Journal articles on the topic 'Gentamicin Physiological effect'
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Handan Mert, Nihat Mert, Mecit Yoruk, Ibrahim Hakki Yoruk, Betul Apaydin Yildirim, and Halil Cumhur Yilmaz. "Effect of coenzyme Q10 and vitamin E on gentamicin-induced nephrotoxicity in rats." GSC Biological and Pharmaceutical Sciences 21, no. 2 (November 30, 2022): 033–40. http://dx.doi.org/10.30574/gscbps.2022.21.2.0419.
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Background/Aim: Gentamicin is an aminoglycoside antibiotic that can cause nephrotoxicity by damaging the kidneys due to high relative blood flow. In this study, the protective and therapeutic effects of CoQ10 and vitamin E on GM-induced nephrotoxicity were investigated. Methods: Fifty Wistar Albino rats were used as live material in this study, which were randomly divided into 5 groups of 10 animals. These groups, and the treatment they received, were as follows: a) control group: Physiological saline (i.p) for 8 days, b) GM group: Gentamycin 80 mg/kg/day/i.p for 8 days, c) GM+CoQ10 group: Gentamycin 80 mg/kg/day/i.p+ CoQ10 10 mg/kg/day/ i.p for 8 days, d) GM+ Vit E group: Gentamycin 80 mg/kg/day/i.p+ Vit E 250 mg/kg /day/ip administrated for 8 days, and e) GM+CoQ10+Vit E group: Gentamycin 80 mg/kg/day/ip + CoQ10 10 mg/kg/day/ip + Vitamin E 250 mg/kg /day/ip for 8 days. Following the test period, urea, creatinine, K, Na, Cl, retinol, vitamin D, and vitamin E levels of the subjects were measured in plasma, while MDA, GSH, AOPP, nitrite, nitrates, CAT, SOD, and GPx activities were measured in kidney tissues. Results: A severe nephrotoxic effect of GM administration in rats were detected as part of this study. The administration of CoQ10 and vitamin E, alone or in combination, was not sufficient to repair the kidney damage at the histopathological level. However, the renal tissue enzyme levels, along with other related to oxidative stress and plasma biochemical parameter analyses, were found to have improved greatly with the administration of vitamin E. Conclusion: CoQ10 and vitamin E can be suggested as supplementary agents to gentamicin treatment to prevent cell degeneration in the kidney and ensure healing
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Karpiński, Robert, Jakub Szabelski, Przemysław Krakowski, Mariusz Jojczuk, Józef Jonak, and Adam Nogalski. "Evaluation of the Effect of Selected Physiological Fluid Contaminants on the Mechanical Properties of Selected Medium-Viscosity PMMA Bone Cements." Materials 15, no. 6 (March 16, 2022): 2197. http://dx.doi.org/10.3390/ma15062197.
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Revision surgeries several years after the implantation of the prosthesis are unfavorable from the patient’s point of view as they expose him to additional discomfort, to risk of complications and are expensive. One of the factors responsible for the aseptic loosening of the prosthesis is the gradual degradation of the cement material as a result of working under considerable loads, in an aggressive environment of the human body. Contaminants present in the surgical field may significantly affect the durability of the bone cement and, consequently, of the entire bone-cement-prosthesis system. The paper presents the results of an analysis of selected mechanical properties of two medium-viscosity bone cements DePuy CMW3 Gentamicin and Heraeus Palamed, for the samples contaminated with saline and blood in the range of 1–10%. The results obtained for compressive strength and modulus of elasticity were subjected to statistical analysis, which estimated the nature of changes in these parameters depending on the amount and type of contamination and their statistical significance.
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Safronyuk, Sergey L., Vlada V. Samolyuk, Alena M. Milova, Yuliia Yu Havrichenko, and Andrey M. Katsev. "Assessment of the applicability of primarily identified natural luminescent bacteria, isolated from the azov and the black seas, to determine the antimicrobial activity of antibiotics." Aspirantskiy Vestnik Povolzhiya 20, no. 5-6 (July 15, 2020): 175–83. http://dx.doi.org/10.17816/2072-2354.2020.20.3.175-183.
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Five isolates of luminous bacteria from aquatic organisms of the Azov and the Black Seas were isolated. The study of morphological, cultural, physiological and biochemical properties showed that isolates M1 and M4 were the representatives of the species harveyi, and isolates Fb, Sh1, and B were the representatives of the species P. leiognathi. It was found that the strain P. leiognathi Sh1 was the most sensitive to zinc sulfate when studying its effect on allocated luminescent bacteria. The effective concentration that reduced the bioluminescent index (BLI) by 50% (EC50) for zinc sulfate, when exposed to the test strain, was 4,0 0,1 g/ml. Experimental data allowed to consider the strain P. leiognathi Sh1 to be the test-object for determining the antimicrobial activity of benzylpenicillin, gentamicin, streptomycin, tetracycline and ceftriaxone. The results of evaluating the effect of antibiotics on the test object, revealed that after 15 minutes of incubation, the BLI values decreased by 50% only in samples containing benzylpenicillin, gentamicin, and tetracycline. Their EC50 were 500.0, 283.0 and 28.5 g/ml respectively. It was found that the exposure of test-strain to all antibacterial agents demonstrated resulted in decrease in BLI by 100% as compared to the control values. Strain P. leiognathi Sh1 can be used as a test-object for determining the antimicrobial activity of antibiotics.
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Gugleva, Viliana, Victoria Michailova, Rositsa Mihaylova, Georgi Momekov, Maya Margaritova Zaharieva, Hristo Najdenski, Petar Petrov, et al. "Formulation and Evaluation of Hybrid Niosomal In Situ Gel for Intravesical Co-Delivery of Curcumin and Gentamicin Sulfate." Pharmaceutics 14, no. 4 (March 30, 2022): 747. http://dx.doi.org/10.3390/pharmaceutics14040747.
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The current study describes the elaboration of a hybrid drug delivery platform for an intravesical application based on curcumin/gentamicin sulfate simultaneously loaded niosomes incorporated into thermosensitive in situ gels. Series of niosomes were elaborated via the thin film hydration method, evaluating the impact of non-ionic surfactants’, cholesterol’s, and curcumin’s concentration. The formulation composed of equimolar ratio of Span 60, Tween 60, and 30 mol% cholesterol was selected as the optimal composition, due to the high entrapment efficiency values obtained for both drugs, and appropriate physicochemical parameters (morphology, size, PDI, and zeta potential), therefore, was further incorporated into Poloxamers (407/188) and Poloxamers and chitosan based in situ gels. The developed hybrid systems were characterized with sol to gel transition in the physiological range, suitable rheological and gelling characteristics. In addition, the formed gel structure at physiological temperatures determines the retarded dissolution of both drugs (vs. niosomal suspension) and sustained release profile. The conducted microbial studies of selected niosomal in situ gels revealed the occurrence of a synergetic effect of the two compounds when simultaneously loaded. The findings indicate that the elaborated thermosensitive niosomal in situ gels can be considered as a feasible platform for intravesical drug delivery.
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Herrera-Alonso, Alejandra E., María C. Ibarra-Alonso, Sandra C. Esparza-González, Sofía Estrada-Flores, Luis A. García-Cerda, and Antonia Martínez-Luévanos. "Biomimetic Growth of Hydroxyapatite on SiO2 Microspheres to Improve Its Biocompatibility and Gentamicin Loading Capacity." Materials 14, no. 22 (November 17, 2021): 6941. http://dx.doi.org/10.3390/ma14226941.
