Gentamicin Group Research Articles

Use of gentamicin-impregnated beads or sponges in the treatment of early acute periprosthetic joint infection: a propensity score analysis.

Early acute periprosthetic joint infections (PJIs) treated with debridement, antibiotics and implant retention (DAIR) have failure rates ranging from 10% to 60%. We determined the efficacy of applying local gentamicin-impregnated beads and/or sponges during debridement in early PJI. Patients with early acute PJI, defined as less than 21 days of symptoms and treated with DAIR within 90 days after index surgery, were retrospectively evaluated. Early failure was defined as PJI-related death, the need for implant removal or a second DAIR or antibiotic suppressive therapy owing to persistent signs of infection, all within 60 days after initial debridement. Overall failure was defined as implant removal at any timepoint during follow-up. A 1:1 propensity score matching was performed to correct for confounding factors. A total of 386 patients were included. Local gentamicin was applied in 293 patients (75.9%) and was withheld in 93 patients (24.1%). Multivariate analysis demonstrated that the use of local gentamicin was independently associated with early failure (OR = 1.97, 95% CI = 1.12-3.48). After propensity matching, early failure was 40.3% in the gentamicin group versus 26.0% in the control group (P = 0.06) and overall failure was 5.2% in the gentamicin group versus 2.6% in the control group (P = 0.40). These numbers remained when solely analysing the application of gentamicin-impregnated sponges. Even after propensity score matching, failure rates remained higher if local gentamicin-impregnated beads and/or sponges were administered in early acute PJI. Based on these results, their use should be discouraged.

The use of passiflora incarnate in pregnant women

Gentamicin (GM) is an effective and common antibiotic against severe gram-negative infections. However, its nephrotoxic action has limited the extent of its use. The aim of this study was to investigate the protective effects of hydroxytyrosol (HT) on gentamicin induced nephrotoxicity in mice.Male mice (n = 27) were randomly assigned to three groups: (1) Sham, (2) GM (100 mg/kg for 7 days) (3) GM + HT (2 mg/kg BW; gastric gavages, for 7 days). 24-h urine samples were collected on day 8 and then animal were anesthetized. The blood and kidney tissue samples were collected.Gentamicin led to increase in plasma BUN and creatinine, fractional excretion of sodium and potassium and decrease in creatinine clearance and urine flow rate. SOD and GSH levels were reduced and MDA was increased in the GM group compared with the sham group. In GM + HT group, plasma BUN and creatinine, fractional excretion of Na, creatinine clearance and urine flow rate were decreased in contrast to GM group. Increase in SOD and GSH activity and decrease in MDA compared to GM group were seen.Findings suggest that HT partly protected the kidneys from gentamicin induced nephrotoxicity and it is partly due to antioxidant effect of HT.

Potassium permanganate soak combined with a negative pressure drainage device for bone and soft tissue infection

Objective To analyze the clinical efficacy of potassium permanganate soak combined with a closed negative pressure drainage device for treatment of bone and soft tissue infection. Methods A retrospective analysis was performed of the 83 patients with bone and soft tissue infection who had been treated at Department of Orthopaedics, The Second People’s Hospital of Fuzhou from July 2010 to March 2017. They were 71 males and 12 females, aged from 15 to 77 years (median, 44 years). Of them, 47 were subjected to soak with 1∶5,000 potassium permanganate solution and 36 to soak with 1∶5,000 gentamycin solution before a negative pressure sealing drainage device was applied for them all. The 2 groups were compared in terms of complications (pain, drainage device blockage or leakage, wound bleeding, tube pressure ulcer, and new nosocomial infection), time for negative bacterial culture, time for drainage device removal, time for wound closure, healing rate and recurrence rate. Results There were no significant differences between the 2 groups in pain, drainage device blockage or leakage, wound bleeding, or tube pressure ulcer (P>0.05). The rate of new nosocomial infection was significantly lower in the potassium permanganate group (2.1%) than in the gentamicin group (13.9%). The time for negative bacterial culture, drainage device removal and wound closure in the potassium permanganate group (6 d, 12 d and 18.5±1.9 d, respectively) was all significantly shorter than in the gentamicin group (9 d, 15 d and 20.0±2.2 d, respectively) (P< 0.05). The healing rate for the potassium permanganate group (100%) was significantly higher than that for the gentamicin group (86.1%); the recurrence rate (0) for the former was significantly lower than that for the latter (13.9%) (P< 0.05). Conclusion Potassium permanganate soak combined with a negative pressure drainage device is effective, economical, convenient and safe for the treatment of bone and soft tissue infection, compared with gentamicin soak combined with the same device. Key words: Potassium permanganate; Negative-pressure wound therapy; Soft tissue infections; Bone

Reno-protective effects of ursodeoxycholic acid against gentamicin-induced nephrotoxicity through modulation of NF-κB, eNOS and caspase-3 expressions.

Gentamicin (GNT) is a potent aminoglycoside antibiotic widely used to treat life-threatening bacterial infections. We aim to investigate the potential protective effect of ursodeoxycholic acid (UDCA) against GNT-induced nephrotoxicity. In this study, 24 male Wistar rats were used and randomly divided into four groups of six animals each. Control group received 0.5% carboxymethyl cellulose orally for 15days, GNT group received GNT 100mg/kg/day i.p. for 8days, UDCA group received UDCA orally for 15 consecutive days at a dose of 60mg/kg/day suspended in 0.5% carboxymethyl cellulose and UDCA-pretreated group received UDCA orally for 7days then co-administered with GNT i.p. for 8days at the same fore-mentioned doses. Serum levels of kidney function parameters (urea, creatinine, uric acid and albumin) were measured. Renal tissues were used to evaluate oxidative stress markers; malonaldehyde (MDA), reduced glutathione (GSH) and the anti-oxidant enzyme superoxide dismutase (SOD) activities and nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and kidney injury molecule-1 (KIM-1) mRNA levels. Immunohistochemical expression of endothelial nitric oxide synthase (eNOS) and caspase-3 and histological and ultrastructural examination were performed. Treatment with GNT increased the serum levels of renal function parameters and renal MDA, NF-κB and KIM-1 mRNA levels, while it decreased GSH and SOD activities. Marked immunohistochemical expression of caspase-3 was observed after GNT administration while it decreased eNOS expression. Histological and ultrastructural alterations were also evident in renal corpuscles and tubules. In contrast, pretreatment with UDCA reversed changes caused by GNT administration. These results suggest that UDCA ameliorates GNT-induced kidney injury via inhibition of oxidative stress, inflammation and apoptosis.

Is gentamicin safe and effective for severe community-acquired pneumonia? An 8-year retrospective cohort study

Gram-negative bacilli are the causative organisms in a significant proportion of patients with severe community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU). Clinical guidelines recommend broad-spectrum antimicrobials for empirical treatment despite alarming global trends in antimicrobial resistance. In this study, we aimed to assess the safety and efficacy of gentamicin, an aminoglycoside with potent bactericidal activity, for empirical Gram-negative coverage of severe CAP in patients admitted to the ICU. A retrospective cohort study was performed at a university teaching hospital where the severe CAP guideline recommends penicillin, azithromycin and gentamicin as empirical cover. Ceftriaxone plus azithromycin is used as an alternative. Adults with radiologically-confirmed severe CAP were included, comparing those who received gentamicin in the first 72 h of admission with those who did not. Participants were identified using ICD-10 codes for bacterial pneumonia and data manually extracted from electronic medical records. Of 148 patients admitted with severe pneumonia, 117 were given at least one dose of gentamicin whereas the remaining 31 were not. The two groups were well matched in terms of demographics, co-morbidities and disease severity. There were no significant differences between the gentamicin and no-gentamicin groups in the incidence of acute kidney injury [60/117 (51%) vs. 16/31 (52%), respectively], hospital mortality [20/117 (17%) vs. 7/31 (23%)] and secondary outcomes including relapse and length of hospital stay. In conclusion, gentamicin is safe and has similar outcomes to alternative Gram-negative antimicrobial regimens for empirical coverage in severe CAP patients admitted to the ICU.

