Behavioral and anatomical abnormalities in a sodium iodate-induced model of retinal pigment epithelium degeneration

We characterized changes in the visual behavior of mice in which a loss of the retinal pigment epithelium (RPE) was experimentally induced with intravenous (i.v.) administration of sodium iodate (NaIO3). We compared and correlated these changes with alterations in neural retinal structure and function. RPE loss was induced in 4-6 week old male C57BL/6 mice with an i.v. injection of 1% NaIO3 at three concentrations: 35, 50, or 70 mg/kg. At 1, 3, 7, 14, 21, and 28 days (d) as well as 6 months post injection (PI) a behavioral test was performed in previously trained mice to evaluate visual function. Eye morphology was then assessed for changes in both the RPE and neural retina. NaIO3-induced RPE degeneration was both dose and PI time dependent. Our low dose showed no effects, while our high dose caused the most damage, as did longer PI times at our intermediate dose. Using the intermediate dose, no changes were detectable in either visual behavior or retinal morphology at 1 d PI. However, at 3 d PI visual behavior became abnormal and patchy RPE cell loss was observed. From 7 d PI onward, changes in retinal morphology and visual behavior became more severe. At 6 months PI, no recovery was seen in any of these measures in mice administered the intermediate dose. These results show that NaIO3 dosage and/or time PI can be varied to produce different, yet permanent deficits in retinal morphology and visual function. Thus, this approach should provide a unique system in which the onset and severity of RPE damage, and its consequences can be manipulated. As such, it should be useful in the assessment of rescue or mitigating effects of retinal or stem cell transplantation on visual function.

Low social support and poor emotional regulation are associated with increased stress hormone reactivity to mental stress in systemic hypertension

CONTEXT: There is strong evidence for a physiological hyperreactivity to stress in systemic hypertension, but data on associated or potentially moderating psychological factors are scarce. OBJECTIVE: The objective of the study was to identify psychological correlates of physiological stress reactivity in systemic hypertension. DESIGN: This was a cross-sectional, quasi-experimentally controlled study. Study participants underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. SETTING: The study was conducted in the population in the state of Zurich, Switzerland. SUBJECTS: Subjects included 22 hypertensive and 26 normotensive men (mean +/- sem 44 +/- 2 yr). MAIN OUTCOME MEASURES: We assessed the psychological measures social support, emotional regulation, and cognitive appraisal of the stressful situation. Moreover, we measured salivary cortisol and plasma epinephrine and norepinephrine before and after stress and several times up to 60 min thereafter as well as blood pressure and heart rate. RESULTS: We found poorer hedonistic emotional regulation (HER) and lower perceived social support in hypertensives, compared with normotensives (P < 0.01). Compared with normotensives, hypertensives showed higher cortisol, epinephrine, and norepinephrine secretions after stress (P < 0.038) as well as higher systolic and diastolic blood pressure (P < 0.001). Cortisol reactivity and norepinephrine secretion were highest in hypertensive men with low HER (P < 0.05). In contrast, hypertensives with high HER did not significantly differ from normotensives in both cortisol and norepinephrine secretion after stress. Epinephrine secretion was highest in hypertensives with low social support but was not different between hypertensives with high social support and normotensives. CONCLUSIONS: The findings suggest that both low social support and low HER are associated with elevated stress hormone reactivity in systemic hypertension.

Emotional stress reactivity in irritable bowel syndrome

OBJECTIVES: Irritable bowel syndrome (IBS) has been proposed to be a stress-related disorder. Research on stress reactivity in IBS has yielded ambiguous results, regarding responses to physical and mental stress. This study aimed to investigate the responses to emotional stress in IBS patients. METHODS: Twelve IBS patients and 12 healthy individuals underwent public speaking anticipation as an emotional stressor and a control situation. Stress reactivity was quantified by subjective and psychophysiological measures. RESULTS: Stress responses were elicited in healthy controls and IBS patients. Differential stress responses were observed in measurements of heart rate. There was no change in rectal sensitivity under stress, whereas patients exhibited lower discomfort thresholds than healthy controls in all conditions. CONCLUSION: This study measured reactivity to an emotional stressor in IBS. It provides evidence that there is a specific alteration of stress responses in IBS patients, but no overall exaggerated stress response. IBS patients showed a broader and less specific response to emotional stress than healthy controls. Rectal sensitivity was unchanged under emotional stress both in IBS patients and healthy controls.