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The interest in multifunctional biomaterials to be implanted are also able to release drugs that reduce pain and inflammation or prevent a possible infection has increased. Bioactive materials such as silica (SiO2) containing surface silanol groups contribute to the nucleation and growth of hydroxyapatite (HAp) in a physiological environment. Regarding biocompatibility, the spherical shape of particles is the desirable one, since it does not cause mechanical damage to the cell membrane. In this work, the synthesis of SiO2 microspheres was performed by the modified Stöber method and they were used for the biomimetic growth of HAp on their surface. The effect of the type of surfactant (sodium dodecyl sulphate (SDS), cetyltrimethylammonium bromide (CTAB), and polyethylene glycol (PEG)), and heat treatment on the morphology and size of SiO2 particles was investigated. Monodisperse, spherical-shaped SiO2 microparticles with an average particle size of 179 nm, were obtained when using PEG (SiO2-PEG). The biomimetic growth of HAp was performed on this sample to improve its biocompatibility and drug-loading capacity using gentamicin as a model drug. Biomimetic growth of HAp was confirmed by FTIR-ATR, SEM-EDX and TEM techniques. SiO2-PEG/HAp sample had a better biocompatibility in vitro and gentamicin loading capacity than SiO2-PEG sample.
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Pavyde, Egle, Romaldas Maciulaitis, Mykolas Mauricas, Gintaras Sudzius, Ernesta Ivanauskaite Didziokiene, Arvydas Laurinavicius, Neringa Sutkeviciene, Edgaras Stankevicius, Justinas Maciulaitis, and Arvydas Usas. "Skeletal Muscle-Derived Stem/Progenitor Cells: A Potential Strategy for the Treatment of Acute Kidney Injury." Stem Cells International 2016 (2016): 1–13. http://dx.doi.org/10.1155/2016/9618480.
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Skeletal muscle-derived stem/progenitor cells (MDSPCs) have been thoroughly investigated and already used in preclinical studies. However, therapeutic potential of MDSPCs isolated using preplate isolation technique for acute kidney injury (AKI) has not been evaluated. We aimed to characterize rat MDSPCs, compare them with bone marrow mesenchymal stem cells (BM-MSCs), and evaluate the feasibility of MDSPCs therapy for gentamicin-induced AKI in rats. We have isolated and characterized rat MDSPCs and BM-MSCs. Characteristics of rat BM-MSCs and MDSPCs were assessed by population doubling time, flow cytometry, immunofluorescence staining, RT-PCR, and multipotent differentiation capacity. Gentamicin-induced AKI model in rat was used to examine MDSPCs therapeutic effect. Physiological and histological kidney parameters were determined. MDSPCs exhibited similar immunophenotype, stem cell gene expression, and multilineage differentiation capacities as BM-MSCs, but they demonstrated higher proliferation rate. Single intravenous MDSPCs injection accelerated functional and morphological kidney recovery, as reflected by significantly lower serum creatinine levels, renal injury score, higher urinary creatinine, and GFR levels. PKH-26-labeled MDSPCs were identified within renal cortex 1 and 2 weeks after cell administration, indicating MDSPCs capacity to migrate and populate renal tissue. In conclusion, MDSPCs are capable of mediating functional and histological kidney recovery and can be considered as potential strategy for AKI treatment.
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Laines-Arce, Irving, Mijail Contreras, and Cesar Olaguivel. "EVALUATION OF TWO CULTURE MEDIA IN IN VITRO PRODUCTION OF ALPACA (Vicugna pacos) EMBRYOS." SPERMOVA 11, no. 1 (August 13, 2021): 46–52. http://dx.doi.org/10.18548/aspe/0009.07.
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The present study aims to evaluate the effect of two culture media on the production of in vitro embryos in alpacas (Vicugna pacos). The ovaries were transported at 10.52° C in 0.9% saline solution supplemented with gentamicin. The ovaries were transported at 10.52° C in 0.9% physiological saline solution supplemented with gentamicin. 492 ovaries were used throughout the experiment. 2142 oocytes of quality I, II and III were recovered. The oocytes were matured in vitro for 32 h and were subsequently fertilized (incubated for 18 h) with sperm obtained from the tail of the epididymis and selected with a 45/90 percoll gradient. Then, the presumed zygotes were denuded from the cumulus cells, to later be cultured in two culture media: synthetic oviductal fluid medium (SOFaa) and simple optimized potassium medium (KSOMaa) and incubated at 38.5 ° C, 5 % CO2, 5%, O2, and 90% relative humidity for 7 days. Morula and blastocyst rate evaluation was performed at the end of embryo culture. The morula rate at 7 days was 41.49 ± 10.52 and 41.51 ± 6.50% for KSOMaa and SOFaa, respectively (P <0.05). The blastocyst rate for the two culture media KSOMaa and SOFaa, was 14.08 ± 5.17 and 11.73 ± 5.69 %, respectively, and there were no statistical differences (P˃0.05). The embryonic quality in KSOMaa and SOFaa media did not show statistical differences. In conclusion, the KSOMaa and SOFaa culture medium can be used in the production of in vitro embryos of alpacas
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Kuang, Lisha, Kei Hashimoto, Eric J. Huang, Matthew S. Gentry, and Haining Zhu. "Frontotemporal dementia non-sense mutation of progranulin rescued by aminoglycosides." Human Molecular Genetics 29, no. 4 (January 8, 2020): 624–34. http://dx.doi.org/10.1093/hmg/ddz280.
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Abstract Frontotemporal dementia (FTD) is an early onset dementia characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5–26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its functions under physiological and pathological conditions remains to be defined. Many FTD-causing non-sense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy. Aminoglycosides are a class of antibiotics that possess a less-known function to induce eukaryotic ribosomal readthrough of PTCs to produce a full-length protein. The aminoglycoside-induced readthrough strategy has been utilized to treat multiple human diseases caused by PTCs. In this study, we tested the only clinically approved readthrough small molecule PTC124 and 11 aminoglycosides in a cell culture system on four PTCs responsible for FTD or a related neurodegenerative disease amyotrophic lateral sclerosis. We found that the aminoglycosides G418 and gentamicin rescued the expression of the progranulin R493X mutation. G418 was more effective than gentamicin (~50% rescue versus <10%), and the effect was dose- and time-dependent. The progranulin readthrough protein displayed similar subcellular localization as the wild-type progranulin protein. These data provide an exciting proof-of-concept that aminoglycosides or other readthrough-promoting compounds are a therapeutic avenue for familial FTD caused by progranulin PTC mutations.
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Fung, Danny K. C., Edward W. C. Chan, Miu L. Chin, and Raphael C. Y. Chan. "Delineation of a Bacterial Starvation Stress Response Network Which Can Mediate Antibiotic Tolerance Development." Antimicrobial Agents and Chemotherapy 54, no. 3 (January 19, 2010): 1082–93. http://dx.doi.org/10.1128/aac.01218-09.
