Effect Of Amikacin Research Articles

The gut bacterial composition across life stages of Sarcophaga peregrina (Diptera: Sarcophagidae) and the effects of amikacin on their development.

Insects and microorganisms, ubiquitous organisms in the natural world, have developed intricate relationships throughout their evolutionary histories. However, most studies have concentrated on specific time points or life stages, but some limited studies have investigated the dynamics of microbial diversity within insects across life stages. Here, 16S rDNA sequencing technology was used to investigate the gut bacterial community across the life stages of Sarcophaga peregrina (Robineau-Desvoidy) (Diptera: Sarcophagidae). The results revealed that the gut bacterial diversity of S. peregrina varied with life stage and showed similarity in the nearby life stages. Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in S. peregrina. Genera such as Providencia, Ignatzschineria, and Myroides are implicated in potentially pivotal roles during the developmental processes of this flesh fly. Furthermore, the effects of amikacin on the growth and development of S. peregrina were not statistically significant. However, we did observe significant changes at the protein level, which suggests a close association between protein-level alterations and growth and development. Additionally, we speculate that S. peregrina regulates its nutritional status during nonfeeding stages to meet the demands of eclosion. This study represents the first comprehensive examination of the intestinal bacterial composition across various life stages of S. peregrina. Our findings deepen our understanding of the gut microbiota in this flesh fly and lay the groundwork for further exploration into the intricate interactions between microorganisms and insects.

Time-dependent pharmacodynamics of amikacin on Mycobacterium abscessus growth and resistance emergence.

Mycobacterium abscessus pulmonary disease is increasing in prevalence globally, particularly for individuals with cystic fibrosis. These infections are challenging to treat due to a high rate of resistance. Amikacin is critical to treatment, but the development of toxicity, amikacin resistance, and treatment failure are significant challenges. Amikacin has been characterized previously as peak-dependent and extended-interval dosing is commonly used. In our hollow fiber infection model of M. abscessus, amikacin exhibited time-dependent rather than the expected peak-dependent pharmacodynamics. Humanized amikacin exposures with more frequent, short-interval dosing (continuous infusion or every 12 hours) yielded improved microbiological response compared to extended-interval dosing (every 24 hours or 1-3 times per week). Short-interval dosing inhibited growth with a mean (SD) maximum Δlog10 colony forming units of -4.06 (0.52), significantly more than extended-interval dosing (P = 0.0013) every 24 hours, -2.40 (0.58), or 1-3 times per week, -2.39 (0.38). Growth recovery, an indicator of resistance emergence, occurred at 6.56 (0.70) days with short-interval dosing but was significantly earlier with extended-interval dosing (P = 0.0032) every 24 hours, 3.88 (0.85) days, and 1-3 times per week, 3.27 (1.72) days. Microbiological response correlated best with the pharmacodynamic index of %T > minimum inhibitory concentration (MIC), with an EC80 for growth inhibition of ~40%T > MIC. We used a previously published population model of amikacin to determine the probability of achieving 40%T > MIC and show that current dosing strategies are far below this target, which may partially explain why treatment failure remains so high for these infections. These data support a cautious approach to infrequent amikacin dosing for the treatment of M. abscessus.IMPORTANCEPulmonary disease caused by Mycobacterium abscessus complex (MABSC) is increasing worldwide, particularly in patients with cystic fibrosis. MABSC is challenging to treat due to high levels of antibiotic resistance. Treatment requires 2-4 antibiotics over more than 12 months and has a significant risk of toxicity but still fails to eradicate infection in over 50% of patients with cystic fibrosis. Antibiotic dosing strategies have been largely informed by common bacteria such as Pseudomonas aeruginosa. The "pharmacodynamic" effects of amikacin, a backbone of MABSC treatment, were thought to be related to maximum "peak" drug concentration, leading to daily or three times weekly dosing. However, we found that amikacin MABSC kill and growth recovery, an indicator of antibiotic resistance, are dependent on how long amikacin concentrations are above the minimum inhibitory concentration, not how high the peak concentration is. Therefore, we recommend a re-evaluation of amikacin dosing to determine if increased frequency can improve efficacy.

