Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “mitigation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources
PubMed2005

Reduction in vertebral fracture risk in teriparatide-treated postmenopausal women as assessed by spinal deformity index.

Teriparatide is the first bone-building drug available for the treatment of osteoporosis. We investigated the efficacy of this compound as assessed by spinal deformity index (SDI) using data from the Fracture Prevention Trial (FPT). The FPT was a randomized, double blind trial of placebo versus teriparatide 20 microg (TPTD20) versus teriparatide 40 microg (TPTD40) administered by daily self-injection. Patients included in the current analyses were those patients from the placebo (n = 398) and TPTD20 (the approved dose, n = 403) groups with baseline and follow-up radiographs and at least one vertebral fracture at baseline. For each vertebra, a visual semiquantitative grade of 0, 1, 2, or 3 was assigned for no fracture or mild, moderate, or severe fracture, respectively; the SDI was calculated by summing the fracture grades of all T4 to L4 vertebrae. The mean SDI increased in the placebo and TPTD20 groups by 0.485 and 0.134, respectively (P < 0.001). The proportions of patients with SDI increases >1, >2, and >3 were reduced by 85%, 80%, and 80%, respectively. In the placebo group, increasing baseline SDI was correlated with the mean increase in SDI during the trial (r = 0.080, P = 0.01), consistent with the progressive natural history of osteoporosis. However, in the TPTD20 group, increasing baseline SDI was not correlated with the mean increase in SDI during the trial (P = 0.297) indicating that teriparatide mitigated or eliminated the increased risk associated with increasing fracture burden. Increases in SDI during the trial were associated with increasing proportions of patients with new or worsening back pain and greater mean height loss (P < 0.0001), demonstrating an association with important clinical consequences. The results indicate that teriparatide greatly reduced the increase in fracture burden in the FPT and mitigated or eliminated the risk for future fractures imparted by increasing baseline fracture burden.

Aged↗
PubMed2005

Medical management after indoor fires: a review.

UNLABELLED: Fires involving mass burn casualties require extreme efforts and flexibility from the regular health care system. The café fire in Volendam, which occurred shortly after midnight on the first of January 2001, resulted in the worst indoor mass burns incident in Dutch history. During the extensive medical evaluation of this disaster, it became obvious that information on similar incidents is relatively scarce in the literature. This article systematically reviews the existing information in the medical literature on indoor fires and provides findings and knowledge used in the evaluation of the medical management after indoor fires and for future mass burn casualty preparedness, mitigation and response. METHODS: A literature review was undertaken for burn disasters with characteristics similar to the indoor Volendam fire disaster. In all fires, the following aspects were investigated: characteristics of the fire; the initial emergency response; triage and on-site treatment; primary and secondary distribution; hospital admission; severity of the sustained injuries and mortality. RESULTS: A total of nine similar indoor fires were selected. The number of people involved was reported in seven fires (range 137-6000). All reports provided the mortality rate (range 1.4% to over 50%). Data regarding the emergency response could be collected in half of the studies. On-scene triage was performed in five fires. The number of hospitals participating in the primary distribution ranged from 1 to 19. Except for the Volendam fire, all patients were primarily distributed to general hospitals. CONCLUSION: Characteristics of indoor fires, which are relevant for disaster preparedness, mitigation and response are not frequently reported in medical literature. The current articles on indoor fires, mainly report on numbers of casualties and the mortality. Limited data are available to provide insight in the characteristics of management and medical treatment and to come up with suggestions for improvement of future burn incidents management. The evaluation of disasters should be based on uniform methods and structured reports and effective record keeping is essential to achieve this.

Burns↗
PubMed2004

Therapeutic efficacy of green tea polyphenols on cellular thiols in 4-Nitroquinoline 1-oxide-induced oral carcinogenesis.