Extrinsic causes of erosion. Behavioral factors

During and after an erosive challenge, behavioral factors play a role in modifying the extent of erosive tooth wear. The manner that dietary acids are introduced into the mouth (gulping, sipping, use of a straw) will affect how long the teeth are in contact with the erosive challenge. The frequency and duration of exposure to an erosive agent is of paramount importance. Night-time exposure (e.g. baby bottle-feeding) to erosive agents may be particularly destructive because of the absence of salivary flow. Health-conscious individuals tend to ingest acidic drinks and juices more frequently and tend to have higher than average oral hygiene. While good oral hygiene is of proven value in the prevention of periodontal disease and dental caries, frequent toothbrushing with abrasive oral hygiene products may enhance erosive tooth wear. Unhealthy lifestyles such as consumption of designer drugs, alcopops and alcohol abuse are other important behavioral factors.

Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen

Glycoprotein (GP) VI, the primary collagen receptor on platelets, has been shown to have variable expression, possibly as a consequence of immune modulation. The present study was designed to determine the mechanism by which GP VI clearance occurs. We found that direct activation of GP VI both by a GP VI-specific antibody and by GP VI ligands (collagen and convulxin) reduced binding of biotinylated convulxin to the stimulated platelets. Analysis of immunoblots of platelets and supernatants showed that the stimulated platelets contained less GP VI, while the soluble fraction contained a 57-kDa cleavage product. Stimulation of platelets with PAR-1 agonists (TRAP peptide and thrombin) also caused GP VI cleavage, although the amount of GP VI loss was less than that observed with direct GP VI ligands. The metalloproteinase (MMP) inhibitors GM6001 and TAPI prevented both the clearance of GP VI from the platelet surface and the appearance of the soluble cleavage product. Induction of GP VI cleavage caused specific down-regulation of collagen-induced platelet aggregation, providing a mechanism for the modulation of platelet responsiveness to this important platelet agonist.

Characterization of Anaplasma phagocytophilum major surface protein 5 and the extent of its cross-reactivity with A. marginale

Major surface protein 5 (Msp5) of Anaplasma marginale is highly conserved in the genus Anaplasma and the antigen used in a commercially available competitive enzyme-linked immunosorbent assay (cELISA) for serologic identification of cattle with anaplasmosis. This study analyzes the degrees of conservation of Msp5 among various isolates of Anaplasma phagocytophilum and the extent of serologic cross-reactivity between recombinant Msp5 (rMsp5) of Anaplasma marginale and A. phagocytophilum. The msp5 genes from various isolates of A. phagocytophilum were sequenced and compared. rMsp5 proteins of A. phagocytophilum and A. marginale were used separately in an indirect ELISA to detect cross-reactivity in serum samples from humans and dogs infected with A. phagocytophilum and cattle infected with A. marginale. Serum samples were also tested with a commercially available competitive ELISA that uses monoclonal antibody ANAF16C1. There were 100% sequence identities in the msp5 genes among all of the A. phagocytophilum isolates from the United States and a horse isolate from Sweden. Sheep isolates from Norway and dog isolates from Sweden were 99% identical to one another but differed in 17 base pairs from the United States isolates and the horse isolate. Serologic cross-reactivity was identified when serum samples from cattle infected with A. marginale were reacted with rMsp5 of A. phagocytophilum and when serum samples from humans and dogs infected with A. phagocytophilum were reacted with rMsp5 of A. marginale in an indirect-ELISA format. Serum samples from dogs or humans infected with A. phagocytophilum did not cross-react with rMsp5 of A. marginale when tested with the commercially available cELISA. These results suggest that rMsp5 of A. phagocytophilum is highly conserved among United States and European isolates and that serologic distinction between A. phagocytophilum and A. marginale infections cannot be accomplished if rMsp5 from either organism is used in an indirect ELISA.

