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The aim of this study was to assess the in vitro adsorption of antibiotics: vancomycin, gentamicin, ciprofloxacin and tigecycline on both polyethyleneimine-treated polyacrylonitrile membrane of AN69ST filter and polysulfone membrane of AV1000 filter using porcine blood as a model close to in vivo conditions. The porcine blood with antibiotic dissolved in it was pumped into hemofiltration circuit (with AN69ST or AV1000 filter), ultrafiltration fluid was continuously returned to the reservoir containing blood with antibiotic. Blood samples to determine antibiotic concentrations were taken at minutes 0, 5, 15, 30, 45, 60, 90 and 120 from the pre- blood pump of the hemofiltration circuit. To assess possible spontaneous degradation of the drug in the solution there was an additional reservoir prepared for each antibiotic, containing blood with the drug, which was not connected to the circuit. In the case of vancomycin, ciprofloxacine and tigecycline, a statistically significant decrease in the drug concentration in the hemofiltration circuit in comparison to initial value as well as to the concentrations in the control blood was observed, both for polyacrylonitrile and plolysulfone membrane. In the case of gentamicin, significant adsorption was noted only on polyacrylonitrile membrane. Our studies demonstrated that in full blood adsorption of antibiotics may be big enough to be of clinical significance. In particular in the case of polyacrylonitrile membrane. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the adsorption of selected antibiotics: vancomycin, gentamicin, ciprofloxacine and tigecycline in an experimental continuous veno-venous hemofiltration circuit with the use of both polyethyleneimine-treated polyacrylonitrile (PAN) and the polysulfone (PS) filter membranes. The crystalloid fluid dosed with one of antibiotic was pumped from a reservoir through a hemofiltration circuit (with PAN or PS membrane) and back to reservoir. All ultrafiltrate was also returned to the reservoir. During the procedures samples were collected from the post-hemofilter port at 5, 15, 30, 45, 60, 90, and 120 min. To determine spontaneous degradation of the antimicrobials, an additional bag with each study drug was prepared, which was not attached to the hemofiltration circuit. The samples from these bags were used as controls. In the case of vancomycin, gentamycin and tigecycline there was a statistically significant decrease in the drug concentration in the hemofiltration circuit in comparison to the control for PAN membrane (P < 0.05, P < 0.001, P < 0.001, respectively). In the case of ciprofloxacine adsorption was reversible and the drug concentrations increase to achieve the initial level for both membranes. Our studies indicated that a large portion of the administered dose of antibiotics may be adsorbed on a PAN membrane. In the case of gentamicin and tigecycline this amount is sufficiently big (over 90% of the administered dose) to be of clinical importance. In turn, adsorption on PS membranes is clearly lower (up to 10%) and may be clinically unimportant. [ABSTRACT FROM AUTHOR]

Gentamycin (GM) is a widely used antibiotic for the treatment of Gram-negative bacterial infections, but nephrotoxic effects limit its use. Selenium nanoparticles (SeNPs) have attracted worldwide research interest due to their high bioavailability and potential antioxidant property. This study was, therefore, designed to examine the protective effect of SeNPs on GM-induced changes in body and kidney weights, blood hematology, serum biochemistry parameters, and renal tissue markers of oxidative stress in female mice. GM was administered intraperitoneally (100 mg/kgb.w) and SeNPs were given by oral gavage (2 mg/kg b.w) for 10 consecutive days. GM treatment caused significant changes in the body and relative kidney weights and significant renal damage, evidenced by increased serum levels of urea, uric acid, creatinine, total proteins, and blood urea nitrogen (BUN), along with noteworthy histopathological alterations. A marked decrease in serum sodium and potassium ions, and kidney tissue antioxidative defense system (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) was observed in GM-treated mice when compared with the normal mice. Furthermore, significant decrease in total white blood corpuscles (WBC) count, total platelets count (PLT), total red blood corpuscles (RBC) count, hemoglobin concentration (Hgb), and packed cell volume (PCV) was also revealed in GM-treated group. However, GM + SeNPs group had effectively reversed GM-induced alteration of both biochemical and renal histological structures. Our results suggested for the first time that SeNPs are potent antioxidant candidate against GM-induced oxidative kidney toxicity and hematoxicity in mice. [ABSTRACT FROM AUTHOR]

