Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using smal...Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using small-molecule drugs to enhance siRNA endo-lysosomal release,addressing this challenge.We encapsulated gentamicin(GM)into the marketed Onpattro■ formulation to establish LNP-siRNA/GM nanoparticles that promote siRNA endo-lysosomal escape through endosomal disruption,mechanistically exhibiting unique functionality and synergistic effects of LNP-siRNA/GM to improve cancer therapy.Besides,GM induced reactive oxygen species(ROS)and phospholipids accumulation in endolysosomes,as well as the physical characteristics of lipid nanoparticles(LNPs)were preserved.We also revealed that GM causes endo-lysosomal swelling and disrupts the endosomal membrane to enable siRNA release,as confirmed by Galectin 3 recruitment and acridine orange release.This approach achieved∼81%mRNA-EGFR silencing,which is more than LNP-siEGFR(∼56.23%)by enhancing siRNA endo-lysosomal escape efficiency.Meanwhile,LNP-siEGFR/GM exhibited significant biological activities in HepG2 cells,driven by the synergistic effects of siEGFR and GM with the VEGF and CXCL12 downregulation of,and ROS and phospholipids upregulation.Furthermore,tumor growth was notably suppressed after intravenous injection of LNP-siEGFR/GM in tumor-bearing nude mice.The combination of EGFR-siRNA and GM could also greatly inhibit angiogenesis,be antiproliferative,and induce tumor cells apoptosis.Therefore,this GM and siRNA co-delivery system would provide an efficient strategy for siRNA endosomal escape,significantly improving knockdown in various LNPs based siRNA delivery systems and efficiently enhancing cancer therapy.展开更多
Aim Intracellular calcium ([Ca^(2+) ]_i) is mainly regulated by mitochondriaand endo-plasmic reticula. This study was carried out to ascertain whether the elementary mechanismof the effects of etimicin (EM) and gentam...Aim Intracellular calcium ([Ca^(2+) ]_i) is mainly regulated by mitochondriaand endo-plasmic reticula. This study was carried out to ascertain whether the elementary mechanismof the effects of etimicin (EM) and gentamicin (GM) on [Ca^(2+) ]_i is related to their effects onmitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake. Methods The effects of GMand EM on [Ca^(2+) ]_i in LLC-PK1 were determined with a fluorescent probe of Fura-2/AM. The effectsof EM and GM on mitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake weredetermined by isotope indicator (^(45)Ca^(2+) ) . Results EM and GM at the concentration of 1mmol·L^(-1) had no significant effect on [Ca^(2+) ]_i(P. > 0.05) and at 10 mmol·L^(-1)significantly caused [Ca^(2+) ]_i to increase (P < 0.01). EM and GM at 1 mmol·L^(-1) causedmitochondrion Ca^(2+)-uptake to ascend dramatically (P < 0.05) and at 10 mmol·L^(-1) causedmitochondrion Ca^(2+) -uptake to descend significantly. EM and GM at more than 0.34 mrnol·L^(-1)significantly inhibited endoplasmic reticulum Ca^(2+) -uptake (P < 0.05 or 0.01). Conclusion Novariation of [Ca^(2+) ]_i caused by EM and GM at lower concentrations might relate to theequilibrium of their promotion of mitochondrion Ca^(2+) -uptake with their inhibition of endoplasmicreticulum Ca^(2+) -uptake. The elevation of [Ca^(2+) ]_i caused by EM and GM at higherconcentrations might correlate with their inhibition of mitochondrion Ca^(2+) -uptake andendoplasmic reticulum Ca^(2+) -uptake.展开更多
Objective: To study the effects of etimicin (EM) and gentamicin (GM) on renal endoplasmic reticulum 45 Ca 2+ uptake and Ca 2+ Mg 2+ ATPase activity. Methods: Using 45 Ca 2+ inc...Objective: To study the effects of etimicin (EM) and gentamicin (GM) on renal endoplasmic reticulum 45 Ca 2+ uptake and Ca 2+ Mg 2+ ATPase activity. Methods: Using 45 Ca 2+ incorporation technique and peacock blue spectrophotometry respectively. Results: EM and GM (≥3.4×10 4 mol·L 1 ) inhibited endoplasmic reticulum 45 Ca 2+ uptake (the rate of inhibition: ≥17.4% and ≥25.5%, respectively); EM and GM (3.4×10 2 mol·L 1 ) inhibited Ca 2+ Mg 2+ ATPase activity (the rate of inhibition: 24.2% and 29.2%, respectively). Conclusion: At high concentration, EM and GM elevated intracellular calcium which may be related to their nephrotoxicity.展开更多
BACKGROUND： Ligustrazine （tetramethylpyrazine） decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE： To explore t...BACKGROUND： Ligustrazine （tetramethylpyrazine） decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE： To explore the protective effects of ligustrazine on gentamicin ototoxicity by determining heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis of guinea pigs at different time points.DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Laboratory of Physiology, Shenyang Medical College of China in 2007.MATERIALS： Ligustrazine parenteral solution （Qiqihar Pharmaceutical Factory, China） and gentamicin sulfate （Shenyang First Pharmaceutical Factory, China） were used in this experiment.METHODS： White guinea pigs with red eyes were randomly intraperitoneally administered gentamicin sulfate injection ＋ saline, gentamicin sulfate injection ＋ ligustrazine, and ligustrazine ＋ saline, respectively.MAIN OUTCOME MEASURES： Auditory brains tern response threshold was measured. Immunohistochemistry, in situ hybridization, and image analyzing techniques were utilized to determine heat shock protein 70 mRNA and protein expression in cochlear stria vascularis of guinea pigs.RESULTS： Following gentamicin ototoxicity, the auditory brainstem response threshold increased, peaked on day 3, and then decreased with increased time after drug withdrawal. The auditory brainstem response threshold was significantly diminished following ligustrazine intervention, but recovered to normal on day 30 （P〉0.05）. Heat shock protein 70 expression also increased, peaked on day 3, and then decreased in the cochlear stria vascularis of guinea pigs following gentamicin ototoxicity. Ligustrazine intervention resulted in decreased heat shock protein 70 expression in the cochlear stria vascularis, which recovered to normal on day 14. Heat shock protein 70 mRNA expression increased in the cochlear stria vascularis following gentamicin ototoxicity, but ligustrazine intervention resulted in decreased levels. CONCLUSION： Ligustrazine significantly ameliorated gentamicin ototoxicity by reducing heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis.展开更多
