Reduction in creatine metabolites in macrophages exposed to small molecule analogues of the anti-inflammatory parasitic worm product ES-62.

ES-62, a protein secreted by Acanthocheilonema viteae, is anti-inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of drug-like small molecule analogues (SMAs) based on its PC moieties has been designed for therapeutic purposes. Two members, SMAs 11a and 12b, were previously found to suppress production of pro-inflammatory cytokines by mouse bone marrow-derived macrophages (BMMs) exposed to cytosine-phosphate-guanosine oligodeoxynucleotides (CpG), agonists for Toll-like receptor 9. In order to explore the mechanism of action underlying such activities, an untargeted mass spectrometry-based metabolomics screen was undertaken. Stimulation of BMMs with CpG produced significant metabolic changes relating to glycolysis and the TCA cycle but the SMAs had little impact on this. Also, the SMAs did not promote alterations in metabolites known to be associated with macrophage M1/M2 polarization. Rather, BMMs exposed to SMAs 11a or 12b prior to CpG treatment, or even alone, revealed downregulation of metabolites of creatine, a molecule whose major role is in the transport of high energy phosphate from the mitochondria to the cytosol. These data therefore provide insight into a possible mechanism of action of molecules with significant therapeutic potential that has not previously been described for parasitic worm products.

Evaluation of amoxicillin, metronidazole and gentamicin dosage regimens for use in antibiotic prophylaxis in colorectal surgery.

OBJECTIVES: To evaluate amoxicillin, metronidazole and gentamicin dosage regimens for antibiotic prophylaxis in colorectal surgery. METHODS: The study was conducted in 20 patients undergoing colorectal surgery. Patients received one or two doses of amoxicillin 1000 mg, metronidazole 500 mg and gentamicin 3 mg/kg ideal body weight, banded by height. Antibiotic concentrations were measured up to 7 h post dose. Population pharmacokinetic (PopPK) analysis with NONMEM followed by Monte Carlo simulation of different dosage regimens was used to estimate the PTA for potential organisms associated with surgical site infections (SSIs). RESULTS: A median of 5 (range 3-6) concentrations were available per patient. CL and V of all antibiotics were related to weight; gentamicin CL was also related to CLCR. The administered doses maintained the desired PTA up to 8 h for the Streptococcus anginosus group but not for enterococci, Bacteroides fragilis group, MSSA, and Escherichia coli. An additional 500 mg amoxicillin every 4 h was sufficient to achieve the PTA for most relevant organisms but 2 hourly dosing was required for patients at risk of infective endocarditis. A metronidazole dose of 1000 mg was required for patients >85 kg. In patients with CLCR >50 mL/min, 5 mg/kg gentamicin (with an additional 2.5 mg/kg in prolonged surgery at 6 h) maintained PTA targets for >10 h. CONCLUSIONS: PopPK analysis with Monte Carlo simulation identified prophylactic antibiotic regimens that would maintain the PTA for organisms associated with SSIs during short- and long-duration colorectal surgery.

Micro-CT for saw mark analysis on human bone.

In toolmark analysis, microscopy techniques, such as micro-CT, are used to visualise and measure toolmarks left on bones by a tool. In dismemberment cases, properties such as the width of the saw mark can provide cues to which tool was used by the culprit. The aim of the current study was to establish whether; (i) micro-CT is an appropriate imaging technique for saw mark analysis, (ii) toolmarks statistically differ when created with different tools, (iii) toolmark width can predict tool blade width, and (iv) toolmarks differ if created under different methodological conditions. Across two experiments, 270 saw marks were created using eight tools with either a controlled or free saw action on either fleshed or defleshed human long bone. Toolmarks were micro-CT scanned and seven toolmark properties were categorised or measured by two independent raters. The current study found that; (i) micro-CT was found to be a powerful and reliable imaging method for the visualisation and measurement of saw mark properties, (ii) toolmark properties differed significantly within and between various methodological conditions (p<.001) when created by eight different tools, (iii) a regression model developed using toolmark widths from Experiment 2 overall predicted 94% of tool widths in Experiment 1, and iv) methodological factors such as tissue presence and saw action significantly and inconsistently influenced toolmark properties for different tools. The study further validates the use of mirco-CT for saw mark analysis and demonstrates the potential of using toolmark properties to determine the tool used in cases of dismemberment. Given the effects that methodological factors such as tissue presence can have on toolmark properties, future studies should use experimental set ups with fleshed human tissue and use a free saw action.

