Adherence of staphylococcus aureus to catheter tubing inhibition by quaternary ammonium compounds.

INTRODUCTION: S. aureus is a Gram positive bacterium which is responsible for a wide range of infections. This pathogen has also the ability to adhere to biotic or abiotic surface such as central venous catheter (CVC) and to produce a biofilm. The aim of this study was to evaluate the effect of hexadecyltrimethyl ammonium bromide (HTAB) and Hexadecylbetainate chloride (HBC) on Staphylococcus aureus adherence to the catheter tubing and on bacteria growth. METHODS: Broth microdilution method was used to determine the Minimal Inhibitory Concentration (MIC). The detection of slime production was done by Congo Red Agar method, and the adherence of bacteria to the catheter tubing was evaluated by the enumeration of bacteria on plate counts. RESULTS: The results of this study showed that the MICs of HTAB were ranged from 0.125 to 0.5 µg/mL, and those of HBC fluctuated between 2 to 8 µg/mL. HTAB and HBC inhibited bacteria adhesion on the surface of the catheter tubing. CONCLUSION: This study showed that HTAB and HBC can prevent the adherence of S. aureus strains to the surface of catheter tubing, suggesting that they could be used to prevent the risk of catheter related bloodstream infections.

Adverse effects of vapocoolant and topical anesthesia for tail biopsy of preweanling mice.

Tail biopsy of laboratory mice for genotyping purposes has been studied extensively to develop refinements for this common procedure. Our prior work assessed tail vertebral development in different mouse strains (age, 3 to 42 d) and analyzed behavior and activity in mice (age, 21 to 45 d) biopsied under isoflurane anesthesia. To assess the effects of biopsy on preweanling mice, we here evaluated BALB/cAnNCrl mice (n = 80; age, 18 to 21 d) that received topical vapocoolant (ethyl chloride), topical anesthetic (Cetacaine), or isoflurane anesthesia before undergoing a 5-mm or sham biopsy. Control mice did not receive any anesthetic intervention. Regardless of the anesthetic used, acute observation scores indicative of distress were increased at 10 min after biopsy, and locomotor activity was decreased, in biopsied compared with control mice. Acute observation scores at 10 min after biopsy were higher in mice that received ethyl chloride compared with isoflurane or no anesthesia. Microscopic analysis revealed that inflammatory changes in the distal tail remained elevated until 7 d after biopsy and were higher in tails exposed to ethyl chloride. Our findings indicate that vapocoolant, topical anesthesia, and inhaled isoflurane do not enhance the wellbeing of preweanling mice undergoing tail biopsy. Due to the lack of appreciable benefits and the presence of notable adverse effects, using vapocoolants or Cetacaine for this tail biopsy procedure in laboratory mice is unadvisable and we encourage the removal of these agents from institutional tail biopsy guidelines.

Antibacterial and anti-biofilm activity of AH plus with chlorhexidine and cetrimide.

INTRODUCTION: The use of root canal filling materials with antibacterial activity can be considered beneficial to reduce the remaining microorganisms in the root canal system, where Enterococcus faecalis is often found, and prevent recurrent infection. The aim of this study was to evaluate the antimicrobial activity and capacity for inhibiting E. faecalis biofilm formation of AH Plus, alone and mixed with chlorhexidine (CHX), cetrimide (CTR), and combinations of the two. METHODS: AH Plus alone and mixed with 1% and 2% CHX, 0.1%-0.5% CTR, and combinations of both were tested to assess antimicrobial activity by a modified direct contact test and determine inhibition of E. faecalis biofilm formation at 24 hours. The results were expressed as log10 viable counts. Eradication and inhibition of biofilm formation were understood as no bacterial growth or log10 reduction = 5 with respect to the control (AH Plus alone). RESULTS: AH Plus + CHX showed a low antimicrobial activity with respect to the control (at 2%, log10 reduction = 1.30). None of the tested concentrations achieved eradication or inhibition of biofilm. AH Plus + CTR showed a direct relationship of concentration-antimicrobial effect, reaching a log10 reduction of 2.92 at 0.5% and inhibition of biofilm formation at 0.2%. With the combination CHX + CTR, lower concentrations were needed for the same effect, and eradication and inhibition of biofilm were achieved. CONCLUSIONS: The addition of CHX, CTR, or some combination of both to AH Plus confers it with bactericidal and anti-biofilm activity against E. faecalis.