The aim of this study is to review the literature on sustained-release vehicles delivering gentamycin in the inner ear of patients suffering from Meniere's disease (MD), and critically assess their respective clinical effectiveness and safety. A systematic literature review was conducted in Medline and other database sources until January 2016, along with critical analysis of pooled data. Overall, six prospective and four retrospective studies were systematically analyzed. The total number of treated patients was 320. A 2 year patient follow up was only reported in 40 % of studies. Inner ear gentamycin delivery using sustained-release vehicles is associated with improved vertigo control (strength of recommendation B), and quality of life (strength of recommendation B) in MD sufferers. In addition, dynamic-release devices seem to achieve high rates of improvement in the appearance of tinnitus (65.4 %) and aural pressure (76.2 %). By contrast, percentages of complete and partial hearing loss appear unacceptably high (31.08 and 23.38 % of patients, respectively), compared to historical data involving simple intratympanic gentamycin injections. Sustained-release vehicles for gentamycin delivery may have a role in the management of MD patients who have previously failed intratympanic gentamycin injections, or those who have already lost serviceable hearing. Their use as first line treatment over single intratympanic injections for all MD patients, who do not respond to conservative treatment should be discouraged. [ABSTRACT FROM AUTHOR]

Background The intratympanic application of the ototoxic aminoglycoside gentamicin has shown promising results as an ablative treatment for vertigo associated with Ménière's disease. Objective To evaluate the efficacy and safety of intratympanic gentamicin and to specifically analyse the effect of this treatment on high and low hearing frequencies in patients with unilateral definite Ménière's disease. Method Subjects were treated with intratympanic gentamicin and were evaluated on vertigo, tinnitus, mean pure tone audiometry threshold and speech discrimination score. Subjects were followed for evaluation for up to 2 years after treatment. Results The number of vertigo spells per month decreased and subjects experienced less tinnitus. During follow up there was an increase of hearing loss in the low (0.25-, 0.5-, 1-kHz) frequency range (13.3 dB; p = 0.03). There was no significant increase of hearing loss in the high (2-, 4-, 8-kHz) frequency range. A clinically significant change in speech discrimination score was found in 50 % of the subjects. Conclusion Our results indicate that intratympanic gentamicin especially affects the mean pure tone audiometry threshold in the low frequency range, which may have clinical implications. Though many of our results are (statistically) substantial the study was limited by the small cohort size. [ABSTRACT FROM AUTHOR]

The frequent use of gentamycin (GM) ointment for the treatment of skin infections has led to an increase in the number of GM-resistant clinical isolates of Staphylococcus aureus. We examined the ultrastructural characteristics of 14 clinical strains of S. aureus by transmission electron microscopy. Seven of these isolates were GM-resistant, and seven isolates were GM-sensitive. We found that the cell wall of GM-resistant strains (32.24 ± 5.99 nm) was significantly thicker than that of GM-sensitive strains (19.02 ± 2.72 nm). We genetically characterized these isolates by polymerase chain reaction, targeting the genes for three aminoglycoside-modifying enzymes, aac(6′)- aph(2′′), aph(3′)- III, and ant(4′)- I. All GM-resistant strains tested carried the gene encoding aac(6′)- aph(2′′). However, we were unable to establish a link between a specific gene and cell wall thickening, because one GM-resistant strain was also positive for aph(3′)- III. We also demonstrated that a GM-resistant mutant strain, derived in vitro from a GM-sensitive S. aureus parent strain (209P), also exhibited a thickened cell wall. These results strongly suggest that a thickened cell wall is a common ultrastructural characteristic of GM-resistant S. aureus clinical strains. [ABSTRACT FROM AUTHOR]

The transfer of aminoglycoside antibiotics streptomycin, kanamycin, and gentamycin induced by dibenzo-18-crown-6 is studied by voltammetry at the interface of two immiscible electrolyte solutions ( ITIES). An assumption about the 1: 1 stoichiometry of the complexes formed is formulated. The method is proposed for use in the analysis of kanamycin and streptomycin in aqueous solutions. The optimal conditions of analysis of these aminoglycosides are found, the detection limits are 8.0 × 10 M for streptomycin and 2.0 × 10 M for kanamycin. The selectivity of streptomycin analysis by ITIES voltammetry in presence of potassium and sodium is studied. An amperometric ion-selective electrode is developed for the determination of streptomycin in drug formulations with a detection limit of 9.0 × 10 M. [ABSTRACT FROM AUTHOR]

