Trimethylamine N-oxide (TMAO) is a counteracting solute of benzyl alcohol for multi-dose formulation of immunoglobulin.

Multi-dose formulation of biopharmaceuticals contains an antimicrobial preservative, which may facilitate aggregation of the proteins due to their hydrophobic protein binding. Here, we have investigated the effects of co-solvents on heat-induced protein aggregation in the presence of an antimicrobial preservative. Human immunoglobulin G (IgG) and benzyl alcohol were chosen because of their wide usage as a pharmaceutical protein and a preservative. Trimethylamine N-oxide (TMAO) was found to be the most effective additive in suppressing benzyl alcohol-induced IgG aggregation among the additives tested. Interestingly, TMAO was less effective in increasing the thermal-unfolding temperature of IgG than trehalose, indicating that the observed suppression of IgG aggregation by TMAO in the presence of benzyl alcohol is not simply due to its stabilization effect of the protein structure. The solubility of benzyl alcohol increased with increasing concentrations of TMAO, suggesting that the hydrophobic interaction of TMAO with benzyl alcohol is responsible for the observed aggregation suppression. Thus, TMAO may be a potential aggregation suppressor in multi-dose formulation of biopharmaceuticals.

The anxiolytic effect of essential oil of Cananga odorata exposure on mice and determination of its major active constituents.

BACKGROUND: Essential oil from Cananga odorata (ylang-ylang essential oil, YYO) is usually used in reducing blood pressure, improving cognitive functioning in aromatherapy in human. Few reports showed its effect on anxiety behaviors. HYPOTHESIS/PURPOSE: To investigate the anxiolytic effects of YYO exposure on anxiety animal models, determine the major active constituents and investigate the change of neurotransmitters after odor exposure. STUDY DESIGN AND METHODS: ICR mice were subjected to three anxiety models including open field, elevated plus maze and light-dark box tests after acute and chronic YYO exposure. Main constituents of YYO were defined using GC/MS. These compounds were then tested on the male mice separately on three anxiety models. The monoamines neurotransmitters and their metabolites were analyzed after acute odor exposure and elevated plus maze test. RESULTS: YYO exposure only showed significant anxiolytic effect on the male mice. It increased the time that mice visited open arms and light box area in elevated plus maze and light-dark box tests after acute and chronic YYO exposures. Three main constituents of YYO, benzyl benzoate, linalool and benzyl alcohol showed anxiolytic effect on the male mice individually. YYO exposure brought changes of neurotransmitters on the male mice more significantly than the female mice. It decreased the dopamine (DA) concentration in the striatum and increased the 5-hydroxytryptamine (5-HT) concentration in the hippocampus of the male mice. The major constituent benzyl benzoate changed neurotransmitters concentration in accordance with the YYO. Moreover, it decreased the ratio of 5-HIAA/5-HT in the hippocampus. CONCLUSION: Both acute and chronic YYO exposure showed anxiolytic effect on the male mice. YYO and its major constituent benzyl benzoate might act on the 5-HTnergic and DAnergic pathways.

A real-world evidence study evaluating a treatment for nappy rash.

This retrospective open study evaluating the efficacy of Sudocrem Antiseptic Healing Cream (SAHC) in infantile nappy rash (NR) was based on real-world evidence collected using an online questionnaire that included Likert scales. Participants who had used SAHC in the past (n=2159) were recruited via social media and email. A total of 1818 respondents who had treated NR in the previous 6 months were asked to take part in the study. Over 50% of respondents saw an improvement in NR on the same day that treatment was started, and within 3 days 94.5% of respondents reported an improvement in NR. Of 1804 subjects who answered the question, 72.5% indicated that the NR had completely healed within 3 days of starting treatment and by the fifth day, 94.7% said that the NR had completely healed. A total of 71% of 1793 respondents said that an episode of NR had either no or minimal impact disrupting their normal lives, but 29% reported a noticeable impact, even though evidence suggests that mild to moderate nappy rash can be treated quickly. Based on this real-world retrospective study, the evidence suggests SAHC is rapidly effective, reduces signs and symptoms of inflammation, and heals NR.

Benzyl alcohol attenuates acetaminophen-induced acute liver injury in a Toll-like receptor-4-dependent pattern in mice.

