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Toxicology and Applied Pharmacology Feb 2012"Lysosomotropic" cationic drugs are known to concentrate in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping); they draw... (Review)
Review
"Lysosomotropic" cationic drugs are known to concentrate in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping); they draw water by an osmotic mechanism, leading to a vacuolar response. Several aspects of this phenomenon were recently reexamined. (1) The proton pump vacuolar (V)-ATPase is the driving force of cationic drug uptake and ensuing vacuolization. In quantitative transport experiments, V-ATPase inhibitors, such as bafilomycin A1, greatly reduced the uptake of cationic drugs and released them in preloaded cells. (2) Pigmented or fluorescent amines are effectively present in a concentrated form in the large vacuoles. (3) Consistent with V-ATPase expression in trans-Golgi, lysosomes and endosomes, a fraction of the vacuoles is consistently labeled with trans-Golgi markers and protein secretion and endocytosis are often inhibited in vacuolar cells. (4) Macroautophagic signaling (accumulation of lipidated and membrane-bound LC3 II) and labeling of the large vacuoles by the autophagy effector LC3 were consistently observed in cells, precisely at incubation periods and amine concentrations that cause vacuolization. Vacuoles also exhibit late endosome/lysosome markers, because they may originate from such organelles or because macroautophagosomes fuse with lysosomes. Autophagosome persistence is likely due to the lack of resolution of autophagy, rather than to nutritional deprivation. (5) Increased lipophilicity decreases the threshold concentration for the vacuolar and autophagic cytopathology, because simple diffusion into cells is limiting. (6) A still unexplained mitotic arrest is consistently observed in cells loaded with amines. An extended recognition of relevant clinical situations is proposed for local or systemic drug administration.
Topics: Animals; Autophagy; Biological Transport; Cations; Endocytosis; Humans; Lysosomes; Mitosis; Myocytes, Smooth Muscle; Pharmaceutical Preparations; Vacuolar Proton-Translocating ATPases; Vacuoles
PubMed: 22198553
DOI: 10.1016/j.taap.2011.12.004 -
Journal of Dairy Science Dec 2023Liquid micellar casein concentrate (MCC) is an ideal milk-based protein ingredient for neutral-pH ready-to-drink beverages. The texture and mouthfeel of liquid MCC-based...
Liquid micellar casein concentrate (MCC) is an ideal milk-based protein ingredient for neutral-pH ready-to-drink beverages. The texture and mouthfeel of liquid MCC-based beverages depend on the beverage protein content, as well as the composition of soluble proteins in the aqueous phase around the casein micelle. The objective of this study was to determine the composition of soluble proteins in the aqueous phase around the casein micelles in skim milk and liquid MCC containing 7.0% and 11.6% protein content. Skim milk was pasteurized and concentrated to 7% protein content by microfiltration and then to 18% protein content by ultrafiltration. The 18% MCC was then serially diluted with distilled water to produce 11.6% and 7.0% protein MCC. Skim milk, 7.0% MCC, and 11.6% MCC representing starting materials with different protein concentrations were each ultracentrifuged at 100,605 × g for 2 h. The ultracentrifugation for each of the starting materials was performed at 3 different temperatures: 4°C, 20°C, and 37°C. The ultracentrifugation supernatants were collected to represent the aqueous phase around the casein micelle in MCC solutions. The supernatants were analyzed by Kjeldahl to determine the crude protein, casein, and casein as a percentage of crude protein content, and by sodium dodecyl sulfate PAGE to determine the composition of the individual proteins. Most of the proteins in MCC supernatant (about 45%) were casein proteolysis products. The remaining proteins in the MCC supernatant consisted of a combination of intact α-, β-, and κ-caseins (about 40%) and serum proteins (14-18%). Concentrations of α-casein and β-casein in the supernatant increased with decreasing temperature, especially at higher protein concentrations. Temperature and interaction between temperature and protein explained about 80% of the variation in concentration of supernatant α- and β-caseins. Concentration of supernatant κ-casein, casein proteolysis products, and serum protein increased with increasing MCC protein concentration, and MCC protein concentration explained most of the variation in supernatant κ-casein, casein proteolysis products, and serum protein concentrations. Predicted MCC apparent viscosity was positively associated with the dissociation of α- and β-caseins. Optimal beverage viscosity could be achieved by controlling the dissociation of these proteins in MCC.