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ABSTRACT This study aimed at elucidating the physiological basis of bacterial antibiotic tolerance. By use of a combined phenotypic and gene knockout approach, exogenous nutrient composition was identified as a crucial environmental factor which could mediate progressive development of tolerance with markedly varied drug specificity and sustainability. Deprivation of amino acids was a prerequisite for tolerance formation, conferring condition-specific phenotypes against inhibitors of cell wall synthesis and DNA replication (ampicillin and ofloxacin, respectively), according to the relative abundances of ammonium salts, phosphate, and nucleobases. Upon further depletion of glucose, this variable phase consistently evolved into a sustainable mode, along with enhanced capacity to withstand the effect of the protein synthesis inhibitor gentamicin. Nevertheless, all phenotypes produced during spontaneous nutrient depletion lacked the sustainable, multidrug-tolerant features exhibited by the stationary-phase population and were attributed to complex interaction between starvation-mediated metabolic and stress protection responses on the basis of the following reasons: (i) the nutrition-dependent tolerance characteristics observed suggested that adaptive biosynthetic mechanisms could suppress but not fully avert tolerance under transient starvation conditions; (ii) formation of specific phenotypes could be inhibited by suppressing protein synthesis prior to nutrient depletion; (iii) bacteriostatic drugs produced only weak tolerance in the absence of starvation signals; and (iv) the attenuation of the stringent and SOS responses, as well as the functionality of other putative tolerance determinants, including rpoS, hipA, glpD, and phoU, could alter the induction requirement and drug specificity of the resultant phenotypes. These data reveal the common physiological grounds characteristic of starvation responses and the onset of antibiotic tolerance in bacteria.
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Stolarek, Paulina, Przemysław Bernat, and Antoni Różalski. "Combined Application of Aminoglycosides and Ascorbic Acid in the Elimination of Proteus mirabilis Rods Responsible for Causing Catheter-Associated Urinary Tract Infections (CAUTIs)—A Molecular Approach." International Journal of Molecular Sciences 23, no. 21 (October 28, 2022): 13069. http://dx.doi.org/10.3390/ijms232113069.
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Proteus mirabilis is a common cause of catheter-associated urinary tract infections (CAUTIs). In this study, we verified the effectiveness of amikacin or gentamicin and ascorbic acid (AA) co-therapy in eliminating uropathogenic cells, as well as searched for the molecular basis of AA activity by applying chromatographic and fluorescent techniques. Under simulated physiological conditions, a combined activity of the antibiotic and AA supported the growth (threefold) of the P. mirabilis C12 strain, but reduced catheter colonization (≤30%) in comparison to the drug monotherapy. Slight modifications in the phospholipid and fatty acid profiles, as well as limited (≤62%) 2’,7’-dichlorofluorescein fluorescence, corresponding to the hydroxyl radical level, allowed for the exclusion of the hypothesis that the anti-biofilm effect of AA was related to membrane perturbations of the C12 strain. However, the reduced (≤20%) fluorescence intensity of propidium iodide, as a result of a decrease in membrane permeability, may be evidence of P. mirabilis cell defense against AA activity. Quantitative analyses of ascorbic acid over time with a simultaneous measurement of the pH values proved that AA can be an effective urine acidifier, provided that it is devoid of the presence of urease-positive cells. Therefore, it could be useful in a prevention of recurrent CAUTIs, rather than in their treatment.
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Matl, F. D., A. Obermeier, S. Repmann, W. Friess, A. Stemberger, and K. D. Kuehn. "New Anti-Infective Coatings of Medical Implants." Antimicrobial Agents and Chemotherapy 52, no. 6 (March 24, 2008): 1957–63. http://dx.doi.org/10.1128/aac.01438-07.
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ABSTRACT Implantable devices are highly susceptible to infection and are therefore a major risk in surgery. The present work presents a novel strategy to prevent the formation of a biofilm on polytetrafluoroethylene (PTFE) grafts. PTFE grafts were coated with gentamicin and teicoplanin incorporated into different lipid-like carriers under aseptic conditions in a dipping process. Poly-d,l-lactic acid, tocopherol acetate, the diglyceride Softisan 649, and the triglyceride Dynasan 118 were used as drug carriers. The drug release kinetics, anti-infective characteristics, biocompatibility, and hemocompatibility of the coatings developed were studied. All coatings showed an initial drug burst, followed by a low continuous drug release over 96 h. The dimension of release kinetics depended on the carrier used. All coated prostheses reduced bacterial growth drastically over 24 h, even below pathologically relevant concentrations. Different cytotoxic levels could be observed, revealing tocopherol acetate as the most promising biocompatible carrier. A possible reason for the highly cytotoxic effect of Softisan 649 could be assessed by demonstrating incorporated lipids in the cell soma with Oil Red O staining. Tromboelastography studies, enzyme-linked immunosorbent assays, and an amidolytic substrate assay could confirm the hemocompatibility of individual coatings. The development of the biodegradable drug delivery systems described here and in vitro studies of those systems highlight the most important requirements for effective as well as compatible anti-infective coatings of PTFE grafts. Through continuous local release, high drug levels can be produced at only the targeted area and physiological bacterial proliferation can be completely inhibited, while biocompatibility as well as hemocompatibility can be ensured.
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Ramirez-Sánchez, Diana Aurora, Noemi Navarro-Lleó, Christine Bäuerl, Samuel Campista-León, José María Coll-Marqués, and Gaspar Pérez-Martínez. "Factors Affecting Spontaneous Endocytosis and Survival of Probiotic Lactobacilli in Human Intestinal Epithelial Cells." Microorganisms 10, no. 6 (May 31, 2022): 1142. http://dx.doi.org/10.3390/microorganisms10061142.
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Mutualistic bacteria have different forms of interaction with the host. In contrast to the invasion of pathogenic bacteria, naturally occurring internalization of commensal bacteria has not been studied in depth. Three in vitro methods, gentamicin protection, flow cytometry and confocal laser scanning microscopy, have been implemented to accurately assess the internalization of two lactobacillus strains—Lacticaseibacillus paracasei BL23 and Lacticaseibacillus rhamnosus GG—in Caco-2 and T84 intestinal epithelial cells (IECs) under a variety of physiological conditions and with specific inhibitors. First and most interesting, internalization occurred at a variable rate that depends on the bacterial strain and IEC line, and the most efficient was BL23 internalization by T84 and, second, efficient internalization required active IEC proliferation, as it improved naturally at the early confluence stages and by stimulation with epidermal growth factor (EGF). IFN-γ is bound to innate immune responses and autolysis; this cytokine had a significant effect on internalization, as shown by flow cytometry, but increased internalization was not perceived in all conditions, possibly because it was also stimulating autolysis and, as a consequence, the viability of bacteria after uptake could be affected. Bacterial uptake required actin polymerization, as shown by cytochalasin D inhibition, and it was partially bound to clathrin and caveolin dependent endocytosis. It also showed partial inhibition by ML7 indicating the involvement of cholesterol lipid rafts and myosin light chain kinase (MLCK) activation, at least in the LGG uptake by Caco-2. Most interestingly, bacteria remained viable inside the IEC for as long as 72 h without damaging the epithelial cells, and paracellular transcytosis was observed. These results stressed the fact that internalization of commensal and mutualistic bacteria is a natural, nonpathogenic process that may be relevant in crosstalk processes between the intestinal populations and the host, and future studies could determine its connection to processes such as commensal tolerance, resilience of microbial populations or transorganic bacterial migration.
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Sandoval, Ruben M., Robert L. Bacallao, Kenneth W. Dunn, Jeffrey D. Leiser, and Bruce A. Molitoris. "Nucleotide depletion increases trafficking of gentamicin to the Golgi complex in LLC-PK1 cells." American Journal of Physiology-Renal Physiology 283, no. 6 (December 1, 2002): F1422—F1429. http://dx.doi.org/10.1152/ajprenal.00095.2002.
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Having shown rapid trafficking of aminoglycosides to the Golgi complex in cell culture, we focused on the injurious interaction that occurs when gentamicin administration is preceded by renal ischemia. Using Texas red-labeled gentamicin as a tracer, we determined that 15 min of cellular nucleotide depletion did not significantly increase subsequent uptake. However, cells previously depleted of nucleotides accumulated significantly more Texas red-labeled gentamicin within a dispersed Golgi complex. Using Ricinus communis and Lens culinaris lectins, which label specific compartments of the Golgi complex ( trans-Golgi network/ trans and medial/ cis compartments, respectively), we determined that the medial/ cis compartment dispersed after 15 min of nucleotide depletion but the trans-Golgi network/ trans compartment remained unaffected. An increase in the number of cells exhibiting disrupted medial/ cis-Golgi morphology after repletion in physiological media containing gentamicin was also seen. In summary, the increase in nephrotoxicity seen when ischemia precedes aminoglycoside uptake may be part of a complex mechanism initially involving increased Golgi accumulation and prolonged Golgi dispersion. The Golgi complex must then endure the effects of gentamicin accumulated in larger quantities in an aberrant physiological state.
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Idkaidek, Nasir, Salim Hamadi, Rabab Bani-Domi, Ibrahim Al-Adham, Motasem Alsmadi, Faten Awaysheh, Hisham Aqrabawi, Ahmad Al-Ghazawi, and Ayman Rabayah. "Saliva versus Plasma Therapeutic Drug Monitoring of Gentamicin in Jordanian Preterm Infants. Development of a Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class II Drugs of Salivary Excretion Classification System." Drug Research 70, no. 10 (September 2, 2020): 455–62. http://dx.doi.org/10.1055/a-1233-3582.
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AbstractGentamicin has proven to be a very successful treatment for bacterial infection, but it also can cause adverse effects, especially ototoxicity, which is irreversible. Therapeutic drug monitoring (TDM) in saliva is a more convenient non-invasive alternative compared to plasma. A physiologically-based pharmacokinetic (PBPK) model of gentamicin was built and validated using previously-published plasma and saliva data. The validated model was then used to predict experimentally-observed plasma and saliva gentamicin TDM data in Jordanian pediatric preterm infant patients measured using sensitive LCMS/MS method. A correlation was established between plasma and saliva exposures. The developed PBPK model predicted previously reported gentamicin levels in plasma, saliva and those observed in the current study. A good correlation was found between plasma and saliva exposures. The PBPK model predicted that gentamicin in saliva is 5–7 times that in plasma, which is in agreement with observed results. Saliva can be used as an alternative for TDM of gentamicin in preterm infant patients. Exposure to gentamicin in plasma and saliva can reliably be predicted using the developed PBPK model in patients.
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Cherry, Katie E., and Mark R. Morton. "Drug Sensitivity in Older Adults: The Role of Physiologic and Pharmacokinetic Factors." International Journal of Aging and Human Development 28, no. 3 (April 1989): 159–74. http://dx.doi.org/10.2190/00x7-hvxq-d3bg-mk76.
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Age-related changes in physiology and pharmacokinetics (how drugs are used in the body) lead to increased drug sensitivity and potentially harmful drug effects. This report addresses the heightened sensitivity to drug effects seen in older adults. The first section of the report presents three examples of physiologic decline: a) decreased plasma protein binding affects drug distribution, b) declining liver function affects drug metabolism, and c) impaired kidney function delays drug elimination. The next section illustrates by example the risks associated with altered physiology: a) decline in plasma protein binding may result in an intensified effect of the drug Phenytoin, b) altered liver function increases the sedative effects of Diazepam, and c) declining kidney function results in accumulation of the drug Gentamicin, where toxic effects include kidney failure and deafness. The last section is a discussion of some broad considerations for geriatric pharmacology. Adverse drug reactions can largely be avoided by carefully weighing the needs and clinical status of older persons on an individual basis both prior to and throughout the course of a given drug therapy.
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Tsuji, Brian T., and Michael J. Rybak. "Short-Course Gentamicin in Combination with Daptomycin or Vancomycin against Staphylococcus aureus in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations." Antimicrobial Agents and Chemotherapy 49, no. 7 (July 2005): 2735–45. http://dx.doi.org/10.1128/aac.49.7.2735-2745.2005.
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ABSTRACT The ability to maximize bactericidal activity while minimizing toxicity is a therapeutic goal in the treatment of infective endocarditis. We evaluated the impact of administering short-course regimens of gentamicin in combination with daptomycin or vancomycin against one methicillin-susceptible (MSSA 1199) and one methicillin-resistant (MRSA 494) Staphylococcus aureus isolate using an in vitro pharmacodynamic model with simulated endocardial vegetations over 96 h. Human therapeutic dosing regimens for daptomycin (6 and 8 mg/kg of body weight), vancomycin, and gentamicin were simulated. Short-course combination regimens involving gentamicin were administered either as a single 5-mg/kg dose or three 1-mg/kg doses for only the first 24 h and compared to the regimens administered for the full 96-h duration. For all experiments, physiologic conditions of albumin, calcium, and pH were simulated. Both regimens of daptomycin achieved 99.9% kill by 32 h and maintained bactericidal activity against both isolates, which was significantly different from vancomycin, which displayed bacteriostatic activity (P < 0.05). The effects of all short-course regimens of gentamicin were equal to those of the full-duration regimens in combination with daptomycin. Adding three doses of gentamicin (1 mg/kg) to daptomycin resulted in enhancement and bactericidal activity at 24 h against both MRSA and MSSA. The addition of a single dose of gentamicin (5 mg/kg) enhanced or improved the activity of daptomycin and resulted in early bactericidal activity at 4 h against both isolates. The addition of three doses of gentamicin (1 mg/kg) did not improve the activity of vancomycin. However, the addition of a single 5-mg/kg dose of gentamicin to vancomycin resulted in early enhancement at 4 h and 99.9% kill at 32 h for MRSA. These results suggest that a single high dose of gentamicin in combination with daptomycin or vancomycin may be of utility to maximize synergistic and bactericidal activity and minimize toxicity. Further investigation is warranted.
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Neeli, Harshith, Nazeeh Hanna, Khaled Abduljalil, Jaclyn Cusumano, and David R. Taft. "Application of Physiologically Based Pharmacokinetic‐Pharmacodynamic Modeling in Preterm Neonates to Guide Gentamicin Dosing Decisions and Predict Antibacterial Effect." Journal of Clinical Pharmacology 61, no. 10 (June 8, 2021): 1356–65. http://dx.doi.org/10.1002/jcph.1890.
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Oller, Inmaculada, Jaime Ruiz-Tovar, Pilar Cansado, Lorea Zubiaga, and Rafael Calpena. "Effect of Lavage with Gentamicin vs. Clindamycin vs. Physiologic Saline on Drainage Discharge of the Axillary Surgical Bed after Lymph Node Dissection." Surgical Infections 16, no. 6 (December 2015): 781–84. http://dx.doi.org/10.1089/sur.2015.020.
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Parsons, T. D., A. L. Obaid, and B. M. Salzberg. "Aminoglycoside antibiotics block voltage-dependent calcium channels in intact vertebrate nerve terminals." Journal of General Physiology 99, no. 4 (April 1, 1992): 491–504. http://dx.doi.org/10.1085/jgp.99.4.491.
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Intrinsic and extrinsic optical signals recorded from the intact nerve terminals of vertebrate neurohypophyses were used to investigate the anatomical site and physiological mechanism of the antagonistic effects of aminoglycoside antibiotics on neurotransmission. Aminoglycoside antibiotics blocked the intrinsic light scattering signal closely associated with neurosecretion in the mouse neurohypophysis in a concentration-dependent manner with an IC50 of approximately 60 microM and the block was relieved by increasing [Ca2+]o. The rank order potency of different aminoglycoside antibiotics for blocking neurosecretion in this preparation was determined to be: neomycin greater than gentamicin = kanamycin greater than streptomycin. Optical recordings of rapid changes in membrane potential using voltage-sensitive dyes revealed that aminoglycoside antibiotics decreased the Ca(2+)-dependent after-hyperpolarization of the normal action potential and both the magnitude and after-hyperpolarization of the regenerative Ca2+ spike. The after-hyperpolarization results from a Ca-activated potassium conductance whose block by aminoglycoside antibiotics was also reversed by increased [Ca2+]o. These studies demonstrate that the capacity of aminoglycoside antibiotics to antagonize neurotransmission can be attributed to the block of Ca channels in the nerve terminal.
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Ferreira, Abigail, Helena Martins, José Carlos Oliveira, Rui Lapa, and Nuno Vale. "PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice." Life 11, no. 11 (October 23, 2021): 1130. http://dx.doi.org/10.3390/life11111130.
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The importance of closely observing patients receiving antibiotic therapy, performing therapeutic drug monitoring (TDM), and regularly adjusting dosing regimens has been extensively demonstrated. Additionally, antibiotic resistance is a contemporary concerningly dangerous issue. Optimizing the use of antibiotics is crucial to ensure treatment efficacy and prevent toxicity caused by overdosing, as well as to combat the prevalence and wide spread of resistant strains. Some antibiotics have been selected and reserved for the treatment of severe infections, including amikacin, gentamicin, tobramycin, and vancomycin. Critically ill patients often require long treatments, hospitalization, and require particular attention regarding TDM and dosing adjustments. As these antibiotics are eliminated by the kidneys, critical deterioration of renal function and toxic effects must be prevented. In this work, clinical data from a Portuguese cohort of 82 inpatients was analyzed and physiologically based pharmacokinetic (PBPK) modeling and simulation was used to study the influence of different therapeutic regimens and parameters as biological sex, body weight, and renal function on the biodistribution and pharmacokinetic (PK) profile of these four antibiotics. Renal function demonstrated the greatest impact on plasma concentration of these antibiotics, and vancomycin had the most considerable accumulation in plasma over time, particularly in patients with impaired renal function. Thus, through a PBPK study, it is possible to understand which pharmacokinetic parameters will have the greatest variation in a given population receiving antibiotic administrations in hospital context.
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Nurabay, Nazerke, M. Abutalip, Raikhan Rakhmetullayeva, and Grigoriy Mun. "Development of the technology for obtaining new hydrogel materials based on acrylic monomers." Chemical Bulletin of Kazakh National University, no. 4 (December 27, 2017): 20–29. http://dx.doi.org/10.15328/cb959.
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Smart water-soluble polymers and hydrogels are capable to reversibly react to insignificant changes of the medium properties (pH, temperature, ionic strength, a presence of some substances, illumination, electric field). The reacting of a system is visible to the naked eye (the formation of a new phase in a homogeneous solution, or compression of the hydrogel). The properties of such polymers and hydrogels are considered. For the first time, the stimuli-responsive polymeric hydrogels based on N-isopropylacrylamide (NIPAAM), 2-hydroxyethyl acrylate (HEA) and acrylic acid (AA) have been synthesized by free initiation of radical copolymerization. The purpose of the research is to obtain stimuli-responsive cross-linked terpolymers based on N-isopropylacrylamide, 2-hydroxyethyl acrylate and acrylic acid and study their physicochemical properties. The physicochemical methods such as scanning electron microscopy, differential scanning calorimetry, infrared spectroscopy, gravimetry, cathetometric and thermogravimetric analyses were used in this study. To determine the thermal and pH – sensitivity of the modified copolymer, the effect of temperature on the NIPAAM-НEA-AA nets (in different pH media) was studied. They are characterized by a thermally induced collapse and a dependence on a medium pH. The interaction of copolymers with drugs such as lincomycin and gentamicin was studied for using the new copolymers as a drug carrier. To study the antibacterial properties and the transportation of physiologically active substances of hydrogel, the elimination of specially prepared bacteria by hydrogels with various medicinal ingredients were conducted.
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Luu, V. V., Z. Namula, Y. Kaedei, F. Tanihara, and T. Otoi. "187 EFFECTS OF OVARY STORAGE TIME ON THE QUALITY AND MEIOTIC COMPETENCE OF CAT OOCYTES." Reproduction, Fertility and Development 24, no. 1 (2012): 205. http://dx.doi.org/10.1071/rdv24n1ab187.
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Unlike the oocytes of other species, cat oocytes have a unique characteristic in that they can mature in vitro after temporary storage at 5°C. Temporal storage of ovaries can aid in preserving oocytes from the ovaries of endangered felids that sometimes die suddenly in the field. The present study was conducted to evaluate the effects of the duration of cold storage of cat ovaries on the quality and meiotic competence of their oocytes. Domestic cat ovaries were collected from sexually mature queens (40 ovary pairs) at various stages of the reproductive cycle, after routine ovariohysterectomy performed at local veterinary clinics. After excision, the ovaries were stored at 5°C in physiological saline for 0, 1, 2, 3, 4 and 5 days until oocyte recovery. The cumulus–oocyte complexes with uniform and dark-pigmented ooplasm and more than 2 layers of cumulus cells were collected (n = 526) and then cultured for 24 h in maturation medium. This maturation medium consisted of tissue culture medium 199 supplemented with 4 mg mL–1 of bovine serum albumin, 0.1 IU mL–1 of human menopausal gonadotropin, 10 IU mL–1 of hCG, 1 μg mL–1 of 17 β-oestradiol and 50 μg mL–1 of gentamicin. The status of meiosis and fragmented chromatin in the oocytes after the 24-h maturation culture was assessed by terminal deoxynucleotidyl transferase dUTP nick end labelling and Hoechst 33342 staining. Data were analyzed using analysis of variance. The percentage of oocytes that reached metaphase II was greater for ovaries kept without cold storage (control group; 60.5%) than for ovaries kept for 1, 2, 3, 4 and 5 days in cold storage (maturation of 28.6, 38.3, 23.2, 1.6 and 2.2%, respectively; P < 0.05). In the cold storage group, the maturation rates (1.6–2.2%) of oocytes from ovaries stored for more than 4 days were significantly lower (P < 0.05) than those (23.2–38.3%) of oocytes from ovaries stored for less than 3 days. Moreover, oocytes with fragmented chromosomes after the maturation culture were not observed in the case of the control group, whereas 24.4 to 51.8% of the oocytes in the cold storage group had fragmented chromosomes, irrespective of the storage period. These results indicate that cold storage of cat ovaries decreases the meiotic competence of oocytes and influences the quality of oocytes matured in vitro.
