Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments

To compare central retinal thickness (CRT) measurements in healthy eyes by different commercially available OCT instruments and to compare the intersession reproducibility of such measurements.

Stereoselective biotransformation of ketamine in equine liver and lung microsomes

Stereoselectivity has to be considered for pharmacodynamic and pharmacokinetic features of ketamine. Stereoselective biotransformation of ketamine was investigated in equine microsomes in vitro. Concentration curves were constructed over time, and enzyme activity was determined for different substrate concentrations using equine liver and lung microsomes. The concentrations of R/S-ketamine and R/S-norketamine were determined by enantioselective capillary electrophoresis. A two-phase model based on Hill kinetics was used to analyze the biotransformation of R/S-ketamine into R/S-norketamine and, in a second step, into R/S-downstream metabolites. In liver and lung microsomes, levels of R-ketamine exceeded those of S-ketamine at all time points and S-norketamine exceeded R-norketamine at time points below the maximum concentration. In liver and lung microsomes, significant differences in the enzyme velocity (V(max)) were observed between S- and R-norketamine formation and between V(max) of S-norketamine formation when S-ketamine was compared to S-ketamine of the racemate. Our investigations in microsomal reactions in vitro suggest that stereoselective ketamine biotransformation in horses occurs in the liver and the lung with a slower elimination of S-ketamine in the presence of R-ketamine. Scaling of the in vitro parameters to liver and lung organ clearances provided an excellent fit with previously published in vivo data and confirmed a lung first-pass effect.

Effects of a low dose infusion of racemic and S-ketamine on the nociceptive withdrawal reflex in standing ponies

OBJECTIVE: To investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies. STUDY DESIGN: Prospective, blinded, cross-over study. ANIMALS: Six healthy 5-year-old Shetland ponies. METHODS: Ponies received either 0.6 mg kg(-1) racemic ketamine (group RS) or 0.3 mg kg(-1) S-ketamine (group S) intravenously (IV), followed by a CRI of 20 microg kg(-1)minute(-1) racemic ketamine (group RS) or 10 microg kg(-1)minute(-1) S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate. RESULTS: The NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL(-1) of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9-15 ng mL(-1)) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5-10 minutes after bolus drug administration in both groups. CONCLUSION: Antinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary.

Content comparison of health-related quality of life instruments for obstructive sleep apnea

BACKGROUND AND PURPOSE: Due to the increasing importance of quality of life assessments in obstructive sleep apnea (OSA) patients and due to an increased use of the International Classification of Functioning, Disability and Health (ICF), for comparative purposes it is essential to understand the relationship between health-related quality of life (HRQOL) instruments and the ICF. The purpose of this study was to compare the content covered by OSA-specific instruments using the ICF. PATIENTS AND METHODS: OSA-specific instruments were identified, including the Calgary Sleep Apnea Quality of Life Index, the Functional Outcomes of Sleep Questionnaire, the Obstructive Sleep Apnea Patient-Oriented Severity Index, and the Quebec Sleep Questionnaire, and linked to the ICF by six health professionals according to standardized guidelines. The degree of agreement between health professionals was calculated by means of the kappa statistic. RESULTS: A total of 308 concepts were identified and linked to 78 different ICF categories; 35 categories of the component body function, one category of the component body structure, 38 categories of the component activities and participation, and four categories of the component environmental factors. Only contents within the chapters mental functions, mobility and social life were addressed by all instruments. Forty-seven categories were covered by only one instrument. CONCLUSION: The ICF proved highly useful for the comparison of HRQOL instruments. This analysis may help researchers and clinicians to choose the most appropriate HRQOL instrument for a specific purpose as well as help to compare study outcomes of studies using different instruments for HRQOL assessment.

Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure

In horses, gastrointestinal (GI) disorders occur frequently and cause a considerable demand for efficient medication. 5-Hydroxytryptamine receptors (5-HT) have been reported to be involved in GI tract motility and thus, are potential targets for treating functional bowel disorders. Our studies extend current knowledge on the 5-HT(7) receptor in equine duodenum, ileum and pelvic flexure by studying its expression throughout the intestine and its role in modulating contractility in vitro by immunofluorescence and organ bath experiments, respectively. 5-HT(7) immunoreactivity was demonstrated in both smooth muscle layers, particularly in the circular one, and within the myenteric plexus. Interstitial cells of Cajal (ICC), identified by c-Kit labeling, show a staining pattern similar to that of 5-HT(7) immunoreactivity. The selective 5-HT(7) receptor antagonist SB-269970 increased the amplitude of contractions in spontaneous contracting specimens of the ileum and in electrical field-stimulated specimens of the pelvic flexure concentration-dependently. Our in vitro experiments suggest an involvement of the 5-HT(7) receptor subtype in contractility of equine intestine. While the 5-HT(7) receptor has been established to be constitutively active and inhibits smooth muscle contractility, our experiments demonstrate an increase in contractility by the 5-HT(7) receptor ligand SB-269970, suggesting it exerting inverse agonist properties.

Insect bite hypersensitivity in the horse: comparison of IgE-binding proteins in salivary gland extracts from Simulium vittatum and Culicoides nubeculosus

Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis of horses caused by bites of insects such as Culicoides or Simulium spp. The aim of the present study was to compare the IgE-binding pattern of sera of IBH-affected horses to Culicoides nubeculosus and Simulium vittatum salivary gland extracts (SGE). Individual IgE responses to proteins of S. vittatum and C. nubeculosus SGEs were evaluated in 15 IBH-affected and three healthy horses on immunoblots. Fourteen out of the 15 IBH-affected but none of the healthy horses showed individual IgE binding patterns to seven and six main protein bands in C. nubeculosus and S. vittatum SGE, respectively. These 14 sera showed IgE-binding to proteins from SGE of both C. nubeculosus and S. vittatum, but they reacted with fewer protein bands derived from S. vittatum than from C. nubeculosus SGE. Sera showing IgE-binding to a 32 kDa band from C. nubeculosus always bound to a 32 kDa band from S. vittatum. Similarly, all sera binding to a 70 kDa band from C. nubeculosus reacted with a corresponding band in S. vittatum SGE. The 70 kDa bands from S. vittatum and C. nubeculosus were identified by mass spectrometry as heat shock protein-70-cognate-3.

Maternal transfer of IgE and subsequent development of IgE responses in the horse (Equus callabus)

Immunoglobulin E (IgE) mediates the immune response to parasites, but can also cause allergies. In humans maternal IgE is not transferred to cord blood and high levels of cord blood IgE are associated with subsequent allergy. In horses, both maternal IgG and IgE are transferred via colostrum; the IgE levels in the mare's serum, the colostrum and the foal's serum are correlated but the consequences of IgE transfer to foals are not known. By about 6 weeks of age the levels of IgE in foal serum have dropped to a nadir, at 6 months of age the level of IgE has risen only very slightly and is no longer correlated with the levels seen at birth, IgE(+) B-cells could be detected in lymphoid follicles of some foals at this age. Surprisingly, the levels of total IgE detected in a foals serum at 6 months of age are significantly correlated with the level in its serum at 1, 2 and even 3 years of age suggesting that by 6 months of age the foals are synthesizing IgE and that a pattern of relatively higher or lower total serum IgE has been established. The neonatal intestinal mucosa contained connective tissue mast cells which stained for bound IgE in foals up to 9 weeks of age but not mucosal mast cells, thereafter, the intestinal mast cells were IgE negative until 6 months of age. IgE antibodies to Culicoides nubeculosus salivary antigens were detected in Swiss born foals from imported Icelandic mares allergic to Culicoides spp. yet the foals showed no signs of skin sensitization and such second generation foals are known not to have an increased risk of developing allergy to Culicoides. Overall this evidence suggests there is a minimal effector role of maternal IgE also that maternal IgE has waned prior to the onset of IgE synthesis in foals and does not support maternal priming of IgE responses in foals. Furthermore the total levels of IgE in any given foal are seen to be relatively high or low from soon after the onset of IgE synthesis, and most likely they are determined by genetic factors.