UNLABELLED: Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in industrialized countries. Understanding the mechanisms of APAP-induced liver injury as well as other forms of sterile liver injury is critical to improve the care of patients. Recent studies demonstrate that danger signaling and inflammasome activation play a role in APAP-induced injury. The aim of these investigations was to test the hypothesis that benzyl alcohol (BA) is a therapeutic agent that protects against APAP-induced liver injury by modulation of danger signaling. APAP-induced liver injury was dependent, in part, on Toll-like receptor (TLR)9 and receptor for advanced glycation endproducts (RAGE) signaling. BA limited liver injury over a dose range of 135-540 µg/g body weight or when delivered as a pre-, concurrent, or post-APAP therapeutic. Furthermore, BA abrogated APAP-induced cytokines and chemokines as well as high-mobility group box 1 release. Moreover, BA prevented APAP-induced inflammasome signaling as determined by interleukin (IL)-1ß, IL-18, and caspase-1 cleavage in liver tissues. Interestingly, the protective effects of BA on limiting liver injury and inflammasome activation were dependent on TLR4 signaling, but not TLR2 or CD14. Cell-type-specific knockouts of TLR4 were utilized to further determine the protective mechanisms of BA. These studies found that TLR4 expression specifically in myeloid cells (LyzCre-tlr4-/-) were necessary for the protective effects of BA. CONCLUSION: BA protects against APAP-induced acute liver injury and reduced inflammasome activation in a TLR4-dependent manner. BA may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury.

Excision biopsy in a patient with suspected local anaesthetic allergy: use of 0.9% saline with benzyl alcohol as local anaesthesia.

Dermatologists may see patients with actual or suspected local anaesthetic (LA) allergy who require an urgent dermatological procedure to be performed without time for formal allergy testing. We report a case of shave biopsy and subsequent excision biopsy of an atypical naevus performed using tumescent analgesia with 0.9% saline containing benzyl alcohol preservative. The tumescence itself and the benzyl alcohol present in the 0.9% saline solution provided sufficient analgesia for excision. This technique may be an option for managing urgent procedures in patients suspected or known to have allergy to LA.

An ex vivo, assessor blind, randomised, parallel group, comparative efficacy trial of the ovicidal activity of three pediculicides after a single application--melaleuca oil and lavender oil, eucalyptus oil and lemon tea tree oil, and a "suffocation" pediculicide.

BACKGROUND: There are two components to the clinical efficacy of pediculicides: (i) efficacy against the crawling-stages (lousicidal efficacy); and (ii) efficacy against the eggs (ovicidal efficacy). Lousicidal efficacy and ovicidal efficacy are confounded in clinical trials. Here we report on a trial that was specially designed to rank the clinical ovicidal efficacy of pediculicides. Eggs were collected, pre-treatment and post-treatment, from subjects with different types of hair, different coloured hair and hair of different length. METHOD: Subjects with at least 20 live eggs of Pediculus capitis (head lice) were randomised to one of three treatment-groups: a melaleuca oil (commonly called tea tree oil) and lavender oil pediculicide (TTO/LO); a eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO); or a "suffocation" pediculicide. Pre-treatment: 10 to 22 live eggs were taken from the head by cutting the single hair with the live egg attached, before the treatment (total of 1,062 eggs). TREATMENT: The subjects then received a single treatment of one of the three pediculicides, according to the manufacturers' instructions. Post-treatment: 10 to 41 treated live eggs were taken from the head by cutting the single hair with the egg attached (total of 1,183 eggs). Eggs were incubated for 14 days. The proportion of eggs that had hatched after 14 days in the pre-treatment group was compared with the proportion of eggs that hatched in the post-treatment group. The primary outcome measure was % ovicidal efficacy for each of the three pediculicides. RESULTS: 722 subjects were examined for the presence of eggs of head lice. 92 of these subjects were recruited and randomly assigned to: the "suffocation" pediculicide (n = 31); the melaleuca oil and lavender oil pediculicide (n = 31); and the eucalyptus oil and lemon tea tree oil pediculicide (n = 30 subjects). The group treated with eucalyptus oil and lemon tea tree oil had an ovicidal efficacy of 3.3% (SD 16%) whereas the group treated with melaleuca oil and lavender oil had an ovicidal efficacy of 44.4% (SD 23%) and the group treated with the "suffocation" pediculicide had an ovicidal efficacy of 68.3% (SD 38%). CONCLUSION: Ovicidal efficacy varied substantially among treatments, from 3.3% to 68.3%. The "suffocation" pediculicide and the melaleuca oil and lavender oil pediculicide (TTO/LO) were significantly more ovicidal than eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO) (P < 0.0001). Ranking: 1. "Suffocation" pediculicide (68.3% efficacy against eggs); 2. Melaleuca oil and lavender oil (44.4%) pediculicide; 3. Eucalyptus oil and lemon tea tree oil (3.3%) pediculicide. The "suffocation" pediculicide and TTO/LO are also highly efficacious against the crawling-stages. Thus, the "suffocation" pediculicide and TTO/LO should be recommended as first line treatments.

