Antibacterial Activity of Leaf Extract of Annona muricata and Simarouba glauca on Enterococcus faecalis.

AIM: To determine the antimicrobial effect of water extracts of leaves of Annona muricata and Simarouba glauca on Enterococcus faecalis using agar diffusion method. MATERIALS AND METHODS: Dried leaves of A. muricata and S. glauca were powdered and extracted in a soxhlet apparatus. Enterococcus faecalis was grown overnight in Trypticase soy agar plates. About 10 µl of each extract was placed on agar plates and incubated overnight. The zone of inhibition was measured after 24 hours. About 1% sodium hypochlorite and distilled water were used as positive and negative controls. RESULTS: The leaf extract of A. muricata showed similar effectiveness as that of sodium hypochlorite, whereas the leaf extract of S. glauca showed only a slight reduction in growth of E. faecalis. CONCLUSION: Leaf extract of A. muricata can be developed as an alternative to sodium hypochlorite for root canal irrigants. CLINICAL SIGNIFICANCE: Success of endodontic treatment depends on complete disinfection of the root canals. Root canal irrigants have a major role in complete disinfection of the root canals. Chemical root canal irrigants are more or less toxic to the oral environment. In this study, naturally derived leaf extracts of A. muricata and S. glauca are compared with sodium hypochlorite for its effectiveness against E. faecalis - the most common pathogen found in the root canals.

Psychological and Neurobiological Correlates of Food Addiction.

Food addiction (FA) is loosely defined as hedonic eating behavior involving the consumption of highly palatable foods (ie, foods high in salt, fat, and sugar) in quantities beyond homeostatic energy requirements. FA shares some common symptomology with other pathological eating disorders, such as binge eating. Current theories suggest that FA shares both behavioral similarities and overlapping neural correlates to other substance addictions. Although preliminary, neuroimaging studies in response to food cues and the consumption of highly palatable food in individuals with FA compared to healthy controls have shown differing activation patterns and connectivity in brain reward circuits including regions such as the striatum, amygdala, orbitofrontal cortex, insula, and nucleus accumbens. Additional effects have been noted in the hypothalamus, a brain area responsible for regulating eating behaviors and peripheral satiety networks. FA is highly impacted by impulsivity and mood. Chronic stress can negatively affect hypothalamic-pituitary-adrenal axis functioning, thus influencing eating behavior and increasing desirability of highly palatable foods. Future work will require clearly defining FA as a distinct diagnosis from other eating disorders.

Analyses of teicoplanin concentrations from 1994 to 2006 from a UK assay service.

Objectives An analysis of the trough serum concentrations sent to the UK Antimicrobial Reference Laboratory for teicoplanin therapeutic drug monitoring (TDM). Methods All trough concentrations over a 13 year period were analysed and the percentages were calculated for the following: <10 mg/L (a sub-optimal concentration for all); ≥10-<20 mg/L (the target used for ordinary Gram-positive infections); ≥20-<60 mg/L (the target for all severe staphylococcal infections including endocarditis); and ≥60 mg/L (the concentration associated with toxicity). Results The percentage of patients with concentrations of <10 mg/L decreased each year to 13% in 2006. Almost 40% of the samples each year were in the ≥10-<20 mg/L range. In 1996, the percentage of samples in the ≥20-<60 mg/L range reached a study high of ∼70%. That percentage then fell to 30% and increased slowly to 50% at the end of the study. Fewer than 5% of the samples were ≥60 mg/L. Conclusions Our study shows that there is a need to increase the initial dose or extend the number of days that the loading dose is used in a significant number of patients. With such a wide optimal range and a low potential for toxicity, it is unclear why optimal therapy is not achieved in a higher percentage of patients.

Right-sided spatial difficulties in ADHD demonstrated in continuous movement control.

Children with Attention Deficit Hyperactivity Disorder (ADHD) often show spatial attentional deficits, exhibiting a subtle rightwards bias, possibly due to dysfunction within the right hemisphere fronto-parietal network. Approximately 50% of children with ADHD also show signs of movement dysfunction. The nature of this movement dysfunction and possible interactions with spatial attention difficulties has not been clearly described. This study compared 31 children with and 31 children without ADHD on a movement kinematic task that tested hand-drawing movement precision. Participants used an electronic pen on a digitizing tablet. The pen tip position was sampled as X and Y coordinates at 200Hz. The task was to join targets of either 10 or 20mm diameter that were separated by a distance of 62.5 or 125 mm. Constant error in the X and Y planes, peak absolute velocity and acceleration, movement time, the number of pauses and pause time were analysed. Apart from a significantly increased rate of acceleration across all conditions, the children with ADHD demonstrated no temporal difficulties with the task; rather they showed subtle spatial difficulties, possibly suggestive of cerebellar involvement. The children with ADHD showed difficulties in accuracy of movement towards the right. They were less accurate in the X plane when moving towards the right-sided targets over the long distance. Greater variability in target accuracy was shown when moving towards the small target on the right side. The children with ADHD made significantly more pauses on the left target, when preparing the right movement, than the control group. These results suggest that the subtle spatial bias towards the right that has been demonstrated in ADHD in spatial attention also extends into the continuous movement domain.

Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations.

OBJECTIVES: The aims of this study were to develop a population pharmacokinetic model of vancomycin in adult patients, to use this model to develop dosage guidelines targeting vancomycin trough concentrations of 10-15 mg/L and to evaluate the performance of these new guidelines. METHODS: All data analyses were performed using NONMEM. A population pharmacokinetic model was first developed from vancomycin dosage and concentration data collected during routine therapeutic drug monitoring in 398 patients, then new vancomycin dosage guidelines were devised by using the model to predict vancomycin trough concentrations in a simulated dataset. Individual estimates of CL and V1 were then obtained in an independent group of 100 patients using the population model and the POSTHOC option. These individual estimates were used to predict vancomycin trough concentrations and steady-state AUC(24)/MIC ratios using the current and new dosage guidelines. RESULTS: The population analysis found that the vancomycin data were best described using a bi-exponential elimination model with a typical CL of 3.0 L/h that changed by 15.4% for every 10 mL/min difference from a CL(CR) of 66 mL/min. V(ss) was 1.4 L/kg. The proposed dosage guidelines were predicted to achieve 55% of vancomycin troughs within 10-15 mg/L and 71% within 10-20 mg/L, which is significantly higher than current guidelines (19% and 22%, respectively). The proportion of AUC(24)/MIC ratios above 400 was also higher, 87% compared with 58%. CONCLUSIONS: New vancomycin dosage guidelines have been developed that achieve trough concentrations of 10-15 mg/L earlier and more consistently than current guidelines.

Health-related quality of life of stroke survivors attending the volunteer stroke scheme.

BACKGROUND: The Volunteer Stroke Scheme (VSS) provides patients with the opportunity to participate in community-based therapeutic activities and physiotherapy sessions. AIMS: To provide the first profile of VSS attendees in terms of their functioning across the range of recommended WHO International Classification of Functioning, Disability and Health (ICF) outcomes. METHODS: A convenience sample of 41 VSS patients completed standardised measures of cognitive functioning (MMSE), activity levels [Frenchay Activity Index (FAI), and Barthel Index (BI)], depression [Hospital Anxiety and Depression Scale (HADS)] and Quality of Life (SF-36). RESULTS: A total of 37% met the criteria for mild cognitive impairment and 44% met the criteria for clinical depression. Scores on the BI (M = 79.5) and FAI (M = 18.4) incidated limitations in activity levels. Quality of life levels was low. CONCLUSIONS: High levels of psychological morbidity, severe disability across a range of domains and poor quality of life were reported.

Effects of adrenal medulla graft on recovery of GABAergic and dopaminergic neuron deficits in mice: behavioural, pharmacological and immunohistochemical study.

We studied the capacity of adrenal medullary transplant to restore the deficits of GABAergic and dopaminergic neurons in mice injected with quinolinic acid (QA), using an open field test as well as pharmacological and immunohistochemical techniques. We analysed behavioural traits-total locomotor activity, peripheral and central activities, grooming, leaning and rearing in the QA-lesioned mice and mice that had undergone adrenal medulla (AM) transplantation. We found that the adrenal transplant recovered a loss of GABAergic neurons. It reduced QA-induced hyperactivity in locomotion and improved emotional indices. In addition, immunohistochemical studies of catecholaminergic markers-tyrosine hydroxylase (TH), dopamine (DA) and neuronal vesicular monoamine transporter type 2- and a single post-trial injection of tetrabenazine (TBZ; 5 mg/kg) indicated that catecholamines-synthesising chromaffin cells in the AM grafts were also involved in the beneficial effects. A likely interpretation of this behavioural pattern of results is that adrenal medullary transplants set into play an interaction between GABAergic and DAergic factors. Our results may contribute to the clarification of the beneficial effects of AM transplants in striatal function.

Vancomycin therapeutic drug monitoring: is there a consensus view? The results of a UK National External Quality Assessment Scheme (UK NEQAS) for Antibiotic Assays questionnaire.

This study investigated vancomycin therapeutic drug monitoring (TDM) and issues related to patient management. Questionnaires were distributed to 310 participants in the UK National External Quality Assessment Scheme (NEQAS) for Antibiotic Assays. The response rate was 57.4%. The majority (76%) had an 'in-house' assay service based, almost exclusively, in the microbiology department, and a fluorescence polarization immunoassay (FPIA) was used by 97%. Almost half (48.7%) had an assay service available for 24 h/day, 7 days/week and 92.7% expected same-day results. The majority (80%) had issued guidelines for vancomycin use. A 12 hourly initial dosing regimen was used by 89%. Trough assay samples were taken <10 min before the dose by 91.5%. For post-dose assay samples, 44% took a sample at 1 h, 28% at 2 h and the remainder at 'other' times. For trough target ranges, 93% quoted <10 mg/L or 5-10 mg/L. There was no consensus with regard to post-dose assay sample times and 23 ranges were quoted. The majority (74.4%) regarded a trough level of >or=10 mg/L as 'toxic' but 13 concentrations were quoted as toxic post-dose measurements. In conclusion, there was a wide variability and poor consensus with regard to post-dose vancomycin assay sampling times, target ranges and what constituted a toxic level.