Antimicrobial activity of root canal irrigants associated with cetrimide against biofilm and planktonic Enterococcus faecalis.

AIM: To evaluate the antibacterial activity of sodium hypochlorite (NaOCl) and chlorhexidine (CHX) alone or associated with cetrimide (CTR), and QMiX against biofilm and planktonic Enterococcus faecalis (E. faecalis) [American type culture collection (ATCC) 29212]. MATERIALS AND METHODS: The solutions 2.5% NaOCl, 2.5% NaOCl + 0.2% CTR, 2% CHX, 2% CHX + 0.2% CTR, 0.2% CTR, and QMiX were evaluated. E. faecalis biofilms were induced for 14 days on bovine dentin blocks. The irrigants were evaluated after contact with E. faecalis suspension and biofilm for 1 and 3 minutes. After that, serial decimal dilutions were made and plated on tryptic soy agar (TSA) medium. Plates were incubated for 24 hours at 37°C and the colony-forming unit (CFU) 1 ml was determined. Data were subjected to ANOVA and Tukey's tests at 5% significance. RESULTS: All microorganisms were eliminated by direct contact of the irrigants with planktonic cells. Only NaOCl and NaOCl + CTR were able to completely eliminate the microorganisms by direct contact with E. faecalis biofilm. CHX presented effectiveness similar to CHX + CTR CTR, and QMiX after 1 minute of contact and similar to NaOCl and NaOCl + CTR after 3 minutes (p > 0.05), but was unable to completely eliminate the microorganisms. CTR and QMiX did not differ from each other. CONCLUSION: CTR addition to CHX and NaOCl solutions did not improve the antimicrobial activity against biofilm. All evaluated irrigants and associations presented activity against planktonic E. faecalis. Only NaOCl and NaOCl + CTR eliminated biofilm after 1 and 3 minutes of direct contact.

The effect of oral topical anesthesia on the characteristics of voice.

OBJECTIVES/HYPOTHESIS: Although oral topical anesthesia is used routinely before rigid laryngeal endoscopy, no study has determined whether oral topical anesthesia changes voice quality. Our goal was to determine the effects of topical anesthesia on voice. STUDY DESIGN: Prospective cohort study. METHODS: Adult patients presenting to a laryngology practice who required rigid laryngeal endoscopy as part of the routine clinical visit were eligible for the study. Voices were recorded before and after oral topical benzocaine (14%)/butamben (2%)/tetracaine (2%) (ie, cetacaine) spray. Consensus auditory perceptual evaluation of voice (CAPE-V) protocol was used for the voice recordings and was the primary outcome measure. Recordings were presented randomly to two blinded speech-language pathologists specialized in voice. Secondary outcome measures were fundamental frequency (F0), jitter, shimmer, and noise-to-harmonics ratio (N/H) on sustained /i/ and speaking F0. RESULTS: One hundred two patients participated in the study. There was no significant difference in CAPE-V measurements before and after topical anesthesia for all six attributes: overall severity (P = 0.145), roughness (P = 0.214), breathiness (P = 0.761), strain (P = 0.053), pitch (P = 0.301), and loudness (P = 0.320). There was no significant difference in jitter (P = 0.315), shimmer (P = 0.942), N/H (P = 0.128), and speaking F0 (P = 0.320). F0 /i/ decreased by a mean of 4.8Hz, which was statistically significant (P = 0.003), but probably not clinically significant. CONCLUSION: There was no clinically significant voice change after oral topical anesthesia.

Topical anesthesia mitigates the pain of castration in beef calves.

Castration involves the removal of the testes and is performed to improve product quality and management of male calves. The procedure has been proven to cause significant pain and stress, and despite several attempts to reduce the impact of castration on animal welfare, there has yet to be a practical and affordable option made available for farmer application. To address this issue, we conducted 2 trials (n = 18 and 27) to examine the efficacy of topical anesthetic Tri-Solfen (TA) to alleviate the pain of surgical castration. Angus bull calves (135.8 ± 5.7 kg) aged 3 to 4 mo were randomly allocated to 3 treatment groups, including surgical castration, castration in combination with TA, and uncastrated controls. In Trial 1, pain-related behavior was assessed using a customized numerical rating scale (NRS) over 4 h. In Trial 2, pre- and postoperative skin sensitivity of the wound and periwound areas was assessed using an electronic von Frey anesthesiometer (IITC Life Sciences, Woodland Hills, CA) and von Frey monofilaments (300 g). Sampling was repeated at 1 min and 2, 4, 6, and 24 h after castration. Pain threshold was measured as maximum pressure (g) exerted by the electronic anesthesiometer to invoke animal reflex, and responses to the von Frey monofilaments were scored from 0 to 3 using a NRS on the basis of local and central motor reflexes. Calves treated with TA displayed significantly less pain-related behaviors up to 3.5 h after castration than untreated calves (P < 0.001) and did not differ from uncastrated controls. Topical anesthetic-treated calves also exhibited significantly greater pain threshold of the wound (559.2 ± 14.3 g) and surrounding skin (602.8 ± 16.5 g) than untreated calves (446.0 ± 18.9 and 515.3 ± 20.4 g, respectively; P < 0.001). Control and TA-treated calves had significantly lower mean response scores to von Frey stimulation than untreated calves (0.333, 0.978, and 4.289, respectively; P < 0.001). Results indicate that TA effects rapid and prolonged pain alleviation in calves up to 24 h after castration. Topical anesthesia may present a cost-effective, practical, on-farm approach to pain alleviation and is proposed as a potential tool for reducing the welfare impact on the beef animal in routine husbandry procedures.

Cetacaine induced methemoglobinemia: overview of analysis and treatment strategies.

Methemoglobin is formed upon iron oxidation of the heme molecule from ferrous (Fe2+) to its ferric (Fe3+) state. Normal methemoglobin levels in the body vary between 1-2% of the total hemoglobin. Cause of methemoglobinemia can be inherited or acquired. Inherited causes include an enzymatic deficiency in the enzyme cytochrome b5 reductase where as acquired causes are most commonly from routinely used medications. Herein, we present to you a case of methemoglobinemia after Cetacaine (a benzocaine based topical anesthetic) utilization during a transesophageal echocardiography. Some of the other common potential inciting agents are also discussed here along with an overview of treatment strategies.

Photodynamic inactivation of chlorin e6-loaded CTAB-liposomes against Candida albicans.

BACKGROUND AND OBJECTIVES: Antimicrobial photodynamic inactivation (PDI) is a promising therapeutic modality for the treatment of local infections. To increase the efficacy of PDI, chlorine e6 (Ce6) was encapsulated in cationic CTAB-liposomes composed of various ratios of dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) and the cationic surfactant, cetyltrimethyl ammonium bromide (CTAB). The PDI efficacy of the liposomal-Ce6 was assessed in vitro against susceptible and drug-resistant clinical isolates of Candida albicans (C. albicans) as well as in infected burn wounds. STUDY DESIGN/MATERIALS AND METHODS: Ce6 was encapsulated in CTAB-liposomes by the film hydration method. Particle size distribution and zeta potential of the cationic liposomes were measured using a Zetasizer Nano-ZS. UV-visible spectra were used to measure lipid/Ce6 (L/C) ratio and drug entrapment efficiency while differential scanning calorimetry (DSC) was used to study the thermotropic behavior of DMPC liposomes upon CTAB addition. In vivo PDI efficacy was carried out in an infected burn wound using a rat model. RESULTS: The increase in zeta potential and a shift in the phase transition temperature (Tm ) upon CTAB addition confirmed its entrapment within the lipid bilayers of the liposome. Meanwhile, the CTAB addition did not affect the Ce6 entrapment efficiency and physical attributes of the liposomes. In vitro studies showed that the PDI effect of the Ce6-loaded CTAB-liposomes was dependent on the lipid to Ce6 molar ratio (L/C), particle size and the concentration of CTAB in the liposomes. The lower L/C ratio and smaller liposomes exerted significantly higher PDI effects. In addition, an increase in the CTAB to lipid ratio led to a significant increase in the PDI effect of Ce6 against susceptible and drug-resistant clinical isolates of C. albicans after light illumination. CONCLUSIONS: Our results indicate that a low L/C ratio, high positive charge, and small particle size of CTAB-liposomes significantly enhances their PDI efficacy against C. albicans.