To gain insights into the ototoxic effects of aminoglycoside antibiotics(AmAn) and delayed peripheral ganglion neuron death in the inner ear.experimental animal models were widely used with several different approache...To gain insights into the ototoxic effects of aminoglycoside antibiotics(AmAn) and delayed peripheral ganglion neuron death in the inner ear.experimental animal models were widely used with several different approaches including AmAn systemic injections,combination treatment of AmAn and diuretics,or local application of AmAn.In these approaches,systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear.Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells,but it is impossible to damage the vestibular system.Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear.Therefore,AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death.In current studies,guinea pigs were unilaterally treated with a high concentration of gentamicin(GM,40 nig/ml) through the tympanic membrane into the middle ear cavity.Auditory functions and vestibular functions were measured before and after GM treatment.The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment.The results showed that both auditory and vestibular functions were completely abolished after GM treatment.The sensory hair cells were totally missing in the cochlea,and severely destroyed in vestibular end-organs.The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%.However,no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment.These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration.This model might be useful for studies of hair cell regenerations,delayed degeneration of peripheral auditory neurons,and/or vestibular compensation.In addition,a potential problem of ABR recording for unilateral deafness and issues about vestibular compensation are also discussed.展开更多
This study was designed to investigate persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis. Milk samples were collected at a 1-d interval after the last administr...This study was designed to investigate persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis. Milk samples were collected at a 1-d interval after the last administration from 34 individual cows that had received intramammary infusions of gentamicin. The doses and treatment times evaluated in this study represented those that have been applied by veterinarians in practice. The tetrazolium chloride assay was used to determine whether there were significant residues of the antibiotic in the samples. Persistence of detectable drug residues in milk from 33 cows (28 cows, ≤6 infusions at ≤0.7 g gentamicin; and 5 cows, 2 infusions at 0.8 g gentamicin) did not exceed 5 d; but 1 cow (5 infusions at 0.8 g gentamicin) had detectable residues in its milk for 9 d. Our results suggest that a 5-d milk withdrawal period might be insufficient to secure the clearance of the contamination of gentamicin, because treatment times and dosages contribute to the antibiotic clearance. A larger scale of samples are needed for further investigations.展开更多
In order to clarify whether gentamicin （GM） could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg...In order to clarify whether gentamicin （GM） could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg·kg<sup>-10</sup>·d<sup>-1</sup> GM for 3 consecutive days.The animals ofthe control group received equal amount of normal saline.It was found that some myelin figuresappeared in the epithelial cells of the proximal tubules as early as 1 h after a single GM injec-tion;severe swelling,degeneration,and obvious changes of the organelles were seen in the en-dothelial cells of the glomerular capillaries,the podocytes and the epithelial cells of the proxi-mal tubules 24 h after an injection of GM;and fusion of the processes of podocytes,thickeningof the glomerular membrane and necrosis of the epithelial cells of a part of the’proximal tubuleswere encountered 24h after the 3rd GM injection.These findings demonstrate that GM can in-jure not only the proximal tubules but also the glomeruli in rabbits.展开更多
Implant-associate infection(IAI)is a major cause of failure of bone implant materials,and one of the significant challenges in clinical managements.A synergistic coating strategy combining montmorillonite(MMT)sustaine...Implant-associate infection(IAI)is a major cause of failure of bone implant materials,and one of the significant challenges in clinical managements.A synergistic coating strategy combining montmorillonite(MMT)sustained release,adsorption of bacteria and gentamicin(GS)bactericidal is proposed herein to tackle infection issues.Surface morphology,microstructure and chemical composition of the samples were investigated using SEM,XRD,FT-IR and XPS.Electrochemical experiments and immersion experiments reveal that corrosion resistance of Mg samples with GS/MMT coatings was higher than that of bare Mg alloy substrate in DMEM solution.In vitro studies demonstrated that the GS/MMT coating had a significant inhibitory effect on Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).The viability of MC3T3-E1 cells was 92.7%after a co-culturing for 72 h.After a subcutaneous transplantation of 90days,the survival rate was 100%for GS/MMT-coated Mg alloy specimens with no infection at the implantation sites and no toxic damage to liver,kidney and local muscles pathological sections.This study provides a novel method for the preparation of sustained-release antimicrobial coatings on biodegradable Mg alloys as promising candidates for orthopedic implant materials.展开更多
The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC.subsp.plicatum ethanol extract（HPE）against gentamicin-induced nephrotoxicity.Thirty-six Sprague Dawley ...The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC.subsp.plicatum ethanol extract（HPE）against gentamicin-induced nephrotoxicity.Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material.They were formed into six groups containing 6rats each and were allowed to adapt to laboratory conditions for 7 d.Group Ⅰ：control,5%DMSO intraperitoneal（i.p.）;Group Ⅱ：HPE 100 mg/（kg·d）i.p.;Group Ⅲ：HPE 200 mg/（kg·d）i.p.;Group Ⅳ：gentamicin as 80 mg/（kg·d）i.p.;Group Ⅴ：gentamicin as 80 mg/（kg·d）i.p.＋HPE 100 mg/（kg·d）i.p.;and Group Ⅵ：gentamicin as 80 mg/（kg·d）i.p.＋HPE 200 mg/（kg·d）i.p.for 8 d.Following treatment,serum,liver,and kidney tissues were used to assess blood urea nitrogen（BUN）,creatinine,enzymatic and non-enzymatic antioxidants,and lipid peroxidation.Gentamicin significantly increased serum BUN,creatinin,and liver and kidney levels of malondialdehyde（MDA）.It also decreased the activity of catalase（CAT）,glutathione peroxidase（GPx）,and superoxide dismutase（SOD）.Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin,liver and kidney oxidant marker,and tubular necrosis as well as by an increase in antioxidant enzymes.It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats.As a result,these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.展开更多
Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were d...Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were divided into four groups(n=6).Control rats that received normal saline(i.p.) and 0.5%carboxymethyl cellulose(p.o.) per day lor 8 d.Nephrotoxicity was induced in rats by intraperitoneal administration of GM(100 mg/kg/d for 8 d) and were treated with SXE(200 and 400 mg/kg/d(p.o.) for 8 d).Plasma and urine urea and creatinine,kidney weight,urine output,blood urea nitrogen,renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.Results:It was observed that the GM treatment induced significant elevation(P【0.001) in plasma and urine urea,creatinine,kidney weight,blood urea nitrogen, renal lipid peroxidation along with significant decrement(P【0.001) in urine output,renal enzymatic and non-enzymatic antioxidants.SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement(up to P【0.001) in plasma and mine urea and creatinine, renal lipid peroxidation along with significanl increment(up to P【0.001) in renal enzymatic and non-enzvmatic antioxidants.Histological obsenatioiis of kidney tissues too correlated with the biochemical obsenatioiis.Conclusions:These finding powerfully supports that S,xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its elhnomedicinal use.展开更多