The cutting edge - Micro-CT for quantitative toolmark analysis of sharp force trauma to bone.

Toolmark analysis involves examining marks created on an object to identify the likely tool responsible for creating those marks (e.g., a knife). Although a potentially powerful forensic tool, knife mark analysis is still in its infancy and the validation of imaging techniques as well as quantitative approaches is ongoing. This study builds on previous work by simulating real-world stabbings experimentally and statistically exploring quantitative toolmark properties, such as cut mark angle captured by micro-CT imaging, to predict the knife responsible. In Experiment 1 a mechanical stab rig and two knives were used to create 14 knife cut marks on dry pig ribs. The toolmarks were laser and micro-CT scanned to allow for quantitative measurements of numerous toolmark properties. The findings from Experiment 1 demonstrated that both knives produced statistically different cut mark widths, wall angle and shapes. Experiment 2 examined knife marks created on fleshed pig torsos with conditions designed to better simulate real-world stabbings. Eight knives were used to generate 64 incision cut marks that were also micro-CT scanned. Statistical exploration of these cut marks suggested that knife type, serrated or plain, can be predicted from cut mark width and wall angle. Preliminary results suggest that knives type can be predicted from cut mark width, and that knife edge thickness correlates with cut mark width. An additional 16 cut marks walls were imaged for striation marks using scanning electron microscopy with results suggesting that this approach might not be useful for knife mark analysis. Results also indicated that observer judgements of cut mark shape were more consistent when rated from micro-CT images than light microscopy images. The potential to combine micro-CT data, medical grade CT data and photographs to develop highly realistic virtual models for visualisation and 3D printing is also demonstrated. This is the first study to statistically explore simulated real-world knife marks imaged by micro-CT to demonstrate the potential of quantitative approaches in knife mark analysis. Findings and methods presented in this study are relevant to both forensic toolmark researchers as well as practitioners. Limitations of the experimental methodologies and imaging techniques are discussed, and further work is recommended.

Hair nicotine concentration measurement in cats and its relationship to owner-reported environmental tobacco smoke exposure.

OBJECTIVES: To investigate the association between hair nicotine concentration in cats and owner-reported exposure to environmental tobacco smoke. MATERIALS AND METHODS: Owner questionnaires documented exposure. Nicotine was extracted from hair by sonification in methanol followed by hydrophilic interaction chromatography with mass spectrometry. Relationships between hair nicotine concentration and owner-reported exposure were examined using hypothesis-testing statistics and receiver operating characteristic curve analysis. RESULTS: The hair nicotine concentration of reportedly exposed cats was significantly higher than unexposed cats and groups of cats with different levels of exposure had significantly different median hair nicotine concentrations corresponding to exposure. A hair nicotine concentration of 0·1 ng/mg had a specificity of 98% (95% confidence interval: 83 to 100) and a sensitivity of 69% (95% confidence interval: 54 to 84) for detecting environmental tobacco smoke exposure. Outdoors access, coat colour, urban or rural environment and length of time living with the owner were not obviously associated with hair nicotine concentration. CLINICAL SIGNIFICANCE: Feline hair nicotine concentration appears strongly associated with owner-reported environmental tobacco smoke exposure. Feline hair nicotine concentration could therefore be used as a biomarker for tobacco smoke exposure, allowing future studies to assess whether exposed cats have an increased risk of specific diseases.

The use of control charts by laypeople and hospital decision-makers for guiding decision making.

Graphs presenting healthcare data are increasingly available to support laypeople and hospital staff's decision making. When making these decisions, hospital staff should consider the role of chance-that is, random variation. Given random variation, decision-makers must distinguish signals (sometimes called special-cause data) from noise (common-cause data). Unfortunately, many graphs do not facilitate the statistical reasoning necessary to make such distinctions. Control charts are a less commonly used type of graph that support statistical thinking by including reference lines that separate data more likely to be signals from those more likely to be noise. The current work demonstrates for whom (laypeople and hospital staff) and when (treatment and investigative decisions) control charts strengthen data-driven decision making. We present two experiments that compare people's use of control and non-control charts to make decisions between hospitals (funnel charts vs. league tables) and to monitor changes across time (run charts with control lines vs. run charts without control lines). As expected, participants more accurately identified the outlying data using a control chart than using a non-control chart, but their ability to then apply that information to more complicated questions (e.g., where should I go for treatment?, and should I investigate?) was limited. The discussion highlights some common concerns about using control charts in hospital settings.