Renal Wasting of Electrolytes: Effect of Amikacin Used to Treat Infections - Tip of Iceberg for the Physicians

Objective: To measure prospectively the effect of treatment with the Amikacin on renal magnesium, potassium and phosphate wasting in patients with extrarenal infections. Study Design: Case series. Place and Duration of Study: Department of Nephrology, Pak Emirates Military Hospital, Rawalpindi Pakistan from Jul toDec 2019. Methodology: A total of 40 cases were included in this study in liaison with other departments who were put on Amikacinstandard dose. Urinary electrolytes including potassium, magnesium and phosphate were measured at day 4 after the use of Amikacin. Factors like age, gender, cause for which Amikacin was used, day 1 creatinine and day 4 creatinine were correlated with presence of electrolyte wasting in the target population. Results: Mean age of study participants was 39.1±12.56 years. 25(62.5%) were males while 15(37.5%) were females. Commonest cause for the use of Amikacin was drug resistant tuberculosis followed by fractures. Mean urinary magnesium was 39.1±12.56 mmol/24 hours, while potassium was 26.1±15.60 meq/24 hours. Mean phosphate was 66.4±53.55 mg/24 hours. Pearson chi-square test revealed that advanced age and day 4 creatinine were strongly linked with the presence of urinary electrolyte wasting among the patients receiving Amikacin for extra-renal infections with p-value<0.05. Conclusion: Electrolyte wasting emerged as a common finding in the patients put on Amikacin suffering from extra renal infections. Patients with advancing age put on Amikacin should be given special attention and screened for electrolyte wasting at priority. ..

Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant Acinetobacter baumannii.

Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant Acinetobacter baumannii at the clinical dose. When polymyxins, aminoglycosides, and sulbactam are co-administered, the combinations exhibit in vitro synergistic activities. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in 11 and 5 clinical resistant isolates of A. baumannii harboring OXA-23, respectively, in order to derive the fraction of time over the 24-h wherein the free drug concentration was within the mutant selection window (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT>MPC) from simulated pharmacokinetic profiles. The combination of these three antibiotics can confer susceptibility in multi-drug resistant A. baumannii and reduce the opportunity for bacteria to develop further resistance. Clinical intravenous dosing regimens of amikacin, polymyxin-B, and sulbactam were predicted to optimize fTMSW and fT>MPC from drug exposures in the blood. Mean fT>MPC were ≥ 60% and ≥ 80% for amikacin and polymyxin-B, whereas mean fTMSW was reduced to <30% and <15%, respectively, in the triple antibiotic combination. Due to the low free drug concentration of amikacin and polymyxin-B simulated in the epithelial lining fluid, the two predicted pharmacodynamic parameters in the lung after intravenous administration were not optimal even in the combination therapy setting.

Microtiter plate with built-in oxygen sensors: a novel approach to investigate the dynamics of Pseudomonas aeruginosa growth suppression in the presence of divalent cations and antibiotics

The depletion of dissolved oxygen in a defined synthetic medium can be measured in real time, using a micro-well plate format, associated with a fluorescent plate reader. This technology is appropriate for investigating the effect of antibiotics on cell kinetics because there is a direct correlation between the latter and the amount of dissolved oxygen in the medium of an assay. In this study, the metabolic activity of the opportunistic human pathogen Pseudomonas aeruginosa PA01 was investigated using the OxoPlate OP96U optical sensor technology. The response of P. aeruginosa to aminoglycoside antibiotics when Ca2+and Mg2+ ions are present in the Evans defined synthetic medium was measured. The results revealed that the effect of antibiotics on P. aeruginosa is influenced by the concentration of divalent cations present in the test medium, although the efficiency of Ca2+ in supressing antibiotic activity was found to be greater than that of Mg2+. By comparison to tobramycin, the effect of amikacin is largely inhibited by the Ca2+and Mg2+concentrations. The study results underscore that the reliability of the observation of growth inhibitors is enhanced by the oxygen consumption measurements. Thus, the OxoPlate OP96U system is proven to be an accurate method to test the effectiveness of antibiotic treatments against P. aeruginosa.

Increment of Lysosomal Biogenesis by Combined Extracts of Gum Arabic, Parsley, and Corn Silk: A Reparative Mechanism in Mice Renal Cells.