Linezolid penetration into osteo-articular tissues.

Penetration of linezolid into osteo-articular tissue and fluid was studied in 10 patients undergoing primary total knee replacement. Linezolid 600 mg 12 hourly was given orally over the 48 h before operation and intravenously 1 h before induction of anaesthesia. Mean concentrations of linezolid at 90 min after the final dose, in serum, synovial fluid, synovium, muscle and cancellous bone, assayed by HPLC, were at least twice the MIC(90) for staphylococci and streptococci. The concentrations obtained indicate good penetration of this antibiotic and support its use in the management of multidrug-resistant Gram-positive bone, joint and deep-seated soft-tissue infections.

A simple, isocratic high-performance liquid chromatography assay for linezolid in human serum.

A rapid high-performance liquid chromatography (HPLC) assay for the detection of linezolid in human serum was developed. The method used a Hypersil 5ODS stationary phase. The mobile phase was 1% ortho-phosphoric acid, 30% methanol, 2 g/L heptane sulphonic acid, pH 5. UV absorbance detection was used (lambda(max) 254 nm). Samples were prepared by mixing with acetonitrile and an injection volume of 20 microL was used. The inter- and intra-day assay reproducibility were assessed. Assay linearity, specificity and accuracy were investigated. The detection limit and recovery of linezolid from serum were determined. In addition, the stability of linezolid, stored under a variety of conditions, was assessed. The retention time of linezolid was c. 6.5 min. The intra- and inter-day reproducibility was good and the assay was linear across the therapeutic range. Serum recovery was c. 100% at all concentrations tested. The detection limit was 0.1 mg/L and the assay was accurate. The assay was specific as there was no significant interference with the linezolid peak. Linezolid was demonstrated to be stable. This rapid assay is ideal for busy clinical laboratories with basic HPLC equipment.

Chlamydia trachomatis: opportunistic screening in primary care.

Following the publication of the Chief Medical Officer's report on chlamydial screening, we identified the sexual health of young women as an area for concern. As part of our review we decided to opportunistically search for chlamydial genital infections using a non-invasive technique. Sexually active women under 25 years of age were invited to submit a first void urine sample for polymerase chain reaction analysis. Over the period of a year we found out that 10.9% of sexually active young women tested positive for chlamydia in our practice.

Involvement of adrenal medulla grafts in the open field behavior.

Immunohistochemical and behavioral techniques were used to study the effects of adrenal medulla grafts, implanted in striatum after bilateral kainic acid (KA) lesions of this structure, on the open field behavior of mice. KA-induced behavioral changes in leaning, grooming and locomotor activity of the open field test were significantly improved after grafting of the adrenal medulla, and in some respects, fully restored. Immunohistochemical identification showed that grafts contained neuron-like cells with a tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase, gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), and enkephalin-like immunostainings. A likely interpretation of this complex pattern of results is that adrenal medullary grafts may restore the deficits of GABAergic neurons which in turn reverse the abnormalities in emotionality and locomotion. Neurobiologically, these behavioral improvements probably involve GABAergic and catecholaminergic factors of adrenal medulla grafts, although other neuroactive substances, such as acetylcholine and enkephalins, cannot be excluded.

Antimicrobial activity of fluoroquinolone photodegradation products determined by parallel-line bioassay and high performance liquid chromatography.

The fluoroquinolones produce multiple photodegradation products. Little is known about these products, particularly whether any possess antimicrobial activity. To investigate this, we used the parallel-line bioassay to investigate discrepancies in zone of inhibition size in conjunction with high performance liquid chromatography (HPLC) analysis. A continuous flow photochemical reaction unit ('Beam-Boost') was used to partially photodegrade the fluoroquinolones ofloxacin, levofloxacin, ciprofloxacin and moxifloxacin (0.02 mM) by between 15 and 89%, as confirmed by HPLC. The concentration of residual parent fluoroquinolone in each irradiated sample was measured by HPLC and a non-irradiated control solution was prepared at the same concentration. These were compared by parallel-line bioassays using Escherichia coli, Enterobacter cloacae and Klebsiella oxytoca. With ofloxacin and levofloxacin, the zone size for the control solution was significantly less than that of the irradiated solutions, with >15% photodegradation in at least two of the indicator organisms, indicating that the photodegradation products possess antimicrobial activity. No difference was seen with ciprofloxacin at any level of photodegradation with any of the indicator organisms, nor with moxifloxacin at 30 and 54% photodegradation. A significant difference was observed with E. cloacae only, at 83% photodegradation.