The effect of detergents on the antibacterial activity of disinfecting solutions in dentin.

INTRODUCTION: Detergents have been added into different disinfecting solutions to lower their surface tension and to enhance their antibacterial effects. The purpose of this study was to evaluate the effectiveness of dentin disinfection by different antibacterial solutions in the presence and absence of detergents using a novel dentin infection model and confocal laser scanning microscopy (CLSM). METHODS: Semicylindrical dentin specimens were infected with Enterococcus faecalis by centrifugation according to a previously described protocol. After 1 day of incubation, the infected dentin specimens were subjected to 1 and 3 minutes of exposure to sterile water, 0.1% cetrimide (CTR), 2% sodium hypochlorite (NaOCl), 2% NaOCl + 0.1% CTR, 6% NaOCl, 6% NaOCl + 0.1% CTR, Chlor-Xtra (Vista Dental, Racine, WI), 2% chlorhexidine (CHX), CHX-Plus (Vista Dental, Racine, WI), 2/4% iodine potassium iodide (IPI), and IPI + 0.1% CTR. The specimens were then stained for bacterial viability and examined by CLSM to analyze the proportions of dead and live bacteria inside dentinal tubules. RESULTS: More bacteria in dentin were killed after 3 minutes of exposure than after 1 minute of exposure to the disinfecting solutions in all experimental groups (P < .05). The antibacterial solutions with detergents (0.1% CTR, 2% NaOCl + 0.1% CTR, CHX-Plus, and IPI + 0.1% CTR) showed a statistically higher proportion of dead bacteria than the corresponding solutions without detergents (sterile water, 2% NaOCl, 2% CHX, and IPI) (P < .05) except for the 6% NaOCl group (6% NaOCl, 6% NaOCl + 0.1% CTR, and Chlor-Xtra) (P > .05). Six percent NaOCl, 6% NaOCl + 0.1% CTR, and Chlor-Xtra were the most effective solutions, killing over 45% and 65% of the bacteria after 1 and 3 minutes of exposure, respectively. Only 3% to 4% of the bacteria were dead in the sterile water group, whereas 0.1% CTR alone was able to kill 24% to 36% of the E. faecalis cells. CONCLUSIONS: The addition of detergents in the disinfecting solutions used in the present study increased their antibacterial effects against E. faecalis in the dentinal tubules. When used alone as a single agent, CTR showed antibacterial effectiveness comparable to 2% NaOCl, 2% CHX, and 2/4% IPI.

Eradication of enterococci biofilms by lactic acid alone and combined with chlorhexidine and cetrimide.

OBJECTIVE: The antimicrobial activity of lactic acid (LA) alone or in combination with chlorhexidine (CHX) and cetrimide (CTR) against three Enterococcus faecalis strains, E. faecalis ATCC 29212, E. faecalis EF-D1 and E. faecalis U-1765, one Enterococcus durans strain and one dual-species biofilm was investigated. STUDY DESIGN: The irrigating solutions tested were 20%, 15%, 10%, 5% and 2.5% LA, alone and in combination with 2% CHX and with 0.2% CTR. The biofilms were grown in the MBECTM high-throughput device for 24 hours and exposed to the solutions for 30 seconds and 1 minute. "Eradication" was defined as 100% bacterial kill. RESULTS: Twenty percent LA eradicated all enterococci biofilms after 30 seconds contact time. The association of LA+0.2% CTR achieved better results than LA alone, in contrast with the results obtained using LA+2% CHX. E. durans was eradicated by all the tested solutions at 1 minute. The dual-species biofilm, E. faecalis ATCC 29212+E. durans, gave intermediate values of the pure cultures. CONCLUSIONS: LA is capable of eradicating enterococci biofilm at a concentration of 20%. The combination of lower concentrations with 0.2% CTR achieved eradication after 1 minute.

Doxorubicin and MBO-asGCS oligonucleotide loaded lipid nanoparticles overcome multidrug resistance in adriamycin resistant ovarian cancer cells (NCI/ADR-RES).