Gum Arabic (GA), parsley, and corn silk have been traditionally used for renal failure patients worldwide. This study aimed at probing the mechanism of the combined extracts, namely, GA (3 g/kg/day), parsley (1 g/kg/day), and corn silk (200 mg/kg/day), as nephroprotective agents in mice after amikacin (1.2 g/kg) single dose through exploration of their action on G-protein coupled receptors (GPR) 41 and 43 and the ensuing lysosomal biogenesis. Western blotting was employed for renal levels of bcl-2-associated X protein (BAX) and cytosolic cathepsin D; cell death markers, nuclear transcription factor EB (TFEB), and lysosomal associated membrane protein-1 (LAMP-1); and lysosomal biogenesis indicators. Liquid chromatography–mass spectrometry (LC-MS) and docking were also employed. After amikacin treatment, BAX and cathepsin D levels were upregulated while LAMP-1 and nuclear TFEB levels were inhibited. The combined extracts inhibited BAX and cytosolic cathepsin D but upregulated LAMP-1 and nuclear TFEB levels. Docking confirmed GPR modulatory signaling. The combined extracts showed GPR signal modulatory properties that triggered lysosome synthesis and contributed to reversing the adverse effects of amikacin on renal tissues.

Mitigation of Antibiotic-Inducted Toxicity in Equine Chondrocytes by Soybean/Glucosamine/Chondroitin Combination

Objectives The aim of this study was to evaluate the effect of amikacin (AK) and enrofloxacin (EF) at concentrations consistent with those obtained by intra-articular and intravenous regional limb perfusion on both cytotoxicity and prostaglandin E2 (PGE2) production by equine chondrocytes. This study also determines if PGE2 production could be reduced by avocado/soybean unsaponifiables (ASU), glucosamine (GLU) and chondroitin sulphate (CS). Study Design Chondrocytes were grown in monolayer from the articular cartilage of 12 horses and treated with clinically relevant concentrations of AK and EF, with or without the combination of ASU + GLU + CS. Positive controls consisted of chondrocytes that were activated with lipopolysaccharide (LPS). Chondrocyte response was evaluated using both MTT cytotoxicity assay and immunoassay for PGE2 production. Results Amikacin and EF generated a dose-dependent cytotoxicity. Amikacin induced 90% cell death at a concentration of 25 mg/mL. Enrofloxacin induced 90% cell death at 1.0 mg/mL and 98% cell death at 10 mg/mL (p &lt; 0.05). Amikacin failed to induce PGE2 production at any of the concentrations studied. In contrast, EF and the positive control (LPS) induced PGE2 production at all concentrations. Induction of PGE2 by EF at all concentrations was significantly reduced (p &lt; 0.05) by pre-treatment with ASU + GLU + CS. Conclusions and Clinical Relevance Horses receiving commonly used dosages of AK and EF may benefit from administration of ASU + GLU + CS.

Role of M.tuberculosis protein Rv2005c in the aminoglycosides resistance

Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis which threatens the globe. Aminoglycosides {Amikacin (AK) & Kanamycin (KM)} are WHO recommended second-line anti-TB drugs used against the treatment of drug-resistant tuberculosis. Aminoglycosides target the steps of protein translation machinery of M.tuberculosis. Several mechanisms have been put forward to elucidate the phenomena of aminoglycosides resistance but our knowledge is still insufficient. The aim of the study was to understand the involvement of Mycobacterium tuberculosis universal stress protein (Rv2005c) in aminoglycosides resistance and virulence. To establish the relationship of universal stress protein Rv2005c with AK & KM resistance, Rv2005c was cloned, expressed in E.coli BL21 using pQE2 expression vector and antimicrobial drug susceptibility testing (DST) was carried out. STRING-10 was also used to predict the interacting protein partners of Rv2005c. DST showed that the minimum inhibitory concentration of induced recombinant cells (Rv2005c) were five and four folds shifted with AK and KM E-strips, respectively. STRING-10 showed the interacting protein partners of Rv2005c. Overexpression of Rv2005c leads to shifting in MIC which might be signifying its involvement in the survival/resistance of Mycobacteria by inhibiting/modulating the effects of AK and KM released from the E-strips. Interactome also suggests that Rv2005c and its interacting protein partners are cumulatively involved in M.tuberculosis resistance, stresses, and latency.