Synergistic and long-lasting antibacterial effect of antibiotic-loaded TiCaPCON-Ag films against pathogenic bacteria and fungi

Implant-related bacterial infections remain a serious problem that is not solved yet. Herein we combined several antibacterial agents to achieve synergistic effects and broader protection of widely used metallic implants. Titanium samples with microcontainers for drug, produced by selective laser sintering, were coated with Ag-doped biocompatible and bioactive TiCaPCON film and loaded with an antibiotic (gentamicin or a mixture of gentamicin and amphotericin B). Bactericide release tests demonstrated that the release rate of one bactericide agent (Ag+ ions or gentamicin) depended on the presence of the other antibacterial component. The antibacterial activity of the biocide-doped samples was evaluated against clinically isolated Escherichia coli O78 (E. coli), Staphylococcus aureus (S. aureus) bacteria, and Neurospora crassa wt-987 (N. crassa) spores. It was found that samples loaded with low gentamicin concentration (0.2 and 0.02 mg/cm2), i.e. 10 and 100 times less than the standard gentamicin concentration (2 mg/cm2), demonstrated a superb antibacterial activity against E. coli bacteria. We showed that a crosslinking reaction between gentamicin and TiCaPCON film proceeded either through the formation of amide bonds or via the electrostatic interaction between amine groups of gentamicin and COOH groups of TiCaPCON and led to the formation of relatively stable drug/film conjugates that prevented a rapid dissolution of gentamicin and ensured its long-term (for 72 h) antibacterial protection. Leaching of silver ions provided an effective antibacterial protection after the depletion of the drug reservoirs. The obtained results clearly show a synergistic antibacterial action of Ag+ ions and gentamicin against S. aureus bacteria. In addition, in the presence of Ag+ ions, the antifungal activity of samples loaded with a mixture of gentamicin and amphotericin B against N. crassa fungus was observed to increase. Thus, it is demonstrated that silver can be successfully coupled with different types of antibiotics to provide innovative hybrid metal-ceramic bioconstructions that are able to deliver precise doses of bactericide agents within a certain period of time and are equally effective against Gram-negative E. coli bacteria, Gram-positive S. aureus, and N. crassa fungus.

Upregulation of PPAR-γ mediates the renoprotective effect of omega-3 PUFA and ferulic acid in gentamicin-intoxicated rats

Ferulic acid (FrA) is a natural product containing phenolic compounds. ω-3 PUFA is the major constituent of fish oil. The aim of this study was to investigate the renoprotective role of FrA and FO in gentamicin (GM)-induced nephrotoxicity in rats. Forty four male rats were divided equally into 4 groups: Control group, GM group, FrA + GM group and FO + GM group. Each of the treated groups was injected with GM (40 mg/kg) i.p. for 9 consecutive days. FrA (100 mg/kg) and FO (5 mL/kg) were given to rats orally daily for 10 days prior to GM and then concomitantly with GM for additional 9 days. Kidney function was assessed by serum BUN and creatinine, urinary albumin excretion and N-acetyl-beta-D-glucosaminidase (NAG) activity and histopathological examination. The anti-inflammatory property was evaluated by measuring renal resolvin E1 and gene expression of PPAR-γ. The antioxidant activity was indicated by renal catalase (CAT) activity. GM-induced nephrotoxicity was evidenced by the renal histopathological changes along with increased renal indices. Prior and concomitant treatment with FrA or FO ameliorated nephrotoxic effect of GM as indicated by the significant decrease of serum BUN and creatinine, urinary albumin excretion and urinary NAG activity. Both treatments significantly enhanced CAT activity and gene expression of PPAR-γ. Resolvin E1 was significantly elevated in FO but not in FrA group. FrA and FO proved anti-inflammatory and renoprotective effects, which could be through their PPAR-γ agonist activity. Because FrA and FO are natural products, they could provide a safe intervention strategy in cases of exposure to nephrotoxins.

