Application Of Gentamicin Research Articles

Role of topical application of gentamicin containing collagen implants in cardiac surgery.

Sternal wound infections (SWI) continue to be a major cause of concern after cardiac surgery. It leads to prolonged hospital stay and increased morbidity, mortality and increased hospital costs. Prophylactic systemic antibiotics have been used to prevent surgical site infection (SSI). However, prolonged postoperative use of systemic antibiotics can lead to emergence of resistant organisms. Gentamycin Containing Collagen Implants (GCCI) when used during sternotomy closure produces high local antibiotic concentrations in the wound with a low serum concentration. There is evidence that the concentration of gentamicin in the mediastinal fluid reaches levels high enough to be effective against bacteria that are considered resistant to gentamycin and other antibiotics.However, questions have been raised about the safety and efficacy of GCCI. There were concerns whether GCCI can lead to systemic absorption with renal impairment and whether use of topical antibiotics can lead to emergence of antimicrobial resistance.We, hereby, review the literature on GCCI (Collatamp) and take the opportunity to appraise the scientific community about their role in cardiac surgery. Several recent studies have supported their clinical effectiveness. They should be used in dry condition and should not be soaked in saline even for a short period prior to use. However, for GCCI to become part of routine practice in cardiac surgery further large randomised studies are required. As the incidence of sternal wound infection is low in the specialty of cardiac surgery, for any study to be sufficiently powered to address this issue, multicenter studies might be the way forward.Based on the evidence presented in this manuscript it is recommended GCCI (Collatamp) can be a cost effective adjunct for prevention of sternal wound infection. They can also be used for treatment of Deep Sternal Wound Infection.

Can gentamicin-containing collagen sponge be used for the protection against leakage following low anterior resection with total mesorectal excision?

Dear Sir, Anterior resection with total mesorectal excision (TME) may result in an increased risk of the anastomotic leakage (AL) because of the short rectal remnant and local oxygen deficiency in the anastomosis associated with the reduced distal blood supply. Moreover, it produces a large splinted cavity within the pelvis, conducive to exudate retention and formation of a hematoma which may become infected. The presence of AL impairs both late functional and oncological outcomes [1]. On the other hand, recent technological innovations such as resorbable implants offer new possibilities to protect the anastomosis and reduce the consequences of leakage. Some years ago, we reported our initial results of the wrapping of anastomosis with the gentamicin-collagen sponge (GCS) as a potential preventive maneuver against the AL—probably limiting the leakage intensity and reducing its clinical symptoms [2]. Now we would like to share our single-center experience of 158 consecutive patients with T1–T3 low rectal cancer who underwent anterior resection with TME and straight end-to-end anastomosis with double-stapling technique. Sixty-five (41 %) patients with T3 or N+ tumors received preoperative radiotherapy 5 × 5 Gy. All anastomoses were wrapped with GCS 10 × 10 × 0.5 cm containing 130 mg of gentamicin sulfate and 280 mg purified bovine tendon type I collagen, which was placed deep in the pre-sacral area at the level of the levators. The sponge was formed and pressed to the bowel wall. A special effort was made to ensure that it’s location and stability were satisfactory (Fig. 1). No patient in this series had a diverting stoma. Fig. 1 Low anastomosis wrapped with GCS Gentamicin-collagen sponge was applied without any technical difficulties and was well tolerated. Neither sponge-related adverse reactions nor drain blockage were noticed. AL developed in five patients (3.2 %) and was associated with peritonitis in one patient (1.6 %), pelvic abscess in another (both without protective stoma) and gas or feculent discharge from the pelvic drain in three others (with stoma). The median time to AL diagnosis was 8 days (range 3–15 days) following surgery. Patients with peritonitis and abscess underwent surgical reintervention: peritoneal lavage and defunctioning transversostomy. The remaining patients had only minor AL and were effectively treated with pelvic lavage through the drain, total parenteral nutrition and antibiotic therapy. There was no leakage-related mortality. AL incidence in our group seems to be relatively low when compared to the vast majority of other series (8–23 %) [1]. Only a few papers concerning the use of GCS in colorectal surgery have been published so far. It remains a subject of debate: findings are contradictory, the importance of results is limited and no statistically significant conclusions can be drawn [3]. Also, little is known about the impact of GCS on anastomosis healing. Some studies suggest local gentamicin has positive effects on collagen content and metabolism. Quicker mucosal, muscular and extra-cellular matrix repair was observed in an experimental study in dogs [4]. Other investigators reported that intra-abdominal application of gentamicin can enhance the healing of anastomosis and increase the collagen type I/III in rats [5]. This topic warrants further investigation. Our recent results may suggest that the low incidence of symptomatic AL might be at least partially influenced by GCS application which could secure the anastomosis area—it reduces tissue exudation and fluids accumulation at the pelvis cavity and also has a local antibacterial and hemostatic activity. Potential benefit from GCS may also be associated with the ability to reduce the extent of dehiscence and its severe consequences and limit pelvic abscess formation, peritonitis and septicemia without the impact on subclinical failure. This may explain the favorable clinical course of AL in our series. Investigation with a longer follow-up are needed to evaluate the pattern and incidence of possible late consequences of GCS implantation (e.g., anastomotic stricture) as well as its cost-effectiveness.

Gentamicin Concentration Gradients in Scala Tympani Perilymph following Systemic Applications

It has been shown in prior studies that round window membrane (RWM) application of gentamicin produced a robust basal-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Ménière's disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg body weight (BW) over a period of 3 h or as a 300 mg/kg BW subcutaneous bolus injection. At 3 and 5 h after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively, and 10 sequential 1-µl perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in the highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with the amount of drug applied and time before sampling. While it is likely that the basal-apical gradient measured after local drug applications to the round window niche is the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from the blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of ST relative to endolymph in the apical turns.

Inhibition of K+ Currents in Type I Vestibular Hair Cells by Gentamicin and Neomycin

Significant ototoxicity limits the use of aminoglycoside (AG) antibiotics. Several mechanisms may contribute to the death of both auditory and vestibular hair cells. In this study the effects of gentamicin and neomycin on K⁺ currents in mature and early postnatal type I vestibular hair cells (HCI) were tested directly. The whole-cell patch clamp technique was used to assess the effects of AG and KCNQ channel modulators on K⁺ currents (I_K) in HCI acutely isolated from gerbil semicircular canals. Extracellular neomycin (1 m<smlcap>M</smlcap>) rapidly reduced peak outward I_K by 16 ± 4% (n = 9) in mature HCI (postnatal days, P, 25-66). Gentamicin (5 m<smlcap>M</smlcap>) reduced outward I_K by 16 ± 3% (n = 8). A similar reduction in outward current was seen in immature HCI (P5-9) that lacked the low-voltage-activated component of I_K observed in mature cells. Intracellular application of gentamicin and neomycin also reduced I_K in mature HCI. Modulators of KCNQ channels were used to probe KCNQ channel involvement. The selective KCNQ antagonist XE991 did not reduce I_K and the neomycin-induced reduction in I_K was not reversed by the KCNQ agonist flupirtine. Application of intracellular poly-<smlcap>D</smlcap>-lysine to sequester PIP₂ did not reduce I_K. Application of the K⁺ channel blocker 4-aminopyridine (4-AP) strongly reduced I_K, and extracellular AG in the presence of 4-AP gave no further inhibition of I_K. In summary, AG significantly reduce the 4-AP-sensitive I_K in early postnatal and mature HCI. K⁺ current inhibition differs from that seen in outer hair cells, since it does not appear to involve PIP₂ sequestration or KCNQ channels.

Local gentamicin application does not interfere with bone healing in a rat model

For the prophylaxis and treatment of bony infections antibiotics are locally used. Since several decades antibiotics mixed with bone cement (methylmethacrylate) are successfully used in prosthetic surgery and a gentamicin coated tibial nail is approved in Europe for fracture stabilization. The goal of the present study was to investigate if gentamicin, locally applied from a polymeric coating of intramedullary nails, might interfere with the bone healing process. Female Sprague Dawley rats (n=72) were used and the tibiae were intramedullary stabilized with Kirschner-wires (k-wires) after osteotomy. This model was established earlier and shows a delayed healing with a prolonged inflammatory reaction. The open approach is clinically more relevant compared to a closed one because it mimics the clinically critical case of an open fracture, which has a higher risk of infection. The k-wire was either coated with the polymer poly(d,l-lactide) (control group) or with 10% gentamicin incorporated into the polymer (gentamicin group). In vivo μCT analyses were performed at days 10, 28, 42, and 84 after osteotomy. Mechanical torsional testing and histological evaluation were done at the days of sacrifice: 28, 42, and 84. The μCT analyses revealed an increase in tissue mineral density (TMD) over the healing period in both groups. In the control group, the torsional stiffness and maximum load did not reach the values of the intact contralateral side at any time point. At day 84 the gentamicin treated tibiae, however, showed significantly better maximum load compared to the control group. The histology showed no bony bridging in the control, whereas in 2 of 5 calluses of the gentamicin group mineralized bridging occurred. Significantly more mineralized tissue was measured in the gentamicin group. This study shows that the local gentamicin application does not negatively interfere with the long term healing process. Local infection prophylaxis is effective without negative effects on bone healing.