Objective:To formulate gentamicin liposphere by solvent-melting method using lipids and polyethylene glycol 4000(PEG-4000) for oral administration.Methods:Gentamicin lipospheres were prepared by melt-emulsification us...Objective:To formulate gentamicin liposphere by solvent-melting method using lipids and polyethylene glycol 4000(PEG-4000) for oral administration.Methods:Gentamicin lipospheres were prepared by melt-emulsification using 30%w/w Phospholipon(?) 90H in Beeswax as the lipid matrix containing PEC-4000.These lipospheres were characterized by evaluating on encapsulation efficiency,loading capacity,change in pH and the release profile. Antimicrobial activities were evaluated against Escherichia coli,Pseudomonas aeruginosa. Salmonella paratyphii and Staphylococcus aureus using the agar diffusion method.Results: Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month.The release of gentamicin in vitro varied widely with the PEC-4000 contents. Moreover,significant(P>0.05) amount of gentamicin was released in vivo from the formulation. The encapsulation and loading capacity were all high,indicating the ability of the lipids to take up the drug.The antimicrobial activities were very high especially against Pseudomonas compare to other test organisms.This strongly suggested that the formulation retain its bioactive characteristics.Conclusions:This study strongly suggest that the issue of gentamicin stability and poor absorption in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.展开更多
A systematic approach was developed to investigate the stability of gentamicin sulfate(GS) and GS/poly(lacticco-glycolic acid)(PLGA) coatings on hydroxyapatite surfaces.The influence of environmental factors(light,hum...A systematic approach was developed to investigate the stability of gentamicin sulfate(GS) and GS/poly(lacticco-glycolic acid)(PLGA) coatings on hydroxyapatite surfaces.The influence of environmental factors(light,humidity,oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry.GS coated rods were found to be stable across the range of environments assessed,with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition.In contrast,rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C,75% relative humidity or exposure to light.The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect.Finally,liquid chromatography–mass spectrometry analysis revealed that known gentamines C_1,C_1 aand C_2were the major degradants formed.Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.展开更多
Objective To study gentamicin injury mechanisms using postnatal mouse cochlear spiral gangcells （SGC）. Methods SGCs were isolated using a combinatorial approach of enzymatic digestion and mechanical separation from ...Objective To study gentamicin injury mechanisms using postnatal mouse cochlear spiral gangcells （SGC）. Methods SGCs were isolated using a combinatorial approach of enzymatic digestion and mechanical separation from P2 - 6 Kunming mouse cochleae. After 4 days, cultured SGCs were fixed with 4% paraformaldehyde at room temperature for immunocytochemical examination using the methods of S-P and the monoclonal antibody against mouse neurofilament protein （Neurofilament-68/200Kda, NF-L＋ H）. SGCs were randomly divided into a blank control group and three gentamicin treatment groups （medium gentamicin concentration at 50 mg/L, 100 mg/L and 150 mg/L respectively）, SGCs were collected and examined under a transmission electron microscope after being cultured for 48 h. Results SGC primary culture was successful. SGC cytoplasm and neurites were dyed brownish yellow by the monoelonal mouse neurofilament protein antibody. SGCs showed classical bipolar neuron appearance. Under the transmission electron microscope,.gentamicin treated SGCs showed morphological features different compared to those in the blank control group, which might indicate apoptosis. Conclusion Our results indicate that gentamicin has direct toxic effects on cochlear SGCs in mice and the injury mechanism is closely related with apoptosis. Damage to mitochor, dria may play an important role in the process.展开更多
A lock solution composed of gentamicin sulfate(5 mg/mL) and ethylenediaminetetraacetic acid disodium salt(EDTA-Na2, 30 mg/mL) could fully eradicate in vivo bacterial biofilms in totally implantable venous access ports...A lock solution composed of gentamicin sulfate(5 mg/mL) and ethylenediaminetetraacetic acid disodium salt(EDTA-Na2, 30 mg/mL) could fully eradicate in vivo bacterial biofilms in totally implantable venous access ports(TIVAP). In this study, fabrication, conditioning and sterilization processes of antimicrobial lock solution(ALS) were detailed and completed by a stability study. Stability of ALS was conducted for12 months in vial(25 °C 7 2 °C, 60% 7 5% relative humidity(RH), and at 40 °C 7 2 °C, RH 75% 7 5%)and for 24 h and 72 h in TIVAP(40 °C 7 2 °C, RH 75% 7 5%). A stability indicating HPLC assay with UV detection for simultaneous quantification of gentamicin sulfate and EDTA-Na2 was developed. ALS was assayed by ion-pairing high performance liquid chromatography(HPLC) needing gentamicin derivatization, EDTA-Na2 metallocomplexation of samples and gradient mobile phase. HPLC methods to separate four gentamicin components and EDTA-Na2 were validated. Efficiency of sterility procedure and conditioning of ALS was confirmed by bacterial endotoxins and sterility tests. Physicochemical stability of ALS was determined by visual inspection, osmolality, pH, and sub-visible particle counting. Results confirmed that the stability of ALS in vials was maintained for 12 months and 24 h and 72 h in TIVAP.展开更多