In cancer, a high flux of oxidants not only depletes the cellular thiols, but damages the whole cell as well. Epidemiological studies suggest green tea may mitigate cancers in human and animal models for which several mechanisms have been proposed. In the present investigation, the levels of cellular thiols such as reduced glutathione (GSH), oxidised glutathione (GSSG), protein thiols (PSH), total thiols, lipid peroxidation product conjugated dienes and the activity of gamma glutamyl transferase (GGT) were assessed in tongue and oral cavity. In 4-Nitroquinoline 1-oxide- (4-NQO) induced rats, there was a decrease in the levels of GSH, PSH and total thiols and an increase in the levels of GSSG, conjugated dienes and the activity of GGT. On supplementation of green tea polyphenols (GTP) for 30 days (200 mg/kg) for the oral cancer-induced rats, there was a moderate increase in the levels of GSH, PSH and total thiols and a decrease in the levels of GSSG, conjugated dienes and the activity of GGT. Thus, GTP reduces the oxidant production thereby maintains the endogenous low molecular weight cellular thiols in oral cancer-induced rats. From the results, it can be concluded that GTP supplementation enhances the cellular thiol status thereby mitigate oral cancer.

4-Nitroquinoline-1-oxide↗
PubMed2025

Modulation of Mettl5 alleviates airway allergy by regulating the epigenetic profile of M2 macrophages.

M2 macrophages (M2 cells) are known to be involved in both Th2 responses and immune regulation. However, the underlying mechanisms remain unclear. Functional abnormalities in macrophages are associated with airway allergy (AA). The objective of this study was to investigate the role of methyltransferase-like 5 (Mettl5) in macrophages and its potential to alleviate AA. In this study, an airway allergy (AA) mouse model was established using dust mite extracts (DME) as the specific antigen. M2 cells were collected from mice with and without AA. The role of Mettl5 in modulating the immune activities of M2 cells was assessed using both epigenetic and immunological approaches. We found that Mettl5 levels were elevated in airway M2 cells from mice with AA. The presence of Mettl5 in airway M2 cells was positively correlated with airway Th2 polarization in these mice. Airway M2 cells from AA mice exhibited impaired immune-suppressive function, which was resolved by ablating the Mettl5 gene in macrophages. Mettl5 was responsible for the hypermethylation of the Il10 promoter in airway M2 cells of AA mice. Exposure to DME induced Mettl5, which in turn recruited USP21 to deubiquitinate GATA3, thereby boosting IL-4 expression in M2 cells. Inhibiting Mettl5 restored the immune-suppressive capacity of airway M2 cells and mitigated experimental AA. In conclusion, Mettl5 plays a critical role in subverting the immune-regulatory capacity and enhancing IL-4 expression in M2 cells. Inhibition of Mettl5 can mitigate experimental AA by restoring the immune-regulatory functions of M2 cells.

Animals↗
PubMed2006

Hydroponic uptake of atrazine and lambda-cyhalothrin in Juncus effusus and Ludwigia peploides.

Phytoremediation encompasses an array of plant-associated processes known to mitigate contaminants from soil, sediment, and water. Modification of pesticides associated with agricultural runoff includes processes directly associated with aquatic macrophytes in addition to changes in soil geochemistry and associated rhizospheric degradation. Remediation attributes of two vegetative species common to agricultural drainages in the Mississippi Delta, USA, were assessed using atrazine and lambda-cyhalothrin. Concentrations used in 8-d hydroponic exposures were calculated using recommended field applications and a 5% runoff model from a 0.65-cm rainfall event on a 2.02-ha field. While greater atrazine uptake was measured in Juncus effusus, greater lambda-cyhalothrin uptake occurred in Ludwigia peploides. Maximum pesticide uptake was reached within 48h for each exposure and subsequent translocation of pesticides to upper plant biomass occurred in macrophytes exposed to atrazine. Sequestration of 98.2% of lambda-cyhalothrin in roots of L. peploides was measured after 8d. Translocation of lambda-cyhalothrin in J. effusus resulted in 25.4% of pesticide uptake partitioned to upper plant biomass. These individual macrophyte remediation studies measured species- and pesticide-specific uptake rates, indicating that seasonality of pesticide applications and macrophyte emergence might interact strongly to enhance mitigation capabilities in edge-of-field conveyance structures.

Agriculture↗
PubMed2006

Cryopreservation of rat hippocampal slices by vitrification.

Although much interest has attended the cryopreservation of immature neurons for subsequent therapeutic intracerebral transplantation, there are no reports on the cryopreservation of organized adult cerebral tissue slices of potential interest for pharmaceutical drug development. We report here the first experiments on cryopreservation of mature rat transverse hippocampal slices. Freezing at 1.2 degrees C/min to -20 degrees C or below using 10 or 30% v/v glycerol or 20% v/v dimethyl sulfoxide yielded extremely poor results. Hippocampal slices were also rapidly inactivated by simple exposure to a temperature of 0 degree C in artificial cerebrospinal fluid (aCSF). This effect was mitigated somewhat by 0.8 mM vitamin C, the use of a more "intracellular" version of aCSF having reduced sodium and calcium levels and higher potassium levels, and the presence of a 25% w/v mixture of dimethyl sulfoxide, formamide, and ethylene glycol ("V(EG) solutes"; Cryobiology 48, pp. 22-35, 2004). It was not mitigated by glycerol, aspirin, indomethacin, or mannitol addition to aCSF. When RPS-2 (Cryobiology 21, pp. 260-273, 1984) was used as a carrier solution for up to 50% w/v V(EG) solutes, 0 degree C was more protective than 10 degrees C. Raising V(EG) concentration to 53% w/v allowed slice vitrification without injury from vitrification and rewarming per se, but was much more damaging than exposure to 50% w/v V(EG). This problem was overcome by using the analogous 61% w/v VM3 vitrification solution (Cryobiology 48, pp. 157-178, 2004) containing polyvinylpyrrolidone and two extracellular "ice blockers." With VM3, it was possible to attain a tissue K(+)/Na(+) ratio after vitrification ranging from 91 to 108% of that obtained with untreated control slices. Microscopic examination showed severe damage in frozen-thawed slices, but generally good to excellent ultrastructural and histological preservation after vitrification. Our results provide the first demonstration that both the viability and the structure of mature organized, complex neural networks can be well preserved by vitrification. These results may assist neuropsychiatric drug evaluation and development and the transplantation of integrated brain regions to correct brain disease or injury.

Animals↗
PubMed2005

Overexpression of Rad51 inhibits double-strand break-induced homologous recombination but does not affect gene conversion tract lengths.

DNA double-strand breaks (DSBs) in yeast are repaired by homologous recombination (HR) and non-homologous end-joining (NHEJ). Rad51 forms nucleoprotein filaments at processed broken ends that effect strand exchange, forming heteroduplex DNA (hDNA) that gives rise to a gene conversion tract. We hypothesized that excess Rad51 would increase gene conversion tract lengths. We found that excess Rad51 reduced DSB-induced HR but did not alter tract lengths or other outcomes including rates of crossovers, break-induced replication, or chromosome loss. Thus, excess Rad51 appears to influence DSB-induced HR at an early stage. MAT heterozygosity largely mitigated the inhibitory effect of excess Rad51 on allelic HR, but not direct repeat HR. Excess Rad52 had no effect on DSB-induced HR efficiency or outcome, nor did it mitigate the dominant negative effects of excess Rad51. Excess Rad51 had little effect on DSB-induced lethality in wild-type cells, but it did enhance lethality in yku70Delta mutants. Interestingly, dnl4Delta showed marked DSB-induced lethality but this was not further enhanced by excess Rad51. The differential effects of yku70Delta and dnl4Delta indicate that the enhanced killing with excess Rad51 in yku70Delta is not due to its NHEJ defect, but may reflect its defect in end-protection and/or its inability to escape from checkpoint arrest. Srs2 displaces Rad51 from nucleoprotein filaments in vitro, suggesting that excess Rad51 might antagonize Srs2. We show that excess Rad51 does not reduce survival of wild-type cells treated with methylmethane sulfonate (MMS), or cells suffering a single DSB. In contrast, excess Rad51 sensitized srs2Delta cells to both MMS and a single DSB. These results support the idea that excess Rad51 antagonizes Srs2, and underscores the importance of displacing Rad51 from nucleoprotein filaments to achieve optimum repair efficiency.