Cloning of IgE-binding proteins from Simulium vittatum and their potential significance as allergens for equine insect bite hypersensitivity

Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by bites of Culicoides and sometimes Simulium spp. The aim of this investigation was to identify Simulium allergens associated with IBH. A phage surface display cDNA library expressing recombinant Simulium vittatum salivary gland proteins was screened using sera of IBH-affected horses sensitized to S. vittatum salivary gland proteins as shown in immunoblot, resulting in the identification of seven cDNAs encoding IgE-binding proteins. The deduced amino acid sequences of these proteins showed sequence similarities to antigen 5 like protein (Sim v 1), to a serine protease inhibitor (Sim v 2), to two alpha-amylases (Sim v 3 and Sim v 4), and to three S. vittatum erythema proteins (SVEPs). The cDNA inserts were subcloned and expressed as [His](6)-tagged protein in Escherichia coli and purified using Ni(2+)-chelate affinity chromatography. Mice were immunised with the seven recombinant proteins and the antibodies tested against the recombinant proteins and salivary gland extract (SGE) of S. vittatum and Culicoides nubeculosus in immunoblot analyses. r-Sim v 1 specific mouse Abs recognized a band of about 32 kDa in immunoblots of both S. vittatum and C. nubeculosus SGE, detectable also by serum IgE of IBH-affected horses. Preincubation of horse serum with r-Sim v 1 completely inhibited IgE binding to the 32 kDa band demonstrating the presence of cross-reactive antigen 5 like proteins in both SGE. Determination of IgE levels against the r-Sim v proteins and crude S. vittatum extract by ELISA in sera from 25 IBH-affected and 20 control horses showed that IBH-affected horses had significantly higher IgE levels than controls against r-Sim v 1, 2, 3, 4 and S. vittatum extract, whereas the r-SVEP showed only marginal IgE binding. Further analyses showed that 60% of IBH-affected horses reacted to r-Sim v 1, suggesting that this could be a major allergen for IBH. Forty to twenty percent of the IBH-affected horses reacted with r-Sim v 2, 3 or 4. Combination of the results obtained with the 4 r-Sim v proteins showed that 92% of the IBH-affected but only 15% of the healthy horses had IgE levels against one or more of the 4 r-Sim v proteins. Seventy percent of the healthy horses had detectable IgE against S. vittatum extract, indicating a low specificity of the detection system used. Optimization of the ELISA system will be required to determine reliable cut-off values for the IBH-related allergens. Their in vivo relevance needs to be carefully assessed.

Small intestinal intussusception in five dogs with acute renal failure and suspected leptospirosis (L. australis)

OBJECTIVES This case series describes 5 dogs with small intestinal intussusception and acute kidney injury due to infection with Leptospira interrogans serovar Australis. CASE SERIES SUMMARY Small intestinal intussusception was observed in 4 dogs diagnosed with acute kidney injury due to leptospirosis presented between 1997 and 2005. Intussusception was diagnosed at initial presentation or later during hospitalization. An additional dog fulfilling our inclusion criteria was presented to a small animal specialty clinic nearby and was included. Upon admission, all dogs were severely azotemic and thrombocytopenic. All 5 dogs showed the strongest microscopic agglutination test serology reaction to L. interrogans serovar Australis. Two dogs survived with no apparent residual renal damage, 1 survived with subsequent mild chronic kidney disease, and 2 dogs were euthanized at the owners' request due to a guarded prognosis. NEW OR UNIQUE INFORMATION PROVIDED Intussusception can occur or may be seen in dogs with leptospirosis due to L. interrogans serovar Australis and patients should be monitored closely for this potential complication. As all 5 dogs described in this case series showed the highest titer for L. interrogans serovar Australis, these precautions may be especially applied in geographic areas where this particular serovar is seen.