Catheter-associated bacterial flora in patients with benign prostatic hyperplasia: shift in antimicrobial susceptibility pattern

BackgroundMen with urinary retention secondary to benign prostatic hyperplasia (BPH) are prone to genitourinary infections. Physicians should be aware of the current antimicrobial susceptibility pattern in this population if empirical treatment is needed. The goal of this study was to evaluate variations in prevalence, composition and antimicrobial susceptibility of bacterial flora in men with indwelling catheters subjected to surgery for BPH in chosen time periods since 1994. Necessary changes in empirical therapy were also assessed.MethodsAll patients with indwelling catheters admitted to a single urological center for BPH surgery in the years 1994–1996, 2004–2006, and 2011–2015 were considered. Catheterization times and results of urine cultures from samples collected at admission were evaluated. Susceptibility for selected antimicrobials was compared separately for Gram negative and Gram positive species. For each agent and for their combinations effectiveness of empirical therapy was calculated dividing the number of patients with bacteriuria susceptible to the agents by the total number of patients with bacteriuria.ResultsBacteriuria was present in 70% of 169, 72% of 132, and 69% of 156 men in the respective time periods. The incidence of Gram-positive strains increased from 10 to 37% (P < 0.001). Their susceptibility to amoxicillin/clavulanate was fluctuating (81, 61, 77%; P=NS). No vancomycin-resistant strain was present. Gram-negative flora composition was stable. Their susceptibility decreased to ciprofloxacin (70 to 53%; P = 0.01) and amoxicillin/clavulanate (56 to 37%; P < 0.01) while it increased to gentamycin (64 to 88%; P < 0.001) and co-trimoxazole (14 to 62%; P < 0.001); susceptibility to amikacin remained high (> 85%). Only two cases of resistance to carbapenems in 2004–2006 were found. In vitro effectiveness of amikacin + amoxicillin/clavulanate in empirical therapy was slowly decreasing (87 to 77%; P=NS). Imipenem was found the most effective single agent (90–95%) and its efficacy was even improved by adding vancomycin (97–98%).ConclusionsSubstantial rise in the incidence of Gram-positive species and fluctuations in antimicrobial susceptibility patterns were found. Empirical therapy of genitourinary infection in catheterized men with BPH should now involve antimicrobial agents effective both to Enterococci and Enterobacteriaceae. Periodic monitoring and publishing data on antimicrobial susceptibility for this population is necessary.

Evaluation of greater wax moth larvae, Galleria mellonella, as a novel in vivo model for non-tuberculosis Mycobacteria infections and antibiotic treatments.

To evaluate the suitability of Galleria mellonella larvae as an in vivo model and drug-screening tool for mycobacteria infections. Larvae were infected using a range of inoculum sizes from a variety of rapid-growing mycobacteria, including strains of M. fortuitum, M. marinum and M. aurum. Larval survival, internal bacterial burden and the effects of amikacin, ciprofloxacin, ethambutol, isoniazid and rifampicin treatment on larval survival were measured over 144 h. The effects of these anti-mycobacterial drugs on phagocytosis and circulating haemocyte numbers were also examined using microscopy. Larval survival decreased after infection with M. fortuitum and M. marinum in a dose-dependent manner, but remained unaffected by M. aurum. Heat-killed bacteria did not cause larval death. Where antibiotic monotherapy was efficacious, larval survival post-infection increased in a dose-dependent fashion. However, efficacy varied between different antibiotics and species of infecting mycobacteria and, apart from rifampicin, efficacy in vivo correlated poorly with the in vitro minimum inhibitory concentrations (MICs). Combinations of antibiotics led to higher survival of infected larvae than antibiotic monotherapy. Selected antibiotic treatments that enhanced larval survival reduced the overall internal burden of infecting mycobacteria, but did not eradicate the pathogens. Administration of amikacin or ethambutol to uninfected larvae induced an initial transient increase in the numbers of circulating haemocytes and reduced the phagocytic rate of haemocytes in larvae infected with M. marinum. This report demonstrates the potential of employing a wax moth larvae model for studying fast-growing mycobacteria infections, and as a cheap, effective system for initial screening of novel treatments.

Effect of amikacin on cell wall glycopeptidolipid synthesis in Mycobacterium abscessus.

Cultivation of the smooth colony Mycobacterium abscessus at the sub-minimum inhibitory concentration (MIC) of amikacin changed its growth pattern including its colony morphology (smooth to rough) and cell arrangement (dispersed to cord formation). In addition, reduced sliding motility and biofilm formation were observed. The amount of glycogpetidolipid (GPL) and mRNA expression of key genes involved in GPL synthesis were decreased in the amikacin-treated M. abscessus strain. An in vitro infection assay revealed that the amikacin-treated smooth M. abscessus strain induced more pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) than that of the smooth strain in murine macrophage cells. These results suggest that long-term exposure to a low concentration of amikacin causes a physical change in the cell wall which may increase its virulence.