In-vitro analysis of the effect of gentamicin and polyhexanide on bone tissue

Though anti-infectives have been used for a long time in surgical procedures, the effect on bone tissue has not been determined for most antibiotics and antiseptics. In our in vitro study, 4x4x8 mm(3) blocks of rabbit cancellous bone tissue were incubated with Ringer's solution, gentamicin and Lavasorb(®) each for time intervals of 15 minutes, 30 minutes, one hour, four hours and eight hours. Samples were examined double blinded through optical and electron microscopy. Tissue degeneration was observed in all samples. It was low in Ringer's solution. Samples with Lavasorb showed a moderate degeneration after 15 and 30 minutes, which was accelerated after one hour. Gentamicin led to a moderate degeneration of bone tissue after 15 and 30 minutes and to a more accelerated degeneration after one hour. The effect of gentamicin on bone tissue was more pronounced than the effect of Lavasorb. This investigation showed that local application of Lavasorb or gentamicin on bone tissue should be restricted to 30 minutes, while Lavasorb showed a better tissue tolerability. This finding could have clinical implications for the management of wounds with open osseous tissue and should be further investigated by in vivo studies.

Cochlear Cell Death Induced Via Cisplatin or Gentamycin in Combination with Furosemide in Rodents

Ototoxic models of animal represent an elemental tool in basic otological research. In the present study, using guinea pigs we compared cochlear lesions mediated via cisplatin applied in terms of two regimens: consecutive application alone and in combination with furosemide. The influences of furosemide alone were also assessed; it was observed to result in temporary hearing loss and reversible damage to the stria vascularis. Consecutive administration of cisplatin alone tended to be disadvantageous because it bred progressive body weight loss and higher mortality compared with the combined regimen, which utilized a smaller cisplatin dose. The combined regimen brought about remarkable hair cell loss without corresponding lesion of spiral ganglion neurons. This difference suggests that the co-administered regimen did not mimic the damage to cochlear neuronal innervation caused by clinical application of cisplatin. In the meantime, we spread this method to the ototoxic model build in mice. Coadministration of gentamicin and furosemide caused marked hair cell loss as well as less mortality compared with consecutive application of gentamicin in mice. Due to different pharmacokinetics between cisplatin in guinea pigs and gentamicin in mice, the injection regimens of co-administration of furosemide - cisplatin in guinea pigs and gentamicin – furosemide in mice were varied. Overall, the methods of co-administration of cisplatin/gentacimin and furosemide in rodents facilitate ototoxic model build.

Gentamicin Reduces Calcific Nodule Formation by Aortic Valve Interstitial Cells In Vitro.

Gentamicin is a widely employed antibiotic, but may reduce calcium uptake by eukaryotic cells. This study was conducted to determine whether gentamicin reduces calcification by porcine aortic valvular interstitial cells (pAVICs) grown in 2D culture, which is a common model for calcific aortic valve disease (CAVD). The presence of gentamicin (up to 0.2 mM) in the medium of pAVICs cultured for 8 days significantly lowered calcification and alkaline phosphatase content in a dose-dependent manner compared to pAVICs cultured without gentamicin. Gentamicin also significantly increased cell proliferation and apoptosis at concentrations of 0.1-0.2 mM. Next, gentamicin was applied to previously calcified pAVIC cultures (grown for 8 days) to determine whether it could stop or reverse the calcification process. Daily application of gentamicin for 8 additional days significantly reduced calcification to below the pre-calcification levels. These results confirm that gentamicin should be used cautiously with in vitro studies of calcification, and suggest that gentamicin may have the ability to reverse calcification by pAVICs. Given the nephrotoxicity and ototoxicity of this antibiotic, its clinical potential for the treatment of calcification in heart valves is limited. However, further investigation of the pathways through which gentamicin alters calcium uptake by valvular cells may provide insight into novel therapies for CAVD.

Local antibiotic therapy in rectal cancer surgery.

Infectious complications and their consequences are still key issues in rectal cancer surgery. Currently, intravenous antibiotic administration is a recognized method for lowering the rate of these complications. The aim of the study was to assess the efficacy of complementary application of a gentamicin-impregnated sponge in the perineal wound or in the vicinity of intestinal anastomosis after abdominoperineal resection or low anterior resection. 112 patients with primary rectal cancer were enrolled in this study. 42 patients were treated with a gentamicin sponge and drainage (group A) and 70 individuals were treated with drainage alone (group B). In the aforementioned groups a routine short-term regimen of antibiotic prophylaxis was used. We applied gentamicin-impregnated sponges in 27 patients in whom anterior resection was performed and in 15 patients from the abdominoperineal resection group (64% and 36%, respectively). In the control group, 44 anterior resections and 26 abdominoperineal resections were carried out (63% and 37%, respectively). We did not observe statistically significant differences in the incidence of suppurative complications (intraabdominal abscess, perineal wound infection): 4 cases (9.52%) in group A and 9 (12.58%) in group B and anastomotic leakage with clinical manifestation after low anterior resection: 1 case (3.7%) in group A and 2 (4.5%) in group B. Postoperative fever of unknown origin was noted more often in group B: 23 patients (32.8%) versus 10 patients (23.8%) in group A and this difference was statistically significant (p<0.05). Hospitalization after surgery was also significantly longer in group B (9-37 days, median 11 days) as compared with group A (8-26 days, median 13 days) (p<0.05). Local antibiotic therapy in rectal cancer surgery lowered the incidence of postoperative fever of unknown origin and permitted shorter hospitalization after surgery. Local gentamicin application in rectal cancer surgery did not change significantly the rate of infectious complications.

Characterization Chlorophytas microalgae with potential in the production of lipids for biofuels

This work is part of a megaproject that seeks to isolate microalgae of the Chlorophyta division native to Norte de Santander and identify their potential applications such as lipid production to be used as biofuel. Here we present the isolation of 11 microalgae strains from the Chlorophyta division found in two different wastewater environments. The collected strains were cultivated in selective media and purified through serial dilutions, depletion culture, and application of penicillin and gentamicin. Biomass production was evaluated and two strains were selected: CHL1 (Chlorella sp.) and DES1 (Desmodesmus sp.). The strains were cultivated on wastewater and PCG media (control), and their biomass concentration and lipid content were measured. Both strains reached similar biomass concentrations compared to their respective controls (CHL1 PCG 1.5 mg/L ± 0.035 mg/L, CHL1 AR 1.68 mg/L ± 0.036, DES1 PCG 1.66 mg/L ± 0.007, DES1 AR 2 mg/L ± 0.03) and their lipid content was slightly higher compared to their controls. The results show that the isolated and evaluated strains may have potential to be lipid producers, since their environmental and nutritional conditions have not been modified yet and adaptation may improve the production yield of lipids.

The effect of topically applied antimycotic agents on inner ear vestibular and cochlear function

To assess and compare the effect of commonly used topical antimycotic agents and their solvents on the function of the vestibular and cochlear parts of the sand rat's inner ear. Prospective, controlled, animal study. Forty-five fat sand rats were randomly assigned to five major groups, each receiving topical application of a different agent: saline (control), gentamicin (ototoxic control), and three antimycotic agents: nystatin, clotrimazole solution (Agisten), and bifonazole solution (Agispor). All animals underwent a right labyrinthectomy, and a polyethylene tube was inserted into the left middle ear followed by baseline recording of vestibular evoked potentials (VsEPs) and auditory nerve and brainstem responses (ABR). Subsequently, each animal received five consecutive daily applications of the specific agent into the left middle ear. Evoked potential recordings were repeated 3 and 10 days after the last application and compared to baseline. For clotrimazole and bifonazole solutions, the effect of the solvents was assessed by comparing ABR recordings at similar intervals. Administration of saline did not affect VsEPs or ABR. Both could not be recorded following gentamicin application. In all three antimycotic agents, no statistically significant difference was found between VsEPs recordings before and after application. Clotrimazole and bifonazole solutions caused a significant ABR threshold elevation similar to that caused by their solvents. Nystatin caused a less significant ABR threshold elevation. The three commonly used topical antimycotic agents investigated here did not affect vestibular function but had a toxic effect on inner ear cochlear function. It seems the main offenders were the solvents.