Objective:To evaluate the effect of Heracleum persicum L.against gentamicin-induced nephrotoxicity in rats.Methods:Thirty-six Wistar rats were divided into 6 groups including control(normal saline),gentamicin(80 mg/kg...Objective:To evaluate the effect of Heracleum persicum L.against gentamicin-induced nephrotoxicity in rats.Methods:Thirty-six Wistar rats were divided into 6 groups including control(normal saline),gentamicin(80 mg/kg/d for 10 d),Heracleum persicum(750 mg/kg/d),and gentamicin(10 d)+Heracleum persicum extract at three different doses(250,500,and 750 mg/kg/d for 40 d).Urine creatinine,urea,protein,and albumin levels were determined.In addition,serum urea,creatinine,sodium,potassium,cytokines(TNF-α,IL-1β,IL-6,and IL-10),glutathione peroxidase activity,total antioxidant capacity,kidney malondialdehyde,stereological parameters,and expressions of apoptosis-related genes(p53,Bax,Bcl-2,and caspase-3)were measured.The LD50 of Heracleum persicum extract was determined based on Lorke’s method.Histopathological evaluation was also performed.Results:In addition to decreased urine protein and albumin,and increased creatinine and urea,co-treatment with gentamicin and Heracleum persicum significantly reduced levels of creatinine and urea,and increased sodium and potassium in serum.Heracleum persicum treatment also improved stereological parameters and serum inflammatory cytokines.There was a significant increase in serum glutathione peroxidase activity and total antioxidant capacity as well as a reduction in malondialdehyde level.Furthermore,treatment with Heracleum persicum extracts downregulated p53,caspase-3,and Bax and upregulated Bcl-2 expressions.In histopathological evaluation,Heracleum persicum extracts showed protection against gentamicin-induced renal damages.Conclusions:Heracleum persicum exhibits protective effects against gentamicin-induced structural and functional renal impairments.展开更多
BACKGROUND Multidrug-resistant Acinetobacter baumannii(MDRAB) has emerged as an increasingly important pathogen that causes nosocomial meningitis. However,MDRAB-associated nosocomial meningitis is rarely reported in c...BACKGROUND Multidrug-resistant Acinetobacter baumannii(MDRAB) has emerged as an increasingly important pathogen that causes nosocomial meningitis. However,MDRAB-associated nosocomial meningitis is rarely reported in children.CASE SUMMARY We report the case of a 1-year-old girl with a choroid plexus papilloma, who developed postoperative nosocomial meningitis due to MDRAB. The bacterial strain was sensitive only to tigecycline and colistin, and showed varying degrees of resistance to penicillin, amikacin, ceftriaxone, cefixime, cefotaxime,ciprofloxacin, levofloxacin, gentamicin, meropenem, imipenem, and tobramycin.She was cured with intravenous doxycycline and intraventricular gentamicin treatment.CONCLUSION Doxycycline and gentamicin were shown to be effective and safe in the treatment of a pediatric case of MDRAB meningitis.展开更多
Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin...Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups:(G1) control group,(G2) gentamicin treated group(100 mg/kg),(G3) nettle treated group(100 mg/kg),(G4) combination treated group with both gentamicin(100 mg/kg) and nettle(100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using dif erent antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased signii cantly in gentamicin treated group; other groups have no signii cant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great ef ect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No signii cant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective ef ect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.展开更多
Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute...Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute toxicity study,single oral dose of 5（KM） mg ethyl acetate floral extract/kg hodv weight was administered to albino rats（five females,five males）.Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin 80 mg/kg/day for eight days.Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100.200 and 300 mg/kg/day given by oral mute was determined using serum creatinine,serum uric acid,blood urea nitrogen and serum urea as indicators of kidney damage.The study groups contained six rats in each group.As nephrotoxicity of gentamicin is known to involve induction of oxidative stress,in vitro antioxidant aclivity and free radical-scavenging activity of this extract was also evaluated.Results:For acute toxicity testing both female and male rats administered with the extract at a dose of 5 000 mg/kg.The results showed no toxicity in terms of general behavior change,mortality,or change in gross appearance of internal organs(LD<sub>50</sub>】5 000 mg/kg). It was observed that the ethyl acetate floral extract of Tecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes.Gentamicin-induced glomerular congestion,peritubular and blood vessel congestion,epithelial desquamation,accumulation ol inflamnialoiy cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract of Tecoma starts along with gentamicin in a dose dependent manner.The floral extract also reduced the gentamicin-induced increase in serum creatinine,serum uric acid,blood urea nitrogen and serum urea levels（P】0.01）.Conclusions: The present study indicates a verv important role of reactive oxygen species（BOS） and the relation to renal dysfunction and point to the therapeutic potential of Tecoma stans in gentamicin induced nephrotoxicity.展开更多
BACKGROUND： It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary...BACKGROUND： It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary auditory center. OBJECTIVE： To explore morphological changes of choline acetyltransferase （ChAT）-positive neurons in the paraolivary nucleus （PON） of guinea pigs, and the effect on hearing following gentamicin injection. DESIGN, TIME AND SETTING： Randomized grouping and morphological observational study was performed at Animal Experimental Center of General Hospital of Shenyang Military Area Command of Chinese PLA from January to August 2007. MATERIALS： A total of 48 healthy guinea pigs were randomly divided into model （n = 40） and control （n = 8） groups. The model group was divided into five subgroups at five time points of 1 and 3 days, 1, 2, and 3 weeks. METHODS： Guinea pigs in the model group were intraperitoneally injected with gentamicin, and those in the control group were intraperitoneally injected with the same volume of saline. MAIN OUTCOME MEASURES： Auditory brainstem-evoked potential was used to record auditory threshold; distribution and morphological changes of ChAT-positive neurons in the PON were observed with immunohistochemistry; section area and gray value of ChAT-positive neurons were measured with Quantimet 570 image-analyzing system. RESULTS： ChAT-positive neurons were diffusedly distributed in the PON. The majority was composed of large, round cells, with positive neurites that could be clearly observed. Following gentamicin injection, the positive neurons displayed an irregular outline, and their neurites began to shorten and disappear. The gray value increased with prolonged gentamicin administration （P 〈 0.05）. In addition, the somatic cross-sectional area was enlarged in the model group at 1 and 3 days after injection （P 〈 0.05）, whereas cell number significantly decreased at ;three weeks after injection （P 〈 0.05）. Starting at 3-4 days, behavioral features and auditory degrees became gradually aggravated with prolonged gentamicin administration （P 〈 0.05）. CONCLUSION： Gentamicin damaged ChAT-positive neurons in the PON, and long-term gentamicin treatment aggravated hearing impairment.展开更多
基金supported by National Natural Science Foundation of China(81502688)Cooperation Research Funding of Capital Medical University(2020KJ000514)+1 种基金Cooperation Research Funding of Capital Medical University(2023KJ000814)R&D Program of Beijing Municipal Education Commission(KM202210025024).