Mycoplasma conjunctivae are etiological agents of infectious keratoconjunctivitis (IKC), commonly known as pink-eye in domestic sheep, goats and other wild animals in many parts of the world. A few young Lohi lambs maintained at Livestock Experiment Station (LES), Bahadurnagar, Okara, Pakistan showed clinical signs and symptoms of conjunctivitis, keratitis, severe lacrimation and varying degree of blindness. During January to March, 2011, a total of 36 ocular swabs were collected from IKC affected animals and were processed for isolation, identification, and characterization of M. conjunctivae. Sixteen (44.44 %) out of 36 samples showed turbidity in PPLO broth. Twelve (75 %) out of 16 broth samples showed colony growth on PPLO agar. All 16 (44.44 %) out of 36 turbid broth samples, 12 (75 %) out of 16 cultured on agar plate samples, and 21 (59 %) out of 36 sheep ocular direct swab samples were found positive for M. conjunctivae through polymerase chain reaction test by using M. conjunctivae-specific primer pair McoF1 and McoR1 and detecting a 750 base pair fragment on agarose gel. Topical application of 0.5 % sterile solution of gentamycin (100 mg/ml) (Gentafar 10 %, FARVET, Netherlands) proved suitable for the treatment of IKC in Lohi lambs as all clinical signs of IKC disappeared after 5 days of treatment with this antibiotic. This is the first report about the prevalence, molecular diagnosis, and treatment of M. conjunctivae in Lohi sheep affected with infectious keratoconjunctivitis at LES, Bahadurnagar, Okara, Pakistan. [ABSTRACT FROM AUTHOR]

BACKGROUND: The influence of topical intraoperative gentamycin on long term recurrence rate in primary pilonidal sinus surgery has not yet been investigated. METHODS: One hundred and eight-seven patients following excision of primary pilonidal sinus disease (PSD) and primary symmetrical midline closure were analysed regarding the use (group 1) or non-use (group 2) of topical application of an intraoperative gentamycin sponge after a median follow-up of 16 years by a specific questionnaire. RESULTS: The actuarial 15-year-recurrence rate in group 1 was 31% (34/111) compared to 26% (20/76) in group 2, which was statistically not different ( p = 0.99). Recurrences occurred with a median 2.7 (range 0.1-20.1) years after primary surgery, so time to recurrence did not differ between both groups (4.3 ± 0.8 years group 1 vs. 6.8 ± 1.5 years group 2; p = 0.99). CONCLUSIONS: The suggested positive effects of topical gentamycin application on long term recurrence rate could not be confirmed. Astonishingly though, surgical infection does not seem to alter long term recurrence rate. [ABSTRACT FROM AUTHOR]

The aim of this paper was to observe the clinical effect of gentamycin combined with sodium bicarbonate for the prevention of irinotecan-induced diarrhea. A total of 98 patients with stage IV cancers were recruited and divided into a prevention group (52 patients) and a control group (46 patients). All patients received the chemotherapy including irinotecan. The prevention group received gentamycin and sodium bicarbonate before the use of irinotecan for 4 days; the control group did not receive any prevention. The use of gentamycin and sodium bicarbonate resulted in significantly higher stool pH ( P<0.001), while the incidence of diarrhea by irinotecan was reduced (prevention group 13.70% versus control group 34.83%; P<0.001). Gentamycin combined with sodium bicarbonate appears to be useful in preventing the diarrhea induced by irinotecan and reducing the dosage of loperamide and fluid replacement. [ABSTRACT FROM AUTHOR]

Objective: The study was carried out to evaluate the efficacy of the gentamycin collagen sponge placed in the pelvic cavity after excision of rectal cancer in view of postoperative complications and the risk of cancer recurrence. Methods: A total of 229 patients were recruited into the study and randomized into two groups: GRM(+), in which a gentamycin collagen sponge was used, and GRM(-), without the sponge. Tumors were resected using a TME technique. In the GRM(+) group, the sponge was placed into the tumor bed. Results: Analysis covered 218 patients for whom all follow-up data were available. There were fewer early postoperative complications in the GRM(+) group: 20.7 vs. 37.5%; p=0.044. This effect was found mainly in patients with surgery lasting longer than 3 h. After 36 months' follow-up, the overall survival after R0 resection for the GRM(+) and GRM(-) groups was: 88.66 vs. 73.96%. There was significant reduction in the distant metastasis rate in favor of the GRM(+) group. Conclusion: The use of the gentamycin collagen sponge after excision of rectal cancer is safe and reduces the rate of early postoperative complications. The reasons for the lower rate of distant metastasis in the GRM(+) group are not clear, but the patients enjoy significant survival benefits. [ABSTRACT FROM AUTHOR]