M. tuberculosis ferritin (Rv3841): Potential involvement in Amikacin (AK) & Kanamycin (KM) resistance

Tuberculosis is an infectious disease, caused by one of the most successful human pathogen, Mycobacterium tuberculosis. Aminoglycosides, Amikacin (AK) & Kanamycin (KM) are commonly used to treat drug resistant tuberculosis. They target the protein synthesis machinery by interacting with several steps of translation. Several explanations have been proposed to explain the mechanism of aminoglycoside resistance but still our information is inadequate. Iron storing/interacting proteins were found to be overexpressed in aminoglycosides resistant isolates. Iron assimilation and utilization in M. tuberculosis plays a crucial role in growth, virulence and latency. To establish the relationship of ferritin with AK & KM resistance ferritin (Rv3841/bfrB) was cloned, expressed and antimicrobial drug susceptibility testing (DST) was carried out. Rv3841/bfrB gene was cloned and expressed in E. coli BL21 using pQE2 expression vector. Etest results for DST against AK & KM showed that the minimum inhibitory concentration (MIC) of ferritin recombinant cells was changed. Recombinants showed two fold changes in MIC with AK and three fold with KM E-strips. Overexpression of ferritin reflect the MIC shift which might be playing a critical role in the survival of mycobacteria by inhibiting/modulating the effects of AK & KM. String analysis also suggests that ferritin interacted with few proteins which are directly and indirectly involved in M. tuberculosis growth, Iron assimilation, virulence, resistance, stresses and latency.

Cloning, Expression and Correlation of Rv0148 to Amikacin &amp; Kanamycin Resistance

Mycobacterium tuberculosis causes tuberculosis, one of the leading causes of fatal infectious diseases worldwide. Aminoglycosides, Amikacin (AK) & Kanamycin (KM) are commonly used in tuberculosis treatment and are drugs of choice especially for category II patients. They inhibit protein synthesis in susceptible bacteria by interacting with several steps of translation. Several explanations have been put forward to explain the mechanism of aminoglycoside resistance but still our knowledge is fragmentary. Rv0148 was found to be overexpressed in AK & KM resistant isolates. To establish the relationship of Rv0148 with AK & KM resistance it was cloned, expressed and antimicrobial drug susceptibility testing (DST) was carried out. Gene was cloned and expressed in E.coli BL21 using pQE2 expression vector. Etest results for drug susceptibility testing against AK & KM showed that the MIC of recombinant cells with Rv0148 was altered. Recombinants showed three fold changes in MIC with AK and two fold with KM E-strips. These MIC shifts speculate, overexpression of Rv0148 protein might be playing a pivotal role in the survival of mycobacteria by inhibiting/modulating the effects of AK & KM. Keywords: Amikacin, Cloning & Expression, Etest, Kanamycin, Rv0148.

Susceptibility of different phases of biofilm of Klebsiella pneumoniae to three different antibiotics

The existence of majority of bacteria in biofilm mode makes it difficult to eradicate them as antibiotics at much higher concentrations than the MICs are required to destroy these bacteria. This study investigated the effect of different classes of antibiotics on different phases of biofilm formed by Klebsiella pneumoniae. The organism was grown in different phases relevant to biofilm formation: planktonic cells at mid-log phase, planktonic cells at stationary phase, adherent monolayers and mature biofilms and their susceptibility to different classes of antibiotics was assessed. The results showed that planktonic organisms were susceptible to ciprofloxacin, amikacin and piperacillin, and their MBC values were same or eight times higher than their corresponding MICs. MBC of ciprofloxacin and amikacin was found to be four and eight times higher for monolayer than planktonic cells. On the other hand, MBC of piperacillin was >1024 μg ml(-1). K. pneumoniae in a biofilm growth mode was more resistant to antibiotics than all other modes. The effect of amikacin and ciprofloxacin on young and older biofilms, at the highest achievable serum concentrations, was also examined. It was observed that amikacin at a concentration of 40 μg ml(-1) was able to eradicate the young biofilms; however, with increase in the age of the biofilm, it became completely ineffective. Calcofluor staining suggested increased production of exopolysaccharide in older biofilm compared with younger biofim that might be responsible for the increased resistance of older biofilm of K. pneumoniae to antibiotics.