Psychophysiological ambulatory assessment of affective dysregulation in borderline personality disorder

Many experts now believe that pervasive problems in affect regulation constitute the central area of dysfunction in borderline personality disorder (BPD). However, data is sparse and inconclusive. We hypothesized that patients with BPD, in contrast to healthy gender and nationality-matched controls, show a higher frequency and intensity of self-reported emotions, altered physiological indices of emotions, more complex emotions and greater problems in identifying specific emotions. We took a 24-hour psychophysiological ambulatory monitoring approach to investigate affect regulation during everyday life in 50 patients with BPD and in 50 healthy controls. To provide a typical and unmanipulated sample, we included only patients who were currently in treatment and did not alter their medication schedule. BPD patients reported more negative emotions, fewer positive emotions, and a greater intensity of negative emotions. A subgroup of non-medicated BPD patients manifested higher values of additional heart rate. Additional heart rate is that part of a heart rate increase that does not directly result from metabolic activity, and is used as an indicator of emotional reactivity. Borderline participants were more likely to report the concurrent presence of more than one emotion, and those patients who just started treatment in particular had greater problems in identifying specific emotions. Our findings during naturalistic ambulatory assessment support emotional dysregulation in BPD as defined by the biosocial theory of [Linehan, M.M., 1993. Cognitive-Behavioral Treatment of Borderline Personality Disorder. The Guildford Press, New York.] and suggest the potential utility for evaluating treatment outcome.

EEG reactivity and EEG activity in never-treated acute schizophrenics, measured with spectral parameters and dimensional complexity

Our approaches to the use of EEG studies for the understanding of the pathogenesis of schizophrenic symptoms are presented. The basic assumptions of a heuristic and multifactorial model of the psychobiological brain mechanisms underlying the organization of normal behavior is described and used in order to formulate and test hypotheses about the pathogenesis of schizophrenic behavior using EEG measures. Results from our studies on EEG activity and EEG reactivity (= EEG components of a memory-driven, adaptive, non-unitary orienting response) as analyzed with spectral parameters and "chaotic" dimensionality (correlation dimension) are summarized. Both analysis procedures showed a deviant brain functional organization in never-treated first-episode schizophrenia which, within the framework of the model, suggests as common denominator for the pathogenesis of the symptoms a deviation of working memory, the nature of which is functional and not structural.

Self-reactivity in the dimeric intravenous immunoglobulin fraction

Therapeutic intravenous immunoglobulin (IVIg) preparations contain antibodies reflecting the cumulative antigen experience of the donor population. IVIg contains variable amounts of monomeric and dimeric IgG, but there is little information available on their comparative antibody specificities. We have isolated highly purified fractions of monomeric and dimeric IgG by size-exclusion chromatography. Following treatment of all fractions at pH4, analyses by immunodot and immunocytology on human cell lines showed a preferential recognition of autoantigens in the dimeric IgG fraction. Investigation of the HEp-2 cytoplasmic proteome by 2D-PAGE, Western blot, and subsequent identification of IVIg reactive spots by mass spectrometry (LC-MS/MS) showed that IVIg recognized only a restricted set of the total proteins. Similar experiments showed that more antigens were recognized by the dimeric IgG fraction, especially when the dissociated dimer fraction was used, as compared to its monomeric counterpart. These observations are consistent with idiotype-anti-idiotype masking of auto-specific Abs in the dimeric fraction of IVIg.

Dimensions of impulsive behavior in adolescents: laboratory behavioral assessments

Impulsivity is a multifaceted construct that defines a range of maladaptive behavioral styles. The present research aimed to identify different dimensions of impulsive behavior in adolescents from a battery of laboratory behavioral assessments. In one analysis, correlations were examined between two self report and seven laboratory behavioral measures of impulsivity. The correlation between the two self report measures was high compared to correlations between the self report and laboratory behavioral measures. In a second analysis, a principal components analysis was performed with just the laboratory behavioral measures. Three behavioral dimensions were identified -- "impulsive decision-making", "impulsive inattention", and "impulsive disinhibition". These dimensions were further evaluated using the same sample with a confirmatory factor analysis, which did support the hypothesis that these are significant and independent dimensions of impulsivity. This research indicates there are at least three separate subtypes of impulsive behavior when using laboratory behavioral assessments with adolescent participants.