The efficacy of stingless bee honey for the treatment of bacteria-induced conjunctivitis in guinea pigs.

The efficacy of the conjunctival application of a crude concentration of stingless bee honey (SBH) for the treatment of bacterial conjunctivitis was investigated in an animal model. Bacterial conjunctivitis caused by Staphylococcus aureus or Pseudomonas aeruginosa was induced in Hartley guinea pigs. The conjunctival application of SBH or gentamicin was used for treatment, and the results of this treatment were compared with control values. Inflammatory signs, duration of infection (ie, positive culture), and time for the complete resolution of infection with S. aureus or P. aeruginosa were shortened by the conjunctival application of 1 drop (70 µL) of crude SBH twice daily. The potency of SBH was comparable with that of gentamicin. SBH may be a rational agent for the treatment of infective conjunctivitis in humans; it is inexpensive and commonly available to the rural population.

Plasmid pUDK-HGF encoding human hepatocyte growth factor gene attenuates gentamicin-induced kidney injury in rats

The clinical application of gentamicin has been limited by its nephrotoxicity, which is characterized by kidney injury, interstitial fibrosis and progressive renal impairment. In this paper, we examine effects of plasmid pUDK-HGF which encodes the human hepatocyte growth factor (HGF) gene on gentamicin-induced renal injury in rats. The kidney injury was intentionally induced by injecting gentamicin intraperitoneally. On the third day after last gentamicin treatment, pUDK-HGF was injected into the left kidney tissue only once via a sterile back incision. At day 30 after gentamicin treatment, RI, Scr, BUN, 24 h-UTP and apoptotic cell death were determined. Tubulointerstitial injury and the renal interstitial vessel regeneration were evaluated by histological scoring. pUDK-HGF treatment significantly improved the renal function with decreasing RI, Scr and BUN. 24 h-UTP also presented ameliorating trend compared to the control group with kidney injury. pUDK-HGF treatment significantly decreased the score of tubulointerstitial injury and enhanced angiogenesis, also prevented kidney cells from apoptosis. The tubulointerstitial injury was significantly reduced in the pUDK-HGF injected left kidney and right kidney also showed some improvements. Our results showed that pUDK-HGF may become a novel therapeutic agent for kidney injury and renal fibrosis.

Acute effects of gentamicin on the ionic currents of semicircular canal hair cells in the frog

The effects of acute gentamicin application on hair cells isolated from the frog semicircular canals have been tested by using the patch-clamp technique in the whole-cell configuration. Extracellular gentamicin (1 mM) mostly affected the Ca 2+ macrocurrent, I Ca, and the Ca-dependent K + current, I KCa. The drug, applied to the hair cell basolateral membrane through a fast perfusion system, produced a rapid and relevant decrease (∼34%) of I Ca amplitude, without apparently affecting its activation–deactivation kinetics. The I KCa component of the delayed I KD was similarly affected: peak and steady-state mean amplitudes were significantly reduced, by about 47 and 54%, respectively, whereas the time constant of the mono-exponential current rising phase did not change. The Ca 2+ independent fraction of I KD, I KV, and the fast IA current were unaffected. Transduction channels (permeable to and blocked by gentamicin) are not available in the isolated hair cell, so the effect of intracellular gentamicin was tested by applying the drug through the patch pipette (1 mM in the pipette): again, it significantly reduced both I Ca and I KD amplitude, without affecting currents kinetics. IA properties were also unaffected. The drug did not affect the onset and removal of I KD inactivation, although the changes were scaled to the reduced I KD amplitude. From these observations, it is expected that hair cells exposed to gentamicin ‘ in vivo’ become unresponsive to physiological stimulation (block of the transduction channels) and transmitter release at the cytoneural junction be drastically depressed due to reduced Ca 2+ inflow. In particular, functional impairment ensues much earlier than biochemical events that lead to hair cell apoptosis.