Ropivacaine plasma levels following high-dose local infiltration analgesia for total knee arthroplasty.

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 28 patients aged 65 years or over undergoing unilateral total knee arthroplasty. Patients received infiltration of ropivacaine 400 mg followed by infusion at 20 mg.h(-1) through an intra-articular catheter. Total and free plasma levels of ropivacaine were measured at specified time intervals during a 24-h period after tourniquet release. Patients were monitored for symptoms and signs of local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.147 to 3.093 µg.ml(-1) (mean (SD) 1.105 (0.518) µg.ml(-1) ). Free levels of plasma ropivaca-ine varied from 0.001 to 0.104 µg.ml(-1) (mean (SD) 0.037 (0.020) µg.ml(-1) ). Six samples had total plasma ropivacaine levels greater the toxic threshold of 2.2 µg.ml(-1) . No samples reached the toxic threshold for free venous ropivacaine concentration. We conclude that the use of high-dose ropivacaine infiltration and catheter infusion for total knee arthroplasty in an elderly population does not result in free plasma ropivacaine levels previously associated with toxicity but that raised total plasma levels may be observed.

Characterisation of triterpenes and new phenolic lipids in Cameroonian propolis.

Chemical investigation of a sample of propolis originating from North-Western Cameroon led to the isolation of thirteen alk(en)ylphenols (1-13) (inseparable mixture) along with α-amyrin (14), ß-amyrin (15), lupeol (16), cycloartenol (17), mangiferonic acid (18), ambonic acid (19), mangiferolic acid (20), ambolic acid (21), isomangiferolic acid (22) and nine alk(en)ylresorcinols (23-31) (inseparable mixture). All compounds were identified following analysis of their spectroscopic data and comparison with previously published reports. Compounds (8), (12), (13) and (30) are new natural products. GC-MS analysis carried out on the alk(en)ylphenol and alk(en)ylresorcinol mixtures (dimethyl disulphide trimethylsilyl derivatives) revealed the presence of saturated and mono-unsaturated compounds with side chain lengths ranging from C11 to C19 and C15 to C19, respectively. The position of the double bond in mono-unsaturated derivatives was established from the characteristic fragments resulting from the cleavage of the bond between the two methylthio-substituted carbons. The most abundant compound in each mixture was 3-(12'Z-heptadecenyl)-phenol (10) and 5-(12'Z-heptadecenyl)-resorcinol (29). This study is the first to report the presence of triterpenes (except for lupeol) and phenolic lipids, including eighteen compounds previously unreported in bee glue, in an African sample.

Ropivacaine plasma levels following local infiltration analgesia for primary total hip arthroplasty.

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 19 patients aged 65 years or over undergoing unilateral total hip arthroplasty. The patients received 180 ml ropivacaine 0.2% (360 mg), which was injected into the deep and peri-capsular tissues, the gluteal muscles and fascia lata, and the subcutaneous tissues and skin. Patients were monitored for clinical symptoms and signs of systemic local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.081 to 1.707 µg.ml(-1) (mean (SD) 0.953 (0.323) µg.ml(-1) ). Free levels of plasma ropivacaine varied from 0.000 to 0.053 µg.ml(-1) (mean (SD) 0.024 (0.011) µg.ml(-1) ). No samples reached the toxic threshold for venous ropivacaine concentration, although four patients exhibited mild symptoms consistent with local anaesthetic toxicity. One patient had episodes of complete heart block on ECG monitoring, but plasma ropivacaine levels were below toxic levels. We conclude that plasma levels for ropivacaine associated with toxicity in a volunteer population (total 2.2 µg.ml(-1) , free 0.15 µg.ml(-1) ) are not reached during local infiltration analgesia for hip arthroplasty in elderly patients.

A validated and stability indicating HPLC method for analysis of diminazene aceturate and antipyrine combination in a ready injectable solution.

