Impact of Human Umbilical Cord Blood Mononuclear Cells on Gentamicin-Induced Renal Injury and Genotoxicity in Rats

Background: Acute kidney injury (AKI), also known as acute renal failure (ARF), has received considerable critical attention in recent years. Gentamicin (GM) is an antibiotic whose prolonged use results in AKI with a high mortality rate.Methods: Fifty adult female albino rats weighing 150–200 g were used. The animals were divided into five groups: the first group was the normal healthy control one, the second group received only 1 × 106 HUCB mononuclear cells (MNCs)/rat by intravenous (iv) injection, the third diseased group was given GM 100 mg/kg for 10 consecutive days by intraperitoneal injections, the fourth preventive group received 1 × 106 HUCB MNCs/rat by iv injection 24 h before gentamicin treatment, and the fifth treated group received 1 × 106 HUCB MNCs/rat by iv injection 24 h after gentamicin treatment. After 1 week of treatment, blood samples were collected, and kidneys were removed for histopathological examination.Results: Rats treated with HUCB MNCs in the treated group had a significant decrease in renal damage, low levels of biomarkers for nephrotoxicities such as serum creatinine and blood urea nitrogen, and low chromosomal aberrations compared to the diseased third group. The gene expression of KIM-1 and NGAL was decreased in response to HUCB treatment.Conclusions: HUCB MNCs have a curative effect against AKI and gentamicin-induced genotoxicity owing to their regenerative property.

Empirical Antimicrobial Therapy of Neonates with Necrotizing Enterocolitis: A Systematic Review

Objective Necrotizing enterocolitis (NEC) is an inflammatory disease of the gastrointestinal tract characterized by ischemic necrosis of the intestinal mucosa, mostly affecting premature neonates. Management of NEC includes medical care and surgical approaches, with supportive care and empirical antibiotic therapy recommended to avoid any disease progression. However, there is still no clear evidence-based consensus on empiric antibiotic strategies or surgical timing. This study was aimed to review the available evidence on the effectiveness and safety of different antibiotic regimens for NEC. Study Design MEDLINE, EMBASE, Cochrane CENTRAL, and CINAHL databases were systematically searched through May 31, 2020. Randomized controlled trials (RCTs) and nonrandomized interventions reporting data on predefined outcomes related to NEC treatments were included. Clinical trials were assessed using the criteria and standard methods of the Cochrane risk of bias tool for randomized trials, while the risk of bias in nonrandomized studies of interventions was evaluated using the ROBINS-I tool. The certainty in evidence of each outcome's effects was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results Five studies were included in this review, two RCTs and three observational studies, for a total amount of 3,161 patients. One RCT compared the outcomes of parenteral (ampicillin plus gentamicin) and oral (gentamicin) treatment with parenteral only. Three studies (one RCT and two observational) evaluated adding anaerobic coverage to different parenteral regimens. The last observational study compared two different parenteral antibiotic combinations (ampicillin and gentamicin vs. cefotaxime and vancomycin). Conclusion No antimicrobial regimen has been shown to be superior to ampicillin and gentamicin in decreasing mortality and preventing clinical deterioration in NEC. The use of additional antibiotics providing anaerobic coverage, typically metronidazole, or use of other broad-spectrum regimens as first-line empiric therapy is not supported by the very limited current evidence. Well-conducted, appropriately sized comparative trials are needed to make evidence-based recommendations. Key Points

Relationship between gentamicin administration and ductal patency in very low birth weight infants