Does intratympanic gadolinium injection predict efficacy of gentamicin partial chemolabyrinthectomy in Menière’s disease patients?

Using actual diagnostic criteria, the diagnosis of certain Menière's disease remains impossible during life without histopathologic confirmation. Assessing the value of a diagnostic test is difficult due to the lack of a gold standard. Recent studies reported on the use of MRI after intratympanic gadolinium injection to demonstrate endolymphatic hydrops in vivo. We evaluate whether MRI after intratympanic gadolinium administration is useful for predicting the effect and outcome of intratympanic gentamicin therapy. The correlation between transtympanic electrocochleographic (TT-ECoG) results and hydrops grade on MRI images is also investigated. Twelve definite Menière's disease patients with incapacitating vertigo attacks, not responding to drug and behavioral treatment, were selected for partial chemolabyrinthectomy with intratympanic gentamicin. All patients underwent transtympanic electrocochleography followed by surgical middle ear inspection, partial chemolabyrinthectomy (gentamicin solution 40 mg/ml applied during 60 min) and intratympanic gadolinium injection with clear exposure of the round window membrane. The MR images were reviewed and a hydrops grade was assigned. Correlation between the hydrops grade and the electrocochleographic data was assessed. Only 5 of 12 patients showed gadolinium enhancement in the inner ear. However, 6 of the 7 patients that did not show postoperative intracochlear or intralabyrinthine gadolinium distribution did report the clinical improvement after intratympanic gentamicin therapy. Hydrops grade correlated with the result of transtympanic electrocochleography in four of five cases that showed gadolinium enhancement. We conclude that the use of intratympanic gadolinium has no added value in predicting the clinical outcome of intratympanic gentamicin application. However, based on these data, a correlation between the result of TT-ECoG and hydrops grading on MRI images can be suggested.

Doxycycline reduces nitric oxide production in guinea pig inner ears

Gentamicin application is an important therapeutic option to control vertigo spells in Ménière's disease. However, even in the case of low-dose intratympanic application, gentamicin might contribute to a pathological NO-increase leading to cochlear damage and hearing impairment. The study was performed to evaluate the nitric oxide (NO) reducing capacity of doxycycline in the inner ear after NO-induction by gentamicin. In a prospective animal study, a single dose of gentamicin (10mg/kg body weight) was injected intratympanically into male guinea pigs (n=48). The auditory brainstem responses (ABRs) were recorded prior to application and 3, 5 and 7 days afterwards. The organ of Corti and the lateral wall of 42 animals were isolated after 7 days and incubated separately for 6h in cell culture medium. Doxycycline was adjusted to organ cultures of 5 animals. Two NOS inhibitors, N(G)-Nitro-l-arginine methyl ester (l-NAME) and NG-monomethyl-l-arginine monoacetate (l-NMMA), were applied in three different concentrations to the organ cultures of 30 animals in total (5 animals per concentration). As controls, seven animals received no further substance except gentamicin. The NO-production was quantified by chemiluminescence. Additional six gentamicin-treated animals were used for immunohistochemical studies. The ABRs declined continuously from the first to the seventh day after gentamicin application. Doxycycline reduced NO-production in the lateral wall by 54% (p=.029) comparable to the effect of the applied nitric oxide inhibitors. In the organ of Corti, NO-production was reduced by about 41% showing no statistical significance in respect to great inter-animal variations. The application of doxycycline might offer a new therapeutic approach to prevent NO-induced cochlea damage through ototoxic substances.

TO THE QUESTION OF EMPIRIC ANTIBIOTIC THERAP OF TROPHIC LESIONS IN VARIOUS VASCULAR DISEASES

The results of 126 bacteriological investigations performed at the Department of vascular surgery, Gomel Regional Cardiologic Dispensary in the period from 2006 to 2007 have been analysed. In all the groups of the examined patients Staphylococcus aureus was the most widespread (33,3-66,7 %) infectious agent. Pseudomonas aeruginosa was most common for the patients suffering from PAD and postphlebitic syndrome (15,4 and 19,3 %, correspondingly) and significantly less prevalent in the group with trophic lesions in varix dilatation (4,8 %). Streptococcus epidermidis was most often revealed in the patients with PAD and varix dilatation (7,7 and 10,5 % correspondingly), аnd Staphylococcus saprophyticus - in the patients with PAD (11,5 %). The carried out analysis provides the ground to consider the application of ciprofloxacin and gentamicin in the initial treatment for all the above listed diseases as the most reasonable.