Wheat germ and vitamin E decrease BAX/BCL-2 ratio in rat kidney treated with gentamicin

The intracellular accumulation of gentamicin acts on mitochondria directly (by increasing oxidative stress) and indirectly (by increasing the proapoptotic BAX gene expression levels) and thus activates intrinsic pathway of apoptosis. This study intended to investigate the probable prophylactic effect of wheat germ as a nephro-protective agent in relation to vitamin E as a well-known natural antioxidant on a nephrotoxic model induced by gentamicin. Forty male Sprague Dawley rats were divided randomly into four groups; of 10 rats each: control group, gentamicin group (120 mg/kg/day i.p. for 15 days), vitamin E group (200 mg/kg orally for 45 days) and wheat germ group (20% of the diet for 45 days). Gentamicin injection was started on the 30th day for both groups (3) and (4). It was noticed that wheat germ significantly decreased BAX/BCL-2 ratio. The significant decrement in MDA level and the significant increment in total antioxidant capacity (TAC) level and catalase (CAT) activity of wheat germ treated rats reflecting its antioxidant activity. Additionally, the wheat germ succeeded in improvement of the kidney function of rats of this group which was manifested by amelioration of deteriorated serum creatinine, urea, sodium and potassium levels. In conclusion, the efficacy of wheat germ as anti-apoptotic and antioxidant was higher than that of vitamin E and it effectively protected against the direct and indirect toxic effects of gentamicin on kidney through regulation of BAX-BCL-2 gene expressions and further inhibition of mitochondrial cytochrome c translocation into cytosol.

Ameliorative Effects of Zataria Multiflora Hydro-Alcoholic extract on Gentamicin Induced Nephrotoxicity in Rats.

Nephrotoxicity is the major side effects of aminoglycoside antibiotics such as gentamicin. The aim of this study was to investigate the therapeutic effects of Z.multiflora (ZM) hydroalcoholic extract on gentamicin-induced nephrotoxicity. Twenty-eight male Wistar rats categorized into four groups: 1) the control group without injection, 2) the gentamicin treated group (100 mg/kg, i.p) 3) the gentamicin and Z. Multiflora treated group; Z. Multiflora extract(0.8 mg/ml in the drinking water) administered after gentamicin (100 mg/kg, i.p) 4) the normal saline and Z. Multiflora treated group; Z. Multiflora extract (0.8 mg/ml in the drinking water) administered after normal saline injection (2 ml/kg,i.p ). Post-treatment with ZM extract caused a significant reduction in the levels of plasma creatinine and blood urea nitrogen (BUN), absolute and fractional excretion of sodium, malondialdehyed (MDA) level in comparison to gentamicin group. In addition, ZM extract significantly increased creatinine clearance, urine osmolarity, and Renal blood flow (RBF) and the Ferric reducing ability of plasma (FRAP) level which had decreased compared to the control group as a result of treatment with gentamicin. The above result indicated that ZM extract improved renal toxicity of gentamicin via reducing oxidative stress, oxygen-free radicals, and lipid peroxidation.

Osteoinduction and -conduction through absorbable bone substitute materials based on calcium sulfate: in vivo biological behavior in a rabbit model.

Calcium sulfate (CS) can be used as an antibiotically impregnated bone substitute in a variety of clinical constellations. Antibiotically loaded bone substitutes find specific application in orthopedic and trauma surgery to prevent or treat bone infections especially in relation to open bone defects. However, its use as a structural bone graft reveals some concerns due to its fast biodegradation. The addition of calcium carbonate and tripalmitin makes CS formulations more resistant to resorption leaving bone time to form during a prolonged degradation process. The aim of the present study was the evaluation of biocompatibility and degradation properties of newly formulated antibiotically impregnated CS preparations. Three different types of CS bone substitute beads were implanted into the tibial metaphysis of rabbits (CS dihydrate with tripalmitin, containing gentamicin (Group A) or vancomycin (Group B); Group C: tobramycin-loaded CS hemihydrate). Examinations were performed by means of x-ray, micro-computed tomography (micro-CT) and histology after 4, 6, 8 and 12 weeks. Regarding biocompatibility of the formulations, no adverse reactions were observed. Histology showed formation of vital bone cells attached directly to the implanted materials, while no cytotoxic effect in the surrounding of the beads was detected. All CS preparations showed osteogenesis associated to implanted material. Osteoblasts attached directly to the implant surface and revealed osteoid production, osteocytes were found in newly mineralized bone. Group C implants (Osteoset®) were subject to quick degradation within 4 weeks, after 6-8 weeks there were only minor remnants with little osteogenesis demonstrated by histological investigations. Group A implants (Herafill®-G) revealed similar degradation within atleast 12 weeks. In contrast, group B implants (CaSO4-V) were still detectable after 12 weeks with the presence of implant-associated osteogenesis atlatest follow-up. In all of these preparations, giant cells were found during implant degradation on surface and inside of resorption lacunae. None of the analyzed CS preparations triggered contact activation. All implants demonstrated excellent biocompatibility, with implants of Group A and B showing excellent features as osteoconductive and -inductive scaffolds able to improve mechanical stability.