Cell Survival↗
PubMed2004

In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp.

Honokiol and magnolol, two major phenolic constituents of Magnolia sp., have been known to exhibit antibacterial activities. However, until now, their antibacterial activity against Propionibacterium sp. has not been reported. To this end, the antibacterial activities of honokiol and magnolol were detected using the disk diffusion method and a two-fold serial dilution assay. Honokiol and magnolol showed strong antibacterial activities against both Propionibacterium acnes and Propionibacterium granulosum, which are acne-causing bacteria. The minimum inhibitory concentrations (MIC) of honokiol and magnolol was 3-4 microg/ml (11.3-15 microM) and 9 microg/ml (33.8 microM), respectively. In addition, the killing curve analysis showed that magnolol and honokiol killed P. acnes rapidly, with 10(5) organisms/ml eliminated within 10 min of treatment with either 45 microg (169.2 microM) of magnolol or 20 microg (75.2 microM) of honokiol per ml. The cytotoxic effect of honokiol and magnolol was determined by a colorimetric (3-(4,5-dimetyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) assay using two animal cell lines, human normal fibroblasts and HaCaT. In this experiment, magnolol exhibited lower cytotoxic effects than honokiol at the same concentration, but they showed similar cytotoxicity when triclosan was employed as an acne-mitigating agent. In addition, they reduced secretion of interleukin-8 and tumor necrosis factor alpha (TNF-alpha) induced by P. acnes in THP-1 cells indicating the anti-inflammatory effects of them. When applied topically, neither phenolic compound induced any adverse reactions in a human skin primary irritation test. Therefore, based on these results, we suggest the possibility that magnolol and honokiol may be considered as attractive acne-mitigating candidates for topical application.

Adult↗
PubMed2006

Air quality impacts of power plant emissions in Beijing.

The CALMET/CALPUFF modeling system was applied to estimate the air quality impacts of power plants in 2000 and 2008 in Beijing, and the intake fractions (IF) were calculated to see the public health risks posed. Results show that in 2000 the high emission contribution induced a relatively small contribution to average ambient concentration and a significant impact on the urban area (9.52 microg/m(3) of SO(2) and 5.29 microg/m(3) of NO(x)). The IF of SO(2), NO(x) and PM(10) are 7.4 x 10(-6), 7.4 x 10(-6) and 8.7 x 10(-5), respectively. Control measures such as fuel substitution, flue gas desulfurization, dust control improvement and flue gas denitration planned before 2008 will greatly mitigate the SO(2) and PM(10) pollution, especially alleviating the pressure on the urban area to reach the National Ambient Air Quality Standard (NAAQS). NO(x) pollution will be mitigated with 34% decrease in concentration but further controls are still needed.

Air Pollutants↗
PubMed2024

Sustainable strategies: Nature-based solutions to tackle antibiotic resistance gene proliferation and improve agricultural productivity and soil quality.

The issue of antibiotic resistance is now recognized by the World Health Organisation (WHO) as one of the major problems in human health. Although its effects are evident in the healthcare settings, the root cause should be traced back to the One Health link, extending from animals to the environment. In fact, the use of organic fertilizers in agroecosystems represents one, if not the primary, cause of the introduction of antibiotics and antibiotic-resistant bacteria into the soil. Since the concentrations of antibiotics introduced into the soil are residual, the agroecosystem has become a perfect environment for the selection and proliferation of antibiotic resistance genes (ARGs). The continuous influx of these emerging contaminants (i.e., antibiotics) into the agroecosystem results in the selection and accumulation of ARGs in soil bacteria, occasionally giving rise to multi-resistant bacteria. These bacteria may harbour ARGs related to various antibiotics on their plasmids. In this context, these bacteria can potentially enter the human sphere when individuals consume food from contaminated agroecosystems, leading to the acquisition of multi-resistant bacteria. Once introduced into the nosocomial environment, these bacteria pose a significant threat to human health. In this review, we analyse how the use of digestate as an organic fertilizer can mitigate the spread of ARGs in agroecosystems. Furthermore, we highlight how, according to European guidelines, digestate can be considered a Nature-Based Solution (NBS). This NBS not only has the ability to mitigate the spread of ARGs in agroecosystems but also offers the opportunity to further improve Microbial-Based Solutions (MBS), with the aim of enhancing soil quality and productivity.

Animals↗
PubMed2005

Cytokine-based treatment of accidentally irradiated victims and new approaches.

A major goal of medical management of acute radiation syndrome following accidental exposures to ionizing radiation (IR) is to mitigate the risks of infection and hemorrhage related to the period of bone marrow aplasia. This can be achieved by stimulating the proliferation and differentiation of residual hematopoietic stem and progenitor cells (HSPC) related to either their intrinsic radioresistance or the heterogeneity of dose distribution. This is the rationale for treatment with hematopoietic growth factors. In fact, apoptosis has recently been shown to play a major role in the death of the continuum of more or less radiosensitive HSPC, soon after irradiation. Therefore, administration of antiapoptotic cytokine combinations such as stem cell factor, Flt-3 ligand, thrombopoietin, and interleukin-3 (4F), may be important for multilineage recovery, particularly when these factors are administered early. Moreover, acute exposure to high doses of IR induces sequential, deleterious effects responsible for a delayed multiple organ dysfunction syndrome. These considerations strongly suggest that therapeutics could include tissue-specific cytokines, such as keratinocyte growth factor, and pleiotropic agents, such as erythropoietin, in addition to hematopoietic growth factors to ensure tissue damage repair and mitigate the inflammatory processes. Noncytokine drugs have also been proposed as an alternative to treat hematopoietic or nonhematopoietic radiation effects. To develop more effective treatments for radiation injuries, basic research is required, particularly to improve understanding of stem cell needs within their environment. In the context of radiological terrorism and radiation accidents, new growth promoting molecules need to be approved and available cytokines stockpiled.

Anemia, Aplastic↗
PubMed2026

Fungal drivers of mycotoxin contamination in wheat: Early warning and plasma-based control.

Mycotoxin contamination in wheat is a major food safety concern; however, quantitative evidence linking fungal community signals, mycotoxin exceedance risk, and wheat quality traits in naturally contaminated wheat remains limited. In this study, wheat samples were collected from mycotoxin-prone monitoring sites under unusually rainy conditions in 2022 to explore early-warning indicators and post-harvest mitigation strategies. According to the National Food Safety Standard of China GB 2761-2017, aflatoxin B1 (AFB1), deoxynivalenol (DON), and zearalenone (ZEN) exceeded the maximum limits in 52.24, 47.76, and 23.88% of samples, respectively; 38.81% exceeded the reference EU threshold for T-2 toxin, and 46.27% showed co-contamination with at least two mycotoxins above their respective thresholds. Although Alternaria, Cladosporium, and Epicoccum dominated the fungal community, Fusarium abundance was significantly associated with DON contamination and Fusarium-damaged kernels (FDKs). Mediation analysis identified DON as a significant mediator linking Fusarium abundance to FDKs, accounting for 68.41% of the total effect. In addition, Fusarium abundance above 3.70% showed strong predictive performance for DON exceedance, with an area under the curve of 0.906, indicating its potential as an early-warning indicator. Culture-based assays confirmed the toxigenic potential of Aspergillus and Fusarium isolates under simulated temperature and moisture conditions. After optimization using a toxin-spiked wheat flour model, dielectric barrier discharge cold plasma degraded AFB1, DON, and ZEN by 29.30-35.68%, disrupted the morphology of toxigenic fungi, and did not significantly affect wheat quality. This study provides practical insights into mycotoxin risk warning and post-harvest mitigation in wheat.