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"Some Physiological Effect of Acacia Gum on Acute Renal Failure Induced by Gentamicin in Male Rabbits." Indian Journal of Forensic Medicine & Toxicology, May 12, 2021. http://dx.doi.org/10.37506/ijfmt.v15i3.15895.
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Vagh, A. A., R. M. Patel, S. V. Mavadiya, S. A. Mehta, C. T. Khasatiya, S. A. Mehta, J. A. Vala, S. M. Parmar, and R. D. Varia. "Clinico-Biochemical and Nephroprotective Effects of Medicinal Herbs on Gentamicin Induced Nephrotoxicity in Wistar Rats." INDIAN JOURNAL OF VETERINARY SCIENCES AND BIOTECHNOLOGY 13, no. 01 (August 10, 2017). http://dx.doi.org/10.21887/ijvsbt.v13i01.8737.
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Nephrotoxicity followed by kidney disease is the main complication of gentamicin treatment. Medicinal plants and herbs have played an important role in the prevention and treatment of kidney diseases. With this concern the ethanol extract of Zingiber officinale rhizomes , ethanol extract of Tinospora cordifolia roots and methanol extract of Cajanus indicus leaves were compared for their nephroprotective effect in the Wistar rats. A total of 48 Wistar rats were distributed into six equal groups (n=8) and were exposed to gentamicin sulphate @ 100 mg/kg orally for 7 days to induce nephrotoxicity in 5 groups. Group G1 was kept as healthy control and group G2 was considered as untreated induced nephrotoxic control, whereas the rats of groups G3, G4, G5 and G6 were given, along with gentamicin sulphate @ 100 mg/kg, extracts of Zingiber officinale @ 400 mg/kg b.wt, Tinospora cordifolia 200 mg/kg b.wt, Cajanus indicus @ 400 mg/kg b.wt and syrup Cystone @ 500 mg/kg b.wt., respectively, orally for 7 consecutive days as neproprotective drugs. A significant (P less than 0.05) increase was observed in the values of plasma BUN, creatinine, urea, ALP, GGT, uric acid, calcium and phosphorus, whereas the total protein and albumin were found significantly (P less than 0.05) decreased on day 7 in rats receiving gentamicin alone (G2). However, there was no significant alteration in the values of above mentioned parameters in rats of G1 (healthy control), G4 and G6, which remained within the normal physiological range, suggesting nephroprotective role of herbal extracts in rats.
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Lotfy, Ghada, Amel Soliman, Nevine Bahaa, and Mohammed Hegazi. "Effect of Experimentally Induced Chronic Kidney disease on Skeletal, Cardiac and Smooth Muscle fibers of albino rat." QJM: An International Journal of Medicine 114, Supplement_1 (October 1, 2021). http://dx.doi.org/10.1093/qjmed/hcab099.006.
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Abstract Background Chronic kidney disease (CKD), or chronic renal failure (CRF) as it was historically termed, includes all degrees of decreased renal function, starting from mild, and moderate, to severe chronic kidney failure. Skeletal muscle atrophy frequently complicates the course of CKD and is associated with excess morbidity and mortality. Cardiovascular diseases have been reported to be the leading causes of death in CKD patients. Chronic Kidney Disease was also reported to be associated with an increased incidence of acid-related gastrointestinal disorders. Aim of the work The aim of this study was to investigate the effect of chronic kidney disease experimentally induced by gentamicin intramuscular injection on the histological structure of gastrocnemius skeletal muscle, left ventricular cardiac muscle and smooth muscle fibers of lower esophagus. Materials and methods Twenty male adult Wistar albino rats were randomly and equally divided into two groups. Group I (control group) received physiological saline intramuscular injection, once daily for 28 consecutive days, in a dose equivalent to that taken in group II. Group II (Gentamicin-treated group) were given Gentamicin intramuscular injection for induction of CKD. Gentamicin was given as Gentamycin sulfate, 40 mg/ml (Sandoz, Switzerland), once daily, in a dose of 80 mg/kg/day for 28 days to induce CKD. After 28 days of the first injection of gentamicin, rats were anaesthetized and blood samples were collected to measure the level of serum urea and creatinine. The left kidneys, the middle third of left gastrocnemius muscle, the lateral wall of left ventricle (LV) and the gastroesophageal junction of all rats of both groups (I and II) were processed for light microscopic study. The middle third of left gastrocnemius muscle, the lateral wall of left ventricle (LV) were further processed for transmission electron microscopic study. Histomorphometrical and statistical analysis were also done. Results The LM examination revealed moderate obliteration of glomeruli, dilatation in some renal tubules and collapse in others, mainly in distal convoluted tubules, with significant fibrosis of renal parenchyma. Serum urea and creatinine levels were increased significantly. The skeletal muscle fibers of the rats in group II (CKD) showed focal areas of myofibers degeneration with siginificant fibrosis. The cardiac muscle fibers of the rats in the group II (CKD) showed focal areas of cardiomyocytes degeneration and other areas of significantly hypertrophied fibers. The smooth muscle fibers of the lower esophageal sphincter of the rats in group II (CKD) showed no significant structural changes compared with the control group, however, the myenetric plexus showed multiple pyknotic and karyolitic nuclei with vacuolated cytoplasm. In addition, insignificant increase in the amount of collagen fibers was observed in almost all layers. Conclusion CKD produced moderate atrophy of skeletal muscle fibers, significant increase in the cardiomyocyte size and no significant structural effect of smooth muscle fibers of the lower esophageal sphincter.
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Hammond, Robert J. H., Kerry Falconer, Thomas Powell, Ruth Bowness, and Stephen H. Gillespie. "A simple label-free method reveals bacterial growth dynamics and antibiotic action in real-time." Scientific Reports 12, no. 1 (November 12, 2022). http://dx.doi.org/10.1038/s41598-022-22671-6.
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AbstractUnderstanding the response of bacteria to environmental stress is hampered by the relative insensitivity of methods to detect growth. This means studies of antibiotic resistance and other physiological methods often take 24 h or longer. We developed and tested a scattered light and detection system (SLIC) to address this challenge, establishing the limit of detection, and time to positive detection of the growth of small inocula. We compared the light-scattering of bacteria grown in varying high and low nutrient liquid medium and the growth dynamics of two closely related organisms. Scattering data was modelled using Gompertz and Broken Stick equations. Bacteria were also exposed meropenem, gentamicin and cefoxitin at a range of concentrations and light scattering of the liquid culture was captured in real-time. We established the limit of detection for SLIC to be between 10 and 100 cfu mL−1 in a volume of 1–2 mL. Quantitative measurement of the different nutrient effects on bacteria were obtained in less than four hours and it was possible to distinguish differences in the growth dynamics of Klebsiellapneumoniae 1705 possessing the BlaKPC betalactamase vs. strain 1706 very rapidly. There was a dose dependent difference in the speed of action of each antibiotic tested at supra-MIC concentrations. The lethal effect of gentamicin and lytic effect of meropenem, and slow bactericidal effect of cefoxitin were demonstrated in real time. Significantly, strains that were sensitive to antibiotics could be identified in seconds. This research demonstrates the critical importance of improving the sensitivity of bacterial detection. This results in more rapid assessment of susceptibility and the ability to capture a wealth of data on the growth dynamics of bacteria. The rapid rate at which killing occurs at supra-MIC concentrations, an important finding that needs to be incorporated into pharmacokinetic and pharmacodynamic models. Importantly, enhanced sensitivity of bacterial detection opens the possibility of susceptibility results being reportable clinically in a few minutes, as we have demonstrated.