Effect of caffeic acid phenethyl ester (CAPE) on vascular endothelial growth factor a (VEGF-A) gene expression in gentamicin-induced acute renal nephrotoxicity

Vascular endothelial growth factor-A (VEGF-A) gene expression in an experimental gentamicin-induced nephrotoxicity and ameliorative effect of caffeic acid phenethyl ester (CAPE) was investigated in rats. Animals were divided into four groups (n=8); control (C) group animals were given 10% dimethylsulfoxide (DMSO); gentamicin (G) group animals were given 100 mg/kg/day gentamicin; CAPE group animals were given 30 mg/kg/day CAPE and CAPE+G group animals were given 100 mg/kg/day gentamicin plus 30 mg/kg/day CAPE. Serum creatinine and BUN levels significantly increased in gentamicin group as compared to the control group (p0.05). Gene expression level of VEGF-A in gentamicin group significantly decreased as compared to the control group, however, CAPE treatment did not have any increasing effect on the gene expression level. According to histopathological investigation, gentamicin treatment caused prominent degeneration in kidney tissue and CAPE treatment had only slight beneficial effect on lowering the tissue degeneration. The results showed that gentamicin decreases VEGF-A gene expression and this might be related to the tissue degeneration at cellular level. However, CAPE treatment did not have significant ameliorative effect in lowering the gentamicin induced nephrotoxicity.

Sex Difference in Gentamicin-induced Nephrotoxicity: Influence of L-arginine in Rat Model.

Background:L-arginine is an important precursor for the formation of nitric oxide (NO). According to previous studies, NO function is related to gender. Likewise, chronic renal diseases have lower prevalence in female. Gentamicin (GM) is an aminoglycoside antibiotic. According to some studies, males are more sensitive to GM renal nephrotoxicity. This study attempts to find protective effects of L-arginine on GM nephrotoxicity in male and female rats.Methods:Male and female rats were divided into eight groups: Rats were randomly assigned to 8 groups each including both male and female rats. The first and second groups received vehicle (saline), the third and fourth groups received gentamicin (80 mg/kg), the fifth and sixth groups received L-arginine (150 mg/kg), and finally, seventh and eighth groups received gentamicin+ L- arginine. Next, 9 days after administering drugs, blood samples were collected from the heart. After making sacrifices, the level of blood urea, creatinine (Cr), nitrite, and malondialdehyde (MDA) was measured in serums. Likewise, nitrite and MDA were measured in the homogenized kidney tissue.Results:GM significantly increased serum level of urea and Cr in male and female rats (P < 0.05). However, co-administration of GM + L-arginine significantly did not decrease urea and Cr level in male rats, whereas, in female rats, they significantly reduced (P < 0.05). In response to GM, renal MDA level increased in male and female rats (P < 0.05), and in the presence of GM + L-arginine, the level of MDA significantly decreased in both genders (P < 0.05).Conclusions:L-arginine demonstrated some protective effects in female rats but did not protect against GM nephrotoxicity in male rats for unknown reasons, probably related to the effects of sex hormones which needs further studies to be confirmed.