Reducing the pain of local 1% lidocaine infiltration with a preceding bacteriostatic saline injection: a double-blind prospective trial.

BACKGROUND: Lidocaine injection for local anesthesia is a common podiatric medical procedure. We tested the hypothesis that injection of bacteriostatic saline solution containing 0.9% benzyl alcohol before the lidocaine infiltration can reduce the burning caused by lidocaine injection. METHODS: This double-blind prospective trial involved 45 participants who each received four injections in two areas of the dorsum of the foot and rated the perceived pain on a visual analog scale. The order of the injections was designed to disguise the control and intervention arms of the study. RESULTS: The sensation of the lidocaine injection after the injection of saline was reduced significantly (P = .028). The percentage of lidocaine injections with visual analog scale scores of 0 increased by 36% after preinjection with bacteriostatic saline solution containing 0.9% benzyl alcohol. CONCLUSIONS: The fact that 40% of the intervention visual analog scale pain scores for lidocaine injections were 0 suggests that a near painless lidocaine injection technique is an achievable goal and that the present technique is a simple and inexpensive method of reducing the pain of lidocaine injections.

The influence of application of different desensitisers on root dentine demineralisation in situ.

AIM: To evaluate the influence of three desensitisers on root caries demineralisation in situ. METHODS: The root surfaces of 36 freshly extracted human molars were used to prepare root dentine specimens. These specimens were distributed among the following groups: A: Admira Protect, V: VivaSens, H: Hyposen, C: control group, untreated. Two dentine specimens of each group were inserted into two buccal aspects of intraoral mandibular appliances. The appliances were worn by nine persons for five weeks, day and night. One side was brushed daily with a toothpaste. On the other side, plaque was allowed to grow. Individual oral hygiene techniques were performed without any fluorides. After the in situ period, two slabs were ground. The depth of the demineralised areas was determined using a polarised light microscope. RESULTS: ANOVA revealed significant differences between brushed and non-brushed specimens. Lesion depths in the brushed group were significantly decreased (p < 0.05, Tukey's test). CONCLUSIONS: Within the limitations of an in situ study it can be concluded that the demineralisation of the root surface can be hampered by application of desensitisers under different oral hygiene conditions. The application of clinical proven desensitising agents might have a caries-protective effect on exposed root surfaces.

The influence of different irradiation doses and desensitizer application on demineralization of human dentin.

The aim of the present study was to evaluate the effect of different irradiation doses after desensitizer application on the onset of initial demineralization of human dentin in situ. The root surfaces of 45 freshly extracted caries-free human molars were cleaned, thereby removing the cementum. From each tooth two root dentin specimens were prepared. The specimens were distributed among the following experimental groups: 0, 0.5, 1, 2 and 5Gy. The irradiation dose was fractionally applied (0.5Gy/day). One dentin specimen of each group was inserted into both buccal aspects of nine intraoral mandibular appliances. On one side the specimens were additionally coated with the desensitizer Hyposen (H). On the other side, the specimens were left untreated (C). The appliances were worn by nine persons for five weeks day and night. During meals, the appliance was stored in 10% sucrose solution. After the in situ period, slabs (150microm) were ground and studied using a polarized light microscope. Concerning radiation dose, significant differences were observed between the control and 5Gy group (p<0.05, Tukey s test). Pairwise comparison showed that lesion depths in groups treated with Hyposen were significantly decreased. Within the limitations of this study it can be concluded that higher radiation doses seem to increase the caries susceptibility of dentin. The additional application of a desensitizer hampers the demineralization and might have a caries-protective effect on exposed irradiated root surfaces.