Triticum↗
PubMed2005

Effective financing of maternal health services: a review of the literature.

Health care can be funded in a number of ways ranging from direct user charges (out of pocket) payments to indirect methods that pool across time (prepayment) and across different risk and wealth groups (insurance and general taxation). All these methods can be used to finance maternal health services. When assessing the impact of financing mechanisms it is important to be aware of the different ways they effect service delivery patterns and utilisation. Specifically most systems have both equity and efficiency aspects that combine to impact on health service utilisation and health status. In general indirect methods that help families to pool the costs of maternal health services are preferable to direct methods of payment. It is also clear, however, that user charges may sometimes help to mitigate deficiencies in systems of pooled funding. Available literature suggests that financing mechanisms for maternal health services could be improved by systems that increase transparency, help to mitigate demand-side costs of services and provide funding for that promote transparent charging for services. While the limited experience of demand-side mechanisms for improving access to maternal health services more evaluation is required.

Maternal Health Services↗
PubMed2006

Effects of sound level on fMRI activation in human brainstem, thalamic and cortical centers.

The dependence of fMRI activation on sound level was examined throughout the auditory pathway of normal human listeners using continuous broadband noise, a stimulus widely used in neuroscientific investigations of auditory processing, but largely neglected in neuro-imaging. Several specialized techniques were combined here for the first time to enhance detection of brainstem activation, mitigate scanner noise, and recover temporal resolution lost by the mitigation technique. The main finding was increased activation with increasing level in cochlear nucleus, superior olive, inferior colliculus, medial geniculate body and auditory cortical areas. We suggest that these increases reflect monotonically increasing activity in a preponderance of individual auditory neurons responsive to broadband noise. While the time-course of activation changed with level, the change was subtle and only significant in a part of the cortex. To our knowledge, these are the first fMRI data showing the effects of sound level in subcortical centers or for a non-tonal, non-speech stimulus at any stage of the pathway. The present results add to the body of parametric data in normal human listeners and are fundamental to the design of any fMRI experiment employing continuous noise.

Acoustic Stimulation↗
PubMed2005

Health information systems: failure, success and improvisation.

BACKGROUND AND PURPOSE: The generalised assumption of health information systems (HIS) success is questioned by a few commentators in the medical informatics field. They point to widespread HIS failure. The purpose of this paper was therefore to develop a better conceptual foundation for, and practical guidance on, health information systems failure (and success). METHODS: Literature and case analysis plus pilot testing of developed model. RESULTS: Defining HIS failure and success is complex, and the current evidence base on HIS success and failure rates was found to be weak. Nonetheless, the best current estimate is that HIS failure is an important problem. The paper therefore derives and explains the "design-reality gap" conceptual model. This is shown to be robust in explaining multiple cases of HIS success and failure, yet provides a contingency that encompasses the differences which exist in different HIS contexts. The design-reality gap model is piloted to demonstrate its value as a tool for risk assessment and mitigation on HIS projects. It also throws into question traditional, structured development methodologies, highlighting the importance of emergent change and improvisation in HIS. CONCLUSIONS: The design-reality gap model can be used to address the problem of HIS failure, both as a post hoc evaluative tool and as a pre hoc risk assessment and mitigation tool. It also validates a set of methods, techniques, roles and competencies needed to support the dynamic improvisations that are found to underpin cases of HIS success.

Information Systems↗
PubMed2025

KDM3B Regulates Postradiation Fibrotic Responses in Prostate Stroma via N6-methyladenosine Modification of LOX.

