The astroglial protein S100 is an established biochemical marker for CNS injury in the adult. The aim was to investigate whether S100 in serum is a prognostic marker of cerebral injury in term newborn infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. Serum S100 was measured on postnatal days 1-4 in 62 term infants with birth asphyxia. The infants were classified for HIE and had follow-up for at least 18 mo. Infants with moderate and severe HIE had significantly higher S100 levels on postnatal day 1 (p ϭ 0.031) and day 2 (p ϭ 0.008) than infants with mild or no HIE. The levels of S100 decreased on days 2 and 3 in all infants with HIE. The median S100 level on postnatal day 1 was higher in nine infants who died neonatally and in 10 infants who developed cerebral palsy (CP), compared with 43 infants with no signs of impairment at follow up, 14.0 (0.5-60.0) g/L, 20.7 (0.2-64.0) g/L and 5.5 (0.7-120.0) g/L, respectively. A level of S100 above 12 g/L the first day of life was significantly more frequent in infants who died or developed CP than in infants with no impairment at follow up (p ϭ 0.02). Increased S100 levels were significantly inversely correlated with perinatal pH in the infants and associated with abnormal CTG at admission to the labor ward. Early determination of serum S100 may reflect the extent of brain damage in infants with HIE after asphyxia. Abbreviations CP, cerebral palsy CSF, cerebrospinal fluid CTG, cardiotocography FHR, fetal heart rate HIE, hypoxic ischemic encephalopathy S100, S100 protein including the subunits ␣␤ and ␤␤ aEEG, amplitude integrated EEG GFAP, glial fibrillary acidic protein Birth asphyxia remains a considerable problem in perinatal medicine with an incidence around 0.6 -0.8% of births (1-3). About half of these infants develop hypoxic ischemic encephalopathy (HIE) (2, 4). Those with moderate and severe HIE are at high risk of developing cerebral palsy (CP) (5-8). Prognostic assessment of brain injury after perinatal asphyxia will become essential for proper selection concerning early cerebroprotective treatment, which might be a likely option in the near future (9, 10). Several biochemical markers in cerebrospinal fluid (CSF) have been associated with cerebral complications in infants after perinatal asphyxia (11-14) and recently also S100 in CSF (15). A prognostic marker in serum would be of great value. S100 is a calcium binding protein present in the CNS. The dimers ␣␤ and ␤␤ of S100 are mainly specific for the nervous system and present chiefly in the astroglial cells of the CNS (16,17). S100 ␣␣ is present in many organs outside the CNS and will not be discussed in this report, where S100 will be used for the brain-specific S100 with subunits ␣␤ and ␤␤.The astroglial protein S100 is an established biochemical marker for CNS injury in the adult, in whom increased levels of S100 in CSF have been reported after cerebral insults (18,19). S100 in blood has been shown to be a marker of brain damage in adult stroke (20, 21) and a potential marker for c...

Background It is currently unknown which of the two devices most commonly used in equine ophthalmology for intraocular pressure (IOP) estimation demonstrates the lowest inter‐user and intra‐user variation. Objectives To assess the inter‐user and intra‐user variation of two tonometers in sedated and unsedated horses. Study design Randomised masked cross‐over trial. Methods Four examiners used the rebound (ICare® TonoVet) and applanation (TonoPen®) tonometers to measure the intraocular pressure (IOP) in triplicate in 10 normal horses before and after sedation with xylazine. For inter‐user variation, coefficient of variation (CV) values were calculated from the mean of each examiner for each condition combination. For intra‐user variation, CV values were calculated from the individual measurements of each examiner for each condition combination. CV values were also assessed in relation to other variables using ANOVA. Results The rebound tonometer was found to have lower inter‐user (15.4% vs 21.7%, P = .01) and intra‐user (9.1% vs 16.1%, P < .0001) variation in unsedated horses and lower intra‐user (8.4% vs 14.7%, P < .0001) variation in sedated horses than the applanation tonometer. Both instruments had similar inter‐user variation in sedated horses. For the rebound tonometer, sedation did not affect inter‐user or intra‐user variation, but for the applanation tonometer inter‐user variation was lowest while horses were sedated (16.0% vs 21.7%, P = .03). No other variable assessed was found to have an effect on IOP. Main limitations No animals with ocular disease were included in this study. Conclusions The rebound tonometer may be the preferred instrument to minimise intra‐user and inter‐user variation for IOP measurement in unsedated horses. The rebound tonometer is also likely to be the preferred instrument to minimise intra‐user variation in sedated horses. If the applanation tonometer is used to perform IOP measurement in horses, it is recommended that this is performed while horses are sedated to minimise inter‐user variation for this instrument.