Summary: The normal-phase (NP) and reversed-phase (RP) thin-layer chromatographic separations of aminoglycosides (streptomycin, kanamycin, gentamycin, and tobramycin) have been investigated on silica gel and C18 plates, respectively. The mobile phase acetone–2% sodium acetate–acetic acid–butanol, 7 + 6 + 4 + 1 (v/v) was successful for NPTLC and acetonitrile–5 mM sodium acetate buffer (pH 4.6) 4 + 18 (v/v) for RPTLC. The spots were located by use of iodine vapor. The minimum detection limits were in the range 0.4–0.6 μg. The method is a simple and direct approach for detection which does not require pre- or post-chromatographic derivatization. [ABSTRACT FROM AUTHOR]

Susceptibility of Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis to gentamicin and cefotaxime was affected by salicylaye. In presence of salicylaye (15 mM) and gentamicin (1.0 ug/m l), log efficiency of plating (log E.O.P.s) for the tested bacteria were −1.24, −2.17 and −1.66 respectively. The activity of cefotaxime against Bacillus subtilis was reduced (log E.O.P.=1.33). The highest potentiating effects of salicylaye were shown when using gentamicin against Staphylococcus aureus, cefotaxime against Ps. aeruginosa, log E.O.P.s were −3.0, and −2.4, respectively. On the other hand, no significant effects were detected with cefotaxime against Staphylococcus aureus (log E.O. P.=−0.04). No significant killing was shown in presence of gentamicin or salicylaye alone. There was no significant effect for salicylaye on MICs (By broth dilution) could be observed except in case of gentamicin against Staphylococcus aureus, which was reduced from 0.02 ug/m l to 0.0012 ug/m l. These results raise the concern that high concentrations of salicylaye in patients might interfere with antibiotic therapies. [ABSTRACT FROM AUTHOR]

The effect of the aminoglycosides amikacin, gentamicin, netilmicin sisomicin and tobramycin on the proximal tubule of the human kidney was investigated in 78 healthy subjects. Fifteen adults were each given gentamicin, sisomicin or tobramycin 3 mg/kg bodyweight, 10 subjects received netilmicin 3 mg/kg or amikacin 15 mg/kg additionally seven subjects amikacin 10 mg and six subjects netilmicin 6 mg on three consecutive days. The principal enzyme of the brush border membrane of the proximal tubule, alanine aminopeptidase (AAP), was determined enzymatically and immunologically in 24-hour urines. The effects of the various aminoglycosides on the membranes were different. Less of membrane AAP was greatest after amikacin and was least after tobramycin. There was no difference between gentamicin, netilmicin, and sisomicin, which had an effect intermediate between the other two compounds. The elimination of AAP occurred at intervals whicht might possibly have been caused by impairment of cell cycles. [ABSTRACT FROM AUTHOR]

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Serum concentrations of gentamycin and ampicillin were investigated at loading and in steady state in two groups of neonates, of 26-33 weeks and 34-40 weeks gestation. At loading the usual intravenous dose of gentamycin (2.5 mg/kg) was increased by 50%, the usual intravenous dose of ampicillin (50 mg/kg) by 100%. Gentamycin and ampicillin were administered subsequently at the same intervals, 12 h in the 34-40 weeks group, and 18 h in the 26-33 weeks group. Adequate serum levels were achieved from the first day of treatment. For practical reasons ampicillin and gentamycin can be administered subsequently at identical intervals also when the intervals exceed 12 h. The ideal dosing interval for gentamycin in very preterm neonates is 24 h. When treating small preterm and term neonates with an aminoglycoside, rapid serum concentration analyses should be available, and the treatment modified accordingly. [ABSTRACT FROM AUTHOR]

Mechanical forces applied to cultured bone cells induce the production of cAMP via stimulation of the formation of prostaglandin E (PGE) and its release into the medium, resulting in stimulation of adenylate cyclase. In this paper we show that either the antibiotic gentamycin (100 μg/ml) or antiphospholipid antibodies (0.1%) which bind to membrane phospholipids abolish cAMP formation induced by mechanical forces; exogenously added arachidonic acid or PGE stimulates cAMP formation, even in the presence of these agents. Addition of exogenous phospholipase A (but not phospholipase C) causes an increase in the formation of cAMP in bone cells, a response that is also inhibited by gentamycin or antiphospholipase antibodies. These observations suggest that mechanical forces exert their effect on bone cells via the following chain of events: (1) activation of phospholipase A, (2) release of arachidonic acid, (3) increased PGE synthesis, (4) augmented cAMP production. [ABSTRACT FROM AUTHOR]