Modulation of nociceptive withdrawal reflexes evoked by single and repeated nociceptive stimuli in conscious dogs by low-dose acepromazine

OBJECTIVES: To investigate the modulation of the nociceptive withdrawal reflex (NWR) and temporal summation (TS) by low-dose acepromazine (ACP) in conscious dogs. To assess the short- and long-term stability of the reflex thresholds. STUDY DESIGN: Randomized, blinded, placebo-controlled cross-over experimental study. ANIMALS: Eight adult male Beagles. METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the ulnar nerve. Repeated stimuli (10 pulses, 5 Hz) were applied to evoke TS. The responses of the deltoideus muscle were recorded and quantified by surface electromyography and the behavioural reactions were scored. Each dog received 0.01 mg kg(-1) ACP or an equal volume saline intravenously (IV) at 1 week intervals. Measurements were performed before (baseline) and 20, 60 and 100 minutes after drug administration. Sedation was scored before drug administration and then at 10 minutes intervals. Data were analyzed with Friedman repeated measures analysis of variance on ranks and Wilcoxon signed rank tests. RESULTS: Acepromazine resulted in a mild tranquilization becoming obvious at 20 minutes and peaking 30 minutes after injection. Single (I(t)) and repeated stimuli (TS(t)) threshold intensities, NWR and TS characteristics and behavioural responses were not affected by the ACP at any time point. Both I(t) and TS(t) were stable over time. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, 0.01 mg kg(-1) ACP IV had no modulatory action on the NWR evoked by single or repeated stimuli, suggesting no antinociceptive activity on phasic nociceptive stimuli. The evidence of the stability of the NWR thresholds supports the use of the model as an objective tool to investigate nociception in conscious dogs. A low dose of ACP administered as the sole drug, can be used to facilitate the recordings in anxious subjects without altering the validity of this model.

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

OBJECTIVE: To evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses. STUDY DESIGN: Prospective, blinded, randomized cross-over study. ANIMALS: Ten healthy adult horses weighing 527-645 kg and aged 11-21 years old. METHODS: Electrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg(-1), romifidine 0.08 mg kg(-1), or xylazine, 1 mg kg(-1), was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation. RESULTS: The administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.

Open Data and Earth Observations The Case of Opening Up Access to and Use of Earth Observation Data Through the Global Earth Observation System of Systems

Earth observations (EO) represent a growing and valuable resource for many scientific, research and practical applications carried out by users around the world. Access to EO data for some applications or activities, like climate change research or emergency response activities, becomes indispensable for their success. However, often EO data or products made of them are (or are claimed to be) subject to intellectual property law protection and are licensed under specific conditions regarding access and use. Restrictive conditions on data use can be prohibitive for further work with the data. Global Earth Observation System of Systems (GEOSS) is an initiative led by the Group on Earth Observations (GEO) with the aim to provide coordinated, comprehensive, and sustained EO and information for making informed decisions in various areas beneficial to societies, their functioning and development. It seeks to share data with users world-wide with the fewest possible restrictions on their use by implementing GEOSS Data Sharing Principles adopted by GEO. The Principles proclaim full and open exchange of data shared within GEOSS, while recognising relevant international instruments and national policies and legislation through which restrictions on the use of data may be imposed.The paper focuses on the issue of the legal interoperability of data that are shared with varying restrictions on use with the aim to explore the options of making data interoperable. The main question it addresses is whether the public domain or its equivalents represent the best mechanism to ensure legal interoperability of data. To this end, the paper analyses legal protection regimes and their norms applicable to EO data. Based on the findings, it highlights the existing public law statutory, regulatory, and policy approaches, as well as private law instruments, such as waivers, licenses and contracts, that may be used to place the datasets in the public domain, or otherwise make them publicly available for use and re-use without restrictions. It uses GEOSS and the particular characteristics of it as a system to identify the ways to reconcile the vast possibilities it provides through sharing of data from various sources and jurisdictions on the one hand, and the restrictions on the use of the shared resources on the other. On a more general level the paper seeks to draw attention to the obstacles and potential regulatory solutions for sharing factual or research data for the purposes that go beyond research and education.

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

OBJECTIVE: To evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Forty horses undergoing elective surgery. METHODS: After sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg(-1) initially, then 2 mg kg(-1) hour(-1)) and ketamine (2 mg kg(-1) hour(-1)), both CRIs reducing to 1.5 mg kg(-1) hour(-1) after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 mug kg(-1) hour(-1), reducing after 50 minutes to 2.75 mug kg(-1) hour(-1), and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE'ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 mug kg(-1) ) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05. RESULTS: FE'ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE'ISO in MILK was 0.65 (0.4-1.0) %, and in ILK was 1 (0.62-1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups. CONCLUSION AND CLINICAL RELEVANCE: A CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.