The objective of this study was to increase the potency of doxorubicin against adriamycin-resistant NCI/ADR-RES cells by concurrent treatment with doxorubicin and MBO-asGCS loaded solid-lipid nanoparticles (SLN). Loading doxorubicin as ion-pair complex with deoxytaurocholate into cationic and neutral SLN was investigated. Fast release and poor entrapment were observed in cationic nanoparticles, which were corrected by entrapping the complex in neutral polyoxyethylene (20) stearyl ether (Brij(®) 78)/VitE-TPGS nanoparticles. Slow doxorubicin release confirmed the influence of charge and electrolytes on the dissociation of ion-pair complexes. To evaluate antitumor activity, NCI/ADR-RES cells were treated with separate SLN: one loaded with doxorubicin and another carrying MBO-asGCS oligonucleotide. The viability of cells treated with 5 µM doxorubicin was reduced to 17.2% whereas viability was reduced to 2.5% for cells treated with both 5 µM doxorubicin SLN and 100 nM MBO-asGCS SLN. This suggested enhanced apoptosis due to sensitization and effective intracellular delivery of MBO-asGCS and doxorubicin by SLN.

The use of nanocrystalline cellulose for the binding and controlled release of drugs.

The objective of this work was to investigate the use of nanocrystalline cellulose (NCC) as a drug delivery excipient. NCC crystallites, prepared by an acid hydrolysis method, were shown to have nanoscopic dimensions and exhibit a high degree of crystallinity. These crystallites bound significant quantities of the water soluble, ionizable drugs tetratcycline and doxorubicin, which were released rapidly over a 1-day period. Cetyl trimethylammonium bromide (CTAB) was bound to the surface of NCC and increased the zeta potential in a concentration-dependent manner from -55 to 0 mV. NCC crystallites with CTAB-modified surfaces bound significant quantities of the hydrophobic anticancer drugs docetaxel, paclitaxel, and etoposide. These drugs were released in a controlled manner over a 2-day period. The NCC-CTAB complexes were found to bind to KU-7 cells, and evidence of cellular uptake was observed.

Residual and antimicrobial activity of final irrigation protocols on Enterococcus faecalis biofilm in dentin.

INTRODUCTION: The use of root canal irrigating solutions exerting antimicrobial activity and prolonged residual activity is desirable in order to control dentin infection and delay reinfection of the root canal. The aim of this study was to evaluate the residual antimicrobial activity and the capacity to eradicate Enterococcus faecalis biofilm of different irrigating solutions, alone and in combination, in a dentin-volumetric test. METHODS: Solutions of 2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX), 0.2% cetrimide (CTR), 17% ethylendiaminetetraacetic (EDTA), 7% maleic acid (MA), and regimens of 2.5% NaOCl followed by 17% EDTA or 7% MA and 0.2% CTR or 2% CHX were used to determine their residual activity by exposing treated dentin blocks to E. faecalis for 24 hours. Antimicrobial activity was assayed on 3-week biofilm formed on dentin blocks. Results of residual activity and antimicrobial activity were respectively expressed as the inhibition percentage of biofilm formation and the kill percentage of biofilm. RESULTS: A 2% CHX and 0.2% CTR solution showed 100% biofilm inhibition; 2.5% NaOCl showed the lowest residual activity (18.10%). The kill percentage of 2.5% NaOCl and 0.2% CTR was 100% followed by 7% MA and 2% CHX, whereas 17% EDTA was the least effective (44%). Solutions of 7% MA or 17% EDTA followed by 0.2% CTR or 2% CHX showed 100% residual and antimicrobial activity. CONCLUSIONS: A 0.2% CTR solution alone and the combinations in which 2% CHX or 0.2% CTR was the final irrigating solution achieved the maximum residual and antimicrobial activity.

A scanning electron microscopy study of diseased root surfaces conditioned with EDTA gel plus Cetavlon after scaling and root planing.