Topics: Animals; Caseins; Temperature; Micelles; Milk Proteins; Milk; Blood Proteins; Ultracentrifugation
PubMed: 37641294
DOI: 10.3168/jds.2023-23595 -
Environmental Research Sep 2020Concentrated human milk (HM-concentrate) can be obtained from the simple and inexpensive method of donated breast milk direct lyophilization. A previous study reported...
Concentrated human milk (HM-concentrate) can be obtained from the simple and inexpensive method of donated breast milk direct lyophilization. A previous study reported that HM-concentrate contains the adequate amount of main macro- and micronutrients for use as a nutritional resource for preterm infants with very low birth weight admitted to neonatal intensive care units. However, further details need to be elucidated about HM-concentrate composition, particularly its content of essential and potentially toxic trace elements. Therefore, this study aimed to determine the concentration of essential and toxic elements in human milk considered baseline (HM-baseline) and HM-concentrate, as well as to quantify changes in concentration of these elements after the HM concentration process. The concentration of Aluminum, Arsenic, Cadmium, Chromium, Iron, Mercury, Manganese, Nickel, Lead, Selenium, Tin, and Thallium was analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Moreover, Bayesian linear mixed effect models were applied to estimate the mean difference between HM-baseline and HM-concentrate samples. After comparison (HM-concentrate versus HM-baseline), a significant increase in concentration was observed only for Manganese (0.80 μg/L; 95% CrI [0.16; 1.43]) and Selenium (6.74 μg/L; 95% CrI [4.66; 8.86]), while Lead concentration (-6.13 μg/L; 95% CrI [-8.63; -3.61]) decreased. This study provides latest and reliable information about HM composition. After milk concentration by lyophilization, there was a significant increase only in the essential elements Manganese and Selenium. The essential micronutrient content in HM-concentrate was similar or higher than that in preterm mothers' milk, which suggests it is viable for nutritional support of preterm infants. In addition, the low concentrations of potentially toxic elements in HM-concentrate indicates that it is safe for consumption by premature newborns.
Topics: Animals; Bayes Theorem; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Milk, Human; Trace Elements
PubMed: 32574850
DOI: 10.1016/j.envres.2020.109733 -
Animals : An Open Access Journal From... Aug 2021Effects of a high-rice dietary proportion on the meat quality, acute phase reaction proteins (APRPs) and colonic microbiota and metabolites in goats are rarely reported....
Effects of a high-rice dietary proportion on the meat quality, acute phase reaction proteins (APRPs) and colonic microbiota and metabolites in goats are rarely reported. This study was designed to investigate the meat quality and metabolism in goats. Sixteen goats were equally divided into two groups and fed a control diet (Con, 55% concentrate) or a high-rice diet (HR, 90% concentrate) for five weeks. We found that the HR diet improved the slaughtering characteristic and meat quality but induced an acute phase reaction and decreased bacterial richness and diversity when compared to the control group. Furthermore, the levels of acetate, propionate and total VFA concentrations were higher in the colonic contents of the HR-fed goats than in those of the control group ( < 0.05). Meanwhile, the HR diet decreased the pH value, lactic acid concentration and increased the activity of amylase and lipopolysaccharide concentration in the colonic contents of goats ( < 0.05). The proportion of increased while and significantly decreased with the HR diet ( < 0.05). Collectively, the HR diet induced an acute phase reaction and altered the colonic bacterial community, which increases the health risk to growing goats.
PubMed: 34438763
DOI: 10.3390/ani11082306 -
Frontiers in Microbiology 2017A decrease in methanogenesis is expected to improve ruminant performance by allocating rumen metabolic hydrogen ([2H]) to more energy-rendering fermentation pathways for...