Protective Role of Pomegranate and Sodium bicarbonate on Acute Renal Failure Induced by Gentamicin In Rabbits Model

Acute renal failure ARF is common condition can be categorized as prerenal, intrinsic or postrenal causes in which the glomerular filtration rate decreases GFR over days to weeks . The aim of this study was to test whether the administration of pomegranate and sodium bicarbonate minimize the adverse health effect of acute renal failure. Methods : twenty female rabbits were assessed in to five groups ( n = 4 ) ,Group 1 : control group (C) .Group 2 : Gentamicin group ( G ): animals were injected with a single dose of Gentamicin ( 80 mg / Kg / bw ) intramuscular , daily for 10 days to induce renal failure. Group 3 : sodium bicarbonate group ( G+S ),animals were treated as in group 2 plus they received sodium bicarbonate ( 1 ml / Kg / bw ) of 8.4% by gavage daily for 10 days .Group 4 : pomegranate group ( G+P ),animals were treated as in group 2 plus they received pomegranate 500 ( mg / Kg / bw ) by gavage. Group 5 : combination group ( G+S+P ),animals were treated as in group 2 plus group 3 and group 4 for 10 days. Results : serum creatinine and blood urea levels were decreased in both groups (G+P) and (( G+S+P ) , p < 0.05 . while in group ( G+S ) they increased more effectively than the ( G) group .Serum electrolytes concentrations and serum ( pH ) shows different response , they were improved mostly in the ( G+S+P ) group, and they fluctuated in (G+S) group showing significant decreasing in serum ( Cl and Ca ) , p < 0.05 . Although the results for the hematological parameters were also improved in the combination group ( G+S+P ) but the differences were non significant between all others measured parameters and control group. Conclusions : the administration of sodium bicarbonate in Gentamicin model to induced acute renal failure inducement has adverse biological effects . but those effects were minimized by the ameliorative effects of the pomegranate administration which was helpful in speeding recovery

Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin.

Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. In this study, we investigated whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the nephrotoxic effect of GM in rats. Rats were divided into five groups. Group 1 and 2 served as control and sham respectively, Group 3 as GM group, Group 4 as GM+CoQ10 and Group 5 as GM+BFT for 8days. At the end of the study, all rats were euthanized by cervical decapitation and then blood samples and kidneys were collected for further analysis. Serum urea, creatinine, cytokine TNF-a, oxidant and antioxidant parameters, as well as histopathological examination of kidney tissues were assessed. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated serum creatinine, urea and KIM-1 level as compared with the controls. Moreover, a significant increase in serum malondialdehyde, reduced glutathione. Histopathological examination of renal tissue in gentamisin administered group, there were extremly pronounced necrotic tubules in the renal cortex and hyalen cast accumulation in the medullar tubuli. BFT given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and KIM-1 were almost normalized in the GM+BFT group. Benfotiamin treatment was significantly decreased necrotic tubuli and hyalen deposition in gentamisin plus benfotiamin group. CoQ10 given to GM rats did not cause any statistically significant alterations in these nephrotoxicity parameters when compared with GM group but histopathological examination of renal tissue in GM+CoQ10 administered group, CoQ10 treatment was decreased necrotic tubuli rate and hyalen accumulation in tubuli. The results from our study indicate that BFT supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells.

Identifying potential liver toxicants using in vitro and in silico methods in a weight-of-evidence based approach

BJcuL is a snake venom galactoside-binding lectin (SVgalL) isolated from Bothrops jararacussu and is involved in a wide variety of biological activities including triggering of pro-inflammatory response, disruption of microbial biofilm structure and induction of apoptosis. In the present work, we determined the crystallographic structure of BJcuL, the first holo structure of a SVgalL, and introduced the fluorescence-based thermal stability assay (Thermofluor) as a tool for screening and characterization of the binding mechanism of SVgalL ligands. BJcuL structure revealed the existence of a porous and flexible decameric arrangement composed of disulfide-linked dimers related by a five-fold symmetry. Each monomer contains the canonical carbohydrate recognition domain, a calcium ion required for BJcuL lectinic activity and a sodium ion required for protein stabilization. BJcuL thermostability was found to be induced by calcium ion and galactoside sugars which exhibit hyperbolic saturation profiles dependent on ligand concentration. Serendipitously, the gentamicin group of aminoglycoside antibiotics (gAGAs) was also identified as BJcuL ligands. On contrast, gAGAs exhibited a sigmoidal saturation profile compatible with a cooperative mechanism of binding. Thermofluor, hemagglutination inhibition assay and molecular docking strategies were used to identify a distinct binding site in BJcuL localized at the dimeric interface near the fully conserved intermolecular Cys86-Cys86 disulfide bond. The hybrid approach used in the present work provided novel insights into structural behavior and functional diversification of SVgaLs.