文摘Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using small-molecule drugs to enhance siRNA endo-lysosomal release,addressing this challenge.We encapsulated gentamicin(GM)into the marketed Onpattro■ formulation to establish LNP-siRNA/GM nanoparticles that promote siRNA endo-lysosomal escape through endosomal disruption,mechanistically exhibiting unique functionality and synergistic effects of LNP-siRNA/GM to improve cancer therapy.Besides,GM induced reactive oxygen species(ROS)and phospholipids accumulation in endolysosomes,as well as the physical characteristics of lipid nanoparticles(LNPs)were preserved.We also revealed that GM causes endo-lysosomal swelling and disrupts the endosomal membrane to enable siRNA release,as confirmed by Galectin 3 recruitment and acridine orange release.This approach achieved∼81%mRNA-EGFR silencing,which is more than LNP-siEGFR(∼56.23%)by enhancing siRNA endo-lysosomal escape efficiency.Meanwhile,LNP-siEGFR/GM exhibited significant biological activities in HepG2 cells,driven by the synergistic effects of siEGFR and GM with the VEGF and CXCL12 downregulation of,and ROS and phospholipids upregulation.Furthermore,tumor growth was notably suppressed after intravenous injection of LNP-siEGFR/GM in tumor-bearing nude mice.The combination of EGFR-siRNA and GM could also greatly inhibit angiogenesis,be antiproliferative,and induce tumor cells apoptosis.Therefore,this GM and siRNA co-delivery system would provide an efficient strategy for siRNA endosomal escape,significantly improving knockdown in various LNPs based siRNA delivery systems and efficiently enhancing cancer therapy.
文摘Aim Intracellular calcium ([Ca^(2+) ]_i) is mainly regulated by mitochondriaand endo-plasmic reticula. This study was carried out to ascertain whether the elementary mechanismof the effects of etimicin (EM) and gentamicin (GM) on [Ca^(2+) ]_i is related to their effects onmitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake. Methods The effects of GMand EM on [Ca^(2+) ]_i in LLC-PK1 were determined with a fluorescent probe of Fura-2/AM. The effectsof EM and GM on mitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake weredetermined by isotope indicator (^(45)Ca^(2+) ) . Results EM and GM at the concentration of 1mmol·L^(-1) had no significant effect on [Ca^(2+) ]_i(P. > 0.05) and at 10 mmol·L^(-1)significantly caused [Ca^(2+) ]_i to increase (P < 0.01). EM and GM at 1 mmol·L^(-1) causedmitochondrion Ca^(2+)-uptake to ascend dramatically (P < 0.05) and at 10 mmol·L^(-1) causedmitochondrion Ca^(2+) -uptake to descend significantly. EM and GM at more than 0.34 mrnol·L^(-1)significantly inhibited endoplasmic reticulum Ca^(2+) -uptake (P < 0.05 or 0.01). Conclusion Novariation of [Ca^(2+) ]_i caused by EM and GM at lower concentrations might relate to theequilibrium of their promotion of mitochondrion Ca^(2+) -uptake with their inhibition of endoplasmicreticulum Ca^(2+) -uptake. The elevation of [Ca^(2+) ]_i caused by EM and GM at higherconcentrations might correlate with their inhibition of mitochondrion Ca^(2+) -uptake andendoplasmic reticulum Ca^(2+) -uptake.
文摘Objective: To study the effects of etimicin (EM) and gentamicin (GM) on renal endoplasmic reticulum 45 Ca 2+ uptake and Ca 2+ Mg 2+ ATPase activity. Methods: Using 45 Ca 2+ incorporation technique and peacock blue spectrophotometry respectively. Results: EM and GM (≥3.4×10 4 mol·L 1 ) inhibited endoplasmic reticulum 45 Ca 2+ uptake (the rate of inhibition: ≥17.4% and ≥25.5%, respectively); EM and GM (3.4×10 2 mol·L 1 ) inhibited Ca 2+ Mg 2+ ATPase activity (the rate of inhibition: 24.2% and 29.2%, respectively). Conclusion: At high concentration, EM and GM elevated intracellular calcium which may be related to their nephrotoxicity.
基金the National Natural Science Foundation of China,No. 30672739the Scientific Research Program of Education Department of Liaoning Province,No. 2008722the Science and Technology Foundation of Liaoning Province,No. 20031032
文摘BACKGROUND： Ligustrazine （tetramethylpyrazine） decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE： To explore the protective effects of ligustrazine on gentamicin ototoxicity by determining heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis of guinea pigs at different time points.DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Laboratory of Physiology, Shenyang Medical College of China in 2007.MATERIALS： Ligustrazine parenteral solution （Qiqihar Pharmaceutical Factory, China） and gentamicin sulfate （Shenyang First Pharmaceutical Factory, China） were used in this experiment.METHODS： White guinea pigs with red eyes were randomly intraperitoneally administered gentamicin sulfate injection ＋ saline, gentamicin sulfate injection ＋ ligustrazine, and ligustrazine ＋ saline, respectively.MAIN OUTCOME MEASURES： Auditory brains tern response threshold was measured. Immunohistochemistry, in situ hybridization, and image analyzing techniques were utilized to determine heat shock protein 70 mRNA and protein expression in cochlear stria vascularis of guinea pigs.RESULTS： Following gentamicin ototoxicity, the auditory brainstem response threshold increased, peaked on day 3, and then decreased with increased time after drug withdrawal. The auditory brainstem response threshold was significantly diminished following ligustrazine intervention, but recovered to normal on day 30 （P〉0.05）. Heat shock protein 70 expression also increased, peaked on day 3, and then decreased in the cochlear stria vascularis of guinea pigs following gentamicin ototoxicity. Ligustrazine intervention resulted in decreased heat shock protein 70 expression in the cochlear stria vascularis, which recovered to normal on day 14. Heat shock protein 70 mRNA expression increased in the cochlear stria vascularis following gentamicin ototoxicity, but ligustrazine intervention resulted in decreased levels. CONCLUSION： Ligustrazine significantly ameliorated gentamicin ototoxicity by reducing heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis.