A decrease in methanogenesis is expected to improve ruminant performance by allocating rumen metabolic hydrogen ([2H]) to more energy-rendering fermentation pathways for the animal. However, decreases in methane (CH) emissions of up to 30% are not always linked with greater performance. Therefore, the aim of this study was to understand the fate of [2H] when CH production in the rumen is inhibited by known methanogenesis inhibitors (nitrate, NIT; 3-nitrooxypropanol, NOP; anthraquinone, AQ) in comparison with a control treatment (CON) with the Rumen Simulation Technique (RUSITEC). Measurements started after 1 week adaptation. Substrate disappearance was not modified by methanogenesis inhibitors. Nitrate mostly seemed to decrease [2H] availability by acting as an electron acceptor competing with methanogenesis. As a consequence, NIT decreased CH production (-75%), dissolved dihydrogen (H) concentration (-30%) and the percentages of reduced volatile fatty acids (butyrate, isobutyrate, valerate, isovalerate, caproate and heptanoate) except propionate, but increased acetate molar percentage, ethanol concentration and the efficiency of microbial nitrogen synthesis (+14%) without affecting gaseous H. Nitrooxypropanol decreased methanogenesis (-75%) while increasing both gaseous and dissolved H concentrations (+81% and +24%, respectively). Moreover, NOP decreased acetate and isovalerate molar percentages and increased butyrate, valerate, caproate and heptanoate molar percentages as well as n-propanol and ammonium concentrations. Methanogenesis inhibition with AQ (-26%) was associated with higher gaseous H production (+70%) but lower dissolved H concentration (-76%), evidencing a lack of relationship between the two H forms. Anthraquinone increased ammonium concentration, caproate and heptanoate molar percentages but decreased acetate and isobutyrate molar percentages, total microbial nitrogen production and efficiency of microbial protein synthesis (-16%). Overall, NOP and AQ increased the amount of reduced volatile fatty acids, but part of [2H] spared from methanogenesis was lost as gaseous H. Finally, [2H] recovery was similar among CON, NOP and AQ but was largely lower than 100%. Consequently, further studies are required to discover other so far unidentified [2H] sinks for a better understanding of the metabolic pathways involved in [2H] production and utilization.
PubMed: 28352256
DOI: 10.3389/fmicb.2017.00393 -
Journal of Pharmaceutical Health Care... Nov 2023Tedizolid is an oxazolidinone anti-MRSA drug with included in the National Health Insurance Drug Price List in 2018. The effect of hemodialysis on tedizolid phosphate...
BACKGROUND
Tedizolid is an oxazolidinone anti-MRSA drug with included in the National Health Insurance Drug Price List in 2018. The effect of hemodialysis on tedizolid phosphate concentrations has been reported; pre-dialysis concentrations decreased by 10% compared to post- dialysis concentrations. However, the material of the dialysis membrane remains unknown. In addition, there have been no reports on the effects of continuous hemodiafiltration. In this study, we investigated the effects of continuous hemodiafiltration on tedizolid using two types of dialysis membranes made of different materials.
METHODS
The adsorption of tedizolid, linezolid, and vancomycin to two different dialysis membranes was investigated, and the clearance of each drug was calculated by experiments using an in vitro continuous hemodiafiltration model.
RESULTS
The adsorption of tedizolid, linezolid, and vancomycin on the dialysis membranes was examined, and no adsorption was observed. Experimental results from the continuous hemodiafiltration model showed that linezolid and vancomycin concentrations decreased over time: after two hours, the respective decreases were 26.48 ± 7.14% and 28.51 ± 2.32% for polysulfone membranes, respectively. The decrease was 23.57 ± 4.95% and 28.73 ± 5.13% for the polymethylmethacrylate membranes, respectively. These results suggested that linezolid and vancomycin were eliminated by continuous hemodiafiltration. In contrast, tedizolid phosphate and tedizolid concentrations decreased slightly in the polysulfone and polymethylmethacrylate membranes. The decrease in concentrations were 2.10 ± 0.77% and 2.97 ± 0.60% for the polysulfone membranes, respectively. For the polymethylmethacrylate membranes, the decrease in concentration were 2.01 ± 0.88% and 1.73 ± 0.27%, respectively.
CONCLUSION
These results suggested that tedizolid should not be considered for dose control during continuous hemodiafiltration.