Diminazene aceturate and Antipyrine combination therapy is widely used in veterinary medicine. A simple reverse HPLC method for the analysis of samples of a ready injectable formulation containing a mixture of active ingredients and inactive excipients has been developed. The HPLC analysis was carried out using a reversed phase (RP)-C18 (250 mm×4.0 mm, 5 µm) column. The isocratic mobile phase consisted of a mixture of acetonitrile, methanol, phosphate buffer and hexane sulfonate; the flow rate was 0.6 mL/min and ultraviolet detection was at 291 nm. This method was validated in accordance with FDA and ICH guidelines and showed good linearity, accuracy, precision, selectivity and the system suitability results were within the acceptance criteria. A stability-indicating study was also carried out and indicated that this method could be used for purity and degradation evaluation of these formulations.

Nicotine hair concentrations in dogs exposed to environmental tobacco smoke: a pilot study.

OBJECTIVES: To investigate the association between dog hair nicotine concentration and owner-reported exposure to environmental tobacco smoke to establish whether dogs are exposed to significant, detectable amounts of environmental tobacco smoke in the home. METHODS: Hair was collected from 23 dogs exposed to environmental tobacco smoke and from 15 dogs reportedly not exposed to environmental tobacco smoke. Hair was washed to remove adhered nicotine, digested in 1 M NaOH and extracted using solid phase extraction. Nicotine concentration was measured by high-resolution mass spectrometry. Results were analysed using a Kruskall-Wallis test and post hoc pair-wise comparisons using a Mann-Whitney test to assess significance between exposure groups. RESULTS: The different exposure groups were significantly different (P < 0·001) for both hair and surface nicotine. Pair-wise comparisons were significant at P < 0·05 for all categories except unexposed and occasionally exposed groups (P = 0·076). CLINICAL SIGNIFICANCE: Dog hair nicotine concentration appears to be strongly associated with reported exposure to environmental tobacco smoke. The range and median of hair nicotine concentration in dogs exposed to environmental tobacco smoke was similar to those reported in children. This suggests that dog hair could provide a useful method of determining the amount of environmental tobacco smoke exposure in all environments common to pets and children.

A stability indicating assay for a combination of morphine sulphate with levomepromazine hydrochloride used in palliative care.

WHAT IS KNOWN AND OBJECTIVE: Morphine is used routinely in clinical practice to manage moderate to severe pain, whereas levomepromazine is commonly used at low doses to manage intractable nausea and vomiting. While it has been reported that an injection combination of morphine sulphate (0·5 mg/mL) and levomepromazine (0·1 mg/mL) was physically compatible, data on the chemical stability of combinations of these drugs has not been reported. Thus, a method was required for the assessment of the stability of morphine sulphate/levomepromazine hydrochloride combinations. METHODS: A high-performance liquid chromatography (HPLC) method was developed to assess the stability of the combinations. The injections were stored at 4 °C in the dark at room temperature under natural light and at 37 °C under artificial lighting. RESULTS AND DISCUSSION: Morphine sulphate was stable under all storage conditions, but the degree of degradation of levomepromazine hydrochloride increased as the storage temperature increased. The disappearance of levomepromazine hydrochloride was correlated with the appearance of a sulphoxide degradant. WHAT IS NEW CONCLUSION: The injection combinations of morphine sulphate and levomepromazine hydrochloride were shown in the current study to have a limited storage life with respect to their levomepromazine hydrochloride content.

Transcriptional regulation of neurodevelopmental and metabolic pathways by NPAS3.

The basic helix-loop-helix PAS (Per, Arnt, Sim) domain transcription factor gene NPAS3 is a replicated genetic risk factor for psychiatric disorders. A knockout (KO) mouse model exhibits behavioral and adult neurogenesis deficits consistent with human illness. To define the location and mechanism of NPAS3 etiopathology, we combined immunofluorescent, transcriptomic and metabonomic approaches. Intense Npas3 immunoreactivity was observed in the hippocampal subgranular zone-the site of adult neurogenesis--but was restricted to maturing, rather than proliferating, neuronal precursor cells. Microarray analysis of a HEK293 cell line over-expressing NPAS3 showed that transcriptional targets varied according to circadian rhythm context and C-terminal deletion. The most highly up-regulated NPAS3 target gene, VGF, encodes secretory peptides with established roles in neurogenesis, depression and schizophrenia. VGF was just one of many NPAS3 target genes also regulated by the SOX family of transcription factors, suggesting an overlap in neurodevelopmental function. The parallel repression of multiple glycolysis genes by NPAS3 reveals a second role in the regulation of glucose metabolism. Comparison of wild-type and Npas3 KO metabolite composition using high-resolution mass spectrometry confirmed these transcriptional findings. KO brain tissue contained significantly altered levels of NAD(+), glycolysis metabolites (such as dihydroxyacetone phosphate and fructose-1,6-bisphosphate), pentose phosphate pathway components and Kreb's cycle intermediates (succinate and α-ketoglutarate). The dual neurodevelopmental and metabolic aspects of NPAS3 activity described here increase our understanding of mental illness etiology, and may provide a mechanism for innate and medication-induced susceptibility to diabetes commonly reported in psychiatric patients.

