Stress and visual function in infantile nystagmus syndrome.

PURPOSE: Infantile nystagmus syndrome (INS) is an involuntary oscillation of the eyes that has been reported to impair vision and worsen under stress. This investigation aimed to measure visual function in terms of visual acuity (VA) and response time (RT), when INS subjects are placed under stress. METHODS: A total of 23 subjects with INS and 20 control subjects performed a 2-alternative forced choice (2AFC) staircase procedure identifying the gap in a Landolt C, under 4 experimental conditions: initial acclimatization (A); task demand (TD), during which subjects received a small electrical shock for every incorrect answer; anticipatory anxiety (AA), during which subjects received a small shock at random intervals; and relaxed (R). Arousal was monitored with galvanic skin conductance (SkC). In addition to VA and eye movements, RTs were recorded. RESULTS: The SkC was higher in the TD and AA periods and lower during A and R. Shock significantly increased nystagmus amplitude (P < 0.01) and intensity (P < 0.007), and reduced foveation periods (FPs, P < 0.022). In both groups, VA was not reduced, but showed a slight improvement. However, shock increased RT (P < 0.009), and INS subjects were slower than controls (P < 0.0005). CONCLUSIONS: Increased arousal ("stress") provoked more intense nystagmus eye movements. As seen in other studies, stress did not reduce VA despite the shorter FPs. Although VA and FP can correlate across subjects, there would appear to be little correlation, if any, within a subject. However, RTs did increase with stress and shorter FPs, which may have an adverse impact on the visual performance of those with INS

Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury

Pontospinal noradrenergic neurons form part of an endogenous analgesic system that suppresses acute pain, but there is conflicting evidence about its role in neuropathic pain. We investigated the chronology of descending noradrenergic control during the development of a neuropathic pain phenotype in rats following tibial nerve transection (TNT). A lumbar intrathecal cannula was implanted at the time of nerve injury allowing administration of selective α-adrenoceptor (α-AR) antagonists to sequentially assay their effects upon the expression of allodynia and hyperalgesia. Following TNT animals progressively developed mechanical and cold allodynia (by day 10) and subsequently heat hypersensitivity (day 17). Blockade of α2-AR with intrathecal yohimbine (30 μg) revealed earlier ipsilateral sensitization of all modalities while prazosin (30 μg, α1-AR) was without effect. Established allodynia (by day 21) was partly reversed by the re-uptake inhibitor reboxetine (5 μg, i.t.) but yohimbine no longer had any sensitising effect. This loss of effect coincided with a reduction in the descending noradrenergic innervation of the ipsilateral lumbar dorsal horn. Yohimbine reversibly unmasked contralateral hindlimb allodynia and hyperalgesia of all modalities and increased dorsal horn c-fos expression to an innocuous brush stimulus. Contralateral thermal hyperalgesia was also reversibly uncovered by yohimbine administration in a contact heat ramp paradigm in anaesthetised TNT rats. Following TNT there is an engagement of inhibitory α2-AR-mediated noradrenergic tone which completely masks contralateral and transiently suppresses the development of ipsilateral sensitization. This endogenous analgesic system plays a key role in shaping the spatial and temporal expression of the neuropathic pain phenotype after nerve injury

The distribution of proenkephalin-derived peptides in the central nervous system of turtles

The present study was carried out to examine if peptides similar to the various opioid peptide products of mammalian proenkephalin are present in the turtle central nervous system and to determine their distribution. Antisera against several enkephalin peptides were used: (1) leucine-enkephalin (LENK), (2) methionine-enkephalin (MENK), (3) methionine-enkephalin-arg 6 -phe 7 (MERF), (4) methionine-enkephalin-arg 6 -gly 7 -leu 8 (MERGL), (5) Peptide E (PEPE), and (6) BAM22P. Their specificity and cross-reactivity were carefully examined. The results indicated that LENK, MENK, and MERF (or highly similar peptides) are present in the turtle central nervous system, and that a peptide showing immunological similarity to BAM22P and PEPE also appeared to be present. In contrast, MERGL did not appear to be present. The distributions of the immunoreactive labeling for LENK, MENK, MERF, BAM22P, and PEPE were indistinguishable, and double-label studies showed that LENK, MERF, and BAM22P were colocalized within individual neurons and fibers. Although all of the above substances were observed in the same cell groups, there was some regional variation, in terms of which enkephalin peptide appeared to be most abundant. The distributions of these enkephalin peptides were very similar to those previously described in mammals and birds. Enkephalin was more abundant in the basal ganglia than in overlying telencephalic regions. Within the basal ganglia, enkephalin was present in striatal neurons and fibers and in pallidal fibers, thereby suggesting the existence of an enkephalinergic striatopallidal projection. Sensory relay nuclei of the thalamus were generally poor in enkephalinergic fibers, whereas the hypothalamus was rich in enkephalinergic neurons and fibers. Enkephalinergic neurons and fibers were present in the midbrain central gray. As is true of neurons of the nucleus spiriformis lateralis of the avian pretectum, the neurons of the homologous cell group in turtles, the dorsal nucleus of the posterior commissure of the pretectum, were found to contain enkephalin and have an enkephalinergic projection to the deep layers of the ipsilateral tectum. Enkephalinergic neurons and fibers were also abundant in the entry zones of the trigeminal nerve and dorsal root fibers of the spinal cord. The present results indicate that: (1) consistent with previously published biochemical studies (Lindberg and White, '86), proenkephalin in reptiles is similar in structure to that of mammals and, with the exception of MERGL, gives rise to similar or identical enkephalin peptides, and (2) the enkephalin peptides are found in many of the same systems of reptilian brain as mammalian and avian brain, and, therefore, may play a role in similar functions (e.g., basal ganglia motor functions) as in mammals and birds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50034/1/902590106_ftp.pd