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Meredith, Emily M., Lauren T. Harven, and Andrew D. Berti. "127. Antimicrobial Efficacy Against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance." Open Forum Infectious Diseases 9, Supplement_2 (December 1, 2022). http://dx.doi.org/10.1093/ofid/ofac492.205.
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Abstract Background Bacteria can adopt an alternate metabolic state favoring small molecule synthesis over growth. In Staphylococcus aureus this is induced by factors present during infection including nutritional limitation and competition with other bacteria. Isogenic “tolerant” subpopulations have variable responses to antibiotics and can remain viable. Survivors resume growth upon cessation of antibiotics and cause relapse or recurrent infection. In this study we compare the capability of antibiotics to reduce viability of S. aureus made tolerant by different mechanisms. Methods Overnight cultures of S. aureus SH1000 were diluted to 106 cfu/mL. Tolerance was induced with mupirocin or 2-n-heptyl-4-hydroxypuinoline N-oxide (HQNO) simulating nutritional or competitive tolerance, respectively. Tolerant cultures were exposed to ceftaroline, daptomycin, gentamicin, levofloxacin, oritavancin or vancomycin at physiological concentrations and viability assessed by dilution plating. Minimum duration for 3-log viability reduction (“bactericidal activity”, MDK99.9) and 24h viability reduction were calculated independently for each of three biological replicates. Significance (P < 0.05) was determined using Student’s t-test. Results Time to bactericidal activity was prolonged for all antibiotics tested against nutritionally-tolerant S. aureus. Time to bactericidal activity was similarly prolonged against competitively-tolerant S. aureus, although the MDK99.9 of oritavancin was not affected. Viability reduction was mitigated for all antibiotics tested against nutritionally-tolerant S. aureus with the exception of oritavancin. In contrast, 24h viability reduction of competitively-tolerant S. aureus only occurred with ceftaroline, gentamicin and vancomycin while daptomycin, levofloxacin and oritavancin remained equally potent. Conclusion Tolerance can alter both the time to bactericidal effect and the extent of killing. Both the antibiotic and the mechanism of tolerance impact time to bacterial effect and extent of killing. Oritavancin was the only antibiotic that maintained the same extent of killing regardless of tolerance mechanism. Further studies to evaluate additional antistaphylococcal antibiotics and different inducers of tolerance are warranted. Disclosures All Authors: No reported disclosures.
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Pereira, Wellison Amorim, Anna Carolina M. Piazentin, Rodrigo Cardoso de Oliveira, Carlos Miguel N. Mendonça, Yara Aiko Tabata, Maria Anita Mendes, Ricardo Ambrósio Fock, et al. "Bacteriocinogenic probiotic bacteria isolated from an aquatic environment inhibit the growth of food and fish pathogens." Scientific Reports 12, no. 1 (April 1, 2022). http://dx.doi.org/10.1038/s41598-022-09263-0.
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AbstractThe conditions of aquatic environments have a great influence on the microbiota of several animals, many of which are a potential source of microorganisms of biotechnological interest. In this study, bacterial strains isolated from aquatic environments were bioprospected to determine their probiotic profile and antimicrobial effect against fish and food pathogens. Two isolates, identified via 16S rRNA sequencing as Lactococcus lactis (L1 and L2) and one as Enterococcus faecium 135 (EF), produced a bacteriocin-like antimicrobial substance (BLIS), active against Listeria monocytogenes, Salmonella Choleraesuis and Salmonella Typhimurium. Antimicrobial activity of BLIS was reduced when exposed to high temperatures and proteolytic enzymes (trypsin, pepsin, papain and pancreatin). All strains were sensitive to 7 types of antibiotics (vancomycin, clindamycin, streptomycin, gentamicin, chloramphenicol, rifampicin and ampicillin), exhibited a high rate of adherence to Caco-2 cells and expressed no hemolysin and gelatinase virulence factors. EF showed some resistance at pH 2.5 and 3.0, and L2/EF showed higher resistance to the action of bile salts. Finally, the presence of bacteriocin genes encoding for proteins, including Nisin (L1 and L2), Enterocin A, B, P, and Mundticin KS (EF) was detected. The molecular and physiological evidence suggests that the bacterial isolates in this study could be used as natural antimicrobial agents and may be considered safe for probiotic application.
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Pietsch, Franziska, Gabriele Heidrich, Niclas Nordholt, and Frank Schreiber. "Prevalent Synergy and Antagonism Among Antibiotics and Biocides in Pseudomonas aeruginosa." Frontiers in Microbiology 11 (February 4, 2021). http://dx.doi.org/10.3389/fmicb.2020.615618.
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Antimicrobials can exert specific physiological effects when used in combination that are different from those when applied alone. While combination effects have been extensively mapped for antibiotic-antibiotic combinations, the combination effects of antibiotics with antimicrobials used as biocides or antiseptics have not been systematically investigated. Here, we investigated the effects of combinations of antibiotics (meropenem, gentamicin, and ciprofloxacin) and substances used as biocides or antiseptics [octenidine, benzalkonium chloride, cetrimonium bromide, chlorhexidine, Povidone-iodine, silver nitrate (AgNO3), and Ag-nanoparticles] on the planktonic growth rate of Pseudomonas aeruginosa. Combination effects were investigated in growth experiments in microtiter plates at different concentrations and the Bliss interaction scores were calculated. Among the 21 screened combinations, we find prevalent combination effects with synergy occurring six times and antagonism occurring 10 times. The effects are specific to the antibiotic-biocide combination with meropenem showing a tendency for antagonism with biocides (6 of 7), while gentamicin has a tendency for synergy (5 of 7). In conclusion, antibiotics and biocides or antiseptics exert physiological combination effects on the pathogen P. aeruginosa. These effects have consequences for the efficacy of both types of substances and potentially for the selection of antimicrobial resistant strains in clinical applications with combined exposure (e.g., wound care and coated biomaterials).
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Yang, Qing, Kayode Olaifa, Fartisincha P. Andrew, Peter A. Ajibade, Obinna M. Ajunwa, and Enrico Marsili. "Assessment of physiological and electrochemical effects of a repurposed zinc dithiocarbamate complex on Acinetobacter baumannii biofilms." Scientific Reports 12, no. 1 (July 9, 2022). http://dx.doi.org/10.1038/s41598-022-16047-z.
