Color vision impairment in type 2 diabetes assessed by the D-15d test and the Cambridge Colour Test

Color vision impairment emerges at early stages of diabetes mellitus type 2 (DM2) and may precede diabetic retinopathy or the appearance of vascular alterations in the retina. The aim of the present study was to compare the evaluation of the color vision with two different tests - the Lanthony desaturated D-15d test (a traditional color arrangement test), and the Cambridge Colour Test (CCT) (a computerized color discrimination test) - in patients diagnosed with DM2 without clinical signs of diabetic retinopathy (DR), and in sex- and age-matched control groups. Both color tests revealed statistically significant differences between the controls and the worst eyes of the DM2 patients. In addition, the degree of color vision impairment diagnosed by both tests correlated with the disease duration. The D-15d outcomes indicated solely tritan losses. In comparison, CCT outcomes revealed diffuse losses in color discrimination: 13.3% for best eyes and 29% for worst eyes. In addition, elevation of tritan thresholds in the DM2 patients, as detected by the Trivector subtest of the CCT, was found to correlate with the level of glycated hemoglobin. Outcomes of both tests confirm that subclinical losses of color vision are present in DM2 patients at an early stage of the disease, prior to signs of retinopathy. Considering the advantages of the CCT test compared to the D-15d test, further studies should attempt to verify and/or improve the efficiency of the CCT test.

Electrophysiological evidence for impairment of contrast sensitivity in mercury vapor occupational intoxication

Contrast sensitivity (CS) was evaluated in 41 former workers from a lamp manufacturing plant who were on disability retirement due to exposure to mercury and 14 age-matched controls. The CS was measured monocularly using the sweep visual evoked potential (sVEP) paradigm at 6 spatial frequencies (0.2, 0.8, 2.0, 4.0, 15.0, and 30 cpd). Statistical difference (p < 0.05) was found between the controls and the patient right and left eyes for 2.0 and 4.0 cpd. According the results in those spatial frequencies the eyes were classified in best and worst. Statistical differences were found between the controls and the best eyes for 2.0 and 4.0 cpd and for 0.8, 2.0, and 4.0 cpd for their worst eyes. No correlation was found between CS results and the time of exposure (mean 8.9 yr +/- 4.1), time away from the mercury source (mean = 6.0 yr +/- 3.9), urinary mercury level at the time of work (mean = 40.6 mu g/g +/-36.3) or with the mercury level at the CS measurement time (mean = 1.6 mu g/g +/-1.1). We show the first evidence of a permanent impairment in CS measured objectively with the sVEP. Our data complement the previous psychophysical works reporting a diffuse impairment in the CS function showing a CS reduction in the low to middle spatial frequencies. In conclusion, non-reversible CS impairment was found in occupational exposure to mercury vapor. We suggest that CS measurement should be included in studies of the mercury effects of occupational exposure. (C) 2007 Elsevier Inc. All rights reserved.

Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer's disease

Studies have shown that platelet APP ratio (representing the percentage of 120-130 kDa to 110 kDa isoforms of the amyloid precursor protein) is reduced in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). In the present study, we sought to determine if baseline APP ratio predicts the conversion from MCI to AD dementia after 4 years of longitudinal assessment. Fifty-five older adults with varying degrees of cognitive impairment (34 with MCI and 21 with AD) were assessed at baseline and after 4 years. MCI patients were re-classified according to the conversion status upon follow-up: 25 individuals retained the diagnostic status of MCI and were considered as stable cases (MCI-MCI); conversely, in nine cases the diagnosis of dementia due to AD was ascertained. The APP ratio (APPr) was determined by the Western blot method in samples of platelets collected at baseline. We found a significant reduction of APPr in MCI patients who converted to dementia upon follow-up. These individuals had baseline APPr values similar to those of demented AD patients. The overall accuracy of APPr to identify subjects with MCI who will progress to AD was 0.74 +/- A 0.10, p = 0.05. The cut-off of 1.12 yielded a sensitivity of 75 % and a specificity of 75 %. Platelet APPr may be a surrogate marker of the disease process in AD, with potential implications for the assessment of abnormalities in the APP metabolism in patients with and at risk for dementia. However, diagnostic accuracy was relatively low. Therefore, studies in larger samples are needed to determine whether APPr may warrant its use as a biomarker to support the early diagnosis of AD.

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders

Rationale Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. Objectives We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Methods Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. Results A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. Conclusions The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

Social phobia in Brazilian university students: Prevalence, under-recognition and academic impairment in women

Background: Despite the fact that public speaking is a common academic activity and that social phobia has been associated with lower educational achievement and impaired academic performance, little research has examined the prevalence of social phobia in college students. The aim of this study was to evaluate the prevalence of social phobia in a large sample of Brazilian college students and to examine the academic impact of this disorder. Methods: The Social Phobia Inventory (SPIN) and the MINI-SPIN, used as the indicator of social phobia in the screening phase, were applied to 2319 randomly selected students from two Brazilian universities. For the second phase (diagnostic confirmation), four psychiatrists and one clinical psychologist administered the SCID-IV to subjects with MINI-SPIN scores of 6 or higher. Results: The prevalence of social phobia among the university students was 11.6%. Women with social phobia had significantly lower grades than those without the disorder. Fear of public speaking was the most common social fear. Only two of the 237 students with social phobia (0.8%) had previously received a diagnosis of social phobia and were under treatment. Limitations: Social phobia comorbidities were not evaluated in this study. The methods of assessment employed by the universities (written exams) may mask the presence of social phobia. This was not a population-based study, and thus the results are not generalizable to the entire population with social phobia. Conclusion: Preventive strategies are recommended to reduce the under-recognition and the adverse impact of social phobia on academic performance and overall quality of life of university students. (C) 2011 Elsevier B.V. All rights reserved.

Lymphocyte transformation assay for C neoformans antigen is not reliable for detecting cellular impairment in patients with Neurocryptococcosis

Background: Cryptococcus neoformans causes meningitis and disseminated infection in healthy individuals, but more commonly in hosts with defective immune responses. Cell-mediated immunity is an important component of the immune response to a great variety of infections, including yeast infections. We aimed to evaluate a specific lymphocyte transformation assay to Cryptococcus neoformans in order to identify immunodeficiency associated to neurocryptococcosis (NCC) as primary cause of the mycosis. Methods: Healthy volunteers, poultry growers, and HIV-seronegative patients with neurocryptococcosis were tested for cellular immune response. Cryptococcal meningitis was diagnosed by India ink staining of cerebrospinal fluid and cryptococcal antigen test (Immunomycol-Inc, SP, Brazil). Isolated peripheral blood mononuclear cells were stimulated with C. neoformans antigen, C. albicans antigen, and pokeweed mitogen. The amount of H-3-thymidine incorporated was assessed, and the results were expressed as stimulation index (SI) and log SI, sensitivity, specificity, and cut-off value (receiver operating characteristics curve). We applied unpaired Student t tests to compare data and considered significant differences for p<0.05. Results: The lymphotoxin alpha showed a low capacity with all the stimuli for classifying patients as responders and non-responders. Lymphotoxin alpha stimulated by heated-killed antigen from patients with neurocryptococcosis was not affected by TCD4+ cell count, and the intensity of response did not correlate with the clinical evolution of neurocryptococcosis. Conclusion: Response to lymphocyte transformation assay should be analyzed based on a normal range and using more than one stimulator. The use of a cut-off value to classify patients with neurocryptococcosis is inadequate. Statistical analysis should be based on the log transformation of SI. A more purified antigen for evaluating specific response to C. neoformans is needed.

Olfactory impairment in familial ataxias

The main clinical manifestations of the spinocerebellar ataxias (SCAs) result from the involvement of the cerebellum and its connections. Cerebellar activity has been consistently observed in functional imaging studies of olfaction, but the anatomical pathways responsible for this connection have not yet been elucidated. Previous studies have demonstrated olfactory deficit in SCA2, Friedreich's ataxia and in small groups of ataxia of diverse aetiology. The authors used a validated version of the 16-item smell identification test from Sniffin' Sticks (SS-16) was used to evaluate 37 patients with genetically determined autosomal dominant ataxia, and 31 with familial ataxia of unknown genetic basis. This data was also compared with results in 106 Parkinson's disease patients and 218 healthy controls. The SS-16 score was significantly lower in ataxia than in the control group (p<0.001, 95% CI for beta=0.55 to 1.90) and significantly higher in ataxia than in Parkinson's disease (p<0.001, 95% CI for beta=-4.58 to -3.00) when adjusted for age (p=0.001, 95% CI for beta=-0.05 to -0.01), gender (p=0.19) and history of tobacco use (p=0.41). When adjusted for general cognitive function, no significant difference was found between the ataxia and control groups. This study confirms previous findings of mild hyposmia in ataxia, and further suggests this may be due to general cognitive deficits rather than specific olfactory problems.

C-Phycocyanin protects SH-SY5Y cells from oxidative injury, rat retina from transient ischemia and rat brain mitochondria from Ca2+/phosphate-induced impairment

Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant reduction of cell viability as assessed by an MTT assay, and the reduction was effectively prevented by treatment with C-PC in the low micromolar concentration range. Transient ischemia in rat retinas was induced by increasing the intraocular pressure to 120 mmHg for 45 min, which was followed by 15 min of reperfusion. This event resulted in a cell density reduction to lower than 50% in the inner nuclear layer (INL), which was significantly prevented by the intraocular pre-treatment with C-PC for 15 min. In the RBM exposed to 3 mM phosphate and/or 100 mu M Ca2+, C-PC prevented in the low micromolar concentration range, the mitochondrial permeability transition as assessed by mitochondrial swelling, the membrane potential dissipation, the increase of reactive oxygen species levels and the release of the pro-apoptotic cytochrome c. In addition, C-PC displayed a strong inhibitory effect against an electrochemically-generated Fenton reaction. Therefore, C-PC is a potential neuroprotective agent against ischemic stroke, resulting in reduced neuronal oxidative injury and the protection of mitochondria from impairment. (C) 2012 Elsevier Inc. All rights reserved.

Spectrum of cognitive impairment in neurocysticercosis Differences according to disease phase

Objectives: Cognitive decline related to neurocysticercosis (NC) remains poorly characterized and underdiagnosed. In a cross-sectional study with a prospective phase, we evaluated cognitive decline in patients with strictly calcified form (C-NC), the epidemiologically largest subgroup of NC, and investigated whether there is a spectrum of cognitive abnormalities in the disease. Methods: Forty treatment-naive patients with C-NC aged 37.6 +/- 11.3 years and fulfilling criteria for definitive C-NC were submitted to a comprehensive cognitive and functional evaluation and were compared with 40 patients with active NC (A-NC) and 40 healthy controls (HC) matched for age and education. Patients with dementia were reassessed after 24 months. Results: Patients with C-NC presented 9.4 +/- 3.1 altered test scores out of the 30 from the cognitive battery when compared to HC. No patient with C-NC had dementia and 10 patients (25%) presented cognitive impairment-no dementia (CIND). The A-NC group had 5 patients (12.5%) with dementia and 11 patients (27.5%) with CIND. On follow-up, 3 out of 5 patients with A-NC with dementia previously still presented cystic lesions with scolex on MRI and still had dementia. One patient died and the remaining patient no longer fulfilled criteria for either dementia or CIND, presenting exclusively calcified lesions on neuroimaging. Conclusions: Independently of its phase, NC leads to a spectrum of cognitive abnormalities, ranging from impairment in a single domain, to CIND and, occasionally, to dementia. These findings are more conspicuous during active vesicular phase and less prominent in calcified stages. Neurology (R) 2012; 78: 861-866

Investigation of auditory processing disorder and language impairment using the speech-evoked auditory brainstem response

This study investigated whether there are differences in the Speech-Evoked Auditory Brainstem Response among children with Typical Development (TD), (Central) Auditory Processing Disorder (C) APD, and Language Impairment (LI). The speech-evoked Auditory Brainstem Response was tested in 57 children (ages 6-12). The children were placed into three groups: TD (n = 18), (C)APD (n = 18) and LI (n = 21). Speech-evoked ABR were elicited using the five-formant syllable/da/. Three dimensions were defined for analysis, including timing, harmonics, and pitch. A comparative analysis of the responses between the typical development children and children with (C)APD and LI revealed abnormal encoding of the speech acoustic features that are characteristics of speech perception in children with (C)APD and LI, although the two groups differed in their abnormalities. While the children with (C)APD might had a greater difficulty distinguishing stimuli based on timing cues, the children with LI had the additional difficulty of distinguishing speech harmonics, which are important to the identification of speech sounds. These data suggested that an inefficient representation of crucial components of speech sounds may contribute to the difficulties with language processing found in children with LI. Furthermore, these findings may indicate that the neural processes mediated by the auditory brainstem differ among children with auditory processing and speech-language disorders. (C) 2012 Elsevier B.V. All rights reserved.

The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder

Background. - Persistent impairment in cognitive function has been described in euthymic individuals with bipolar disorder. Collective work indicates that obesity is associated with reduced cognitive function in otherwise healthy individuals. This sub-group post-hoc analysis preliminarily explores and examines the association between overweight/obesity and cognitive function in euthymic individuals with bipolar disorder. Methods. - Euthymic adults with DSM-IV-TR-defined bipolar I or II disorder were enrolled. Subjects included in this post-hoc analysis (n = 67) were divided into two groups (normal weight, body mass index [BMI] of 18.5-24.9 kg/m(2); overweight/obese, BMI >= 25.0 kg/m(2)). Demographic and clinical information were obtained at screening. At baseline, study participants completed a comprehensive cognitive battery to assess premorbid IQ, verbal learning and memory, attention and psychomotor processing speed, executive function, general intellectual abilities, recollection and habit memory, as well as self-perceptions of cognitive failures. Results. - BMI was negatively correlated with attention and psychomotor processing speed as measured by the Digit Symbol Substitution Test (P < 0.01). Overweight and obese bipolar individuals had a significantly lower score on the Verbal Fluency Test when compared to normal weight subjects (P < 0.05). For all other measures of cognitive function, non-significant trends suggesting a negative association with BMI were observed, with the exception of measures of executive function (i.e. Trail Making Test B) and recollection memory (i.e. process-dissociation task). Conclusion. - Notwithstanding the post-hoc methodology and relatively small sample size, the results of this study suggest a possible negative effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder. Taken together, these data provide the impetus for more rigorous evaluation of the mediational role of overweight/obesity (and other medical co-morbidity) on cognitive function in psychiatric populations. (C) 2011 Elsevier Masson SAS. All rights reserved.

Impairment on sperm quality and fertility of adult rats after antiandrogen exposure during prepuberty

This study evaluated the effects of antiandrogen exposure during the prepubertal period on reproductive development and reproductive competence in adults. Male rats were divided into two groups: flutamide, receiving 25 mg/kg/day of flutamide by oral gavage and control, receiving vehicle daily. Dosing continued from PND 21 to 44, and animals were killed on PND 50 or PND 75-80. The epididymis, prostate, vas deferens and seminal vesicle weights were lower in Flutamide group on PND 50, while on PND 80 only seminal vesicle weight was reduced. Fertility assessed by IUI revealed a decrease in the fertility potential in the flutamide-treated adults. Flutamide accelerated sperm transit time through the epididymis, impairing sperm motility and storage. A quantitative analysis of the cauda sperm membrane proteome revealed a few significant changes in protein expression. Thus, exposure to flutamide during the prepubertal period compromises the function of the epididymis along with epididymal sperm quality at adulthood. (C) 2011 Elsevier Inc. All rights reserved.

Cyclosporin A causes impairment of the ventral prostate tissue structure of Wistar rats

Cyclosporin A (CsA) is an immunosuppressive drug widely used in medicine to reduce the immune system activity and, therefore, the risk of organ rejection after transplantation. However, many side effects can be related to its use, such as, reduction in serum testosterone levels due to damage of the testis structure and, consequently, male infertility. The present study aims to evaluate the effects of chronic CsA administration on the ventral prostate tissue ( 1 5 mg/kg per d, for 56 days). Stereological, morphometrical, morphological and ultrastructural observations were employed. The plasmatic testosterone and glucose levels were measured. An androgen receptor (AR) immunohistochemical method was applied on ventral prostate sections. Apoptosis was detected with the terminal deoxynucleotidyl transferase dUTP nick end labeling technique. CsA treatment caused reduction in plasmatic testosterone levels and an increase in glycemia. The volume of all ventral prostate tissue components (lumen, epithelium and muscular and nonmuscular stroma) and ventral prostate weight were reduced in the CsA-treated group. Light and transmission electron microscopy confirmed epithelium atrophy of treated animals. There was no alteration of AR expression or apoptotic index. CsA chronic treatment in the therapeutic doses caused damage to prostate tissue of adult Wistar rats, probably due to increase in the glucose levels and reduction in the plasmatic testosterone levels.

Visual impairment in children with spastic cerebral palsy measured by psychophysical and electrophysiological grating acuity tests

Background: This study measured grating visual acuity in 173 children between 6-48 months of age who had different types of spastic cerebral palsy (CP). Method: Behavioural acuity was measured with the Teller Acuity Cards (TAC) using a staircase psychophysical procedure. Electrophysiological visual acuity was estimated using the sweep VEP (sVEP). Results: The percentage of children outside the superior tolerance limits was 44 of 63 (69%) and 50 of 55 (91%) of tetraplegic, 36 of 56 (64%) and 42 of 53 (79%) of diplegic, 10 of 48 (21%) and 12 of 40 (30%) of hemiplegic for sVEP and TAC, respectively. For the sVEP, the greater visual acuity deficit found in the tetraplegic group was significantly different from that of the hemiplegic group (p < 0.001). In the TAC procedure the mean visual acuity deficits of the tetraplegic and diplegic groups were significantly different from that of hemiplegic group (p < 0.001). The differences between sVEP and TAC means of visual acuity difference were statistically significant for the tetraplegic (p < 0.001), diplegic (p < 0.001), and hemiplegic group (p = 0.004). Discussion: Better visual acuities were obtained in both procedures for hemiplegic children compared to diplegic or tetraplegic. Tetraplegic and diplegic children showed greater discrepancies between the TAC and sVEP results. Inter-ocular acuity difference was more frequent in sVEP measurements. Conclusions: Electrophysiologically measured visual acuity is better than behavioural visual acuity in children with CP.

Secondary succession impairment in restored mangroves

In this work it was hypothesized that secondary succession on sites that have been managed by single planting of mangrove species is compromised by residual stressors, which could reduce the ecosystem's structural development and lower its functions. Forest structure and environmental characteristics of three planted mangrove stands are compared with reference sites. Structural attributes showed significant differences in the comparison of planted and reference stands. Avicennia schaueriana was the dominant species within both natural regeneration and old-growth stands in terms of basal area (99.2 and 99.4 %, 69.6 and 84.5 %, and 59.0 and 87.1 % for Itacorubi, Saco Grande, and Ratones, respectively). Restoration stands were dominated by Laguncularia racemosa (80.6 and 94.2 % for Saco Grande and Ratones, respectively), except at one site (Itacorubi), where A. schaueriana prevailed (99.7 %). Even though restoration and regeneration stands at Itacorubi showed similar species composition and dominance, cohort sorting revealed an inferior regeneration potential in the restoration stand. Multiple correlation analysis indicated that variables related to elevation disruptions (p (w) = 0.521) were the environmental drivers responsible for the differences observed in forest structure. At restoration sites an impaired pattern of secondary succession was observed, indicating that single species plantings may be ineffective if characteristics of the site, as well as of the area surrounding it, are not considered. The inadequate management of restoration sites can therefore have implications for both immediate and long-term large-scale ecosystem services.