基金supported by the National Nature Science Foundation of China(No.81170912)the Major State Basic Research Development Program of China(973 Program,No.2014CB943003)
文摘To gain insights into the ototoxic effects of aminoglycoside antibiotics(AmAn) and delayed peripheral ganglion neuron death in the inner ear.experimental animal models were widely used with several different approaches including AmAn systemic injections,combination treatment of AmAn and diuretics,or local application of AmAn.In these approaches,systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear.Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells,but it is impossible to damage the vestibular system.Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear.Therefore,AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death.In current studies,guinea pigs were unilaterally treated with a high concentration of gentamicin(GM,40 nig/ml) through the tympanic membrane into the middle ear cavity.Auditory functions and vestibular functions were measured before and after GM treatment.The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment.The results showed that both auditory and vestibular functions were completely abolished after GM treatment.The sensory hair cells were totally missing in the cochlea,and severely destroyed in vestibular end-organs.The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%.However,no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment.These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration.This model might be useful for studies of hair cell regenerations,delayed degeneration of peripheral auditory neurons,and/or vestibular compensation.In addition,a potential problem of ABR recording for unilateral deafness and issues about vestibular compensation are also discussed.
基金supported by the Science and Technology Department of Zhejiang Province (Nos. 2005C12015 and 2007C32025)the Education Department of Zhejiang Province (No. 20061319), China
文摘This study was designed to investigate persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis. Milk samples were collected at a 1-d interval after the last administration from 34 individual cows that had received intramammary infusions of gentamicin. The doses and treatment times evaluated in this study represented those that have been applied by veterinarians in practice. The tetrazolium chloride assay was used to determine whether there were significant residues of the antibiotic in the samples. Persistence of detectable drug residues in milk from 33 cows (28 cows, ≤6 infusions at ≤0.7 g gentamicin; and 5 cows, 2 infusions at 0.8 g gentamicin) did not exceed 5 d; but 1 cow (5 infusions at 0.8 g gentamicin) had detectable residues in its milk for 9 d. Our results suggest that a 5-d milk withdrawal period might be insufficient to secure the clearance of the contamination of gentamicin, because treatment times and dosages contribute to the antibiotic clearance. A larger scale of samples are needed for further investigations.
文摘In order to clarify whether gentamicin （GM） could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg·kg<sup>-10</sup>·d<sup>-1</sup> GM for 3 consecutive days.The animals ofthe control group received equal amount of normal saline.It was found that some myelin figuresappeared in the epithelial cells of the proximal tubules as early as 1 h after a single GM injec-tion;severe swelling,degeneration,and obvious changes of the organelles were seen in the en-dothelial cells of the glomerular capillaries,the podocytes and the epithelial cells of the proxi-mal tubules 24 h after an injection of GM;and fusion of the processes of podocytes,thickeningof the glomerular membrane and necrosis of the epithelial cells of a part of the’proximal tubuleswere encountered 24h after the 3rd GM injection.These findings demonstrate that GM can in-jure not only the proximal tubules but also the glomeruli in rabbits.
基金financially supported by the National Natural Science Foundation of China(No.52071191)the Natural Science Foundation of Shandong Province(No.ZR 2020ME011)。
文摘Implant-associate infection(IAI)is a major cause of failure of bone implant materials,and one of the significant challenges in clinical managements.A synergistic coating strategy combining montmorillonite(MMT)sustained release,adsorption of bacteria and gentamicin(GS)bactericidal is proposed herein to tackle infection issues.Surface morphology,microstructure and chemical composition of the samples were investigated using SEM,XRD,FT-IR and XPS.Electrochemical experiments and immersion experiments reveal that corrosion resistance of Mg samples with GS/MMT coatings was higher than that of bare Mg alloy substrate in DMEM solution.In vitro studies demonstrated that the GS/MMT coating had a significant inhibitory effect on Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).The viability of MC3T3-E1 cells was 92.7%after a co-culturing for 72 h.After a subcutaneous transplantation of 90days,the survival rate was 100%for GS/MMT-coated Mg alloy specimens with no infection at the implantation sites and no toxic damage to liver,kidney and local muscles pathological sections.This study provides a novel method for the preparation of sustained-release antimicrobial coatings on biodegradable Mg alloys as promising candidates for orthopedic implant materials.
基金Unsal Sami AKTAS(Ani-Med Pharmacy,Turkey)for the financial support
文摘The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC.subsp.plicatum ethanol extract（HPE）against gentamicin-induced nephrotoxicity.Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material.They were formed into six groups containing 6rats each and were allowed to adapt to laboratory conditions for 7 d.Group Ⅰ：control,5%DMSO intraperitoneal（i.p.）;Group Ⅱ：HPE 100 mg/（kg·d）i.p.;Group Ⅲ：HPE 200 mg/（kg·d）i.p.;Group Ⅳ：gentamicin as 80 mg/（kg·d）i.p.;Group Ⅴ：gentamicin as 80 mg/（kg·d）i.p.＋HPE 100 mg/（kg·d）i.p.;and Group Ⅵ：gentamicin as 80 mg/（kg·d）i.p.＋HPE 200 mg/（kg·d）i.p.for 8 d.Following treatment,serum,liver,and kidney tissues were used to assess blood urea nitrogen（BUN）,creatinine,enzymatic and non-enzymatic antioxidants,and lipid peroxidation.Gentamicin significantly increased serum BUN,creatinin,and liver and kidney levels of malondialdehyde（MDA）.It also decreased the activity of catalase（CAT）,glutathione peroxidase（GPx）,and superoxide dismutase（SOD）.Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin,liver and kidney oxidant marker,and tubular necrosis as well as by an increase in antioxidant enzymes.It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats.As a result,these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.