A solvent-free matrix application method for matrix-assisted laser desorption/ionization imaging of small molecules.

Matrix application continues to be a critical step in sample preparation for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). Imaging of small molecules such as drugs and metabolites is particularly problematic because the commonly used washing steps to remove salts are usually omitted as they may also remove the analyte, and analyte spreading is more likely with conventional wet matrix application methods. We have developed a method which uses the application of matrix as a dry, finely divided powder, here referred to as dry matrix application, for the imaging of drug compounds. This appears to offer a complementary method to wet matrix application for the MALDI-MSI of small molecules, with the alternative matrix application techniques producing different ion profiles, and allows the visualization of compounds not observed using wet matrix application methods. We demonstrate its value in imaging clozapine from rat kidney and 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylic acid from rat brain. In addition, exposure of the dry matrix coated sample to a saturated moist atmosphere appears to enhance the visualization of a different set of molecules.

Use of a solvent-free dry matrix coating for quantitative matrix-assisted laser desorption ionization imaging of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate in rat brain and quantitative analysis of the drug from laser microdissected tissue regions.

A dry matrix application for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was used to profile the distribution of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate, monohydrochloride (BDNC, SSR180711) in rat brain tissue sections. Matrix application involved applying layers of finely ground dry alpha-cyano-4-hydroxycinnamic acid (CHCA) to the surface of tissue sections thaw mounted onto MALDI targets. It was not possible to detect the drug when applying matrix in a standard aqueous-organic solvent solution. The drug was detected at higher concentrations in specific regions of the brain, particularly the white matter of the cerebellum. Pseudomultiple reaction monitoring imaging was used to validate that the observed distribution was the target compound. The semiquantitative data obtained from signal intensities in the imaging was confirmed by laser microdissection of specific regions of the brain directed by the imaging, followed by hydrophilic interaction chromatography in combination with a quantitative high-resolution mass spectrometry method. This study illustrates that a dry matrix coating is a valuable and complementary matrix application method for analysis of small polar drugs and metabolites that can be used for semiquantitative analysis.

A survey on two years of medication regulation in horse races in Iran.

REASONS FOR PERFORMING STUDY: The present survey evaluated the use of prohibited substances cases in the first 2 years of medication regulation in horseracing in Iran so that the impact of these regulations on the level of positive cases over the period could be assessed. OBJECTIVES: To determine the prevalence of positive tests for prohibited substances in horse races during 2 years of a drugs testing programme in Iran. METHODS: A total of 656 horses that were winners or second in races were tested during the 2 year study. In the first year 354 horses (209 males and 145 females) and in the second year 302 horses (155 males and 147 females) were tested. In the 2 years, 306 were found to be positive. Urine samples were taken from candidate horses and sent to the Central Doping Laboratory. Blood samples were taken from those horses where a urine sample could not be taken within one hour. Detection and measurement of prohibited substances were carried out by ELISA, GC and HPLC using standard methods. RESULTS: Thirty-two percent of males were positive for prohibited substances, which was not significantly different from the percentage of females (25.5%). In the second year, of the 302 horses tested for prohibited substances, 33.5% of males were positive, again similar to females (33.3%). Almost 83% of horses tested positive for prohibited substances once in the first year, 15% tested positive twice and 2% tested positive 3 times. In the second year 78% tested positive once, 15% tested positive twice and 7% tested positive 3 times. Morphine was the most used prohibited substance and was detected 42 times during the survey, followed by caffeine and phenylbutazone. Morphine was also the most used drug in combination with other drugs in both years. CONCLUSIONS: Morphine and caffeine were the most popular prohibited substances found in the measurements. As these substances were found in the environment and food stuffs, their presence in the samples may be due to unintentional feeding of contaminated materials (bread, hay and chocolate).