In the present investigation, a scanning electron microscopy analysis was performed to evaluate the effects of the topical application of ethylenediaminetetraacetic acid (EDTA) gel associated with Cetavlon (EDTAC) in removing the smear layer and exposing collagen fibers following root surface instrumentation. Twenty-eight teeth from adult humans, single rooted and scheduled for extraction due to periodontal reasons, were selected. Each tooth was submitted to manual (scaling and root planing) instrumentation alone or combined with ultrasonic instruments, with or without etching using a 24% EDTAC gel. Following extraction, specimens were processed and examined under a scanning electron microscope. A comparative morphological semi-quantitative analysis was performed; the intensity of the smear layer and the decalcification of cementum and dentinal surfaces were graded in 12 sets using an arbitrary scale ranging from 1 (area covered by a smear layer) to 4 (no smear layer). Root debridement with hand instruments alone or combined with ultrasonic instruments resulted in a similar smear layer covering the root surfaces. The smear layer was successfully removed from the surfaces treated with EDTAC, which exhibited numerous exposed dentinal tubules and collagen fibers. This study supports the hypothesis that manual instrumentation alone or instrumentation combined with ultrasonic instrumentation is unable to remove the smear layer, whereas the subsequent topical application of EDTAC gel effectively removes the smear layer, uncovers dentinal openings and exposes collagen fibers.

Preparation of a cationic nanoemulsome for intratumoral drug delivery and its enhancing effect on cellular uptake in vitro.

To develop an appropriate carrier for intratumoral drug delivery, cetyltrimethylammonium bromide (CTAB) modified nanoemulsome (CTAB-NES) was designed and prepared by solvent evaporation method. Coumarin-6 was chosen as the fluorescent probe and the conventional nanoemulsome (NES) without CTAB modification served as a control. The results demonstrated that CTAB-NES had a smaller particle size of 71.9 +/- 4.32 nm, considerate positive zeta potential of +48.7 +/- 0.2 mV, preferably entrapment efficiency of 97.483 +/- 0.693% and the release of coumarin-6 in 24 h was little. The in vitro cytotoxicity of CTAB-NES to the CHO cells and MCF-7 cells increased consistently with concentrations and was higher than that of NES, especially to the cancer cells. Both the fluorescence microscopy images and HPLC assay verified that the cellular uptake of CTAB-NES in MCF-7 cells was much higher than that of NES, and the uptake was time-, concentration- and temperature- dependent. The uptake mechanism results demonstrated that the internalization of CTAB-NES and NES involved clathrin- and caveolae-mediated endocytosis while macropinocytosis only influenced the uptake of CTAB-NES in MCF-7 cells for CTAB could mediate adsorptive pinocytosis. Thus, CTAB-NES with high positive charge and good intracellular uptake ability could be a promising drug carrier for intratumoral drug delivery.

The first account of a bite by the New Zealand native spider Trite planiceps (Araneae: Salticidae).

New Zealand has very few arthropods that pose a threat to human health. While most New Zealand spiders are considered harmless, the bite effects of most species are unknown. Here, we describe a case of a bite by a native spider, in which a young man was bitten after rolling over in his bed. The spider was collected and identified as Trite planiceps (Salticidae, black headed jumping spider), a native species commonly encountered around homes. The initial reaction was a relatively painful, sting-like, sensation, followed by the appearance of two red puncture marks and an urticarial wheal. Symptoms eventually disappeared after 72 hours, and he has had no further dermatological problems. Trite planiceps is considered to be a rather docile spider with regard to humans, but even a docile species may still bite defensively as a last resort. Notes on this species and on treatment of spider bites are provided.

Eradication of Enterococcus faecalis biofilms by cetrimide and chlorhexidine.