PubMed: 37957772
DOI: 10.1186/s40780-023-00307-9 -
American Journal of Botany Oct 2020Atmospheric carbon dioxide (CO ) concentration is increasing, as is the frequency and duration of drought in some regions. Elevated CO can decrease the effects of...
PREMISE
Atmospheric carbon dioxide (CO ) concentration is increasing, as is the frequency and duration of drought in some regions. Elevated CO can decrease the effects of drought by further decreasing stomatal opening and, hence, water loss from leaves. Both elevated CO and drought typically decrease plant nutrient concentration, but their interactive effects on nutrient status and uptake are little studied. We investigated whether elevated CO helps negate the decrease in plant nutrient status during drought by upregulating nutrient-uptake proteins in roots.
METHODS
Barley (Hordeum vulgare) was subjected to current vs. elevated CO (400 or 700 ppm) and drought vs. well-watered conditions, after which we measured biomass, tissue nitrogen (N) and phosphorus (P) concentrations (%N and P), N- and P-uptake rates, and the concentration of the major N- and P-uptake proteins in roots.
RESULTS
Elevated CO decreased the impact of drought on biomass. In contrast, both drought and elevated CO decreased %N and %P in most cases, and their effects were additive for shoots. Root N- and P-uptake rates were strongly decreased by drought, but were not significantly affected by CO . Averaged across treatments, both drought and high CO resulted in upregulation of NRT1 (NO transporter) and AMT1 (NH transporter) per unit total root protein, while only drought increased PHT1 (P transporter).
CONCLUSIONS
Elevated CO exacerbated decreases in %N and %P, and hence food quality, during drought, despite increases in the concentration of nutrient-uptake proteins in roots, indicating other limitations to nutrient uptake.
Topics: Biomass; Carbon Dioxide; Droughts; Hordeum; Nutrients; Plant Leaves; Plant Roots
PubMed: 33021337
DOI: 10.1002/ajb2.1542 -
Dentistry Journal Oct 2023In dental implantology, alveolar ridge preservation (ARP) has emerged as a standard technique to address dimensional changes that affect alveolar ridge morphology... (Review)
Review
In dental implantology, alveolar ridge preservation (ARP) has emerged as a standard technique to address dimensional changes that affect alveolar ridge morphology following tooth loss. Various alternative graft materials, including xenografts, alloplasts, and allografts, have been effectively employed in fresh extraction sites for ARP. Current evidence suggests that these materials primarily serve as bio-scaffolds, which are slowly incorporated, thus necessitating a waiting period of at least 4-6 months before implant placement. Consequently, the ARP technique extends the overall duration of implant treatment by several months. Recently, the incorporation of a form of autologous platelet concentrate, known as platelet-rich fibrin (PRF), has been advocated in conjunction with ARP as a method of bioenhancement of soft- and hard-tissue healing and regeneration. PRF contains platelet-derived growth factors, hormones, and bioactive components like cytokines that have demonstrated the ability to stimulate angiogenesis and tissue regeneration throughout all phases of wound healing. Additionally, the concentration of leukocytes present in the PRF matrix plays a vital role in tissue healing and regeneration as part of the osteoimmune response. The reported advantages of incorporating autogenous PRF platelet concentrates during ARP encompass reduced healing time, improved angiogenesis and bone regeneration, socket sealing through the fibrin matrix, antibacterial properties, and decreased post-extraction pain and infection risk. Therefore, the objective of this paper is to review the existing evidence regarding the application of PRF in alveolar ridge preservation (ARP) following tooth extraction. Two clinical case studies are presented, wherein ARP was enhanced with PRF, followed by implant placement within a relatively short period of 8 weeks. These cases serve as further proof of concept for supporting the adjuvant use of PRF to enhance healing and accelerate implant placement after ARP.
PubMed: 37886929
DOI: 10.3390/dj11100244 -
Frontiers in Nutrition 2023Reputed as a significant metabolic disorder, non-alcoholic fatty liver disease (NAFLD) is characterized by high-fat deposits in the liver and causes substantial economic...
Reputed as a significant metabolic disorder, non-alcoholic fatty liver disease (NAFLD) is characterized by high-fat deposits in the liver and causes substantial economic challenges to any country's workforce. Previous studies have indicated that some lactic acid bacteria may effectively prevent or treat NAFLD. Overall, KLDS1.0901 protected against HFD-induced NAFLD by improving liver characteristics and modulating microbiota composition, and thus could be a candidate for improving NAFLD. This study aimed to assess the protective effects of KLDS1.0901 on a high-fat diet(HFD)-induced NAFLD. First, hepatic lipid profile and histological alterations were determined to study whether KLDS1.0901 could ameliorate NAFLD. Then, the intestinal permeability and gut barrier were explored. Finally, gut microbiota was analyzed to elucidate the mechanism from the insights of the gut-liver axis. The results showed that KLDS1.0901 administration significantly decreased body weight, Lee's index body, fat rate, and liver index. KLDS1.0901 administration significantly improved lipid profiles by decreasing the hepatic levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) and by increasing the high-density lipoprotein cholesterol (HDL-C) levels. A conspicuous decrease of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum was observed after KLDS1.0901 administration. Meanwhile, the H&E and Oil Red O-stained staining showed that KLDS1.0901 significantly reduced liver lipid accumulation of HFD-fed mice by decreasing the NAS score and lipid area per total area. Our results showed that KLDS1.0901 administration decreased the interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) concentrations accompanied by the increase of interleukin-10 (IL-10). KLDS1.0901 administration could improve the intestinal barrier function by upregulating the mRNA levels of occludin, claudin-1, ZO-1, and Muc-2, which were coupled to the decreases of the concentration of LPS and D-lactic acid. Notably, KLDS1.0901 administration modulated the gut microbiota to a near-normal pattern. Hence, our results suggested that KLDS1.0901 can be used as a candidate to ameliorate NAFLD.
PubMed: 37020807
DOI: 10.3389/fnut.2023.1147423 -
Metabolism: Clinical and Experimental Jan 2013To investigate the effect of acute hyperinsulinemia and the resulting decrease in plasma free fatty acid (FFA) concentrations on intramuscular TG synthesis.
OBJECTIVE
To investigate the effect of acute hyperinsulinemia and the resulting decrease in plasma free fatty acid (FFA) concentrations on intramuscular TG synthesis.
MATERIALS/METHODS
U-(13)C(16)-palmitate was infused for 3 h in anesthetized rabbits after overnight food deprivation. Arterial blood and leg muscle were sampled during the tracer infusion. Plasma samples were analyzed for free and TG-bound palmitate enrichments and concentrations. The enrichments and concentrations of palmitoyl-CoA and palmitoyl-carnitine as well as the enrichment of palmitate bound to TG were measured in muscle samples. Fractional synthetic rate (FSR) of intramuscular TG was calculated using the tracer incorporation method. The rabbits were divided into a control group and a hyperinsulinemic euglycemic clamp group. Insulin infusion decreased the rate of appearance of plasma free palmitate (2.00±0.15 vs 0.68±0.20 μmol⋅kg(-1)⋅min(-1); P<.001), decreased plasma FFA concentration (327±61 vs 72±25 nmol/mL; P<.01), decreased the total concentration of intramuscular fatty acyl-CoA plus fatty acyl-carnitine (12.1±1.6 vs 7.0±0.7 nmol/g; P<.05), and decreased intramuscular TG FSR (0.48±0.05 vs 0.21±0.06%/h; P<.01) in comparison with the control group. Intramuscular TG FSR was correlated (P<.01) with both plasma FFA concentrations and intramuscular fatty acyl-CoA concentrations.
CONCLUSIONS
Fatty acid availability is a determinant of intramuscular TG synthesis. Insulin infusion decreases plasma and intramuscular fatty acid availability and thereby decreases TG synthesis.
Topics: Animals; Hyperinsulinism; Kinetics; Male; Muscle, Skeletal; Palmitates; Palmitoyl Coenzyme A; Rabbits; Triglycerides
PubMed: 22898252
DOI: 10.1016/j.metabol.2012.06.002