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

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

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

Diurnal trends in responses of blood plasma concentrations of glucose, insulin, and C-peptide following high- and low-fat meals and their relation to fat metabolism in healthy middle-aged volunteers

An experiment was conducted in twelve healthy middle-aged volunteers, six of each sex, with a mean BMI of 27 kg/m(2) to detect differences between morning and afternoon in postprandial blood glucose, insulin and C-peptide concentrations. These responses were measured following the consumption of isoenergetic meals that were high or low in fat content, at breakfast and at lunch. Over 4d each subject received the high-carbohydrate (L, 5.5 g mixed fat/meal) and moderately high-fat (M, 33 g mixed fat/meal) breakfasts and lunches, in three combinations (LL, MM, LM), or they fasted at breakfast time and received a moderately high-fat lunch (NM), in three Latin squares. Each evening a standard meal was given. Plasma glucose, insulin and C-peptide responses were greater following L than M meals and within both MM and LL treatments insulin and C-peptide responses were greater following breakfast than following lunch. The incremental C-peptide response to a fatty lunch following a fast at breakfast time (MM) was similar to that to a fatty breakfast, but the incremental insulin response for the same comparison was marginally lower at lunch (P=0.06). The relationship of C-peptide and insulin concentrations was assessed. Plasma glucose response to a fatty lunch was increased by a fatty breakfast. The relationships of these metabolic events with fat metabolism are discussed

Effects of high- and low-fat meals on the diurnal response of plasma lipid metabolite concentrations in healthy middle-aged volunteers

Three experiments were conducted in healthy middle-aged volunteers (six males and six females in Expt 1, six males and two females in Expt 2 and twelve males in Expt 3) with a mean BMI of 27 kg/m(2) to determine whether there is a difference between morning and afternoon dietary fat clearance and utilization, and to determine in what way the fat and starch contents of the meal influence postprandial blood lipid metabolites over 4.5 h. Over 4 days in Expt 1 each subject received isoenergetic, high-carbohydrate (L, 5.5 g mixed fat/meal) and moderately high-fat (M, 33 g mixed fat/meal) breakfasts and lunches, in three combinations (LL, MM, LM), or they fasted at breakfast time and received a high fat lunch (MM) in a randomized and balanced arrangement. Each evening a standard meal was given. The following effects were significant (P < 0.05): plasma triacylglycerol (TAG) responses were greater following RI meals; plasma TAG concentrations were greater in the afternoon than in the morning, following two meats of the same composition, although the postprandial incremental response was less following lunch than following breakfast and peak responses were reached much earlier than after breakfast; a low-fat breakfast, or fasting at breakfast time, delayed the peak TAG response to a M lunch. The plasma concentrations of nonesterified fatty acids (NEFA) and of free glycerol were higher in the afternoon following M meals at breakfast and lunch, especially in males. This response was reduced, by the L breakfast preceding the M lunch. Two M meals in succession lowered plasma HDL-cholesterol concentration. In Expt 2 each subject received a very low-fat (VL) breakfast, followed by a lunch of the same composition. Each of these meals was followed, 110 min from the start of eating, by an infusion of Intralipid 10 % emulsion at the rate of 1 ml/kg body weight over 60 s. Clearance rates of Intralipid were faster in the afternoon than in the morning (P = 0.024). In Expt 3 twelve subjects were randomly allocated to either treatment MM or LM meal patterns, as given in Expt 1. These were given daily for a period of 17 d, during which the change in fasting plasma TAG concentration was similar in both treatments. On days 1, 16 and 17 responses were measured to the M lunch and to a glucose tolerance test (GTT), conducted 2 h 17 min after lunch. The post-lunch responses confirmed those found in Expt 1; but immediately following the glucose dose there was an abrupt increase in plasma TAG that was greater in treatment LM than in treatment MM (P = 0.025), whereas plasma NEFA concentration decreased rapidly in both treatments at that time (P = 0.00066)

Prevalence and predictors of video game addiction: a study based on a national representative sample of gamers

Video gaming has become a popular leisure activity in many parts of the world, and an increasing number of empirical studies examine the small minority that appears to develop problems as a result of excessive gaming. This study investigated prevalence rates and predictors of video game addiction in a sample of gamers, randomly selected from the National Population Registry of Norway (N =3389). Results showed there were 1.4 % addicted gamers, 7.3 % problem gamers, 3.9 % engaged gamers, and 87.4 % normal gamers. Gender (being male) and age group (being young) were positively associated with addicted-, problem-, and engaged gamers. Place of birth (Africa, Asia, South- and Middle America) were positively associated with addicted- and problem gamers. Video game addiction was negatively associated with conscientiousness and positively associated with neuroticism. Poor psychosomatic health was positively associated with problem- and engaged gaming. These factors provide insight into the field of video game addiction, and may help to provide guidance as to how individuals that are at risk of becoming addicted gamers can be identified

Effect of breakfast fat content on glucose tolerance and risk factors of atherosclerosis and thrombosis

Twenty-four middle-aged healthy men were given a low-fat high-carbohydrate (5.5 g fat; L), or a moderately-fatty, (25.7 g fat; M) breakfast of similar energy contents for 28 d. Other meals were under less control. An oral glucose tolerance test (OGTT) was given at 09.00 hours on day 1 before treatment allocation and at 13.30 hours on day 29. There were no significant treatment differences in fasting serum values, either on day 1 or at the termination of treatments on day 29. The following was observed on day 29: (1) the M breakfast led to higher OGTT C-peptide responses and higher areas under the curves (AUC) of OGTT serum glucose and insulin responses compared with the OGTT responses to the L breakfast (P < 0.05); (2) treatment M failed to prevent OGTT glycosuria, eliminated with treatment L; (3) serum non-esterified fatty acid (NEFA) AUC was 59% lower with treatment L than with treatment M, between 09.00 and 13.20 hours (P < 0.0001), and lower with treatment L than with treatment M during the OGTT (P = 0.005); (4) serum triacylglycerol (TAG) concentrations were similar for both treatments, especially during the morning, but their origins were different during the afternoon OGTT when the Svedberg flotation unit 20-400 lipid fraction was higher with treatment L than with treatment M (P = 0.016); plasma apolipoprotein B-48 level with treatment M was not significantly greater than that with treatment L (P = 0.086); (5) plasma tissue plasminogen-activator activity increased after breakfast with treatment L (P = 0.0008), but not. with treatment M (P = 0.80). Waist:hip circumference was positively correlated with serum insulin and glucose AUC and with fasting LDL-cholesterol, Waist:hip circumference and serum TAG and insulin AUC were correlated with factors of thrombus formation; and the OGTT NEFA and glucose AUC were correlated. A small difference in fat intake at breakfast has a large influence on circulating diurnal NEFA concentration, which it is concluded influences adversely glucose tolerance up to 6 h later