文摘Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were divided into four groups(n=6).Control rats that received normal saline(i.p.) and 0.5%carboxymethyl cellulose(p.o.) per day lor 8 d.Nephrotoxicity was induced in rats by intraperitoneal administration of GM(100 mg/kg/d for 8 d) and were treated with SXE(200 and 400 mg/kg/d(p.o.) for 8 d).Plasma and urine urea and creatinine,kidney weight,urine output,blood urea nitrogen,renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.Results:It was observed that the GM treatment induced significant elevation(P【0.001) in plasma and urine urea,creatinine,kidney weight,blood urea nitrogen, renal lipid peroxidation along with significant decrement(P【0.001) in urine output,renal enzymatic and non-enzymatic antioxidants.SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement(up to P【0.001) in plasma and mine urea and creatinine, renal lipid peroxidation along with significanl increment(up to P【0.001) in renal enzymatic and non-enzvmatic antioxidants.Histological obsenatioiis of kidney tissues too correlated with the biochemical obsenatioiis.Conclusions:These finding powerfully supports that S,xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its elhnomedicinal use.
文摘Objective:To formulate gentamicin liposphere by solvent-melting method using lipids and polyethylene glycol 4000(PEG-4000) for oral administration.Methods:Gentamicin lipospheres were prepared by melt-emulsification using 30%w/w Phospholipon(?) 90H in Beeswax as the lipid matrix containing PEC-4000.These lipospheres were characterized by evaluating on encapsulation efficiency,loading capacity,change in pH and the release profile. Antimicrobial activities were evaluated against Escherichia coli,Pseudomonas aeruginosa. Salmonella paratyphii and Staphylococcus aureus using the agar diffusion method.Results: Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month.The release of gentamicin in vitro varied widely with the PEC-4000 contents. Moreover,significant(P>0.05) amount of gentamicin was released in vivo from the formulation. The encapsulation and loading capacity were all high,indicating the ability of the lipids to take up the drug.The antimicrobial activities were very high especially against Pseudomonas compare to other test organisms.This strongly suggested that the formulation retain its bioactive characteristics.Conclusions:This study strongly suggest that the issue of gentamicin stability and poor absorption in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.
基金jointly funded by De Puy Synthes and Enterprise Ireland IP 2010-0068
文摘A systematic approach was developed to investigate the stability of gentamicin sulfate(GS) and GS/poly(lacticco-glycolic acid)(PLGA) coatings on hydroxyapatite surfaces.The influence of environmental factors(light,humidity,oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry.GS coated rods were found to be stable across the range of environments assessed,with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition.In contrast,rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C,75% relative humidity or exposure to light.The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect.Finally,liquid chromatography–mass spectrometry analysis revealed that known gentamines C_1,C_1 aand C_2were the major degradants formed.Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.
文摘Objective To study gentamicin injury mechanisms using postnatal mouse cochlear spiral gangcells （SGC）. Methods SGCs were isolated using a combinatorial approach of enzymatic digestion and mechanical separation from P2 - 6 Kunming mouse cochleae. After 4 days, cultured SGCs were fixed with 4% paraformaldehyde at room temperature for immunocytochemical examination using the methods of S-P and the monoclonal antibody against mouse neurofilament protein （Neurofilament-68/200Kda, NF-L＋ H）. SGCs were randomly divided into a blank control group and three gentamicin treatment groups （medium gentamicin concentration at 50 mg/L, 100 mg/L and 150 mg/L respectively）, SGCs were collected and examined under a transmission electron microscope after being cultured for 48 h. Results SGC primary culture was successful. SGC cytoplasm and neurites were dyed brownish yellow by the monoelonal mouse neurofilament protein antibody. SGCs showed classical bipolar neuron appearance. Under the transmission electron microscope,.gentamicin treated SGCs showed morphological features different compared to those in the blank control group, which might indicate apoptosis. Conclusion Our results indicate that gentamicin has direct toxic effects on cochlear SGCs in mice and the injury mechanism is closely related with apoptosis. Damage to mitochor, dria may play an important role in the process.
基金supported by Centre de Recherche Translationnelle de I'Institut Pasteur, grant Number S- PI15007-02Asupported by the French Government's Investissement d'Avenir program:Laboratoire d'Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX62-IBEID.)+1 种基金the Fondation pour la Recherche Médicale (grant no. DEQ. 20140329508)the Center for Translational Science of the Institut Pasteur (S-PI15007-02A)
文摘A lock solution composed of gentamicin sulfate(5 mg/mL) and ethylenediaminetetraacetic acid disodium salt(EDTA-Na2, 30 mg/mL) could fully eradicate in vivo bacterial biofilms in totally implantable venous access ports(TIVAP). In this study, fabrication, conditioning and sterilization processes of antimicrobial lock solution(ALS) were detailed and completed by a stability study. Stability of ALS was conducted for12 months in vial(25 °C 7 2 °C, 60% 7 5% relative humidity(RH), and at 40 °C 7 2 °C, RH 75% 7 5%)and for 24 h and 72 h in TIVAP(40 °C 7 2 °C, RH 75% 7 5%). A stability indicating HPLC assay with UV detection for simultaneous quantification of gentamicin sulfate and EDTA-Na2 was developed. ALS was assayed by ion-pairing high performance liquid chromatography(HPLC) needing gentamicin derivatization, EDTA-Na2 metallocomplexation of samples and gradient mobile phase. HPLC methods to separate four gentamicin components and EDTA-Na2 were validated. Efficiency of sterility procedure and conditioning of ALS was confirmed by bacterial endotoxins and sterility tests. Physicochemical stability of ALS was determined by visual inspection, osmolality, pH, and sub-visible particle counting. Results confirmed that the stability of ALS in vials was maintained for 12 months and 24 h and 72 h in TIVAP.