Copper-modified palygorskite is effective in preventing and treating diarrhea caused by Salmonella typhimurium.

The aim of this research was to develop effective alternative therapies to reduce antibiotic use in animal agriculture. In this study, the efficacy of copper-modified palygorskite (CM-Pal) in preventing diarrhea caused by Salmonella was specifically examined both in vitro and in vivo. The CM-Pal was prepared with palygorskite (Pal) and copper nitrate. The antibacterial activity of the CM-Pal was detected by comparing the differences in cell numbers on plate count agar before and after adding the CM-Pal to Salmonella typhimurium cultures. Seventy ICR mice were then allocated into seven groups. Five groups (the treatment groups) were infected with S. typhimurium by intraperitoneal (i.p.) injection and were given Pal, CM-Pal, montmorillonite powder, gentamicin, and physiological saline, respectively. One group (the prevention group) was given CM-Pal before infection with S. typhimurium. Another group (the uninfected group) was not infected with S. typhimurium. The effects of Pal, CM-Pal, montmorillonite powder, and gentamicin on the treatment or prevention of diarrhea in the mice were examined by stool studies, fecal scoring, and assessment of growth performance and villus height. The CM-Pal had satisfactory anti-bacterial properties in vitro: the antibacterial rate was 100% after 2 h incubation with S. typhimurium NJS1 cultures (1×106 colony-forming units (CFU)/ml). In the in vivo experiment, the CM-Pal exerted superior effects in the treatment and prevention of diarrhea in mice compared with Pal, montmorillonite powder, and gentamicin. In the CM-Pal group, no mice showed signs of diarrhea at 24 h post infection (p.i.), and all mice fully recovered from infection. However, the Pal group, montmorillonite group, and gentamicin group only recovered after 48, 48, and 96 h, respectively. The villus height level in the CM-Pal treatment group recovered at 3 d p.i. However, the recovery time of the other groups was longer (at least 5 d). The CM-Pal prevention group had a better effect on weight gain than the other groups. This study suggested that CM-Pal may be an effective alternative to conventional antibiotics for the treatment and prevention of animal diarrhea caused by Salmonella.

Hypolipidemic and hepatoprotective activities of rosemary and thyme in gentamicin-treated rats.

Rosemary ( Rosmarinus officinalis; RM) and thyme ( Thymus vulgaris; TV) are used as remedies. We designed this work to investigate the preventive effect of aqueous extracts of RM or TV on the gentamicin (GM)-induced hepatotoxicity and abnormalities of lipid profile in rats. Both plant extracts exhibited an in vitro antioxidant activity as determined by the 1,1-diphenyl-2-picrylhydrazyl assay. Radical scavenging activity for TV extract was 48.7% and for RM extract was 25.6%. Polyphenolic determination by high-performance liquid chromatography for both extracts revealed that catechin, coumarin, cinnamic acid and rutin were detected in both extracts. RM extract had higher values than TV extract in all except rutin. Ferulic acid and quercetin were also detected in TV extract and sinapic acid and oleuropein were detected in RM extract. In rats given GM intraperitoneally for 10 days and coadministered either RM extract or TV extract orally, both aqueous extracts demonstrated similar hepatoprotective effects manifested by approximate normalization of plasma liver enzymes (AST and ALT), bilirubin level and total protein concentration compared with the group given GM only. Abnormal lipid parameters and raised hydrogen peroxide levels were ameliorated by both extracts. Pancreatic lipase activity was markedly reduced by RM extract. Also, the atherogenic index value was significantly reduced by both extracts as compared to that of GM group. DNA fragmentation analysis confirmed tissue damage by GM and its amelioration by the extracts. These findings suggest that RM and TV extracts could be helpful in ameliorating some aspects of gentamicin toxicity.

Ototoxicity associated with topical administration of diclofenac sodium as an otic drop: An experimental animal study

ObjectivesThe aim of the study is to evaluate the ototoxicity of topical diclofenac sodium in comparison to positive and negative controls prior to the investigation of analgesic and anti-inflammatory efficacy of the agent in otic administration. MethodsTwenty four ears of 12 guinea pigs were included in the study. Wide myringotomy was performed on all tympanic membranes under general anesthesia and auditory brainstem responses (ABR) were evaluated. The subjects were separated into four groups, two groups received diclofenac sodium at low and high doses, positive controls received gentamicin and negative controls received isotonic sodium chloride topically for 14 days and ABRs were reevaluated. ResultsNo significant difference were observed between the pre and post-treatment click response, 1 kHz and 8 kHz response threshold levels after isotonic sodium chloride administration. All threshold levels were elevated in the positive control group. In the low and high dose diclofenac sodium groups, click response, 1 kHz and 8 kHz response threshold levels were significantly higher compared to the baseline values. Pre and post-treatment mean threshold level changes were not significantly different between the low and high dose diclofenac sodium groups. Pre and post-treatment mean threshold level changes in the gentamicin group were not significantly different from low or high dose diclofenac sodium groups. ConclusionDiclofenac sodium, considered as an analgesic and anti-inflammatory otic preparation, is shown to be as ototoxic as gentamicin in chronic use which may lead to loss of hearing especially when used topically in chronic otitis cases with tympanic membrane damage.

Comparison of topical mupirocin and gentamicin in the prevention of peritoneal dialysis-related infections: A systematic review and meta-analysis

BackgroundTopical antibiotics have been shown to reduce exit-site infection and peritonitis. The aim of this study was to compare infection rates between mupirocin and gentamicin. MethodsMultiple comprehensive databases were searched systematically to include relevant randomized controlled trials and observational studies. Pooled risk ratios (RRs) and 95% confidence intervals were calculated for the incidences of exit-site infection and peritonitis. ResultsSeven studies (mupirocin group n = 458, gentamicin group n = 448) were analyzed for exit-site infection. The risk of gram-positive exit-site infection was similar between the groups. Gram-negative exit-site infection rate was higher in the mupirocin group (RR = 2.125, P = 0.037). Six studies were assessed the peritonitis risk. There was no difference in the gram-positive and -negative peritonitis rate. ConclusionsTopical use of gentamicin is associated with fewer exit-site infections caused by gram-negative organisms. Gentamicin has comparable efficacy to mupirocin for peritonitis and gram-positive exit-site infection.

Protective Effects of Acupuncture Against Gentamicin-Induced Ototoxicity in Rats: Possible Role of Neurotrophin-3.

BackgroundThe aim of this study was to investigate the protective effects of acupuncture against gentamicin-induced ototoxicity and explore the possible protective role of neurotrophin-3 (NT-3).Material/MethodsTwenty-four rats were divided randomly into 4 groups: control group, gentamicin group, neitinggong group, and tinggong group. Rats in the gentamicin, neitinggong, and tinggong groups received intraperitoneal injection of gentamicin (100 mg/kg) for 14 consecutive days. Rats in the neitinggong and tinggong groups further received acupuncture at neitinggong or tinggong acupoints once every 2 days for 20 days. Rats in the control group received intraperitoneal injection of saline. Auditory brainstem response (ABR) was tested in all rats on the day before treatment (day 0), and again on day 14 and day 20 to determine the average threshold value of ABR for each treatment group. The expression of NT-3 in the cochlear nucleus and the inferior colliculus nucleus were detected by immunohistochemical staining.ResultsThe average threshold value of ABR was significantly higher in the gentamicin group as compared with that of the control group on day 14 (P<0.05). On day 20, the average threshold values of ABR in the neitinggong and tinggong groups were significantly lower than that of the gentamicin group (P<0.05). No statistically significant differences in NT-3 expression in the cochlear nucleus were observed among the groups (P>0.05). However, the expression of NT-3 in the inferior colliculus nucleus in both the neitinggong and tinggong groups was significantly higher than that of the gentamicin group (P<0.01).ConclusionsA decrease in NT-3 expression in the inferior colliculus nucleus may contribute to gentamicin-induced ototoxicity in rats. Acupuncture at neitinggong or tinggong acupoints effectively improved hearing, which was attributed partially to the rescue of NT-3 expression in the inferior colliculus nucleus. Therefore, preserving NT-3 expression in the auditory system may be a viable strategy to counteract gentamicin-induced ototoxicity.