Effects of Amikacin on Maturation of the Auditory Analyzer in Rabbits

We studied the dynamics of maturation of the hearing function by records of short-term latent brainstem evoked potentials and the effect of amikacin on maturation of the hearing function. The peripheral compartment of the auditory analyzer matures sooner than the central structures. Amikacin in therapeutic doses exhibited an ototoxic effect on the peripheral compartment of the auditory analyzer without impairing its central structures.

The effects of amikacin on autonomic and neuromuscular transmission [proceedings

Journal Article The Effects of Amikacin on Autonomic and Neuromuscular Transmission Get access Y N Singh, Y N Singh Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1XW Search for other works by this author on: Oxford Academic Google Scholar I G Marshall, I G Marshall Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1XW Search for other works by this author on: Oxford Academic Google Scholar A L Harvey A L Harvey Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1XW Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 29, Issue Supplement_1, December 1977, Page 50P, https://doi.org/10.1111/j.2042-7158.1977.tb11518.x Published: 12 April 2011

Effect of amikacin on the expression of phosphorylated JNK in cochlea of guinea pig

Effect of amikacin on the expression of phosphorylated JNK in cochlea of guinea pig

Inhibition of amikacin on platelet aggregation and blood coagulation

Objective To observe the inhibition of amikacin in vitro on platelet aggregation and blood coagulation tests, and to study its effects on hemostasis and the related mechanisms.Methods Plateletrich plasma and platelet-poor plasma from donors were mixed with different concentration of amikacin, which was divided into four groups:0 mg/L, 30 mg/L, 91 mg/L and 910 mg/L group.The maximial ratio of platelet aggregation induced by ADP were measured with Platelet Aggregation Analyzer.The expression levels of P-selectin, GP Ⅱ b/Ⅲ a and Fg-R were determined with Flow Cytometer.The PT, APTT, TT and Fg of platelet-poor plasma were detected with Blood Coagulation Analyzer. The four concentration of amikacin mentioned above and two anticoagulants (62.5 U/ml of sodium heparin and 109 mmol/L of sodium citrate)were interacted with fresh whole blood, in which the blood CT and plasma Ca2+ were detected. Blood samples were collected from 10 patients with acute lower respiratory tract infection before and 30 minutes after routine amikcin treatment respectively.The maximial ratio of platelet aggregation, the expression levels of P-selectin, GPⅡ b/Ⅲa and Fg-R induced by ADP were measured; while PT, APTT, CT and plasma Ca2+ were determined.Results At 30 mg/L of amikacin group, the maximal ratios of platelet aggregation (65.8±3.9)%, the expression levels of P-selectin (9.2 ± 1.0)% and Fg-R (12.6 ± 1.7)% were statistically lower than those [(88.0 ±4.6%, (16.1 ± 1.3)% and (31.0 ±2.5)%]at 0 mg/L of amikacin group ( t = 9.442,8.432,9.993,P ＜ 0.01 ).At 30 mg/L of amikacin group, the APTT (80.5 ±6.8) s and CT ( 857 ± 66) s were significantly higher than those [(33.0 ± 3.6) s and (447 ± 35 ) s] at 0 mg/L of amikacin group ( t = 11.312, 13.211, P ＜ 0.01 ). There was a negative correlation between amikacin concentration and maximial ratio of platelet aggregation ( r = - 0.832, P ＜ 0.05 ), but a positive correlation between amikacin concentration and inhibitory rates of platelet aggregation ( r = 0.939, P ＜0.05) was observed, as well as APTT (r ＞0.870, P＜0.05).At 30 mg/L, 91 mg/L, and 910 mg/L of amikacin groups, the P-selectin and Fg-R expression were remarkably inhibited with a dose-dependent manner, the CT was notably enhanced [Fwithin subjects =21.44, 26.24, ( ＞29.81 ), P ＜0.01].At 0 mg/L,30 mg/L, 91 mg/L and 910 mg/L of amikacin groups, the PT values were ( 14.7 ± 1.9) s, ( 15.2 ± 1.7) s,(15.6±1.5) s and (22.1 ±2.1) s, respectively (F=8.21,P＜0.05), but there was no markeddifference for the levels of GP Ⅱ b/Ⅲ a, TT, Fg and plasma Ca2+ among the four groups ( P ＞ 0.05 ).After 30 minutes of amikacin treatment, the maximial ratio of platelet aggregation (51.6 ± 10.1)%, the expression levels of P-selectin (6.8 ± 1.8) % and Fg-R ( 20.1 ± 5.8 ) % were significantly lower than those [(66.8 ± 11.4)%, ( 10.9 ±3.1 )% and (28.5 ±7.4)%] before amikacin treatment, but APTT (49.8 ±5.9) s and CT (660 ±59) s were remarkably higher than those [(26.9 ±3.8) s and (410 ±45) s] before amikacin treatment, respectively ( t = 5.456,8.875,7.423,10.012,11.322, P ＜ 0.01 ), while the GP Ⅱ b/Ⅲ a expression, PT and Ca2+ concentration had no significant changes ( P ＞ 0.05).Conclusions There are inhibitory effects of amikacin on platelet aggregation mainly through the inhibition of both fibrinogen receptor activation and secretion reaction of activated platelet. Amikacin may also inhibit pathway of coagulation system factor to prevent blood coagulation.Therefore, risk of hemorrhage may be investigated in the patients with amikacin for anti-infection treatment. Key words: Amikacin; Platelet aggregation; Blood coagulation; Receptors,fibrinogen