Intratympanic gentamicin for Ménière's disease or syndrome

Ménière's disease is characterised by three major symptoms: vertigo, deafness and tinnitus, which may be accompanied by aural fullness, all of which are discontinuous and variable in intensity. While discontinuous, these symptoms are synchronous. Intratympanic application of gentamicin, an ototoxic aminoglycoside, is a relatively new ablative treatment for vertigo in Ménière's disease with promising results. To assess the effectiveness of intratympanic gentamicin in the treatment of vertigo in Ménière's disease. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 30 June 2010. All randomised or quasi-randomised controlled trials of intratympanic gentamicin versus placebo, or versus another treatment for Ménière's disease. Two review authors independently assessed trial quality and extracted data. We contacted study authors for further information. We identified two trials, involving 50 participants, which fulfilled the inclusion criteria. Both of these trials are prospective, double-blind, placebo-controlled randomised clinical trials on the effect of intratympanic gentamicin on vertigo complaints. Both of these trials found a significant reduction in vertigo complaints in the gentamicin group when compared to the placebo group. Due to clinical heterogeneity we could not perform a meta-analysis. Based on the results of the two included studies, intratympanic gentamicin seems to be an effective treatment for vertigo complaints in Ménière's disease, but carries a risk of hearing loss.

EGb 761 ( Ginkgo biloba) protects cochlear hair cells against ototoxicity induced by gentamicin via reducing reactive oxygen species and nitric oxide-related apoptosis

Gentamicin is an effective and powerful antibiotic. Extended use or excessive dosages of which can result in irreversible damage to the inner ear. The development of otoprotective strategies is a primary and urgent goal in research of gentamicin ototoxicity. Ginkgo biloba leaves and their extracts are among the most widely used herbal products and/or dietary supplements in the world. We investigated the protection of EGb 761 (a standardized preparation of EGb) on gentamicin ototoxicity and the involvement of reactive oxygen species (ROS) and nitric oxide (NO)-related mechanisms using in vitro organ cultures and an in vivo animal model. Gentamicin induced hair cell damage in cochlear cultures that could be prevented by EGb 761. EGb 761 also significantly reduced gentamicin-induced ROS and NO production. Furthermore, EGb 761 inhibited cellular apoptosis in cultured cochleae treated with gentamicin. In guinea pigs with gentamicin application onto the round window membrane, the mean auditory brain stem response threshold, ratio of cochlear hair cell damage and apoptosis were significantly elevated compared with those in the control group, and this could be prevented by oral administration of EGb 761. Individual EGb 761 components quercetin, bilobalide, ginkgolide A and ginkgolide B, but not kaempferol, significantly prevented gentamicin-induced hair cell damage. These results indicate that EGb 761 has a protective effect against gentamicin ototoxicity through a reduction in the formation of ROS and NO and subsequent inhibition of hair cell apoptosis in the cochlea.

Intratympanic gentamicin injections for the treatment of Ménière's disease

ObjectiveTo assess the success rate and complications of treatment with injections of intratympanic gentamicin to the middle ear of patients with Ménière's disease.Study DesignCase series with chart review.SettingA tertiary otologic private ENT clinic.Subjects and MethodsPatients with Ménière's disease, who had not responded to medical treatment. Included in the sample were patients with Ménière's disease who had been treated with injections of gentamicin into the middle ear. After each gentamicin application, patients were monitored for their symptoms and hearing. If symptoms persisted, they received another intratympanic injection of gentamicin. This method is referred to as the variable titration method. A retrospective chart review was performed, and questionnaires were used to assess hearing, functional status, tinnitus, ear fullness sensation, and the control of vertigo attacks in response to treatment.ResultsNineteen patients were sampled. Eighteen patients (94%) had complete or substantial control of vertigo. Five patients (26%) had worse hearing results on their post‐treatment audiogram, averaging 13 dB hearing loss (range, 5‐25 dB). In response to the questionnaires, all patients reported a significant improvement in the quality of life after treatment.ConclusionThe treatment was found to be highly effective. The variable titration method of injection prevents unnecessary injections for patients whose symptoms have already subsided.