rich feedstock brown seaweed hydrolysate. Remarkably, rice husk hydrolysate provided 30% higher riboflavin yields compared to glucose in the bioreactors.
Asunto(s)
Corynebacterium glutamicum , Ingeniería Metabólica , Riboflavina , Riboflavina/biosíntesis , Riboflavina/química , Riboflavina/metabolismo , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Xilosa/metabolismo , Fermentación , Glucosa/metabolismo , Operón , Manitol/metabolismo , Manitol/química , Reactores Biológicos , Ingeniería GenéticaRESUMEN
BACKGROUND: This study examined the efficacy of del Nido cardioplegia compared with traditional blood cardioplegia in adult cardiac surgery for isolated coronary artery bypass grafting by evaluating the early postoperative outcomes. METHODS: A total of 119 patients who underwent isolated conventional coronary artery bypass grafting were enrolled and divided into two groups (del Nido cardioplegia group [n = 36] and blood cardioplegia group [n = 50]) based on the type of cardioplegia used. This study compared the preoperative characteristics, intraoperative data, and early postoperative outcomes. Further subgroup analyses were conducted for high-risk patient groups. RESULTS: The 30-day mortality and morbidity rates were not significantly different between groups. The del Nido cardioplegia group exhibited advantageous myocardial protection outcomes, demonstrated by a significantly smaller rise in Troponin I levels post-surgery (2.8 [-0.4; 4.2] vs. 4.5 [2.9; 7.4] ng/mL, p = 0.004) and fewer defibrillation attempts during weaning off of cardiopulmonary bypass (0.0 ± 0.2 vs. 0.4 ± 1.1 times, p = 0.011) when compared to the blood cardioplegia group. Additionally, the del Nido group achieved a reduction in surgery duration, as evidenced by the reduced aortic cross-clamping time (64.0 [55.5; 75.5] vs. 77.5 [65.0; 91.0] min, p = 0.001) and total operative time (287.5 [270.0; 305.0] vs. 315.0 [285.0; 365.0] min, p = 0.008). Subgroup analyses consistently demonstrated that the del Nido cardioplegia group had a significantly smaller postoperative increase in Troponin I levels across all subgroups (p < 0.05). CONCLUSIONS: del Nido cardioplegia provided myocardial protection and favorable early postoperative outcomes compared to blood cardioplegia, making it a viable option for conventional coronary artery bypass grafting. Establishing a consensus on the protocol for Del Nido cardioplegia administration in adult surgeries is needed.
Asunto(s)
Soluciones Cardiopléjicas , Puente de Arteria Coronaria , Paro Cardíaco Inducido , Humanos , Paro Cardíaco Inducido/métodos , Puente de Arteria Coronaria/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Complicaciones Posoperatorias/prevención & control , Enfermedad de la Arteria Coronaria/cirugía , Troponina I/sangre , Cloruro de Potasio , Manitol , Lidocaína , Soluciones , Electrólitos , Sulfato de Magnesio , Bicarbonato de SodioRESUMEN
Osmotic stress significantly hampers plant growth and crop yields, emphasizing the need for a thorough comprehension of the underlying molecular responses. Previous research has demonstrated that osmotic stress rapidly induces calcium influx and signaling, along with the activation of a specific subset of protein kinases, notably the Raf-like protein (RAF)-sucrose nonfermenting-1-related protein kinase 2 (SnRK2) kinase cascades within minutes. However, the intricate interplay between calcium signaling and the activation of RAF-SnRK2 kinase cascades remains elusive. Here, in this study, we discovered that Raf-like protein (RAF) kinases undergo hyperphosphorylation in response to osmotic shocks. Intriguingly, treatment with the calcium chelator EGTA robustly activates RAF-SnRK2 cascades, mirroring the effects of osmotic treatment. Utilizing high-throughput data-independent acquisition-based phosphoproteomics, we unveiled the global impact of EGTA on protein phosphorylation. Beyond the activation of RAFs and SnRK2s, EGTA treatment also activates mitogen-activated protein kinase cascades, Calcium-dependent protein kinases, and receptor-like protein kinases, etc. Through overlapping assays, we identified potential roles of mitogen-activated protein kinase kinase kinase kinases and receptor-like protein kinases in the osmotic stress-induced activation of RAF-SnRK2 cascades. Our findings illuminate the regulation of phosphorylation and cellular events by Ca2+ signaling, offering insights into the (exocellular) Ca2+ deprivation during early hyperosmolality sensing and signaling.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ácido Egtácico , Manitol , Presión Osmótica , Proteómica , Arabidopsis/metabolismo , Arabidopsis/efectos de los fármacos , Fosforilación , Proteínas de Arabidopsis/metabolismo , Proteómica/métodos , Ácido Egtácico/farmacología , Ácido Egtácico/análogos & derivados , Manitol/farmacología , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Quinasas raf/metabolismoRESUMEN
OBJECTIVES: Controlling elevated intracranial pressure following brain injury with hyperosmolar agents is one of the mainstay treatments in traumatic brain injury patients. In this study, we compared the effects of hypertonic saline (HS) and mannitol in reducing increased intracranial pressure. METHODS: A total of 637 patients from 15 studies were included in our meta-analysis. The primary outcomes were mortality, the length of stay in the hospital and ICU, and the Glasgow Outcome Scale at follow-up. RESULTS: The mortality in the mannitol group was not statistically different compared to the HS group (RR = 1.55; 95% CI = [0.98, 2.47], p = 0.06). The length of stay in the ICU was significantly shorter in the HS group (MD = 1.18, 95% CI = [0.44, 1.92], p < 0.01). In terms of favorable neurological outcomes, there was no significant difference between the two agents (RR = 0.92, 95% CI = [0.11, 7.96], p = 0.94). The duration of the effect was shorter in the mannitol group than in the HS group (MD = -0.67, 95% CI = [-1.00, -0.33], p < 0.01). DISCUSSION: The results showed that HS and mannitol had similar effects in reducing ICP. Although the HS was associated with a longer duration of effect and shorter ICU stay, other secondary outcomes including mortality rate and favorable neurological outcomes were similar between the two drugs. In conclusion, considering the condition of each patient individually, HS could be a reasonable option than mannitol to reduce ICP in TBI patients.