INTRODUCTION: Enterococcus faecalis is the most commonly isolated bacteria from root canals of teeth with persistent periapical periodontitis. Its ability to grow as a biofilm impedes the elimination of E. faecalis by using irrigating solutions. The purpose of this study was to assess the efficacy of cetrimide and chlorhexidine (CHX), alone and in association, in combined and alternating form, in eradicating biofilms of E. faecalis. METHODS: Biofilms grown in the MBEC-high-throughput device for 24 hours were exposed to irrigating solutions for 30 seconds and 1 and 2 minutes. Eradication was defined as 100% kill of biofilm bacteria. The Student t test was used to compare the efficacy of the associations of the 2 irrigants. RESULTS: Cetrimide eradicated E. faecalis biofilms at concentrations of 0.5%, 0.0312%, and 0.0078% at 30 seconds and 1 and 2 minutes of contact time, respectively. CHX did not eradicate the biofilms at any of the concentrations (4% initial concentration) or times assayed. The association of 0.1% and 0.05% cetrimide with any concentration of CHX, whether in combined or alternating application, effectively eradicated E. faecalis biofilms at all the contact times tested. Eradication was also achieved with 0.02% and 0.01% cetrimide at 2 minutes. Statistical analysis revealed significantly better results with alternating rather than combined use of cetrimide and CHX (P < .05). CONCLUSIONS: The associated use of cetrimide and CHX provided better results than their applications as single agents against E. faecalis biofilms, and the alternating application was significantly more effective than the combined mode of application.

Effectiveness of a non-surgical alternative to the Mules operation in sheep.

OBJECTIVE: To measure changes to the perineal bare area, local tissue reaction and healing responses of young sheep, following intradermal administration of cetrimide and polyvinylpyrrolidone (PVP), with and without ethanol, to the breech and tail. METHOD: A needle-less injector was used to deposit formulations containing 40 g/L cetrimide and 30 g/L PVP (group 2) or 20 g/L cetrimide, 30 g/L PVP and 15 g/L ethanol (group 3), within the dermis of the tail and the region surrounding the perineal bare breech area of groups (N = 8) of Merino weaner sheep. The dimensions of the perineal bare area (length, width and diagonal distances left and right) and tail width were recorded before and at intervals after treatment for 60 days. Observations of swelling and bruising and scab formation at the treatment sites were recorded for up to 35 days after treatment. Rectal temperatures were monitored for up to 35 days after treatment and bodyweight for up to 60 days after treatment. An untreated control group (group 1) was included. RESULTS: Comparison of day -3 and day 35 measurement data showed that both treated groups had significantly (P < 0.05) wider breech bare areas compared to the untreated controls and that group 2 sheep had significantly (P < 0.05) longer breech bare areas compared to group 3 sheep or to the untreated controls, which were not significantly different. At this time scabs were still firmly in place on many treated sheep. At day 35 there was no increase in tail bare area caused by either treatment. By day 60 there was no significant difference between the treated and control groups in either the breech or tail regions indicating that the changes present at day 35, were not permanent. Mean weight gain in the groups throughout the 60-day interval was unaffected by treatment. Intradermal treatment was associated with a significant elevation in body temperature. This effect lasted for 3 days and was associated with signs of discomfort and depressed appearance in at least some of the treated sheep. Bruising was mild to severe in all treated sheep within two days of treatment but was not evident in any sheep by day 21. Mild to moderate swelling was also associated with treatment but was not uniform across sheep in the groups. The tail of one sheep was severely swollen for several days. Swelling remained obvious in most treated sheep until day 14 but was not present at day 21. CONCLUSION: Under the conditions of this study intradermal injection of cetrimide had no permanent effect on bare area measurements on the breech or the amount of wool-bearing skin on the tail. It also caused signs of discomfort and pain that raise welfare concerns.

Using biorelevant dissolution to obtain IVIVC of solid dosage forms containing a poorly-soluble model compound.

The usefulness of selected biorelevant dissolution media (BDM) to predict in vivo drug absorption was studied. Dissolution profiles of solid formulations of a poorly soluble model compound were compared in BDM simulating fasted and two levels of fed state. A non-physiologically relevant medium containing the cationic surfactant, cetrimide, was also investigated. All the media studied were capable of differentiating between the formulations employed, with formulation A consistently ranking high and formulations C and D ranking low. An in vivo dog study was carried out and an attempt was made to obtain a level A correlation between the plasma absorption curves and in vitro dissolution curves, using non-linear regression software. The in vitro-in vivo correlation (IVIVC) models developed indicated that fed state media (BDM 3) containing high levels of both bile salts (BS) and lipolysis products (LP) were best able to predict in vivo pharmacokinetic parameters (Cmax and AUC) with prediction errors lower than 10%. Overall, design and use of appropriate media for in vitro dissolution is extremely important. This study demonstrates the potential of physiologically relevant media containing both BS and LP for use in formulation and early drug development.