Background: Patent ductus arteriosus (PDA) is associated with adverse clinical outcomes in very low birth weight (<1500g) infants. Objective: In our study, it was aimed to investigate the effect of gentamicin treatment, which is frequently used for early-onset sepsis on ductal patency. Method: We performed a single-center retrospective review of charts of preterm infants <32 weeks gestation with birth weight <1500 grams born between June 1, 2015, and December 31, 2019, at the neonatal intensive care unit. All infants underwent an echocardiogram (ECHO) at 72 hours. To determine the effect of gentamicin treatment on hemodynamically significant PDA (hsPDA), we compared the frequency and duration of gentamicin administration between infants with hsPDA and without hsPDA. Results: During the study period, 792 patients were evaluated. Gentamicin was given to more infants with hsPDA than to those without hsPDA (89.2 % vs. 64.6 %, p<0.001), and the duration of therapy was longer in those infants with hsPDA (7 days vs. 9 days, p<0.001). The area under the curve for duration of gentamicin was 0.772 (%95 CI: 0.742-0.804, P=0.0001), sensitivity: 59 (%95 CI: 53-65), specificity: 82 (%95 CI: 78-88), with a cut-off day for duration of gentamicin >7 days. Conclusion: In our study, it was found that ductal contraction decreased and hsPDA rate increased as the rate and duration of gentamicin increased.

Nano-Scale Modifications of Amniotic Membrane Induced by UV and Antibiotic Treatment: Histological, AFM and FTIR Spectroscopy Evidence

The efficiency of amniotic membrane (AM) transplantation in different types of ocular surface disorders is due to its outstanding properties such as antifibrotic, antibacterial, anti-inflammatory and antiangiogenic, working as a versatile scaffold to promote corneal tissue epithelialization. A proper preparation, preservation and clinical application are crucial for the best outcomes in the treatment of different severe ocular disorders, taking into account its fragility. In this context, by combining high-sensitivity tools such as atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy with histological and immunohistochemical examination, we aimed to investigate the ultrastructural modifications of the amniotic membrane (AM) upon UV exposure and/or antibiotic treatment, with relevance for clinical applications in ocular surface surgery. From the morphological point of view, we noticed a loss of cuboidal cells in the basal membrane, accompanied by the splitting of collagen fibers upon UV and/or gentamicin treatment, while structural alteration of proteins was evidenced by the FTIR quantitative analysis of the secondary structure. A decrease in α-helix and β-sheet content, accompanied by increased content in less ordered structures (turns, random and side chains), was noticed after all the treatments. At the nano-scale, AFM details showed modifications of collagen fibrils in terms of their thickness and network compaction upon gentamicin and/or UV treatment. The enzymatic digestion assay demonstrated that UV exposure significantly reduces the degradation rate of the AM, while gentamicin treatment promotes an accelerated enzymatic digestion upon UV exposure. In order to highlight the clinical impact of the research, a clinical case is presented showing the relevance of amniotic membrane transplantation in pterygium surgery.

Oxymatrine Reverses Gentamicin-Induced Nephrotoxicity via Ameliorating the Immune Response for Gentamicin Therapy

Background: The aminoglycoside antibiotic gentamicin (GM) is widely used to fight infections caused by Gram-positive and Gram-negative aerobic bacteria. However, its clinical application is limited by serious side effects. Based on this, this study aims to screen drugs that have protective effects on gentamicin-induced kidney injury. Methods : After screening a series of candidate compounds, we found that a natural quinoline alkaloid-oxymatrine showed well protective effects on GM-induced kidney injury. We used gentamicin (100 mg/ kg/d, 7 days) treatment to establish a rat model of kidney injury, and set up control groups and oxymatrine-pretreatment groups to study the protective effect of oxymatrine on kidney injury.Methods: After screening a series of candidate compounds, we found that a natural quinoline alkaloid-oxymatrine showed well protective effects on GM-induced kidney injury. We used gentamicin (100 mg/ kg/d, 7 days) treatment to establish a rat model of kidney injury, and set up control groups and oxymatrine-pretreatment groups to study the protective effect of oxymatrine on kidney injury.Results: The results indicated that Gentamicin treatment of normal rats produced marked renal damage and resulted in significant elevation of blood urea nitrogen and creatinine, as well as N-acetyl-β-D-glucosaminidase. Oxymatrine co-administration could decrease levels of IL-1β, IL-6, and TNF-α (All P <0.01 or P <0.001), as well as N-acetyl-β-D-glucosaminidase. In addition, oxymatrine treatment significantly reduced the expression of Bax and NF-κB mRNA in the kidney (both P <0.01), and increased the expression of Bcl-2, Nrf2 and HO-1 mRNA.Conclusions: The results demonstrate that oxymatrine down-regulates the inflammatory response and reduces the apoptosis by activating antioxidant defense, thereby reducing gentamicin-induced nephrotoxicity.

Serum amoxicillin levels in young infants (0–59 days) with sepsis treated with oral amoxicillin

BackgroundWHO recommends simplified antibiotics for young infants with sepsis in countries where hospitalisation is not feasible. Amoxicillin provides safe, Gram-positive coverage. This study was done to determine pharmacokinetics, drug disposition and interpopulation variability of oral amoxicillin in this demographic.MethodsYoung infants with signs of sepsis enrolled in an oral amoxicillin/intramuscular gentamicin treatment arm of a sepsis trial in Karachi, Pakistan, were studied. Limited pharmacokinetic (PK) sampling was performed at 0, 2–3 and 6–8 hours following an index dose of oral amoxicillin. Plasma concentrations were determined by high-performance liquid chromatography/mass spectrometry. Values of ≥2 mg/L were considered as the effect threshold, given the regional minimal inhibitory concentration (MIC) of resistant Streptococcus pneumoniae.ResultsAmoxicillin concentrations were determined in 129 samples from 60 young infants. Six of 44 infants had positive blood cultures with predominant Gram-positive organisms. Forty-four infants contributing blood at ≥2 of 3 specified timepoints were included in the analysis. Mean amoxicillin levels at 2–3 hours (11.6±9.5 mg/L, n=44) and 6–8 hours (16.4±9.3 mg/L, n=20) following the index dose exceeded the MIC for amoxicillin (2.0 mg/L) against resistant S. pneumoniae strains. Of 20 infants with three serum levels, 7 showed a classic dose–exposure profile and 13 showed increasing concentrations with time, implying delayed absorption or excretion.ConclusionAmoxicillin concentrations in sera of young infants following oral administration at 75–100 mg/kg/day daily divided doses exceeds the susceptibility breakpoint for >50% of a 12-hour dosing interval.Oral amoxicillin may hold potential as a safe replacement of parenteral ampicillin in newborn sepsis regimens, including aminoglycosides, where hospitalisation is not feasible.Trial registration numberNCT01027429.

Testicular toxicity of gentamicin in adult rats: Ameliorative effect of lycopene

The current study was aimed to investigate the ameliorative effect of lycopene against gentamicin-induced testicular toxicity in adult rat testes. Pretreatment with lycopene (4 mg/kg/day) significantly prevented the decrease in the absolute testes weight and relative testes weight and the reduction in sperm count, motility, viability, and daily sperm production in gentamicin (100 mg/kg/day)-treated rats. Gentamicin significantly decreased the level of serum testosterone and testicular lactate dehydrogenase-X and G6PDH activities but a marked increase was observed upon pretreatment with lycopene. Testicular caspase-3 and -9 activities were significantly increased but lycopene showed significant protection from gentamicin-induced apoptosis. Oxidative stress was induced by gentamicin treatment as evidenced by increased hydrogen peroxide level and lipid peroxidation and decreased the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and glutathione content. These alterations were effectively prevented by lycopene pretreatment. Histopathological examination showed loss of spermatogenesis and morphological abnormalities of the testis after treatment with gentamycin. These abnormalities were effectively normalized by pretreatment with lycopene. In conclusion, gentamicin decreases rat testes weight and inhibits spermatogenesis. It induces oxidative stress and apoptosis by possible mitochondrial dysfunction. These data provide insight into the mode of action of gentamicin-induced testicular toxicity and the beneficial role provided by lycopene to restore the suppressed spermatogenesis.