PURPOSE: Genome-wide association studies have uncovered single-nucleotide polymorphisms (SNPs) linked to radiation therapy (RT)-induced toxicities in patients with prostate cancer. SNP rs17599026, located in intron 21 of the KDM3B gene, has been associated with late-onset urinary toxicity, with an increased frequency of urination observed 2 years post-RT compared with pretreatment conditions. This study aimed to explore the underlying mechanisms driving this association. METHODS AND MATERIALS: A clustered regularly interspaced short palindromic repeats-dead Cas9 prime editing system was used to mimic KDM3B genetic variants in prostate stromal cell lines. Murine models with wild-type and heterozygous Kdm3b genotypes were used to assess fibrosis following radiation. RNA immunoprecipitation, transcript stability assays, and protein analysis elucidated the role of N6-methyladenosine (m6A) modification in regulating lysyl oxidase (LOX) expression. &#x3b1;-ketoglutarate (&#x3b1;-KG) supplementation was tested for its effects on KDM3B protein stability, LOX expression, and fibrosis mitigation. RESULTS: The rs17599026 SNP reduced KDM3B protein expression via circular RNA and microRNA-mediated mechanisms, leading to decreased m6A modification and increased stability of LOX messenger RNA. Elevated LOX expression promoted collagen cross-linking and fibrosis in prostate stroma. &#x3b1;-KG supplementation restored KDM3B protein levels, reduced LOX expression, and mitigated fibrosis in vitro and in vivo. CONCLUSIONS: KDM3B genetic variations influence radiation-induced fibrosis through posttranscriptional regulation of LOX. Dietary &#x3b1;-KG supplementation may serve as a mechanism-based strategy to alleviate radiation toxicity in patients with prostate cancer, offering a potential therapeutic pathway to improve treatment outcomes.

Male↗
PubMed2005

Effects of amino acid additions on ammonium stressed CHO cells.

Ammonium is a toxic and inhibitory byproduct of mammalian cell metabolism. At the end of a typical recombinant protein production campaign, the ammonium concentration can be as high as 10 mM, mainly due to glutamine metabolism. Intracellular pH (pH(i)) levels are sensitive to ammonium, which negatively impacts both cell growth and recombinant protein productivity. Ammonium also negatively affects the recombinant protein glycosylation profile, thus altering quality. Many strategies have been adopted to reduce ammonium accumulation, with limited results. This study investigated the addition of amino acids to the growth media for Chinese hamster ovary (CHO) cell cultures as a means of mitigating the negative effects of ammonium. Threonine, proline, and glycine additions improved CHO cell growth and recombinant protein levels. Further, the threonine, proline, and glycine additions positively impacted important metabolic parameters, including glucose consumption, lactate production, glutamine utilization, and final ammonium levels. Additionally, threonine, proline, and glycine increased the level of alpha(2,3)-linked sialic acid, galactose-beta(1,4)-N-acetylglucosamine, and alpha(2,6)-linked sialic acid residues on the recombinant tissue plasminogen activator (t-PA). Thus, threonine, proline, and glycine can be used to mitigate some of the toxic effects of ammonium on cell growth, recombinant protein productivity, and protein quality.

Amino Acids↗
PubMed2005

Enhancement of electrodialysis performances using pulsing electric fields during extended period operation.

Many methods have been considered for mitigating and minimizing fouling potentials in the electrodialysis process, because fouling of ion exchange membranes is one of the significant considerations in process design and operation. In the observation of foulant behaviors, it was observed that the humate was deposited and formed a loosely packed fouling layer on the anion-exchange membrane surfaces, thus having reversible fouling effects on the process. In order to investigate the effects of the frequencies on the electrodialysis performance during fouling experiments in the presence of humate, the square-wave powers having various frequencies in the electric fields were employed. The results showed that the pulsing electric fields mitigated the fouling potential and that there exists an optimal frequency for the minimization of the fouling potential. Also, the pulsation of the electric field with an optimal frequency reduced the fouling potential of the already fouled membrane systems in the continuous batch runs. It was suggested that the electric field with pulsing effects enhanced the electrophoretic mobilities of the charged foulants, thus decreasing fouling potentials.

Anion Exchange Resins↗