The potential of mass spectrometry for the global profiling of parasite metabolomes.

The strengths and limitations of existing mass spectrometry methods for metabolite detection and identification are discussed. A brief review is made of the methods available for quenching and extraction of cells or organisms prior to instrumental analysis. The techniques available for carrying out mass spectrometry-based profiling of metabolomes are discussed using the analysis of extracts from trypanosomes to illustrate various points regarding methods of separation and mass spectrometric analysis. The advantages of hydrophilic interaction chromatography (HILIC) for the analysis of polar metabolites are discussed. The challenges of data processing are outlined and illustrated using the example of ThermoFisher's Sieve software. The existing literature on applications of mass spectrometry to the profiling of parasite metabolomes is reviewed.

Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death.

Cells exposed to low-oxygen conditions (hypoxia) alter their metabolism to survive. This response, although vital during development and high-altitude survival, is now known to be a major factor in the selection of cells with a transformed metabolic phenotype during tumorigenesis. It is thought that hypoxia-selected cells have increased invasive capacity and resistance to both chemo- and radiotherapies, and therefore represent an attractive target for antitumor therapy. Hypoxia inducible factors (HIFs) are responsible for the majority of gene expression changes under hypoxia, and are themselves controlled by the oxygen-sensing HIF prolyl hydroxylases (PHDs). It was previously shown that mutations in succinate dehydrogenase lead to the inactivation PHDs under normoxic conditions, which can be overcome by treatment with alpha-ketoglutarate derivatives. Given that solid tumors contain large regions of hypoxia, the reactivation of PHDs in these conditions could induce metabolic catastrophe and therefore prove an effective antitumor therapy. In this report we demonstrate that derivatized alpha-ketoglutarate can be used as a strategy for maintaining PHD activity under hypoxia. By increasing intracellular alpha-ketoglutarate and activating PHDs we trigger PHD-dependent reversal of HIF1 activation, and PHD-dependent hypoxic cell death. We also show that derivatized alpha-ketoglutarate can permeate multiple layers of cells, reducing HIF1alpha levels and its target genes in vivo.

A chemometric study of chromatograms of tea extracts by correlation optimization warping in conjunction with PCA, support vector machines and random forest data modeling.

A reverse phase high performance liquid chromatography (HPLC) separation was established for profiling water soluble compounds in extracts from tea. Whole chromatograms were pre-processed by techniques including baseline correction, binning and normalisation. In addition, peak alignment by correction of retention time shifts was performed using correlation optimization warping (COW) producing a correlation score of 0.96. To extract the chemically relevant information from the data, a variety of chemometric approaches were employed. Principle component analysis (PCA) was used to group the tea samples according to their chromatographic differences. Three principal components (PCs) described 78% of the total variance after peak alignment (64% before) and analysis of the score and loading plots provided insight into the main chemical differences between the samples. Finally, PCA, support vector machines (SVMs) and random forest (RF) machine learning methods were evaluated comparatively on their ability to predict unknown tea samples using models constructed from a predetermined training set. The best predictions of identity were obtained by using RF.

Penetration of topical and subconjunctival corticosteroids into human aqueous humour and its therapeutic significance.

Topical and subconjunctival corticosteroids are some of the most effective and compelling treatment options in ocular inflammatory diseases. A systematic review of literature indexed by Ovid MEDLINE & EMBASE was performed up to December 2008. There are few studies on their aqueous penetration in human subjects. This review article discusses the penetration of different ocular corticosteroids into human aqueous humour along with the therapeutic implications on management of ocular surface diseases, immune-related corneal diseases, anterior uveitis and postoperative anti-inflammatory use. In the context of the paucity of well-constructed, prospective clinical trials comparing the efficacy of different corticosteroids, it provides guiding principles for the use of topical corticosteroids. Dexamethasone alcohol 0.1% and prednisolone acetate 1% are potent corticosteroids, but the latter achieves the highest aqueous concentration within 2 h and maintains higher levels for 24 h. Subconjunctival corticosteroids provide very high concentrations in the aqueous which maintain higher concentrations for longer periods.