Topical Cross-Linked HA-Based Hydrogel Accelerates Closure of Corneal Epithelial Defects and Repair of Stromal Ulceration in Companion Animals.

Abstract Purpose: The purpose of this study was to determine the safety of topical ocular administration of a cross-linked, modified hyaluronic acid (xCMHA-S) hydrogel, and its effectiveness in accelerating repair and closure of acute and nonhealing corneal ulcers in companion animals as a veterinary treatment and its utility as a model for therapy in human corneal ulceration. Methods: Two concentrations of xCMHA-S (0.33% and 0.75%) were topically administered to the eyes of rabbits six times daily for 28 days to assess safety. Then, 30 dogs and 30 cats with spontaneous acute corneal ulcers were treated with either xCMHA-S (0.75%) or a non–cross-linked hyaluronic acid (HA) solution (n = 15 per group for each species), three times daily until the ulcer had healed. Finally, 25 dogs with persistent nonhealing corneal ulcers were treated with xCMHA-S (0.75%) twice daily until the ulcer had healed. Results: Both concentrations of the xCMHA-S hydrogel were well tolerated, safe, and nontoxic in the 28-day exaggerated dosing study in healthy rabbits. Topically applied xCMHA-S significantly accelerated closure of acute corneal stromal ulcers in dogs and cats compared with a non–cross-linked HA solution. Further, topical administration of the xCMHA-S aided in closure of nonhealing corneal stromal ulcers in dogs. Conclusions: Hyaluronic acid has previously been shown to aid in corneal wound repair. This study demonstrates that a cross-linked, modified HA hydrogel provides further benefit by accelerating time to corneal wound closure compared to a non–cross-linked HA solution in companion animals, and therefore may be beneficial in fulfilling an unmet need in humans

Tear ferning in normal dogs and dogs with keratoconjunctivitis sicca

This study evaluates tear ferning as an ancillary technique for the evaluation of the canine tear film in normal eyes and eyes affected by keratoconjunctivitis sicca (KCS). Thirty dogs with KCS and 50 control dogs with normal tear film were evaluated with a full ophthalmoscopic examination and a Schirmer tear test type 1 (STT) determined before tear samples were obtained from the medial canthus with a microhaematocrit capillary tube. 10ul of tear was placed on a microscope slide and the time to first formation of a fern of crystallised tear solute was determined. The appearance of the ferning pattern was graded and correlated with the STT value. All eyes with KCS had abnormal ferning patterns while 39 out of the 50 normal dogs (78%) had so-called ‘normal’ ferning patterns. The mean STT for dogs showing ‘normal’ ferning patterns was 20.6mm/min for the left eye and 21.3mm/min for the right eye. STT values for eyes with ‘abnormal’ ferning patterns were 10.9mm/min and 12.4mm/min, these differing from the normal eyes with STT above 15mm/min significantly. These findings suggest that tear ferning could be a valuable technique for assessment of the tear film in dogs with KCS

Insulin response and changes in composition of non-esterified fatty acids in blood plasma of middle-aged men following isoenergetic fatty and carbohydrate breakfasts

It was previously shown that a high plasma concentration of non-esterified fatty acids (NEFA) persisted after a fatty breakfast, but not after an isoenergetic carbohydrate breakfast, adversely affecting glucose tolerance. The higher concentration after the fatty breakfast may in part have been a result of different mobilization rates of fatty acids. This factor can be investigated as NEFA mobilized from tissues are monounsaturated to a greater extent than those deposited from a typical meal. Twenty-four middle-aged healthy Caucasian men were given oral glucose tolerance tests (OGTT), and for 28 d isoenergetic breakfasts of similar fat composition but of low (L) or moderate (M) fat content. The composition of NEFA in fasting and postprandial plasma was determined on days 1 and 29. No significant treatment differences in fasting NEFA composition occurred on day 29. During the OGTT and 0-1 h following breakfast there was an increase in plasma long-chain saturated NEFA but a decrease in monounsaturated NEFA (mug/100 mug total NEFA; Pg/100 mug total NEFA; P<0.05), expressed as an increase in 18:1 and decreases in 16:0 and 17:0 in treatment M relative to treatment L (P<0.05). Serum insulin attained 35 and 65 mU/l in treatments M and L respectively during this period. Negative correlations were found between 16:0 in fasting plasma and both waist:hip circumference (P=0.0009) and insulin response curve area during OGTT (within treatment M, P=0.0001). It is concluded that a normal postprandial insulin response is associated with a rapid change in plasma saturated:monounsaturated NEFA. It is proposed that this change is the result of a variable suppression of fat mobilization, which may partly account for a large difference in postprandial total plasma NEFA between fatty and carbohydrate meals

Is it Advisable to Rehabilitate and Release Owls with Monocular Vision?