Effect of Amikacin on the Postnatal Development of the Cochlea in Albino Rats

Background: The cochlea is the anterior part of the labyrinth and its development is sensitive to large variety of noxious influences. Aim of the Work: This work was conducted to study the effect of amikacin on the postnatal development of cochlea in albino rats. Material and Methods: A total number of 30 albino rats were divided into two groups, a control group and an experimental group. The ages studied in this research were newborn, 7 days, 15 days, 1 month and 3 months postnatally in both control and experimental groups. The pregnant mothers of the experimental group received 250 mg/kg body weight of amikacin intraperitoneally daily from day 10 of gestation until the end of pregnancy. The same dose was given to the offsprings from day 1 until day 16 postnatally. The specimens were processed for histological study and stained with H&E. Ultrastructural study of the inner and outer hair cells and the large spiral ganglion cells was done through preparation of semithin and ultrathin sections. Morphometric measurements were performed to study the number of spiral ganglion cells in all the studied groups and were statistically analyzed. Results: This study revealed that the cochlea was still immature at birth and reached the adult appearance at the age of 15 days postnatally. The cochlear structures including the organ of Corti were found to be mature from the base to the apex of the cochlea. We observed that amikacin has no apparent effect on development of the cochlea in the newborn rats. In the 7-day-old rats, some degenerative changes appeared in the outer and inner hair cells. This effect became manifested in 15-day-old animals. Ultrastructural study of the outer hair cells showed peripheral condensation of nuclear chromatin with presence of many cytoplasmic vacuoles. At 1-month-age, there was disorganization of the organ of Corti, where atypical cells found in the region of the outer hair cells while the inner hair cells showed signs of degeneration. At the age of three months, there was complete destruction of the organ of Corti along the whole cochlea. Morphometric study for the number of the spiral ganglion cells showed highly significant decrease in the amikacin treated animals at the age of 15- day-old rats. This decrease became very highly significant at the age of one month and three months old amikacin treated rats Conclusions: Amikacin has a damaging effect on the organ of Corti and so considered as one of the causes of sensory deafness. The effect of amikacin was manifested during the second postnatal week is corresponding to the period of maturity of the cochlea.

Effects of Pentoxifylline on Amikacin-Induced Nephrotoxicity in Rats

The nephrotoxicity of amikacin (AK) was prevented with pentoxifylline (PTX) in a rat model. Rats were received a single injection of AK (1.2 g/kg, i.p.) with or without PTX pretreatment (25 mg/kg, orally). Renal morphology was investigated by light microscopy. Tissue samples and trunk blood were also obtained to determine renal malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine (Cr) levels. MDA production was found to be higher in AK group. PTX administration caused a significant decrease in MDA production. Morphological damage in rats given AK was severe in the kidney, whereas in rats given AK plus PTX, no histological changes occurred. It is concluded that PTX could be useful for reducing the nephrotoxic effects of AK.