Clinical effectiveness of a strontium chloride- containing desensitizing agent over 6 months: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The aim of this multicenter study was to evaluate the clinical efficacy of a strontium chloride-containing desensitizer, Hyposen (Lege Artis), over 6 months. METHOD AND MATERIALS: A total of 142 patients with hypersensitivity in 9 dental practices and 2 clinical departments were included in the double-blind, randomized, placebo-controlled study. Each patient exhibited at least 2 hypersensitive and caries-free teeth with exposed dentin surfaces. One tooth was treated with strontium chloride (SR) as recommended by the manufacturer, another with a placebo. Levels of hypersensitivity were assessed after 2, 8, 12, and 24 weeks by cold air and tactile stimuli. After 6 months 132 patients could be reexamined. RESULTS: A reduction of discomfort and pain was observed in 95 patients (72%) after treatment with SR. Statistical analysis showed a significant positive effect of SR compared to the placebo group (P < .05, McNemar test). CONCLUSION: Use of SR for desensitizing hypersensitive dentin is an effective alternative to existing desensitizing agents.

In vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole on Malassezia organisms from dogs with otitis externa.

The purpose of this study was to evaluate the in vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole in purified water on Malassezia organisms from dogs with otitis externa. Malassezia organisms were collected from ear swab samples from the external ear canal of 19 dogs with otitis externa plus one control strain of Malassezia pachydermatis. Three test solutions were evaluated: ER (EDTA, tromethamine, benzyl alcohol), ER + keto (EDTA, tromethamine, benzyl alcohol, ketoconazole), and H2O (purified water). Ten-millilitre aliquots of each test solution was transferred into 20 tubes and inoculated with one of the isolates (1 tube per isolate: 19 clinical and 1 control strain). Samples were retrieved from each tube at five time points (0, 15, 30, 45 and 60 min), transferred to Petri dishes, mixed with Sabouraud dextrose agar supplemented with 0.5% Tween 80 and incubated. Following incubation, the plates were examined for growth and colonies counted as colony-forming units per millilitre. The data were analysed using a repeated measures analysis, with pair-wise comparisons of solution-time combinations. There was a significant reduction in Malassezia growth in ER + keto at all time points (P < 0.0001) compared to time zero. Neither ER nor H2O had any effect on the growth of Malassezia. ER + keto was significantly more effective in reducing Malassezia growth (P < 0.0001) at all time points compared to both ER and H2O. ER + keto may be useful in the treatment of Malassezia otitis externa. Future studies should be performed to evaluate the in vivo efficacy of ER + keto as treatment for otic infections caused by Malassezia.

Influence of three different sealants on root dentin demineralization in situ.

PURPOSE: To evaluate in situ the onset of initial demineralization in human dentin pretreated either with two different dentin bonding agents or a desensitizer. METHODS: 28 freshly extracted human molars were included in this study. The root surfaces were thoroughly cleaned, thereby removing the cementum. From each tooth four root dentin specimens were prepared. The specimens were distributed among the following experimental groups: C: control group (untreated), S: Syntac Classic, X: Xeno III, and H: Hyposen. For each subject, one dentin specimen of each group was inserted into both buccal aspects of a bilateral intraoral mandibular appliance. The appliances were worn by 14 subjects for 5 weeks day and night. One side was brushed daily with fluoride-containing toothpaste (Aronal) (B). On the other side, plaque was allowed to grow (NB). Individual oral hygiene techniques were performed without any fluorides. During meals, the appliance was stored in 10% sucrose solution. After the in situ period, slabs (150 microm) were ground and studied using polarized light microscopy. RESULTS: For lesion depth, ANOVA revealed significant differences between brushed and unbrushed specimens. In the brushed groups, the following lesion depths were evaluated (mean values and standard deviation in microns): Group B-C: 74.1 (+/- 18.5), Group B-S: 27.6 (+/- 9.6); Group B-X: 28.7 (+/- 9.6), and Group B-H: 34.3 (+/- 20.6). The non-brushed specimens showed following lesion depths: Group NB-C: 101.7 (+/- 23.9), Group NB-S: 59.9 (+/- 13.1), Group NB-X: 52.5 (+/- 12.1), and Group NB-H: 72.9 (+/- 19.9). Compared to the non-brushed groups, lesion depths in the brushed group were significantly decreased (P < 0.05, Tukey's test). The reduction of lesion depths after application of the three agents was significant in both cases (brushed and non-brushed groups). Within the limitations of an in situ study it can be concluded that the demineralization of the root surface can be inhibited by application of dentin adhesives and desensitizers under different oral hygiene conditions.