Targeting a Newly Established Spontaneous Feline Fibrosarcoma Cell Line by Gene Transfer

Fibrosarcoma is a deadly disease in cats and is significantly more often located at classical vaccine injections sites. More rare forms of spontaneous non-vaccination site (NSV) fibrosarcomas have been described and have been found associated to genetic alterations. Purpose of this study was to compare the efficacy of adenoviral gene transfer in NVS fibrosarcoma. We isolated and characterized a NVS fibrosarcoma cell line (Cocca-6A) from a spontaneous fibrosarcoma that occurred in a domestic calico cat. The feline cells were karyotyped and their chromosome number was counted using a Giemsa staining. Adenoviral gene transfer was verified by western blot analysis. Flow cytometry assay and Annexin-V were used to study cell-cycle changes and cell death of transduced cells. Cocca-6A fibrosarcoma cells were morphologically and cytogenetically characterized. Giemsa block staining of metaphase spreads of the Cocca-6A cells showed deletion of one of the E1 chromosomes, where feline p53 maps. Semi-quantitative PCR demonstrated reduction of p53 genomic DNA in the Cocca-6A cells. Adenoviral gene transfer determined a remarkable effect on the viability and growth of the Cocca-6A cells following single transduction with adenoviruses carrying Mda-7/IL-24 or IFN-γ or various combination of RB/p105, Ras-DN, IFN-γ, and Mda-7 gene transfer. Therapy for feline fibrosarcomas is often insufficient for long lasting tumor eradication. More gene transfer studies should be conducted in order to understand if these viral vectors could be applicable regardless the origin (spontaneous vs. vaccine induced) of feline fibrosarcomas

Neurodevelopmental dimensional assessment of young children at high genomic risk of neuropsychiatric conditions

Background Individuals with 22q11.2 deletion are at considerably increased risk of neurodevelopmental and psychiatric conditions. There have been very few studies investigating how this risk manifests in early childhood and what factors may underlie developmental variability. Insights into this can elucidate transdiagnostic markers of risk that may underlie later development of neuropsychiatric outcomes. Methods Thirty two children with 22q11.2 Deletion Syndrome (22q11.2DS) (mean age = 4.1 [SD = 1.2] years) and 12 sibling controls (mean age = 4.1 [SD = 1.5] years) underwent in-depth dimensional phenotyping across several developmental domains selected as being potential early indicators of neurodevelopmental and psychiatric liability. Comparisons were conducted of the dimensional developmental phenotype of 22q11.2DS and sibling controls. For autistic traits, both parents and children were phenotyped using the Social Responsiveness Scale. Results Young children with 22q11.2DS exhibited large impairments (Hedge's g ≥ 0.8) across a range of developmental domains relative to sibling controls, as well as high rates of transdiagnostic neurodevelopmental and psychiatric traits. Cluster analysis revealed a subgroup of children with 22q11.2DS (n = 16; 53%) in whom neurodevelopmental and psychiatric liability was particularly increased and who differed from other children with 22q11.2DS and non-carrier siblings. Exploratory analyses revealed that early motor and sleep impairments indexed liability for neurodevelopmental and psychiatric outcomes. Maternal autism trait scores were predictive of autism traits in children with 22q11.2DS (intraclass correlation coefficients = 0.47, p = 0.046, n = 31). Conclusions Although psychiatric conditions typically emerge later in adolescence and adulthood in 22q11.2DS, our exploratory study was able to identify a range of early risk indicators. Furthermore, findings indicate the presence of a subgroup who appeared to have increased neurodevelopmental and psychiatric liability. Our findings highlight the scope for future studies of early risk mechanisms and early intervention within this high genetic risk patient group

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24&nbsp;h. In both studies, patients were followed for outcome until death, hospital discharge or for 60&nbsp;days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24&nbsp;h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (&gt; 29 cmH2O) and driving pressure (&gt; 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (&gt; 8&nbsp;ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure &gt; 29 cmH2O and driving pressure &gt; 14 cmH2O on the first day of mechanical ventilation but not tidal volume &gt; 8&nbsp;ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies