Beneficial effects of spraying low mineral content thermal spring water after fractional photothermolysis in patients with dermal melasma.

INTRODUCTION: Melasma is a common dermatological skin disease that can now be treated by fractional photothermolysis (fractional resurfacing). Past studies have shown that thermal spring water (TSW) spray can reduce local inflammatory symptoms after dermatological surgery, laser surgery or chemical peelings. The aim of this study was to evaluate the clinical efficacy and safety of spraying TSW post-fractional resurfacing treatment in patients with dermal melasma. METHODS: Twenty patients with bilateral dermal melasma were included in this split-face comparative study. Patients were treated by fractional resurfacing laser and then TSW was sprayed generously unilaterally. For the next 48 h, patients were instructed to spray thermal water at least six times a day on one side. Patient's self-assessment conducted 10 min and 2 days after TSW spraying (stinging, pain, skin dryness, swelling, and redness) and investigator's 48-h post-treatment evaluation (purpura, skin dryness, erythema, swelling, scars, hyper- or hypopigmentation) were recorded for the treated and control sides using visual analogue scales. RESULTS: Pain, dryness, and redness were significantly lower 10 min after spraying on the TSW-treated side in comparison with the untreated side, as assessed by the patients (P < 0.05). Two days after fractional resurfacing, dryness and redness were still improved on the TSW-treated side. The investigator's evaluation revealed that erythema, the only perceivable sign following irradiation, was significantly reduced by TSW spraying (P < 0.01). CONCLUSION: This split-face comparative study conducted in patients with dermal melasma showed that spraying TSW after fractional laser resurfacing significantly reduced short-term adverse effects associated with the procedure.

CSF 5-HIAA concentration as an early screening tool for predicting significant life history outcomes in female specific-pathogen-free (SPF) rhesus macaques (Macaca mulatta) maintained in captive breeding groups.

We examined relationships among cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite (5-HIAA, 5-hydroxyindoleacetic acid) and significant medical and behavioral outcomes for female rhesus macaques. Based on earlier findings with males we predicted that low CSF 5-HIAA concentrations would be associated with a range of negative life history outcomes in our captive specific-pathogen-free (SPF) breeding colony. We found that the mean CSF 5-HIAA concentration among animals that died over the course of the study period was significantly lower than among animals that survived. Further examination indicated an inverse relationship between CSF 5-HIAA concentration and number of treatments for illness, further suggesting a link between serotonergic functioning and overall animal health. Examination of behavioral data indicated that individuals with low CSF 5-HIAA concentrations were more often the targets of aggressive bouts than were individuals with high CSF 5-HIAA concentrations. Finally, we found a positive relationship between CSF 5-HIAA concentration and infant survivorship. These results suggest negative life history consequences of impaired serotonergic functioning in captive female rhesus macaques, and indicate that CSF 5-HIAA concentration sampled early in life may provide a useful tool in facilitating colony management decisions concerning utilization of scarce and increasingly valuable non-human primate resources.

Left-handedness is correlated with CSF monoamine metabolite and plasma cortisol concentrations, and with impaired sociality, in free-ranging adult male rhesus macaques (Macaca mulatta).

In this research we examined biological and behavioural correlates of handedness in free-ranging adult male rhesus macaques (Macaca mulatta). Specifically, we examined relationships between handedness and cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma concentrations of the hormones cortisol and adrenocorticotropin (ACTH), and multiple indices of social behaviour, including occurrences of proximity to other animals, grooming, submission, and aggression. We determined handedness through systematic observation of animals reaching for food in their unrestricted home environment. The frequency of right- versus left-hand use was significantly positively correlated with CSF 5-HIAA, CSF MHPG, and plasma cortisol concentrations, and with social proximity and the frequency and duration of bouts in which animals received grooming. The frequency of right- versus left-hand use was significantly negatively correlated with the frequency of submissive behaviour, and with the frequency and intensity of bouts in which animals received aggression. We conclude that handedness is associated with an array of biological and behavioural processes in free-ranging adult male rhesus macaques and that left-handedness may be used to identify individuals at increased risk for impaired functioning of the serotonin, norepinephrine, and hypothalamic-pituitary-adrenal systems, and for social isolation and susceptibility to violent attack.

Variation in reproductive outcomes for captive male rhesus macaques (macaca mulatta) differing in CSF 5-hydroxyindoleacetic acid concentrations.

In rhesus macaque males, lower than average cerebrospinal fluid (CSF) concentrations of the principle metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), have been linked to impulsivity, involvement in escalated aggression, failure to elicit consort relationships, production of fewer sperm plugs, and a relatively early age of mortality. Given these potential fitness costs, we performed two studies aimed at elucidating the effects of CSF 5-HIAA on reproduction. Study 1 retrospectively evaluated over a four-year period, the relative reproductive outcome for pairs of adult male rhesus macaques (n = 15) who lived in social groups and who differed in concentrations of CSF 5-HIAA. Study 2 examined the relationship between CSF 5-HIAA and sperm motility and density (n = 12), as a potential mechanism for maintaining variability in CSF 5-HIAA. For Study 1, an average measure from two CSF 5-HIAA samples was calculated for the two males who were present during the time when conception most likely took place (offspring birth date -165 +/- 14 days). Within-pair comparisons of CSF 5-HIAA concentrations between the sire and the non-successful male were drawn for each of the 72 offspring in the study. We found that while sires were typically the male with relatively higher CSF 5-HIAA within the pair, there were no absolute differences in CSF 5-HIAA between males who sired at least one offspring (sires) and those who failed to reproduce (non-sires). Furthermore, while absolute age was not predictive of reproductive outcome, sires with relatively high CSF 5-HIAA also tended to be also relatively older than their competitors. By contrast, for the males with relatively low CSF 5-HIAA who reproduced, sires were relatively younger than the non-sires. These differences in reproductive outcome for males differing in CSF 5-HIAA could not be explained by variability in sperm quantity or quality as we did not find evidence of a relationship between CSF 5-HIAA and either sperm measure. The results of this study suggest that as serotonergic function affects many aspects of behavior and survivorship, it might also be associated with reproductive outcome and different life-history strategies for males differing in concentrations of CSF 5-HIAA.

Between-species variation in the development of hand preference among macaques.

This research examined between-species variation in the development of hand preference among Macaca. Specifically, we examined hand preference using juveniles and adults of three macaque species that differ in social and reactive tendencies in order to examine whether the correlation between temperament and handedness that has been noted within Macaca mulatta occurs between closely related species. Each of the species studied exhibited a different pattern of hand preference development. Both juvenile and adult M. mulatta exhibited group-level left-hand bias. Juvenile Macaca nemestrina were not biased towards either hand at the group-level, whereas adults exhibited a group-level left-hand bias. Neither juvenile nor adult Macaca fascicularis exhibited manual bias at the group-level. Analysis of variance indicated statistically significant main effects of species and age class on hand preference measures. Post-hoc analysis indicated greater use of the left- versus right-hand, and greater hand preference strength independent of direction, among M. mulatta and M. nemestrina than among M. fascicularis, and among adults than among juveniles. These results indicate significant between-species variation in the development of hand preference within the genus Macaca, and are inconsistent with any one single-factor theory yet offered to explain the etiology of primate laterality. We hypothesize that the relationship between handedness and temperament that has been shown within M. mulatta may generalize across closely related primate species.

Stimulation of the ICAM-1 gene transcription by the peroxovanadium compound [bpV(Pic)] involves STAT-1 but not NF-kappa B activation in 293 cells.

Vanadate and peroxovanadium derivatives are potent inhibitors of protein tyrosine phosphatases (PTPs) and exhibit insulinomimetic activities in several cell systems. We have found that in 293 and 293T cells, intercellular adhesion molecule-1 (ICAM-1) gene transcription is activated by bpV(Pic), a picolinic acid-stabilized peroxovanadium derivative. To identify the bpV(Pic)-responsive element(s), several deletion and site-specific mutants of the ICAM-1 gene promoter cloned upstream from the firefly luciferase reporter gene were transiently transfected into both cell lines. Deletion or site-specific mutation of the NF-kappa B site did not affect bpV(Pic) responsiveness, whereas deletion or mutation of the palindromic interferon-gamma-responsive element (pI gamma RE)/gamma-interferon activated sequence site greatly decreased bpV(Pic) responsiveness in both cell types. bpV(Pic) synergistically co-operated with interferon-gamma to increase the transcriptional activity of the ICAM-1 promoter. Electrophoretic mobility-shift assays showed that bpV(Pic) induces signal transducers and activators of transcription (STAT)-1 binding to the ICAM-1 pI gamma RE/GAS in 293T cells, suggesting that the peroxovanadium compound specifically inhibits the phosphatase(s) required to regulate the JAK/STAT signal-transduction pathway.

Memory and attention deficits in drug naive patients with schizophrenia.

The present study was designed to evaluate the integrity of cognitive fronto-temporal processes in drug naive patients with schizophrenia. The evaluation of drug naive patients discards the potential influence of medication, and may allow the specification of cognitive impairments that are truly illness-related. Subcomponents of long-term memory as well as several measures of attention were examined. A group of 16 patients who had never taken antipsychotics and a group of 20 normal controls underwent tests of alertness, information maintaining, and sustained and selective attention, as well as tests of explicit and implicit recall. The psychopathological manifestations of patients were also assessed with the BPRS, PANSS, ESRS clinical scales. Attention test performances revealed that drug naive patients presented a decrease in their ability to respond promptly to a stimulus, sustain their attention on a task, display normal selective attention strategies, and maintain information for on-line processing. The results also suggest that the drug naive patients are impaired when both strategic and associative processes must be triggered to explicitly recover information in long-term memory. In contrast, the results revealed that implicit access to perceptual mental representations is spared in schizophrenic patients. Finally, features of the patients' clinical symptomatology and some cognitive deficits were also shown to be correlated. Overall, results showed that, in relation to normals, drug naive patients were mildly impaired, with little intersubject variability, and that not all cognitive processes were equally disturbed in relation to the normal subjects' performances. Results support the idea that an important part of the impairments seen in schizophrenia is present before the introduction of neuroleptic medication and chronic illness.

Stress correlates of hand preference in rhesus macaques.

In this research we examined stress-related correlates of hand preference in monkeys. Specifically, we tested the hypothesis that stress reactivity and plasma levels of the stress hormone cortisol are developmentally related to handedness in rhesus macaques (Macaca mulatta). We found a significant positive correlation between cortisol levels sampled in juveniles and the frequency of right- versus left-hand use sampled in these same animals during adulthood. Right-hand preference was negatively correlated with stress reactivity. These data are consistent with the view that stress functioning and reactivity are associated with the development of hemispheric specialization in primates.

Familial influences on hand preference: genotypic variation between closely related primate species.

The emergence of hemispheric specialization has important implications for the development of higher order cognitive processes, including language and spatial skills. In this research we sought to further understand psychobiological processes associated with the development of hemispheric specialization by examining and comparing familial influences on hand preference in two closely related macaque species: rhesus macaques (Macaca mulatta) and pigtailed macaques (Macaca nemestrina). The results of our study indicate contrasting patterns of familial influence on hand preference in each species. For the rhesus macaque we found a positive correlation in the direction of hand preference between mothers and their juvenile offspring, and for the pigtailed macaque we found a negative mother-offspring correlation in the direction of hand preference. Fathers did not contribute significantly to the direction of hand preference in either species. There was a trend toward a positive correlation for strength and consistency of hand preference between parents and offspring in rhesus macaques but not in pigtailed macaques. These findings indicate that maternal influences on offspring hand preference vary between closely related primate species and lead us to question the generalizability of universal single-factor theories used to explain intergenerational transmission of hand preference in humans.

A double-blind, placebo-controlled study of the effects of lithium on cognition in healthy subjects: mild and selective effects on learning.

BACKGROUND: Several studies have shown cognitive impairment in short-term memory, long-term memory and psychomotor speed in bipolar patients taking lithium. The aim of the study was to look at the effect of lithium in normal subjects (N=30) taking lithium for 3 weeks. A comprehensive battery was used to assess attention and memory. METHODS: Subjects were randomized to double-blind treatment with either lithium (N=15) or placebo (N=15) for a 3-week period. Thirteen participants in the lithium group and 15 in the placebo group completed the study. The lithium and placebo were administered twice daily in doses varying from 1050 to 1950 mg (mean=1569 mg). The initial daily dose was calculated according to the Pepin formula to achieve a blood serum lithium level of about 0.8 mmol/l. Cognitive performance (attention, memory) was assessed in each subjects during three periods, i.e. at baseline, after 3 weeks of lithium or placebo, and 2 weeks after discontinuation of study medication. RESULTS: In short-term memory tasks, the performance of subjects in the lithium group was worst 3 weeks after lithium treatment compared to 2 weeks after discontinuation. In long-term memory, a significantly higher number of words was recalled by the placebo group but not the lithium group. CONCLUSIONS: Lithium may have an effect on learning when long-term explicit memory test are administered repeatedly. It means that the practice effect when a subject performs the same task several times is less in the lithium-treated group than in the placebo group. This practice effect is related to the learning of a task.

Hormonal correlates of hand preference in free-ranging primates.

In this research we examined hormonal correlates of hand preference in free-ranging primates. Specifically, we tested the hypothesis that levels of the stress hormone cortisol and the male sex hormone testosterone are correlated with handedness in male rhesus macaques (Macaca mulatta). We found significant positive relationships between cortisol and testosterone levels sampled during adolescence and the frequency of right- versus left-hand use sampled during adulthood. These data indicate that adolescent measures of cortisol and testosterone are correlated with hemispheric specialization in adult free-ranging primates.

Left-handedness and longevity in primates.

In the present research we used the rhesus macaque to model the decline in the incidence of left-handedness that has been noted in the aged human population. We found a significant group-level bias towards use of the left hand among young-adult macaques, and a significant group-level bias towards use of the right hand among aged macaques. The distribution of hand preference across age classes cannot be explained through simple elimination of left-handed subjects in the aged population. Rather, our data are consistent with a maturational view positing increased use of the right hand with increased age. Similar findings across phylogenetically diverse primate taxa suggest that this phenomenon is an evolutionarily ancient trait. Greater use of the left hand in male versus female macaques indicates that sex differences in hand preference are also deeply rooted in our primate origins.

[Atypical neuroleptics and selective attention]. / Neuroleptiques atypiques et attention sélective.

GOALS: The aim of this study was to examine selective attention in patients with chronic and refractory schizophrenia who had been exposed for six months to atypical neuroleptic medications: risperidone or clozapine. METHOD: 17 patients satisfying DSM III-R criteria for schizophrenia were assessed according to BPRS and PANSS and abnormal involuntary movements to ESRS. Selective attention tasks were performed before treatment with risperidone or clozapine and at two times during the treatment (6 weeks, T1, and 24 weeks, T2). Patients' performance data were compared to data from a group of general population at T1. Selective attention refers to the ability to discriminate relevant information from irrelevant one. This was measured by a visual search task. Subjects had to search for a target specified by a conjunction of features (color and shape). The target was a black X, while the distracters were white X's, black O's and white O's. The stimuli were displayed on a Macintosh SE computer. A two-button response box was used for response production and the experiment was run in a dimly lit room. A white-fixation stimulus was shown at the center of the display screen between trials. The number of stimuli displayed on a single trial was 1, 4, 7 or 10. The median RTs and error rates of subjects were computed for each factor (target presence and number of stimuli). RESULTS: A Group X Number of items X Presence of target ANOVA applied on median correct RTs revealed a significant Group X Presence interaction [F(1,176) = 60.433, p < .0001]. Performances improved with the time (F2, p < .01). Correlations were found between positive score on PANSS and performance on selective attention (r39 = -.391). CONCLUSION: Atypical neuroleptic do not have a deleterious effect on selective attention but a favorable effect on the schizophrenic patients' performance.

Discriminant cognitive factors in responder and non-responder patients with schizophrenia.

UNLABELLED: To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics. DESIGN: a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine). SETTING: Inpatient and outpatient units, Institute of Psychiatry. PATIENTS: Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial. INTERVENTIONS: New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n = 15) and non-responders if it did not (n = 10). OUTCOME MEASURES: a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS. RESULTS: A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response. CONCLUSION: Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.

[Selective attention and schizophrenia before the administration of neuroleptics]. / Attention sélective et schizophrénie avant l'administration de neuroleptiques.

In recent years, the presence of attention deficits has been recognized as a key feature of schizophrenia. Past studies reveal that selective attention, or the ability to select relevant information while ignoring simultaneously irrelevant information, is disturbed in schizophrenic patients. According to Treisman feature-integration theory of selective attention, visual search for conjunctive targets (e.g., shape and color) requires controlled processes, that necessitate attention and operate in a serial manner. Reaction times (RTs) are therefore function of the number of stimuli in the display. When subjects are asked to detect the presence or absence of a target in an array of a variable number of stimuli, different performance patterns are expected for positive (present target) and negative trials (absent target). For positive trials, a self-terminating search is triggered, that is, the search is ended when the target is encountered. For negative trials, an exhaustive search strategy is displayed, where each stimulus is examined before the search can end; the RT slope pattern is thus double that of the positive trials. To assess the integrity of these processes, thirteen drug naive schizophrenic patients were compared to twenty normal control subjects. Neuroleptic naive patients were chosen as subjects to avoid the potential influence of medication and chronicity-related factors on performance. The subjects had to specify as fast as possible the presence or absence of the target in an array of a variable number of stimuli presented in a circular display, and comprising or not the target. Results showed that the patients can use self-terminating search strategies as well as normal control subjects. However, their ability to trigger exhaustive search strategies is impaired. Not only were patients slower than controls, but their pattern of RT results was different. These results argue in favor of an early impairment in selective attention capacities in schizophrenia, which appears before the introduction of neuroleptics. The attention performance was also shown to present some association to clinical symptoms.

Multidrug-resistance drug-binding peptides generated by using a phage display library.

A phage display library of random decapeptides was used to generate peptide ligands that can bind multidrug-resistance (MDR) drugs mimicking, in this respect, the drug-binding activity of P-glycoprotein. Seven peptide sequences were identified that specifically bound doxorubicin. Five of these sequences expressed the core consensus motif WXXW. The displacement assay showed that the phages expressing these peptides bound MDR type drugs (vinblastine, doxorubicin, verapamil, and genistein) with the same selectivity as P-glycoprotein and did not interact with non-MDR type drugs, such as arabinosylcytosine (Ara-C) and melphalan. One of the selected peptides that showed a highest capacity for the binding (VCDWWGWGIC) was synthesized and displayed competition with the phage for doxorubicin binding. The structure modeling suggested that all the selected sequences contained a hydrophobic envelope in which MDR drugs could be docked with substantial energy minimization. Western blot analysis showed that monospecific antibody obtained against the phage expressing VCDWWGWGIC peptide could specifically recognize P-glycoprotein in the membrane fraction of MDR phenotype MCF-7ADR cells. The MDR drug-binding sequences generated during this work could provide an important tool for design and screening of new chemotherapeutic agents.

The effect of risperidone on cognition in patients with schizophrenia.

OBJECTIVE: To evaluate the effect of risperidone on cognitive functions after both 6 weeks and 6 months of treatment and to determine whether any improvement on neuropsychological function relates to improvement in psychopathology. METHOD: Patients' psychiatric and extrapyramidal symptoms were assessed while they were receiving classical neuroleptic treatment and adjunctive medications. Patients were then reassessed after changing to a new treatment of risperidone. RESULTS: During treatment with risperidone, schizophrenic patients displayed improved performance mainly on attentional components, specifically, selective attention and alertness. CONCLUSION: In patients who were given risperidone, there was a positive correlation between improvement in psychopathology and improvement in cognitive tests of explicit memory and alertness.

The heterogeneity of memory dysfunction in schizophrenia.

OBJECTIVE: To characterize the memory dysfunction of schizophrenic patients. METHOD: The components of the human memory system are described, and then a review of the various memory deficits identified among patients suffering from schizophrenia is presented. Finally, an overview of the latest developments in the comprehension of schizophrenia and a discussion on certain proposals advanced by various researchers in the field intended to shed light on the disorder is provided. RESULTS: Schizophrenia appears to be an amalgamation of many different disorders. No single model for identifying the disorder has been able to encompass every aspect of schizophrenia. CONCLUSION: Future studies will need to consider new ways of selecting and grouping schizophrenic patients.