trans-4-Acetylaminostilbene (AAS) is a complete carcinogen in rats and produces quite selectively tumors in Zymbal's glands. On the basis of DNA adduct formation, it has been proposed that this model arylamine initiates neoplastic transformation of cells in many tissues, particularly liver and kidney, which, in the classical sense are considered to be non-target tissues for this chemical. In the present study an initiating treatment with AAS was followed by unilateral nephrectomy and the application of two nephrotoxic substances, gentamycin or β-cyclodextrin which, among other activities, stimulate cell proliferation specifically in kidney. The initiating dose of AAS, given alone, gave rise to Zymbal's gland and mammary tumors in female Wistar rats within 88 weeks but not to liver or kidney tumors. When the initiation treatment was followed by unilateral nephrectomy, alone or in combination with gentamycin, or by β-cyclodextrin, four tumors in two out of ten animals, eight tumors in three/ten, and seven tumors in three/ten, respectively, were observed in the kidney. The administered dose of gentamycin was not sufficient to induce tumors on its own. The results support the view that the genotoxic effects of AAS produce promotable lesions in rat kidney. None of the animals that had been treated with AAS, with or without other treatments, developed tumors or the predominant types of preneoplastic lesions in the liver within 88 weeks; this supports the notion that liver, like kidney, is not a target for complete carcinogenesis for this chemical. [ABSTRACT FROM AUTHOR]

The Stüve–Wiedemann Syndrome (SWS) is a frequently lethal chondrodysplasia caused by null mutations in the leukemia inhibitory factor receptor gene (LIFR) responsible for an impaired activation of the JAK–STAT pathway after LIF stimulation. Most LIFR mutations are nonsense mutations, thus prompting us to investigate the impact of aminoglycosides on the readthrough of premature termination codons (PTCs). Culturing skin fibroblasts from three SWS patients and controls for 48 h in the presence of gentamycin (200–500 μg/ml) partially restored the JAK–STAT3 pathway when stimulated by LIF. Consistently, quantitative RT-PCR analysis showed that gentamycin stabilized LIFR mRNAs carrying UGA premature termination codons. We conclude that high gentamycin concentrations can partially restore functional LIFR protein synthesis in vitro, prompting us to investigate PTC readthrough using less toxic and more efficient drugs in this presently untreatable lethal condition. [ABSTRACT FROM AUTHOR]

Sucralfate is widely used as a cytoprotective agent in patients with peptic ulcer and other intestinal mucosal damage. In this study, the effects of sucralfate and/or selective intestinal decontamination with gentamycin on bacterial translocation (BT) in rats with experimentally-induced mechanical jaundice were investigated. Seventy-five adult male Wistar albino rats were divided into five groups of 15 each. In all except a sham group, we performed ligation of the common bile duct (CBD) via a vertical laparatomy. After surgery, the rats in group 1 were treated with oral sucralfate (5 mg/kg per day); those in group 2 underwent oral gentamycin therapy (5 mg/kg per day) for 5 days. Group 3 rats were treated with sucralfate and gentamycin for 5 days subsequent to the operation. The rats in group 4 served as controls, and received only 0.9% saline solution. Group 5 was a sham group. After 5 days of surgery, all rats were killed; the mesenteric lymph nodes (MLN), liver, and a segment of terminal ileum were harvested aseptically. The collected tissues were cultured in McCaunkey medium and chocolate agar. For each specimen, the colony-forming units (CFU) were calculated and the percentage of viable translocated micro-organisms was counted. In all rats who had ligation of the CBD, high numbers of bacteria were demonstrated in the liver, MLN, and ileum. In the liver of rats with sucralfate and/or gentamycin treatment, there was a marked reduction in CFU compared to the control group. Similarly, in the MLN measurements of CFU were higher in the control rats than the study groups. In both McCaunkey and chocolate media, the numbers of bacteria in control rats were significantly higher than in the study groups (P < 0.001). However, among the study groups themselves there was no significant difference in CFU in any of the specimens or culture media (P > 0.05). Experimentally-induced mechanical jaundice from ligation of the CBD causes significant BT in rats. Sucralfate and/or gentamycin may reduce the degree of BT from the bowel mucosa. We did not find any difference in protection from BT between sucralfate and gentamycin or both in rats with experimentally-induced mechanical jaundice. [ABSTRACT FROM AUTHOR]

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