基金financially supported by Kermanshah University of Medical Science(grant number 981004)
文摘Objective:To evaluate the effect of Heracleum persicum L.against gentamicin-induced nephrotoxicity in rats.Methods:Thirty-six Wistar rats were divided into 6 groups including control(normal saline),gentamicin(80 mg/kg/d for 10 d),Heracleum persicum(750 mg/kg/d),and gentamicin(10 d)+Heracleum persicum extract at three different doses(250,500,and 750 mg/kg/d for 40 d).Urine creatinine,urea,protein,and albumin levels were determined.In addition,serum urea,creatinine,sodium,potassium,cytokines(TNF-α,IL-1β,IL-6,and IL-10),glutathione peroxidase activity,total antioxidant capacity,kidney malondialdehyde,stereological parameters,and expressions of apoptosis-related genes(p53,Bax,Bcl-2,and caspase-3)were measured.The LD50 of Heracleum persicum extract was determined based on Lorke’s method.Histopathological evaluation was also performed.Results:In addition to decreased urine protein and albumin,and increased creatinine and urea,co-treatment with gentamicin and Heracleum persicum significantly reduced levels of creatinine and urea,and increased sodium and potassium in serum.Heracleum persicum treatment also improved stereological parameters and serum inflammatory cytokines.There was a significant increase in serum glutathione peroxidase activity and total antioxidant capacity as well as a reduction in malondialdehyde level.Furthermore,treatment with Heracleum persicum extracts downregulated p53,caspase-3,and Bax and upregulated Bcl-2 expressions.In histopathological evaluation,Heracleum persicum extracts showed protection against gentamicin-induced renal damages.Conclusions:Heracleum persicum exhibits protective effects against gentamicin-induced structural and functional renal impairments.
基金Supported by The Shanghai Pujiang Program,No.12PJ1401500
文摘BACKGROUND Multidrug-resistant Acinetobacter baumannii(MDRAB) has emerged as an increasingly important pathogen that causes nosocomial meningitis. However,MDRAB-associated nosocomial meningitis is rarely reported in children.CASE SUMMARY We report the case of a 1-year-old girl with a choroid plexus papilloma, who developed postoperative nosocomial meningitis due to MDRAB. The bacterial strain was sensitive only to tigecycline and colistin, and showed varying degrees of resistance to penicillin, amikacin, ceftriaxone, cefixime, cefotaxime,ciprofloxacin, levofloxacin, gentamicin, meropenem, imipenem, and tobramycin.She was cured with intravenous doxycycline and intraventricular gentamicin treatment.CONCLUSION Doxycycline and gentamicin were shown to be effective and safe in the treatment of a pediatric case of MDRAB meningitis.
文摘Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups:(G1) control group,(G2) gentamicin treated group(100 mg/kg),(G3) nettle treated group(100 mg/kg),(G4) combination treated group with both gentamicin(100 mg/kg) and nettle(100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using dif erent antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased signii cantly in gentamicin treated group; other groups have no signii cant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great ef ect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No signii cant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective ef ect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.
基金supported by Chairman,Mother Mary education Society,Vikas nagar,Hyderabad,Andhra Pradesh,India
文摘Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute toxicity study,single oral dose of 5（KM） mg ethyl acetate floral extract/kg hodv weight was administered to albino rats（five females,five males）.Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin 80 mg/kg/day for eight days.Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100.200 and 300 mg/kg/day given by oral mute was determined using serum creatinine,serum uric acid,blood urea nitrogen and serum urea as indicators of kidney damage.The study groups contained six rats in each group.As nephrotoxicity of gentamicin is known to involve induction of oxidative stress,in vitro antioxidant aclivity and free radical-scavenging activity of this extract was also evaluated.Results:For acute toxicity testing both female and male rats administered with the extract at a dose of 5 000 mg/kg.The results showed no toxicity in terms of general behavior change,mortality,or change in gross appearance of internal organs(LD<sub>50</sub>】5 000 mg/kg). It was observed that the ethyl acetate floral extract of Tecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes.Gentamicin-induced glomerular congestion,peritubular and blood vessel congestion,epithelial desquamation,accumulation ol inflamnialoiy cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract of Tecoma starts along with gentamicin in a dose dependent manner.The floral extract also reduced the gentamicin-induced increase in serum creatinine,serum uric acid,blood urea nitrogen and serum urea levels（P】0.01）.Conclusions: The present study indicates a verv important role of reactive oxygen species（BOS） and the relation to renal dysfunction and point to the therapeutic potential of Tecoma stans in gentamicin induced nephrotoxicity.
文摘BACKGROUND： It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary auditory center. OBJECTIVE： To explore morphological changes of choline acetyltransferase （ChAT）-positive neurons in the paraolivary nucleus （PON） of guinea pigs, and the effect on hearing following gentamicin injection. DESIGN, TIME AND SETTING： Randomized grouping and morphological observational study was performed at Animal Experimental Center of General Hospital of Shenyang Military Area Command of Chinese PLA from January to August 2007. MATERIALS： A total of 48 healthy guinea pigs were randomly divided into model （n = 40） and control （n = 8） groups. The model group was divided into five subgroups at five time points of 1 and 3 days, 1, 2, and 3 weeks. METHODS： Guinea pigs in the model group were intraperitoneally injected with gentamicin, and those in the control group were intraperitoneally injected with the same volume of saline. MAIN OUTCOME MEASURES： Auditory brainstem-evoked potential was used to record auditory threshold; distribution and morphological changes of ChAT-positive neurons in the PON were observed with immunohistochemistry; section area and gray value of ChAT-positive neurons were measured with Quantimet 570 image-analyzing system. RESULTS： ChAT-positive neurons were diffusedly distributed in the PON. The majority was composed of large, round cells, with positive neurites that could be clearly observed. Following gentamicin injection, the positive neurons displayed an irregular outline, and their neurites began to shorten and disappear. The gray value increased with prolonged gentamicin administration （P 〈 0.05）. In addition, the somatic cross-sectional area was enlarged in the model group at 1 and 3 days after injection （P 〈 0.05）, whereas cell number significantly decreased at ;three weeks after injection （P 〈 0.05）. Starting at 3-4 days, behavioral features and auditory degrees became gradually aggravated with prolonged gentamicin administration （P 〈 0.05）. CONCLUSION： Gentamicin damaged ChAT-positive neurons in the PON, and long-term gentamicin treatment aggravated hearing impairment.