Objectives Feline herpesvirus-1 (FHV-1) is a prevalent cause of ocular disease in cats and limited topical options for treatment currently exist. The first objective of this study was to confirm the efficacy of ganciclovir against FHV-1 in vitro. The second objective was to assess the safety and ocular tolerability of topically applied ganciclovir eye gel (GEG) in healthy cats. Methods FHV-1 was used to infect tissue culture wells covered in maximally confluent Crandall–Rees feline kidney cells prior to the addition of three molarities of ganciclovir (8.9 µM, 17.8 µM and 89 µM) before being incubated for 48 h. Ganciclovir efficacy in vitro was then assessed using standard plaque reduction assay. Commercially available GEG (0.15%) was applied q8h to one randomly chosen eye of four healthy cats for 7 days. Commercially available lubricating eye gel (LEG) was applied to the opposite eye q8h. Complete blood counts (CBC), blood chemistry panels (CHEM) and urinalysis (UA) were performed on all cats before and after the study period. Ocular lesions were assessed daily using a standardized scheme. Results Ganciclovir led to a significant reduction in FHV-1 plaque number, area and diameter at all tested molarities in vitro. The highest molarity assessed (89 µM) caused a 100% reduction in viral plaque number. There was no significant difference in lesion scores between eyes receiving GEG and LEG. Animals remained healthy throughout the study period with CBC, CHEM and UA showing no clinically significant alterations. Conclusions and relevance Based on the in vitro results, ganciclovir appears to be effective against FHV-1 in vitro. When applied q8h as a commercial 0.15% gel to a small group of cats with normal eyes, this medication was well tolerated. Taken together, these data suggest this medication warrants further investigation in cats with ocular disease caused by FHV-1.

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Bovine herpesvirus-1 (BoHV-1) infection contributes to keratoconjunctivitis, respiratory disease, and reproductive losses in cattle. The objective of this study was to determine the most appropriate ophthalmic antiviral agent for BoHV-1 inhibition using in-vitro culture and novel ex-vivo bovine corneal modeling. Half-maximal inhibitory concentrations of BoHV-1 were determined for cidofovir, ganciclovir, idoxuridine, and trifluridine via in-vitro plaque reduction assays. In-vitro cytotoxicity was compared amongst these compounds via luciferase assays. Trifluridine and cidofovir were the most potent BoHV-1 inhibitors in vitro, while trifluridine and idoxuridine were the most cytotoxic agents. Therefore, cidofovir was the most potent non-cytotoxic agent and was employed in the ex-vivo corneal assay. Corneoscleral rings (n = 36) from fresh cadaver bovine globes were harvested and equally divided into an uninfected, untreated control group; a BoHV-1-infected, untreated group; and a BoHV-1-infected, cidofovir-treated group. Virus isolation for BoHV-1 titers was performed from corneal tissue and liquid media. Histologic measurements of corneal thickness, epithelial cell density, and tissue organization were compared between groups. Substantial BoHV-1 replication was observed in infected, untreated corneas, but BoHV-1 titer was significantly reduced in cidofovir-treated (1.69 ± 0.08 × 103 PFU/mL) versus untreated (8.25 ± 0.25 × 105 PFU/mL, p < 0.0001) tissues by day 2 of culture. No significant differences in histologic criteria were observed between groups. In conclusion, cidofovir warrants further investigation as treatment for BoHV-1 keratoconjunctivitis, with future studies needed to assess in-vivo tolerability and efficacy.