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AbstractAcinetobacter baumannii is an infectious agent of global proportion and concern, partly due to its proficiency in development of antibiotic resistance phenotypes and biofilm formation. Dithiocarbamates (DTC) have been identified as possible alternatives to the current antimicrobials. We report here the evaluation of several DTC-metal complexes against A. baumannii planktonic cells and biofilms. Among the DTC-metal complexes and DTCs tested, ZnL1 (N-methyl-1-phenyldithiocarbamato-S,S′ Zn(II)), originally designed as an antitumor agent, is effective against biofilm forming A. baumannii. A MIC value of 12.5 µM, comparable to that of Gentamicin (5 µM) was measured for planktonic cells in tryptic soy broth. Spectroscopy, microscopy and biochemical analyses reveal cell membrane degradation and leakage after treatment with ZnL1. Bioelectrochemical analyses show that ZnL1 reduces biofilm formation and decreases extracellular respiration of pre-formed biofilms, as corroborated by microscopic analyses. Due to the affinity of Zn to cells and the metal chelating nature of L1 ligand, we hypothesize ZnL1 could alter metalloprotein functions in the membranes of A. baumannii cells, leading to altered redox balance. Results indicate that the DTC-Zn metal complex is an effective antimicrobial agent against early A. baumannii biofilms under laboratory conditions.
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Abd-Elhakim, Yasmina M., Sabry M. Abdel-Motal, Seham M. Malhat, Hend I. Mostafa, Walied M. Ibrahim, Rasha R. Beheiry, Attia A. A. Moselhy, and Enas N. Said. "Curcumin attenuates gentamicin and sodium salicylate ototoxic effects by modulating the nuclear factor-kappaB and apoptotic pathways in rats." Environmental Science and Pollution Research, July 20, 2022. http://dx.doi.org/10.1007/s11356-022-21932-1.
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AbstractThis study aimed to investigate the effectiveness of curcumin (CCM) against gentamicin (GEN) and sodium salicylates (NaS)-induced ototoxic effects in rats. For 15 consecutive days, seven rat groups were given 1 mL/rat physiological saline orally, 1 mL/rat olive oil orally, 50 mg/kg bwt CCM orally, 120 mg/kg bwt GEN intraperitoneally, 300 mg/kg bwt NaS intraperitoneally, CCM+GEN, or CCM+NaS. The distortion product otoacoustic emission measurements were conducted. The rats’ hearing function and balance have been behaviorally assessed using auditory startle response, Preyer reflex, and beam balance scale tests. The serum lipid peroxidation and oxidative stress biomarkers have been measured. Immunohistochemical investigations of the apoptotic marker caspase-3 and the inflammatory indicator nuclear factor kappa (NF-κB) in cochlear tissues were conducted. GEN and NaS exposure resulted in deficit hearing and impaired ability to retain balance. GEN and NaS exposure significantly decreased the reduced glutathione level and catalase activity but increased malondialdehyde content. GEN and NaS exposure evoked pathological alterations in cochlear and vestibular tissues and increased caspase-3 and NF-κB immunoexpression. CCM significantly counteracted the GEN and NaS injurious effects. These outcomes concluded that CCM could be a naturally efficient therapeutic agent against GEN and NaS-associated ototoxic side effects. Graphical abstract
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Achberger, Kevin, Christopher Probst, Jasmin Haderspeck, Sylvia Bolz, Julia Rogal, Johanna Chuchuy, Marina Nikolova, et al. "Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform." eLife 8 (August 27, 2019). http://dx.doi.org/10.7554/elife.46188.
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The devastating effects and incurable nature of hereditary and sporadic retinal diseases such as Stargardt disease, age-related macular degeneration or retinitis pigmentosa urgently require the development of new therapeutic strategies. Additionally, a high prevalence of retinal toxicities is becoming more and more an issue of novel targeted therapeutic agents. Ophthalmologic drug development, to date, largely relies on animal models, which often do not provide results that are translatable to human patients. Hence, the establishment of sophisticated human tissue-based in vitro models is of upmost importance. The discovery of self-forming retinal organoids (ROs) derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) is a promising approach to model the complex stratified retinal tissue. Yet, ROs lack vascularization and cannot recapitulate the important physiological interactions of matured photoreceptors and the retinal pigment epithelium (RPE). In this study, we present the retina-on-a-chip (RoC), a novel microphysiological model of the human retina integrating more than seven different essential retinal cell types derived from hiPSCs. It provides vasculature-like perfusion and enables, for the first time, the recapitulation of the interaction of mature photoreceptor segments with RPE in vitro. We show that this interaction enhances the formation of outer segment-like structures and the establishment of in vivo-like physiological processes such as outer segment phagocytosis and calcium dynamics. In addition, we demonstrate the applicability of the RoC for drug testing, by reproducing the retinopathic side-effects of the anti-malaria drug chloroquine and the antibiotic gentamicin. The developed hiPSC-based RoC has the potential to promote drug development and provide new insights into the underlying pathology of retinal diseases.
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Soylu, H. Melis, Pascale Chevallier, Francesco Copes, Federica Ponti, Gabriele Candiani, Fatma Yurt, and Diego Mantovani. "A Novel Strategy to Coat Dopamine-Functionalized Titanium Surfaces With Agarose-Based Hydrogels for the Controlled Release of Gentamicin." Frontiers in Cellular and Infection Microbiology 11 (June 10, 2021). http://dx.doi.org/10.3389/fcimb.2021.678081.
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IntroductionThe use of spinal implants for the treatment of back disorders is largely affected by the insurgence of infections at the implantation site. Antibacterial coatings have been proposed as a viable solution to limit such infections. However, despite being effective at short-term, conventional coatings lack the ability to prevent infections at medium and long-term. Hydrogel-based drug delivery systems may represent a solution controlling the release of the loaded antibacterial agents while improving cell integration. Agarose, in particular, is a biocompatible natural polysaccharide known to improve cell growth and already used in drug delivery system formulations. In this study, an agarose hydrogel-based coating has been developed for the controlled release of gentamicin (GS).MethodsSand blasted Ti6Al4V discs were grafted with dopamine (DOPA) solution. After, GS loaded agarose hydrogels have been produced and additioned with tannic acid (TA) and calcium chloride (CaCl2) as crosslinkers. The different GS-loaded hydrogel formulations were deposited on Ti6Al4V-DOPA surfaces, and allowed to react under UV irradiation. Surface topography, wettability and composition have been analyzed with profilometry, static contact angle measurement, XPS and FTIR spectroscopy analyses. GS release was performed under pseudo-physiological conditions up to 28 days and the released GS was quantified using a specific ELISA test. The cytotoxicity of the produced coatings against human cells have been tested, along with their antibacterial activity against S. aureus bacteria.ResultsA homogeneous coating was obtained with all the hydrogel formulations. Moreover, the coatings presented a hydrophilic behavior and micro-scale surface roughness. The addition of TA in the hydrogel formulations showed an increase in the release time compared to the normal GS-agarose hydrogels. Moreover, the GS released from these gels was able to significantly inhibit S. aureus growth compared to the GS-agarose hydrogels. The addition of CaCl2 to the gel formulation was able to significantly decrease cytotoxicity of the TA-modified hydrogels.ConclusionsDue to their surface properties, low cytotoxicity and high antibacterial effects, the hereby proposed gentamicin-loaded agarose-hydrogels provide new insight, and represent a promising approach for the surface modification of spinal implants, greatly impacting their application in the orthopedic surgical scenario.