Defective vision is frequent in owls presented to rehabilitation centers. While there is a common consensus that completely blind owls should not be released, there is less certainty when considering owls with monocular vision. To address this issue, surveys of rehabilitation centers and veterinarians were conducted regarding their opinion and experience on the feasibility and ethics of rehabilitating and releasing owls with only one functional eye. Results show conflicting opinions between rehabilitation centers and also veterinarians, with a lack of agreement on what would be best in terms of welfare. This research also compared flight and landing behaviour of four barn owls, of which two had lens opacities to differing degrees and one had only one eye. No significant differences were found between the one-eyed barn owl and the three birds with two eyes in any of the aspects analyzed, namely flight trajectory and time and landing ability on a perch or a handler’s glove. Finally, from a literature review and reports from the centers surveyed, successful cases of rehabilitation and release of owls with monocular vision were documented. The findings of our research suggest that new UK guidelines which describe the prerequisites for release of owls with monocular vision should be develope

Student attitudes regarding the educational value and welfare implications in the use of model eyes and live dogs in teaching practical fundus examination: evaluation of responses from 40 students

This study sought to document student opinions on the educational value and welfare implications of use of artificial model eyes and live dogs in the training of veterinary students in examination of the canine fundus. Forty students who had undertaken a practical class on canine fundoscopy involving both use of artificial model eyes and live dogs were asked to complete a short questionnaire using a Likert scale to gauge their opinion on whether the use of live dogs and artificial eyes was very valuable (scoring 2), valuable (1), a neutral response (0), not particularly valuable (-1) or not at all valuable (-2) and to write a free text response on their views of the educational value and welfare implications of using artificial model eyes or live dogs in training for ophthalmic examination of the canine ocular fundus. Likert responses were 1.84±0.37 for using live greyhounds and 0.58±0.79 for using simulator eyes (p<0.0001). Thematic analysis of the written responses showed that while the artificial eyes were considered somewhat valuable in initial training, the live dogs were significantly preferred for their realism and the opportunity to examine the eye while handling a live animal. In conclusion, while model eyes are valuable initial training in use of the ophthalmoscope for funduscopic examination, students consider that examining the eye in the live dog is significantly more valuable and that the welfare of dogs thus used is not in their view unduly compromised

Expedient Organocatalytic Aza-Morita–Baylis–Hillman Reaction through Ball-Milling

A ball-milling enabled tertiary amine catalyzed aza-Morita–Baylis–Hillman reaction is reported. The reaction process does not require solvent, has significantly shorter reaction times than previous methods and is reported on a range of imines and acrylate Michael acceptors across than 26 examples. A 12-fold scaled-up example is also reported as well as experimental comparisons to solution-based experiments and neat-stirred reactions

Mechanochemical Organocatalysis: Do High Enantioselectivites Contradict what we Might Expect?

Ball mills input energy to samples by pulverising the contents of the jar. Each impact on the sample or wall of the jar results in an instantaneous transmission of energy in the form of a temperature and pressure increase (volume reduction). Conversely, enantioselective organocatalytic reactions proceed through perceived delicate and well-organised transition states. Does there exist a dichotomy in the idea of enantioselective mechanochemical organocatalysis? This Review provides a survey of the literature reporting the combination of organocatalytic reactions with mechanochemical ball milling conditions. Where possible, direct comparisons of stirred in solution, stirred neat and ball milled processes are drawn with a particular focus on control of stereoselectivity

Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia

The neuropsychological effect of hyperammonemia is variable. This study tests the hypothesis that the effect of ammonia on the neuropsychological function in patients with cirrhosis is determined by the ability of the brain to buffer ammonia-induced increase in glutamine within the astrocyte by losing osmolytes like myo-inositol (mI) and not by the magnitude of the induced hyperammonemia. Fourteen cirrhotic patients with no evidence of overt hepatic encephalopathy were given a 75-g amino acid (aa) solution mimicking the hemoglobin molecule to induce hyperammonemia. Measurement of a battery of neuropsychological function tests including immediate memory, ammonia, aa, and short-echo time proton magnetic resonance spectroscopy were performed before and 4 h after administration of the as solution. Eight patients showed deterioration in the Immediate Memory Test at 4 h. Demographic factors, severity of liver disease, change in plasma ammonia, and as profiles after the as solution were similar in those that showed a deterioration compared with those who did not. In patients who showed deterioration in the memory test, the mI-to-creatine ratio (mI/Cr) was significantly lower at baseline than those that did not deteriorate. In contrast, the glutamate/glutamine-to-Cr ratio was significantly greater in the patients that deteriorated. The observation that deterioration in the memory test scores was greater in those with lower mI/Cr supports the hypothesis that the neuropsychological effects of induced hyperammonemia is determined by the capacity of the brain to handle ammonia-induced increase in glutamine

Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis

Background/Aims: Studies in acute liver failure show correlation between evidence of a systemic inflammatory response syndrome (SIRS) and progression of hepatic encephalopathy (HE). We tested the hypothesis that SIRS mediators, such as nitric oxide and proinflammatory cytokines, may exacerbate the neuropsychological effects of hyperammonemia in cirrhosis.Methods: Ten patients with cirrhosis were studied, 24-36 h after admission with clinical evidence of infection, and following its resolution. Hyperammonemia was induced by oral administration of an amino-acid (aa) solution mimicking hemoglobin composition. Inflammatory mediators, nitrate/nitrite, ammonia, aa profiles and a battery of neuropsychological tests were measured.Results: The hyperammonemia generated in response to the aa solution was similar prior to, and after resolution, of the inflammation (P = 0.77). With treatment of the infection there were significant reductions in white blood cell count (WBC), C-reactive protein (CRP), nitrate/nitrite, interleukin-6, interieukin-1beta and tumour necrosis factor alpha. Induced hyperammonemia resulted in significant worsening of the neuropsychological scores when patients showed evidence of SIRS but not after its resolution.Conclusions: The significant deterioration of neuropsychological test scores following induced hyperammonemia during the inflammatory state, but not after its resolution, suggests that the inflammation and its mediators may be important in modulating the cerebral effect of ammonia in liver disease. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved